Autism Research: 2002-2006
     
Child Care Health Dev. 2006 Nov;32(6):752.
Joint attention and symbolic play in young children with autism: a randomized controlled intervention study.
McConachie H.
Professor of Child Clinical Psychology Newcastle University Newcastle, UK.

Joint attention and symbolic play in young children with autism: a randomized controlled intervention study. KasariC., FreemanS. & PaparellaT. (2006) Journal of Child Psychology and Psychiatry (formerly Journal of Child Psychology and Psychiatry and Allied Disciplines), 47, 611-620. Background Delays and deficits in joint attention and symbolic play constitute two important developmental problems in young children with autism. These areas of deficit have been well studied in autism but have rarely been the focus of treatment efforts (see Kasari, Freeman & Paparella 2001). In this study, we examine the efficacy of targeted interventions of joint attention and symbolic play. Methods Participants were 58 children with autism aged 3 and 4 years old (46 boys). Children were randomized to a joint attention intervention, a symbolic play intervention, or control group. Interventions were conducted 30 min daily for 5-6 weeks. Both structured assessments of joint attention and play skills and mother-child interactions were collected pre and post intervention by independent assessors. Results Results indicate that both intervention groups improved significantly over the control group on certain behaviours. Children in the joint attention intervention initiated significantly more showing and responsiveness to joint attention on the structured joint attention assessment and more child-initiated joint attention in the mother-child interaction. The children in the play group showed more diverse types of symbolic play in interaction with their mothers and higher play levels both on the play assessment and in interaction with their mothers. Conclusions This randomized controlled trial provides promising data on the specificity and generalizability of joint attention and play interventions for young children with autism. Future studies need to examine the long-term effects of these early interventions on children's development.

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Int Clin Psychopharmacol. 2006 Nov;21(6):363-7.
Levetiracetam versus placebo in childhood and adolescent autism: a double-blind placebo-controlled study.
Wasserman S, Iyengar R, Chaplin WF, Watner D, Waldoks SE, Anagnostou E, Soorya L, Hollander E.
aDepartment of Psychiatry, Mount Sinai School of Medicine, New York bDepartment of Psychology, St Johns University, Jamaica, New York, USA.

The purpose of this study was to determine the safety and efficacy of the anticonvulsant levetiracetam in the treatment of children with autism. A previous open-label study in autistic children treated with levetiracetam demonstrated effectiveness in hyperactivity, impulsivity/aggression, and mood lability. Twenty patients with autism ranging from 5 to 17 years of age were entered into a 10-week, placebo-controlled, double-blind trial of levetiracetam versus placebo. The mean maximum dosage for levetiracetam was 862.50+/-279.19 mg/day. We evaluated global improvement of autism with the Clinical Global Impression-Improvement (CGI-I) Scale and aggression and affective instability with the Aberrant Behavior Checklist (ABC) parent and teacher ratings. We measured repetitive behaviors using the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score and impulsivity and hyperactivity with the Conners' Rating Scale-Revised: Long Version for parent and teacher. No significant difference was found between levetiracetam and placebo groups comparing the change in CGI-I (t=0.350, d.f.=13.621, P=0.765), nor on change in ABC, CY-BOCS or Conners' scales. These findings suggest that levetiracetam does not improve behavioral disturbances of autism, but are limited by the small sample size and lack of stratification of the autistic sample at baseline.

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J Autism Dev Disord. 2006 Oct 4; [Epub ahead of print]
Risperidone Improves Behavioral Symptoms in Children with Autism in a Randomized, Double-Blind, Placebo-Controlled Trial.
Pandina GJ, Bossie CA, Youssef E, Zhu Y, Dunbar F.
Medical Affairs, Janssen Pharmaceutica, Inc., Titusville, NJ, USA.

Subgroup analysis of children (5-12 years) with autism enrolled in an 8-week, double-blind, placebo-controlled trial of risperidone for pervasive developmental disorders. The primary efficacy measure was the Aberrant Behavior Checklist-Irritability (ABC-I) subscale. Data were available for 55 children given risperidone (n = 27) or placebo (n = 28); mean baseline ABC-I ( +/- SD) was 20.6 (8.1) and 21.6 (10.2). Risperidone [mean dose ( +/- SD): 1.37 mg/day (0.7)] resulted in significantly greater reduction from baseline to endpoint in ABC-I versus placebo [mean change ( +/- SD): -13.4 (1.5) vs. -7.2 (1.4), P < 0.05; ES = -0.7]. The most common adverse effect with risperidone was somnolence (74% vs. 7% with placebo). Risperidone treatment was well tolerated and significantly improved behavioral problems associated with autism.

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J Am Acad Child Adolesc Psychiatry. 2006 Oct;45(10):1196-205.
Atomoxetine for hyperactivity in autism spectrum disorders: placebo-controlled crossover pilot trial.
Arnold LE, Aman MG, Cook AM, Witwer AN, Hall KL, Thompson S, Ramadan Y.
The authors are with Ohio State University's Nisonger Center, Columbus, OH 43210, USA. arnold.6@osu.edu

OBJECTIVE: To explore placebo-controlled efficacy and safety of atomoxetine (ATX) for attention-deficit/hyperactivity disorder (ADHD) symptoms in children with autism spectrum disorders (ASD). METHOD: Children ages 5 to 15 with ASD and prominent ADHD symptoms were randomly assigned to order in a crossover of clinically titrated ATX and placebo, 6 weeks each, separated by 1-week washout. Slopes for each condition were compared by paired t test. RESULTS: In 2004-2005, 12 boys and 4 girls (7 with autistic disorder, 1 Asperger's, 8 pervasive developmental disorder not otherwise specified) all completed at least 3 weeks of each condition. On the primary outcome, the Hyperactivity subscale of the Aberrant Behavior Checklist, ATX was superior to placebo (p =.043, effect size d = 0.90). It was also superior on a 0 to 3 rating of nine DSM-IV ADHD hyperactive/impulsive symptoms (p =.005, d = 1.27), but missed significance on nine inattentive symptoms (p =.053, d= 0.89). Nine subjects responded to ATX, four to placebo (25% improvement on the Hyperactivity subscale plus Clinical Global Impressions-Improvement of 1-2. One was rehospitalized for recurrent violence on ATX. Adverse events were otherwise tolerable, with no tendency to stereotypy. CONCLUSIONS: ATX appears safe and effective for treating hyperactivity in some children with autism spectrum disorders. The effect appears as large as in a multisite methylphenidate trial in the same population, with fewer intolerable side effects. Further study in autism spectrum disorders is indicated.

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Autism. 2006 Sep;10(5):495-510.
Read my lips: The importance of the face in a computer-animated tutor for vocabulary learning by children with autism.
Massaro DW, Bosseler A.
University of California,USA.

A computer-animated tutor, Baldi, has been successful in teaching vocabulary and grammar to children with autism and those with hearing problems. The present study assessed to what extent the face facilitated this learning process relative to the voice alone. Baldi was implemented in a Language Wizard/Tutor, which allows easy creation and presentation of a vocabulary lesson involving the association of pictures and spoken words. The lesson plan included both the receptive identification of pictures and the production of spoken words. A within-subject design with five children with autism followed an alternating treatment in which each child continuously learned to criterion sets of words with and without the face. The rate of learning was significantly faster and the retention was better with the face. The research indicates that at least some children with autism benefit from the face in learning new language within an automated program.

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Semin Speech Lang. 2006 Aug;27(3):161-72.
Teaching young children with autism to talk.
Yoder P, McDuffie A.
Department of Special Education, Vanderbilt University, Nashville, Tennessee 37203, USA. paul.yoder@vanderbilt.edu

Frequent functional spoken communication is a common goal for young children with autism. We propose that the number of different nonimitative, referential, conventional, and communicative words used in a language sample is a reasonable measure of the behavior we wish to increase in such children. We review our own and others' studies focusing on young (i.e., 2 to 3 years old) children with autism to provide a rationale for including object play and nonverbal communication as potentially important treatment goals. Children who are not yet fluent in object play and nonverbal communication may need to improve these skills to facilitate the implementation and uptake of direct language therapy. Past research has shown that object play, nonverbal communication, and useful speech all are influenced by various types of interventions in young children with autism.

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Phys Occup Ther Pediatr. 2006;26(1-2):13-22.
Clinicians' perceptions of the benefits of aquatic therapy for young children with autism: a preliminary study.
Vonder Hulls DS, Walker LK, Powell JM.
Hoquiam School District, Hoquiam, WA, USA.

OBJECTIVE: This purpose of this study was to identify clinicians' perceptions of the benefits of aquatic therapy for young children with autism. METHODS: Eighteen aquatic occupational therapists treating young children with autism responded to a survey soliciting their opinions on changes in skill performance resulting from aquatic therapy. RESULTS: A majority of clinicians reported a substantial increase in swim skills, attention,muscle strength, balance, tolerating touch, initiating/maintaining eye contact, and water safety. CONCLUSION: The impairments, activity limitations, and participation restrictions seen in children with autism can be wide-ranging and outcomes can be difficult to operationally define and measure. In this preliminary study, clinicians identified the areas they perceived as improving as a result of aquatic therapy. This information could help narrow the field of likely outcomes as a first step toward studies of the effectiveness of aquatic therapy for children with autism.

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Biol Psychiatry. 2006 Aug 22; [Epub ahead of print]
Omega-3 Fatty Acids Supplementation in Children with Autism: A Double-blind Randomized, Placebo-controlled Pilot Study.
Amminger GP, Berger GE, Schafer MR, Klier C, Friedrich MH, Feucht M.
Department of Child and Adolescent Neuropsychiatry (GPA, MRS, CK, MHF, MF), Medical University of Vienna; Vienna, Austria; and ORYGEN Research Centre (GPA, GEB), University of Melbourne, Melbourne, Australia.

BACKGROUND: There is increasing evidence that fatty acid deficiencies or imbalances may contribute to childhood neurodevelopmental disorders. METHODS: We conducted a randomized, double-blind, placebo-controlled 6-week pilot trial investigating the effects of 1.5 g/d of omega-3 fatty acids (.84 g/d eicosapentaenoic acid, .7 g/d docosahexaenoic acid) supplementation in 13 children (aged 5 to 17 years) with autistic disorders accompanied by severe tantrums, aggression, or self-injurious behavior. The outcome measure was the Aberrant Behavior Checklist (ABC) at 6 weeks. RESULTS: We observed an advantage of omega-3 fatty acids compared with placebo for hyperactivity and stereotypy, each with a large effect size. Repeated-measures ANOVA indicated a trend toward superiority of omega-3 fatty acids over placebo for hyperactivity. No clinically relevant adverse effects were elicited in either group. CONCLUSIONS: The results of this study provide preliminary evidence that omega-3 fatty acids may be an effective treatment for children with autism.

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J Speech Lang Hear Res. 2006 Aug;49(4):698-711.
A randomized comparison of the effect of two prelinguistic communication interventions on the acquisition of spoken communication in preschoolers with ASD.
Yoder P, Stone WL.
Vanderbilt University, Nashville, TN 37203-5701, USA. paul.yoder@vanderbilt.edu

PURPOSE: This randomized group experiment compared the efficacy of 2 communication interventions (Responsive Education and Prelinguistic Milieu Teaching [RPMT] and the Picture Exchange Communication System [PECS]) on spoken communication in 36 preschoolers with autism spectrum disorders (ASD). METHOD: Each treatment was delivered to children for a maximum total of 24 hr over a 6-month period. Spoken communication was assessed in a rigorous test of generalization at pretreatment, posttreatment, and 6-month follow-up periods. RESULTS: PECS was more successful than RPMT in increasing the number of nonimitative spoken communication acts and the number of different nonimitative words used at the posttreatment period. Considering growth over all 3 measurement periods, an exploratory analysis showed that growth rate of the number of different nonimitative words was faster in the PECS group than in the RPMT group for children who began treatment with relatively high object exploration. In contrast, analogous slopes were steeper in the RPMT group than in the PECS group for children who began treatment with relatively low object exploration.

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Autism. 2006 Jul;10(4):317-29.
Long-term outcome of social skills intervention based on interactive LEGO play.
Legoff DB, Sherman M.
Bancroft NeuroHealth, Haddonfield, NJ 08033, USA. dlegoff@aol.com

LEGO building materials have been adapted as a therapeutic modality for increasing motivation to participate in social skills intervention, and providing a medium through which children with social and communication handicaps can effectively interact. A 3 year retrospective study of long-term outcome for autistic spectrum children participating in LEGO therapy (N = 60) compared Vineland Adaptive Behavior Scale socialization domain (VABS-SD) and Gilliam Autism Rating Scale social interaction subscale (GARS-SI) scores preand post-treatment with a matched comparison sample (N = 57) who received comparable non-LEGO therapy. Although both groups made significant gains on the two outcome measures, LEGO participants improved significantly more than the comparison subjects. Diagnosis and pre-treatment full-scale IQ scores did not predict outcome scores; however, Vineland adaptive behavior composite, Vineland communication domain, and verbal IQ all predicted outcome on the VABS-SD, especially for the LEGO therapy group. Results are discussed in terms of implications for methods of social skills intervention for autistic spectrum disorders.

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Res Dev Disabil. 2006 Apr 5; [Epub ahead of print]
The effect of a parent-implemented imitation intervention on spontaneous imitation skills in young children with autism.
Ingersoll B, Gergans S.
Department of Psychology, Lewis & Clark College, 0615 SW Palatine Hill Rd., Portland, OR 97219, United States.

Children with autism exhibit significant deficits in their ability to spontaneously imitate the play actions and descriptive gestures of others. Reciprocal imitation training (RIT) is a naturalistic imitation intervention designed to teach spontaneous imitation skills during play. This study assessed the effectiveness of parent-implemented RIT using a multiple-baseline design across three young children with autism and their mothers. After an initial baseline, mothers were taught to implement RIT techniques with their child twice a week for 10 weeks in a clinic setting. Two mothers were taught to use RIT to teach object imitation. The third mother was taught to use RIT to target both object and gesture imitation in a multiple-baseline design across behaviors. Generalization was assessed in the families' homes at the end of treatment and a 1-month follow-up. Parents learned to use the intervention strategies and their children exhibited increases in spontaneous imitation. These findings replicate the results from previous studies, indicating that RIT is effective for teaching imitation skills to young children with autism in a naturalistic setting and extend the findings to parents.

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J Appl Behav Anal. 2006 Spring;39(1):91-102.
Enhancing job-site training of supported workers with autism: a reemphasis on simulation.
Lattimore LP, Parsons MB, Reid DH.
J. Iverson Riddle Developmental Center.

Currently recommended practice in supported work emphasizes training job skills to workers with severe disabilities while on the job. Early behavioral research indicated that skills needed in natural environments could also be trained in simulated settings. We compared job-site plus simulation training for teaching job skills to supported workers with autism to provision of training exclusively on the job. Job-site training occurred in a small publishing company during the regular work routine, and simulation training occurred in an adult education site for people with severe disabilities. Two pairs of workers received training on two job skills; one skill was trained at the job site and the other was trained using job-site plus simulation training. Results indicated that for 3 of the 4 comparisons, job-site plus simulation training resulted in a higher level of skill or more rapid skill acquisition than did job-site-only training. Results suggested that job-site training, the assumed best practice for teaching vocational skills, is likely to be more effective if supplemented with simulation training. Directions for future research include expanding applications of behavioral technologies to other aspects of the current support paradigm.

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Prescrire Int. 2006 Apr;15(82):43-4.
Risperidone: new indication. Behavioural disorders in children with autism or mental disabilities: no progress.
[No authors listed]

(1) Sedative drugs are one option when autistic or mentally disabled children have behavioural disorders that place them (or other people) in physical danger. Among the classic neuroleptics, haloperidol is the drug with the best-documented efficacy and safety. Placebo-controlled trials have also shown lithium to be effective for this use. (2) Clinical evaluation of risperidone in children with mental disabilities includes 3 placebo-controlled double-blind trials, 2 of which involved 118 and 110 children aged from 5 to 12 years who were treated for 6 weeks. All 3 trials showed a partial behavioural improvement in about 75% of children receiving risperidone, versus about 30% of children in the placebo groups. (3) Clinical evaluation of risperidone in autistic children includes 2 placebo-controlled double-blind trials involving 110 and 79 children who were treated for 8 weeks. One of these studies has been published in detail: 69% of children partially improved with risperidone, versus 12% of the children on placebo. (4) Given the absence of clinical trials comparing risperidone with haloperidol or lithium, there is no evidence that risperidone is more effective than these other treatments. (5) The principal adverse events observed in short-term trials of risperidone were drowsiness (affecting about 50% of children), weight gain (about 1.2 kg per month during the first months of treatment), and hyperprolactinaemia (affecting about 12% of children). Extrapyramidal disorders were infrequent during short-term trials, but their incidence reached about 25% after a year of risperidone treatment. (6) The impact of long-term risperidone therapy on growth and mental development is not known. (7) In France treatment is about 7 times more expensive with risperidone than with haloperidol. (8) In practice, the risk-benefit balance of risperidone in the treatment of autistic or mentally disabled children with behavioural disorders is no better overall than that of older products such as haloperidol and lithium, which, in the absence of anything better, remain the standard drugs.

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J Am Acad Child Adolesc Psychiatry. 2006 Apr;45(4):431-9.
Risperidone and adaptive behavior in children with autism.
Williams SK, Scahill L, Vitiello B, Aman MG, Arnold LE, McDougle CJ, McCracken JT, Tierney E, Ritz L, Posey DJ, Swiezy NB, Hollway J, Cronin P, Ghuman J, Wheeler C, Cicchetti D, Sparrow S.
Yale University, New Haven, CT 06520-7900, USA.

OBJECTIVE: To evaluate the impact of risperidone on adaptive behavior in children with autistic disorder who have serious behavior problems and to examine different methods of scoring the Vineland Adaptive Behavior Scales to measure change. METHOD: Forty-eight children (5 years to 16 years, 5 months) who showed behavioral improvement during acute treatment with risperidone were followed for 6 months and assessed with the Vineland Scales. RESULTS: Raw scores, age-equivalents, and special norm percentile scores all showed significant increases in adaptive behavior in the areas of communication, daily living skills, and socialization (p <.01). During a period of 6 to 8 months, children gained an average of 7.8 age-equivalent months in the area of socialization, a > 6% improvement beyond what would be expected based on baseline growth rates. CONCLUSIONS: Although limited by the absence of a control group, these results suggest that risperidone may improve adaptive skills in children with autistic disorder accompanied by serious behavioral problems. Vineland age-equivalent scores appear to be most useful in assessing change with treatment over time.

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J Autism Dev Disord. 2006 Apr 6; [Epub ahead of print]
The Effect of Coloured Overlays on Reading Ability in Children with Autism.
Ludlow AK, Wilkins AJ, Heaton P.
Department of Psychology, Goldsmiths College, University of London, New Cross, London, UK.

Abnormalities of colour perception in children with autistic spectrum disorders have been widely reported anecdotally. However, there is little empirical data linking difficulties in colour perception with academic achievement. The Wilkins Rate of Reading Test was administered with and without Intuitive Coloured Overlays to 19 children with autistic spectrum disorders and to the same number of controls individually matched for age and intelligence. Findings showed that 15 out of 19 (79%) children with autism showed an improvement of at least 5% in reading speed when using a coloured overlay. In contrast only 3 of 19 (16%) control group children showed such an improvement. The findings suggest that coloured overlays may provide a useful support for reading for children with autism.

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NeuroRx. 2006 Apr;3(2):207-16.
Intervention for autistic spectrum disorders.
Filipek PA, Steinberg-Epstein R, Book TM.
Department of Pediatrics, University of California, Irvine, School of Medicine, 92868, USA. ForOCKids@uci.edu

A comprehensive approach to the assessment of any child with autism must be matched specifically to each individual child and family. This premise holds for medical therapies and special education services as well as psychopharmacologic interventions. Behavioral, as opposed to pharmacologic, treatment is the hallmark of effective intervention for autism. Physicians involved in the care of children with autism need to become familiar with educational law and intervention recommendations. Goals should include improved functional verbal and nonverbal communication and social skills, increased engagement in developmentally appropriate activities, improved fine and gross motor skills, and the development of independent academic and organizations skills, as well as replacement of problem behaviors with developmentally appropriate behaviors.. Medicating children with autism is difficult, but is often necessary for chronic behavioral difficulties. In the absence of clear and present guidelines, we have attempted to use evidence and clinical experience to suggest an algorithm based on symptom clusters. Although children with autism may be responsive to medications at lower doses and more susceptible to side effects than other children, medical intervention can produce a significant improvement in the quality of life for the child and family. Careful thought leading to correct identification of target behaviors can appropriately direct better alternatives for medication. Although these approaches are costly and time-consuming endeavors, the expenditure of such efforts is the only available pathway to improve the potential outcomes for individuals with autism as well as decrease the lifetime societal costs for each individual.

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Med Hypotheses. 2006 Mar 20; [Epub ahead of print]
Hyperbaric oxygen therapy may improve symptoms in autistic children.
Rossignol DA, Rossignol LW.
Blue Ridge Medical Center, 4038 Thomas Nelson Highway, Arrington, VA 22922, USA; University of Virginia, P.O. Box 800729, Charlottesville, VA, USA.

Autism is a neurodevelopmental disorder that currently affects as many as 1 out of 166 children in the United States. Recent research has discovered that some autistic individuals have decreased cerebral perfusion, evidence of neuroinflammation, and increased markers of oxidative stress. Multiple independent single photon emission computed tomography (SPECT) and positron emission tomography (PET) research studies have revealed hypoperfusion to several areas of the autistic brain, most notably the temporal regions and areas specifically related to language comprehension and auditory processing. Several studies show that diminished blood flow to these areas correlates with many of the clinical features associated with autism including repetitive, self-stimulatory and stereotypical behaviors, and impairments in communication, sensory perception, and social interaction. Hyperbaric oxygen therapy (HBOT) has been used with clinical success in several cerebral hypoperfusion syndromes including cerebral palsy, fetal alcohol syndrome, closed head injury, and stroke. HBOT can compensate for decreased blood flow by increasing the oxygen content of plasma and body tissues and can even normalize oxygen levels in ischemic tissue. In addition, animal studies have shown that HBOT has potent anti-inflammatory effects and reduces oxidative stress. Furthermore, recent evidence demonstrates that HBOT mobilizes stem cells from human bone marrow, which may aid recovery in neurodegenerative diseases. Based upon these findings, it is hypothesized that HBOT will improve symptoms in autistic individuals. A retrospective case series is presented that supports this hypothesis.

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J Child Adolesc Psychopharmacol. 2006 Feb-Apr;16(1-2):181-6.
The use of selective serotonin reuptake inhibitors in autism and related disorders.
Posey DJ, Erickson CA, Stigler KA, McDougle CJ.
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. dposey@iupui.edu

This paper reviews the published literature on the use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of symptoms associated with autistic disorder and other pervasive developmental disorders (PDDs) in both children and adults. To date, placebocontrolled studies of SSRIs have involved only fluvoxamine (in children and adults) and fluoxetine (in children). Open-label and retrospective studies of all other SSRIs in PDDs have also been published that suggest effectiveness. Despite these positive reports, there continues to be questions about the tolerability and appropriate dosing of SSRIs in children with PDDs. Because of the limited number of placebo-controlled studies, definitive conclusions about the role SSRIs should play in the clinical treatment of children with PDDs cannot be drawn. Larger, placebo-controlled studies of SSRIs are needed to guide clinical treatment.

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J Intellect Disabil Res. 2006 Feb;50(Pt 2):139-50.
Verbal communication outcomes in children with autism after in-home father training.
Seung HK, Ashwell S, Elder JH, Valcante G.
Department of Communicative Disorders, College of Health Professions, University of Florida, FL, USA.

Abstract Background This retrospective study examined the efficacy of in-home father training on the communicative outcomes of children with autism. The in-home training consisted of two components: (1) expectant waiting; and (2) imitation with animation. Methods Efficacy of parent training was examined by measuring the ratio of utterances produced by the parents to the utterances produced by the children and the number of verbal imitation by the parents. Outcomes of the children's verbal production were examined by measuring the number of (1) single word utterances; (2) different words produced; and (3) verbal response to questions. Results Following training there was a decrease in the ratio of parent to child utterances and an increase in (1) the use of imitation by the parents; and (2) the number of single words and different words produced by the children. Discussion Results of this study suggested that the parents had learned to wait for their children to communicate verbally during communicative interactions and to interact more efficiently with their children by using verbal imitation. Overall, the results of this study support the efficacy of parent training that focuses on promotion of social reciprocity, and have important implications for clinicians and future research.

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Child Adolesc Psychiatr Clin N Am. 2006 Jan;15(1):161-75.
An update on pharmacologic treatments for autism spectrum disorders.
King BH, Bostic JQ.
Children's Hospital and Regional Medical Center, University of Washington, Seattle, WA, USA.

Increasingly recognized over the past 20 years, autism spectrum disorders (ASD) are heterogeneous. Medication treatments remain fundamentally ameliorative, so prioritizing symptoms and matching medications to the patient's constellation of symptoms remains the psychopharmacologic approach to ASD. Atypical antipsychotic medications and glutamatergic agents are receiving increased attention, and antidepressants are being examined for specific symptoms and for younger patients who have autism. Large multisite networks (Research Units on Pediatric Psychopharmacology; Studies to Advance Autism Research and Treatment) have been constructed to expedite studies to elucidate effective treatments for ASD. Findings from these networks are coupled with those from recent independent trials.

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Med Hypotheses. 2006 Jan 6; [Epub ahead of print]
Nicotinic cholinergic antagonists: A novel approach for the treatment of autism.
Lippiello PM.
Preclinical Research, Targacept, Inc., 200 East First Street, Suite 300, Winston-Salem, NC 27101, United States.

Evidence supports the hypothesis that normalization of cholinergic tone by selective antagonism of neuronal nicotinic acetylcholine receptors (NNRs) may ameliorate the core symptoms of autism. As often is the case, epidemiology has provided the first important clues. It is well recognized that psychiatric patients are significantly more often smokers than the general population. The only known exceptions are obsessive-compulsive disorder (OCD), catatonic schizophrenia and interestingly, autism. In this regard, clinical studies with nicotine have demonstrated amelioration of symptoms of a number of diseases and disorders, including Alzheimer's disease, Parkinson's disease, ADHD and Tourette's syndrome. Nicotine's agonist properties at CNS NNRs have been implicated in these effects and support the concept of self-medication as a strong motivation for smoking in cognitively compromised individuals. On the other hand, the inverse correlation between autism and smoking suggests that smoking does not provide symptomatic relief and may actually be indicative of an active avoidance of nicotine's agonist effects in this disorder. Neuroanatomical evidence is consistent with this idea based on the presence of hypercholinergic architecture in the autistic brain, particularly during the first few years of development, making the avoidance of further stimulation of an already hyperactive cholinergic system plausible. This may also explain why stimulants (known to increase dopamine levels as do NNR agonists) appear to aggravate autistic symptoms and why studies with cholinesterase inhibitors that increase acetylcholine levels in the brain have yielded variable effects in autism. Taken together, the evidence suggests the possibility that nicotinic cholinergic antagonism may in fact be palliative. Pharmacological evidence supports this hypothesis. For example, antidepressants, many of which are now known to be non-competitive NNR antagonists, have been used successfully to treat a number of autistic symptoms. More specifically, there is anecdotal evidence from at least one medical practitioner that mecamylamine, a non-selective NNR antagonist, is effective in treating many autistic symptoms, particularly those that are refractory to most other treatments. Clearly there is a need for carefully controlled clinical studies with novel selective NNR antagonists to explore their potential as a new and exciting approach for the treatment of autism.

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J Clin Psychiatry. 2005;66 Suppl 10:38-45.
Treatment planning for patients with autism spectrum disorders.
Aman MG.
>From The Nisonger Center, Ohio State University, Columbus, Ohio.

Patients with autism spectrum disorders (ASDs) can present with extremely heterogeneous issues, and, therefore, their treatment can be very challenging. Most patients with ASDs will benefit from contact with a multitude of disciplines. In this article, treatment planning is structured in terms of the patient's life stages. Early on, assessment of developmental milestones, metabolic conditions, and hearing; making the diagnosis of ASD; and providing genetic counseling are salient. As the child grows, speech and language therapy, early intensive intervention, special education, parent training, and neurologic assessment become important. With greater age, behavior therapy, pharmacotherapy, occupational therapy, and sexuality issues are often in ascendancy. As the patient approaches and proceeds through adulthood, transition training, housing options, and guardianship issues may be priorities. Advocacy is relevant throughout the life span. Professionals have an obligation to familiarize parents with interventions likely to be fruitful or unhelpful. There is growing evidence that early intensive behavior intervention, though expensive, may produce lifelong gains in functioning. A variety of experimental and/or unproven treatments are identified; mental health professionals can help families with members who have ASDs by guiding them toward effective treatments and away from therapies of unknown value but with potential risks and/or costs.

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J Clin Psychiatry. 2005;66 Suppl 10:32-7.
Safety issues with drug therapies for autism spectrum disorders.
McCracken JT.
>From the University of California, Los Angeles, Neuropsychiatric Institute, Los Angeles.

Although currently no medication has been approved to treat autism spectrum disorders, survey data show that community practitioners are prescribing a broad range of medication treatments, including, but not limited to, antidepressants, stimulants, antipsychotics, alpha agonists, and anticonvulsants. Patients with autism spectrum disorders are also taking alternative treatments, including herbal remedies, immunologic treatments, and vitamin therapies, which may themselves produce side effects and/or create drug interactions with traditional medications. Although short-term data on the efficacy and safety of commonly prescribed treatments for autism spectrum disorders are increasing, few data are currently available on long-term treatment for autism spectrum disorders, but available studies and clinical experience can offer preliminary recommendations on the safety of and monitoring needs for the medications currently used for these disorders. Monitoring the safety and tolerability of drugs used in patients with these disorders should minimize the burden of side effects and optimize treatment outcome.

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J Child Adolesc Psychopharmacol. 2005 Dec;15(6):869-84.
Acute and long-term safety and tolerability of risperidone in children with autism.
Aman MG, Arnold LE, McDougle CJ, Vitiello B, Scahill L, Davies M, McCracken JT, Tierney E, Nash PL, Posey DJ, Chuang S, Martin A, Shah B, Gonzalez NM, Swiezy NB, Ritz L, Koenig K, McGough J, Ghuman JK, Lindsay RL.
The Nisonger Center, Ohio State University, Columbus, Ohio 43210-1296, USA. aman.1@osu.edu

Treatment-emergent adverse events (AEs) were monitored during an 8-week, double-blind, placebo-controlled trial of risperidone (0.5-3.5 mg/day) in 101 children and adolescents with a lifetime diagnosis of autistic disorder. In addition, 37 placebo nonresponders received open-label risperidone for another 8 weeks. Of all the risperidone responders (n=65), 63 entered an open extension of another 16 weeks (6 months total risperidone exposure), and 32 of them were rerandomized to either continued risperidone therapy (n=16) or gradual replacement with placebo (n=16) over 8 weeks. We collected the following measures of safety and tolerability: (1) laboratory blood assessments (CBC with differential, electrolytes, and liver function tests) and urinalyses, (2) vital signs, (3) Side Effects Review of AEs thought to be associated with risperidone, (4) sleep records, (5) Simpson Angus Neurological Rating Scale (SARS), (6) Abnormal Involuntary Movement Scale (AIMS), and (7) height and weight. No clinically significant changes were found on the lab tests. During the 8-week acute trial, the most common AEs on the Side Effects Review, scored as moderate or higher, were as follows (placebo and risperidone, respectively): Somnolence (12% and 37%), enuresis (29% and 33%), excessive appetite (10% and 33%), rhinitis (8% and 16%), difficulty waking (8% and 12%), and constipation (12% and 10%). "Difficulty falling asleep" and anxiety actually favored the risperidone condition at statistically significant levels. The same AEs tended to recur through 6 months of treatment, although often at reduced levels. Using Centers for Disease Control (CDC) standardized scores, both weight and body mass index (BMI) increased with risperidone during the acute trial (0.5 and 0.6 SDs, respectively, for risperidone; 0.0 and 0.1 SDs, respectively, for placebo) and into open-label extension (0.19 and 0.16 SDs, respectively), although the amount of gain decelerated with time. Extrapyramidal symptoms, as assessed by the SARS, were no more common for drug than placebo, although drooling was reported more often in the risperidone group. There were no differences between groups on the AIMS. Two subjects had seizures (one taking placebo), but these were considered unrelated to active drug. Most AEs were mild to moderate and failed to interfere with therapeutic changes; there were no unanticipated AEs. The side effects of most concern were somnolence and weight gain.

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J Child Health Care. 2005 Dec;9(4):245-55.
Exploring a massage intervention for parents and their children with autism: the implications for bonding and attachment.
Cullen-Powell LA, Barlow JH, Cushway D.
Interdisciplinary Research Centre in Health, Coventry University. l.powell@coventry.ac.uk

This exploratory study aimed to address two questions: (1) What does touch mean between parents and their children with autism on completion of a massage intervention? (2) Do parents feel that their relationship with their children has changed on completion of a massage intervention? Fourteen parents agreed to be interviewed. Data were collected before the massage intervention (baseline), immediately after the massage intervention and 16 weeks from baseline and were analysed using interpretative phenomenological analysis. At baseline, parents felt distressed that they felt unable to get 'close' to their children. After the intervention, parents reported feeling physically and emotionally closer to their children. Children expressed a range of cues to initiate massage at home. These benefits were maintained at follow-up for parents who continued to use massage at home. In conclusion, giving massage to children with autism may help to enhance the emotional bond between parent and child.

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Indian J Pediatr. 2005 Nov;72(11):949-52.
Complementary and alternative medicine in developmental disabilities.
Brown KA, Patel DR.
Kalamazoo Center for Medical Studies, Michigan State University College of Human Medicine, Kalamazoo, Michigan, USA.

Developmental disabilities (DD) are defined as a diverse group of severe chronic conditions due to mental and/or physical impairments. Individuals with developmental disabilities have difficulty with major life activities including language, mobility, and learning. Developmental disabilities can begin anytime during development--from prenatal up to 22 years of age, and the disability usually lasts throughout a person's lifetime. Autism spectrum disorders, cerebral palsy, mental retardation, and attention deficit hyperactivity disorder are common conditions falling within the definition of developmental disabilities. Complementary and alternative medicine (CAM) is becoming increasingly utilized in the general population for treatment of everything from the common cold to complex and chronic medical conditions. This article reviews the prevalence of different types of CAM used for various developmental disabilities.

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CNS Drugs. 2005;19(11):923-34.
Advances in drug treatments for children and adolescents with autism and other pervasive developmental disorders.
Malone RP, Gratz SS, Delaney MA, Hyman SB.
Department of Psychiatry, Drexel University College of Medicine, Philadelphia, PA 19124-8358, USA. rmalone@drexelmed.edu

Autism is a disorder characterised by abnormalities in language and social development, and repetitive behaviours. Antipsychotics, including haloperidol and risperidone, are the most widely studied drugs for reducing symptoms in children and adolescents with autism. When administered at relatively low dosages, antipsychotics have been shown to reduce repetitive behaviours (stereotypies) and social withdrawal, as well as a number of related symptoms, such as hyperactivity, aggression, self-abusive behaviour, temper tantrums, lability of mood and irritability. Adverse effects of antipsychotics include sedation, dizziness, increased appetite, weight gain, changes in the electrocardiogram parameters, drooling, hyperprolactinemia and a risk of drug-related dyskinesias. Other agents have been less well studied for the treatment of autism, but there are suggestive data regarding their safety and efficacy. Of these agents, a number have been investigated, based on theories about the aetiology of autism, including SSRIs and naltrexone, although the efficacy of these agents has been limited. Stimulant drugs have been shown to reduce hyperactivity and improve focus, but they may cause behavioural worsening, weight loss and stereotypies de novo. Secretin is a treatment that has received much media attention after reports of efficacy from small open studies, but all controlled studies have failed to show any benefit. In autism, alternative treatments have also been used, but none have shown benefit in well-designed studies.

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Am Acad Child Adolesc Psychiatry. 2005 Nov;44(11):1137-1144.
Long-Term Effects of Risperidone in Children With Autism Spectrum Disorders: A Placebo Discontinuation Study.
Troost PW, Lahuis BE, Steenhuis MP, Ketelaars CE, Buitelaar JK, van Engeland H, Scahill L, Minderaa RB, Hoekstra PJ.
Drs. Troost, Hoekstra, Ketelaars, and Minderaa, and M.-P. Steenhuis are with the Department of Psychiatry, University Medical Center Groningen, University of Groningen, The Netherlands; Drs. Lahuis and Van Engeland are with the Department of Child Psychiatry and Rudolf Magnus Institute for Neuroscience, University Medical Center Utrecht, The Netherlands; Dr. Buitelaar is with the Department of Psychiatry, University Medical Center, St. Radboud, Nijmegen, The Netherlands; and Dr. Scahill is with the Child Study Center, Yale University, New Haven, CT.

OBJECTIVE:: The short-term benefit of risperidone in ameliorating severe disruptive behavior in pediatric patients with autism spectrum disorders is well established; however, only one placebo-controlled, long-term study of efficacy is available. METHOD:: Thirty-six children with an autism spectrum disorder (5-17 years old) accompanied by severe tantrums, aggression, or self-injurious behavior, started 8-week open-label treatment with risperidone. Responders (n = 26) continued treatment for another 16 weeks, followed by a double-blind discontinuation (n = 24; two patients discontinued treatment because of weight gain) consisting of either 3 weeks of taper and 5 weeks of placebo only or continuing use of risperidone. Relapse was defined as a significant deterioration of symptoms based on clinical judgment and a parent questionnaire. RESULTS:: Risperidone was superior to placebo in preventing relapse: this occurred in 3 of 12 patients continuing on risperidone versus 8 of 12 who switched to placebo (p = .049). Weight gain, increased appetite, anxiety, and fatigue were the most frequently reported side effects. CONCLUSIONS:: This study indicates the effectiveness of risperidone during a period of several months, reducing disruptive behavior in about half of the children with autism spectrum disorders. The results provide a rationale for the continuing use of risperidone beyond 6 months, although considerable weight gain can limit the use of this agent.

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Am J Ment Retard. 2005 Nov;110(6):417-38.
Intensive behavioral treatment for children with autism: four-year outcome and predictors.
Sallows GO, Graupner TD.
Wisconsin Early Autism Project (Madison).

Twenty-four children with autism were randomly assigned to a clinic-directed group, replicating the parameters of the early intensive behavioral treatment developed at UCLA, or to a parent-directed group that received intensive hours but less supervision by equally well-trained supervisors. Outcome after 4 years of treatment, including cognitive, language, adaptive, social, and academic measures, was similar for both groups. After combining groups, we found that 48% of all children showed rapid learning, achieved average posttreatment scores, and at age 7, were succeeding in regular education classrooms. Treatment outcome was best predicted by pretreatment imitation, language, and social responsiveness. These results are consistent with those reported by Lovaas and colleagues (Lovaas, 1987; McEachin, Smith, & Lovaas, 1993).

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Cochrane Database Syst Rev. 2005 Oct 19;(4):CD003497.
Combined vitamin B6-magnesium treatment in autism spectrum disorder.
Nye C, Brice A, Nye C.

BACKGROUND: The use of mega-vitamin intervention began in the 1950s with the treatment of schizophrenic patients. Pyroxidine (vitamin B6) was first used with children diagnosed with "autism syndrome" when speech and language improvement was observed in some children as a result of large doses of B6. A number of studies attempted to assess the effects of vitamin B6-Magnesium (Mg) was found to reduce undesirable side effects from B6) on characteristics such as verbal communication, non-verbal communication, interpersonal skills, and physiological function, in individuals with autism. OBJECTIVES: To determine the efficacy of vitamin B6 and magnesium (B6-Mg) for treating social, communication, and behavioural responses of children and adults with autism. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2002), MEDLINE (1966 to January 2002), EMBASE (1980 to January 2002), PsycINFO (1887 to January 2002), Dissertation Abstracts International (1861 to January 2002). The search engine FirstSearch was also used (January 2002). All searches were updated in April 2005. Reference lists for all the obtained studies and other review articles were examined for additional studies. SELECTION CRITERIA: All studies in which the participants had been diagnosed with autistic spectrum disorder were randomly allocated prior to intervention and in which outcomes were compared to either a placebo or non-treated group were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated and extracted data from all potential studies identified for inclusion. MAIN RESULTS: This update includes a new trial (Kuriyama 2002) to bring the total of included studies to three (total n=33). One study, which used a cross-over design (Tolbert 1993) provided insufficient data to conduct an analysis. Another crossover study (Findling 1997) yielded no significant differences between treatment and placebo group performances following the B6 intervention on measures of social interaction, communication, compulsivity, impulsivity, or hyperactivity. The latest study (Kuriyama 2002) was motivated by evidence from epilepsy research and was focussed on a subgroup of children with pervasive developmental disorders (PDDs) who exhibited clinical features similar to those with pyroxidine-dependent epilepsy. This small study (n=8) only measured IQ and 'Social Quotient' and found a statistically significant benefit for IQ (5.2, 95% CI = [0.2 to 10.3]) when in the treated group, by using change scores. AUTHORS' CONCLUSIONS: Due to the small number of studies, the methodological quality of studies, and small sample sizes, no recommendation can be advanced regarding the use of B6-Mg as a treatment for autism.

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J Clin Psychopharmacol. 2005 Oct;25(5):485-9.
Tetrahydrobiopterin in the treatment of children with autistic disorder: a double-blind placebo-controlled crossover study.
Danfors T, von Knorring AL, Hartvig P, Langstrom B, Moulder R, Stromberg B, Torstenson R, Wester U, Watanabe Y, Eeg-Olofsson O.
Department of Neuroscience, Hospital Pharmacy, Uppsala University, PET-Centre, Uppsala Imanet AB, Sweden.

Twelve children, all boys, aged 4 to 7 years, with a diagnosis of autistic disorder and low concentrations of spinal 6R-l-erythro-5,6,7,8-tetrahydrobiopterin (tetrahydrobiopterin) were selected to participate in a double-blind, randomized, placebo-controlled, crossover study. The children received a daily dose of 3 mg tetrahydrobiopterin per kilogram during 6 months alternating with placebo. Treatment-induced effects were assessed with the Childhood Autism Rating Scale every third month. The results showed small nonsignificant changes in the total scores of Childhood Autism Rating Scale after 3- and 6-month treatment. Post hoc analysis looking at the 3 core symptoms of autism, that is, social interaction, communication, and stereotyped behaviors, revealed a significant improvement of the social interaction score after 6 months of active treatment. In addition, a high positive correlation was found between response of the social interaction score and IQ. The results indicate a possible effect of tetrahydrobiopterin treatment.

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J Pediatr. 2005 Sep;147(3):335-40.
A controlled trial of a training course for parents of children with suspected autism spectrum disorder.
McConachie H, Randle V, Hammal D, Le Couteur A.
School of Clinical Medical Sciences, University of Newcastle, Sir James Spence Institute, Royal Victoria Infirmary, Newcastle, United Kingdom. h.r.mcconachie@newcastle.ac.uk

OBJECTIVE: To evaluate a training course for parents, designed to help them understand autism spectrum disorder and to facilitate social communication with their young child. STUDY DESIGN: Controlled trial for 51 children aged 24 to 48 months, whose parents received either immediate intervention or delayed access to the course. Outcome was measured 7 months after recruitment in parents' use of facilitative strategies, stress, adaptation to the child; and in children's vocabulary size, behavior problems, and social communication skills. RESULTS: Taking into account scores at recruitment, child's level of ability, diagnostic grouping, and the interval between assessments, a significant advantage was found for the intervention group in parents' observed use of facilitative strategies and in children's vocabulary size. CONCLUSIONS: The training course is well received by parents and has a measurable effect on both parents' and children's communication skills.

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J Sch Nurs. 2005 Aug;21(4):208-17.
Caring for children with autism in the school setting.
Galinat K, Barcalow K, Krivda B.
Karen Galinat, RN, BSN, wrote this paper while she was in the School Nurse Certificate Program at Rutgers University, Camden, NJ. She is currently a school nurse with the Mercer County Special Services School District in Mercer County, NJ.

Children with autism present unique challenges related to communication, behavior, and social skills. Each child with an autistic spectrum disorder (ASD) exhibits individual characteristics of the disorder. Early identification of autistic spectrum disorder has been shown to improve the child's benefit from educational interventions. There may be health issues related to autism including seizure disorders and dietary restrictions. Students with autism need special consideration when they come to the health office for screening, assessment of injuries, or administration of medication. Collaboration between educators and school nurses is needed to develop and implement Individual Education Plans and Individual Healthcare Plans. Community resources provide valuable assistance to families of children with this challenging disorder.

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Complement Ther Clin Pract. 2005 Aug;11(3):182-9.
Positive touch, the implications for parents and their children with autism: an exploratory study.
Cullen LA, Barlow JH, Cushway D.
School of Health and Social Science, Interdisciplinary Research Centre in Health, Coventry University, Priory Street, Coventry CV1 5FB, UK. l.powell@coventry.ac.uk

The aims of this study were (1) to explore the experience of touch between parents and children with autism before, during, and after a Training and Support Programme (TSP), and (2) to develop a model of the process of touch therapy for this group of parents and children. Fourteen parents and their children agreed to take part in the study. Five of these parents withdrew. Reasons for withdrawal included personal circumstances and ill health. Data were collected by semi-structured interviews with parents before attending the TSP and Home Record Sheets completed by parents during the TSP. Results indicate that before the TSP touch was experienced as out of parents' control. During the TSP, the experience of touch appeared to change. A key benefit gained by parents was the feeling of closeness to children. The key benefits gained by children were perceived by the parents as improved sleep patterns, children were more relaxed after receiving the massage and appeared more amenable to touch. Of interest was children's request for massage at home. At 16-week follow-up both parents and children continue to enjoy giving and receiving touch therapy, respectively.

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Ment Retard Dev Disabil Res Rev. 2005;11(2):164-70.
Placebo effects in developmental disabilities: implications for research and practice.
Sandler A.
Department of Pediatrics, University of North Carolina at Chapel Hill, 28801, USA. adsandler@POL.net

Recent clinical trials of secretin in children with autism showed robust placebo effects and no benefit of secretin over placebo. This article explores the reasons for the observed placebo effects, focusing on the heightening of positive expectancy by media attention and by the sensory experiences associated with intravenous injections. Comparisons are drawn with research involving other novel treatments and other clinical populations of children with developmental disabilities and neurobehavioral disorders. Research regarding mechanisms of placebo effects is reviewed, including patient and clinician attributes, expectancy effects, participation effects, changes in caregiver behavior, and conditioning. New evidence regarding the biological basis of placebo effects is briefly presented. Since placebo effects are ubiquitous and may operate by a variety of mechanisms, research design is critical in designing clinical trials and in evaluating other outcomes research. Measurement issues important for research in developmental disabilities are emphasized. Ethical concerns have been raised regarding the use of placebo in clinical research, but current analysis suggests that placebo controls are necessary and defensible on ethical grounds, if certain conditions are met. The study of placebo effects ("placebology") holds great promise as a new area of research in therapeutics. The author's research in the potential augmentation of stimulant effects in children with attention deficit/hyperactivity disorder (ADHD) by adding placebo in open label is briefly presented. The placebo has always been integral to the practice of medicine, but advances in scientific medicine and medical ethics have diminished the role and use of placebo in practice. An innovative approach to the ethical use of placebo is proposed. Copyright 2005 Wiley-Liss, Inc.

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J Neural Transm. 2005 Aug 3; [Epub ahead of print]
Self injurious behavior in autism: clinical aspects and treatment with risperidone.
Canitano R.
Division of Child Neuropsychiatry, University General Hospital of Siena, Italy.

Self injurious behavior (SIB) is frequent in autistic spectrum disorders. The aim of this study was to investigate the phenomenology of SIB in a group of children with autistic disorder, and to test whether treatment with risperidone might reduce it. A group of eleven children diagnosed with autistic disorder according to the DSM-IV criteria (mean age 8.7+/-2.2 ys) and with severe SIB were recruited for an open study of six months of treatment with risperidone. The Yale-Paris Self-Injurious Behavior Scale was used to delineate the clinical characteristics and as an outcome measure. Head-hitting and hand biting were the most frequent forms of self aggression observed. Nine children presented a mild improvement in SIB and 2 did not show any variation. A decrease in Yale-Paris Self Injurious Behavior Scale score (from M 15.1+/-1.4 to 13.3+/-1.4) was noted mainly due to the reduction of frequency. Side effects of risperidone were not severe.

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J Am Acad Nurse Pract. 2005 Aug;17(8):302-8.
Asperger syndrome in children.
Schnur J.

Purpose To review Asperger syndrome characteristics, assessment tools, interventions, outcomes, and the role of the nurse practitioner in diagnosing and caring for children with Asperger syndrome. Data sources Review of published literature on and diagnostic criteria of the condition. Conclusions Asperger syndrome is a pervasive developmental disorder or an autism spectrum disorder that is thought to have an incidence higher than that of autism. Asperger syndrome is different from autism, with a lack of delayed language as the most distinct difference between Asperger syndrome and autism. Implications for practice Because of the importance of early diagnosis of Asperger syndrome for outcome improvement, screening at all well-child visits from infancy on is of utmost importance to primary care pediatric nurse practitioners. With early diagnosis, timely intervention is possible, which is proven to show improvement in outcomes.

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Expert Opin Emerg Drugs. 2005 Aug;10(3):521-36.
Autism spectrum disorders: emerging pharmacotherapy.
Bostic JQ, King BH.
Harvard Medical School, Boston, MA, USA.

Autism, Asperger and other pervasive developmental disorders (PDDs) are an increasingly commonly identified group of conditions wherein patients experience significant difficulty in social interactions, communicating with others, and inflexible adherence to unusual, unhelpful and frequently stereotyped routines and behaviour. These autism spectrum disorders are now being diagnosed earlier in life (approximately 15 months), and often remain a chronic, daily burden for those afflicted. In addition to the often profound impact on an individual's quality of life, the familial, social and economic burdens of PDDs can be enormous. No treatments are curative, and most pharmacological treatments are employed to treat specific troubling symptoms rather than the core features of the disorder itself. Therefore, more effective pharmacotherapies are desperately needed. This review describes current and emerging pharmacotherapies that may advance care of people with PDDs.

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Res Dev Disabil. 2005 Jul 25; [Epub ahead of print]
Stepping Stones Triple P: A pilot study to evaluate acceptability of the program by parents of a child diagnosed with an Autism Spectrum Disorder.
Whittingham K, Sofronoff K, Sheffield JK.
School of Psychology, University of Queensland, Brisbane, Qld 4072, Australia.

The experience of parents of children with Autism Spectrum Disorder (ASD) in standard parenting programs has not been researched, although anecdotal evidence suggests that they do not find them acceptable. Forty-two parents of children with ASD were asked to view a DVD explaining individual parenting strategies from Stepping Stones, a new branch of the Triple P program targeted specifically at parents of children with disabilities. Parents were asked to rate each strategy for acceptability, usability and behavioural intention, i.e., their intention to use the strategy. Additionally, parental attributions and parental perceived control were explored as possible barriers to positive evaluations of Stepping Stones parenting strategies. A focus group of parents was used to gather more detailed parent response to the program. Parent responses to the program were generally positive and attribution of the child's behaviour to uncontrollable factors was found to predict higher ratings of usability. The results were interpreted within the context of Weiner's attributional theory and the theory of reasoned action. The limitations of this study and suggestions for future research are discussed.

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Cochrane Database Syst Rev. 2005 Jul 20;(3):CD003495.
Intravenous secretin for autism spectrum disorder.
Williams K, Wray J, Wheeler D.
Clinical Epidemiology, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, AUSTRALIA, 2145.

BACKGROUND: Secretin is a gastro-intestinal hormone which has been presented as an effective treatment for autism based on anecdotal evidence. OBJECTIVES: To determine if intravenous secretin:1. improves the core features of autism (social interaction, communication and behaviour problems); 2. improves the non-core aspects of behaviour or function such as self injurious behaviour;3. improves the quality of life of affected individuals and their carers; 4. has short term and long term effects on outcome; 5. causes harm. SEARCH STRATEGY: Results of electronic searches of CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL, ERIC, HealthStar and Sociofile (1998 - March 2005) were independently examined by two authors. Reference lists of trials and reviews were searched; experts and trialists were contacted to find unpublished studies. SELECTION CRITERIA: Randomised controlled trials of intravenous secretin comparing secretin with a placebo treatment in children or adults diagnosed with autism spectrum disorders, where at least one standardised outcome measure was reported. DATA COLLECTION AND ANALYSIS: Fourteen studies met inclusion criteria. All outcome data were continuous. Where trials used cross-over designs, analysis was conducted on results from first treatment phase, allowing combined analysis with parallel design trials. Where standardised assessment tools generated scores as outcome measures, comparisons were made between means of these scores. Where baseline means were reported, differences between treatment and control were determined to assess possible bias. Where mean change from baseline was reported, this was used in preference to post-treatment scores for meta-analyses or forest plots. As meta-analysis was possible for only one outcome (Childhood Autism Rating Scale), it was impossible to use sensitivity or subgroup analyses to assess impact of study quality, clinical differences in the intervention, or clinically relevant differences between groups, such as age or presence of gastrointestinal symptoms. MAIN RESULTS: Twenty-five established standardised outcome measures were reported to assess core features of autism, communication, behaviour, visio-spatial skills, affect and adverse events within fourteen included studies. No more than four studies used any one outcome measure similarly. Outcomes were reported between three and six weeks. RCTs of efficacy of secretin in autism have not shown improvements for core features of autism. AUTHORS' CONCLUSIONS: There is no evidence that single or multiple dose intravenous secretin is effective and as such it should not currently be recommended or administered as a treatment for autism. Further experimental assessment of secretin's effectiveness for autism can only be justified if methodological problems of existing research can be overcome.

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Am J Psychiatry. 2005 Jun;162(6):1142-8.
Risperidone for the core symptom domains of autism: results from the study by the autism network of the research units on pediatric psychopharmacology.
McDougle CJ, Scahill L, Aman MG, McCracken JT, Tierney E, Davies M, Arnold LE, Posey DJ, Martin A, Ghuman JK, Shah B, Chuang SZ, Swiezy NB, Gonzalez NM, Hollway J, Koenig K, McGough JJ, Ritz L, Vitiello B.
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202-4800, USA. cmcdougl@iupui.edu

OBJECTIVE: Risperidone has been found efficacious for decreasing severe tantrums, aggression, and self-injurious behavior in children and adolescents with autistic disorder (autism). The authors report on whether risperidone improves the core symptoms of autism, social and communication impairment and repetitive and stereotyped behavior. METHOD: The database from an 8-week double-blind, placebo-controlled trial (N=101) and 16-week open-label continuation study (N=63) of risperidone for children and adolescents with autism was used to test for drug effects on secondary outcome measures: scores on the Ritvo-Freeman Real Life Rating Scale, the Children's Yale-Brown Obsessive Compulsive Scale, and the maladaptive behavior domain of the Vineland Adaptive Behavior Scales. RESULTS: Compared to placebo, risperidone led to a significantly greater reduction in the overall score on the Ritvo-Freeman Real Life Rating Scale, as well as the scores on the subscales for sensory motor behaviors (subscale I), affectual reactions (subscale III), and sensory responses (subscale IV). No statistically significant difference was observed, however, on the subscale for social relatedness (subscale II) or language (subscale V). Risperidone also resulted in significantly greater reductions in scores on the Children's Yale-Brown Obsessive Compulsive Scale and Vineland maladaptive behavior domain. This pattern of treatment response was maintained for 6 months. CONCLUSIONS: Risperidone led to significant improvements in the restricted, repetitive, and stereotyped patterns of behavior, interests, and activities of autistic children but did not significantly change their deficit in social interaction and communication. Further research is necessary to develop effective treatments for the core social and communicative impairments of autism.

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Pediatr Rehabil. 2005 Apr-Jun;8(2):104-12.
Managing autism and Asperger's syndrome in current educational provision.
Jordan R.
School of Education, University of Birmingham, Birmingham B15 2TT, UK. r.r.jordan@bham.ac.uk

There is a need to understand the difficulties faced by those with autistic spectrum disorders (ASD) in educational settings if one is to manage and help them manage their learning. This paper explores some of the most pertinent problems that arise. It analyses perceptual, social, conceptual, emotional and memorizing barriers to learning and shows how difficulties in communication are exacerbated by educational language, which gives a poor model for those who have no prior understanding of inter-personal communication. The notion of an 'autism-friendly' environment is examined as is the process of how schools and other learning institutions might be helped to create such an environment. Education as entitlement is distinguished from education as therapy and the implications for inclusion are examined. It is argued that the best teaching arises from an empathetic understanding and a willingness to be flexible, the worst, from rigidity and an expectation that it is the child who must change. There is no single approach that can meet all the needs of those with ASDs, but nor are needs entirely determined by individual behaviour. It is the understanding of ASD that enables the teacher to correctly identify the child's learning needs and begin to meet them.

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J Music Ther. 2005 Spring;42(1):2-19.
An analysis of music therapy program goals and outcomes for clients with diagnoses on the autism spectrum.
Kaplan RS, Steele AL.
The Cleveland Music School Settlement.

The researchers analyzed data related to goals and outcomes over 2 program years for 40 music therapy clients, ranging in age from 2-49 years, with diagnoses on the autism spectrum. They investigated music therapy interventions, session types, and formats most frequently used; goals most frequently addressed; assessed level of difficulty of clients and their situations; and generalization of skills attained in music therapy to other settings. The most common session type was individual, followed by partner, small or large groups, peer model, or a combination. Primary goal areas were ranked from language/communication (41%), behavioral/psychosocial (39%), cognitive (8%), and musical (7%), to perceptual/motor (5%). One hundred percent of subjects reached their initial objectives in these goal areas within one year or less, regardless of session type, level of difficulty, or goal area. Seventy-seven percent of intermediate objectives were reached within that time. The most frequently utilized interventions were interactive instrument playing, musical instrument instruction, interactive singing, instrument choices, and song choices. Specific interventions chosen did not affect accomplishment of initial objectives. However, there was more variation among interventions in terms of achievement of intermediate objectives. Session formats were ranked from activity-based as most frequent to lesson-based, client-led/"shadow," and ensemble format. All formats were successful when addressing initial objectives, with lesson-based format being most effective in reaching intermediate objectives. Lastly, 100% of parents and caregivers surveyed indicated subjects generalized skills/responses acquired in music therapy to nonmusic therapy environments.

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Med J Aust. 2005 Apr 4;182(7):354-360.
Language disorders and autism.
Wray J, Silove N, Knott H.
c/o State Child Development Centre, Women's and Children's Health Service, PO Box 510, West Perth, WA 6872, Australia. john.wray@health.wa.gov.au.

Early diagnosis of language disorders and autism is important, and early intervention for autism and some language disorders makes a difference. Developmental surveillance of children to detect these disorders should be a routine part of medical practice. The persistence and pervasiveness of communication and socialising deficits differentiate children with autism from those with specific developmental language disorders. Hearing and vision assessment is essential in any communication disorder. Interventions, targeted to identified areas of need, should encompass communication enhancement, behavioural therapy, educational modification, parent education and family support. Pharmacological interventions have an important but discrete role in autism, but there are no magic bullets. It is important to remember that the normal childhood illnesses occur in children with developmental disorders. Parents should be directed to reliable websites on the Internet, and given information and books to read as well as phone numbers of relevant services (eg, autism associations). There is a need for increased government financial support for early intervention programs.

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Am J Pharmacogenomics. 2005;5(2):71-92.
What is Known About Autism : Genes, Brain, and Behavior.
Santangelo SL, Tsatsanis K.
Psychiatric & Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital and Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USADepartment of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.

Autism is a neurodevelopmental disorder of genetic origins, with a heritability of about 90%. Autistic disorder is classed within the broad domain of pervasive developmental disorders (PDD) that also includes Rett syndrome, childhood disintegrative disorder, Asperger syndrome, and PDD not otherwise specified (PDD-NOS). Prevalence estimates suggest a rate of 0.1-0.2% for autism and 0.6% for the range of PDD disorders. There is considerable phenotypic heterogeneity within this class of disorders as well as continued debate regarding their clinical boundaries. Autism is the prototypical PDD, and is characterized by impairments in three core domains: social interaction, language development, and patterns of behavior (restricted and stereotyped). Clinical pattern and severity of impairment vary along these dimensions, and the level of cognitive functioning of individuals with autism spans the entire range, from profound mental retardation to superior intellect.There is no single biological or clinical marker for autism, nor is it expected that a single gene is responsible for its expression; as many as 15+ genes may be involved. However, environmental influences are also important, as concordance in monozygotic twins is less than 100% and the phenotypic expression of the disorder varies widely, even within monozygotic twins. Multiple susceptibility factors are being explored using varied methodologies, including genome-wide linkage studies, and family- and case-control candidate gene association studies. This paper reviews what is currently known about the genetic and environmental risk factors, neuropathology, and psychopharmacology of autism. Discussion of genetic factors focuses on the findings from linkage and association studies, the results of which have implicated the involvement of nearly every chromosome in the human genome. However, the most consistently replicated linkage findings have been on chromosome 7q, 2q, and 15q. The positive associations from candidate gene studies are largely unreplicated, with the possible exceptions of the GABRB3 and serotonin transporter genes.No single region of the brain or pathophysiological mechanism has yet been identified as being associated with autism. Postmortem findings, animal models, and neuroimaging studies have focused on the cerebellum, frontal cortex, hippocampus, and especially the amygdala. The cerebello-thalamo-cortical circuit may also be influential in autism. There is evidence that overall brain size is increased in some individuals with autism.Presently there are no drugs that produce major improvements in the core social or pragmatic language deficits in autism, although several have limited effects on associated behavioral features.The application of new techniques in autism research is being proposed, including the investigation of abnormal regulation of gene expression, proteomics, and the use of MRI and postmortem analysis of the brain.

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Indian J Pediatr. 2005 Mar;72(3):227-30.
Autism -- experiences in a tertiary care hospital.
Kalra V, Seth R, Sapra S.
Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. Kalra_veena@hotmail.com

Pervasive developmental disorders (PDD) or Autistic Spectrum Disorders (ASD) include Autistic Disorder (commonest), Asperger's syndrome, Childhood Disintegrative Disorders, Rett's syndrome and PDD-NOS (not otherwise specified). OBJECTIVE: Autism is an important cause of social disability and reported more often from the developed world than from the developing countries. The present study was aimed to establish the diagnosis of autism amongst children with derangements of language, communication and behavior; ascertain and treat the co-morbidities; identify underlying cause and create a sensitivity and awareness among various health care professionals. METHODS: Sixty-two of the seventy-five referred patients fulfilled the DSM-IV (Diagnostic and Statistical Manual of Mental Disorder) criteria for autism. Evaluation included a detailed history, clinical examination, IQ assessment, Connor's scoring for hyperactivity and Fragile-X screening. Management of co-morbidities was done. A follow up of these patients was done. Parents' assessment of the child was also done. A registry for autistic children was established at the Department of Pediatrics with other major institutions of Delhi. RESULTS : The male:female ratio was 8:1 and missed diagnosis was common. Professional awareness is merited. Behavioral modification by early intervention and stimulation improved the core symptoms of autism. Important co-morbidities included mental retardation (95%), hyperactivity (53%) and seizures (10%) cases. Control of co-morbidities in these children facilitated child's periodic assessment and implementation of intervention programmes. In the registry initiated 62 patients were enrolled at AIIMS and 6 were identified from other hospitals. CONCLUSION: Autism does occur in Indian children too. Diagnosis is often missed. Capacity building among health professionals by a more structured teaching of developmental disabilities in the medical curriculum is required. The need to attend to co-morbidities and associated symptoms was clear. The initiation of the registry and beginning of networking was important.

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Eur Child Adolesc Psychiatry. 2005 Mar;14(2):65-72.
What distinguishes autism spectrum disorders from other developmental disorders before the age of four years?
Trillingsgaard A, Ulsted Sorensen E, Nemec G, Jorgensen M.
Psychiatric Hospital for Children and Adolescents, University Hospital of Aarhus, Harald Selmersvej 66, 8240 Risskov, Denmark. Atr@buh.aaa.dk

The increasing recognition of the benefits of early intervention for children with autism spectrum disorder (ASD) stresses the importance of early identification of children who might benefit from those programs. However, in the early years of life it may be difficult to distinguish children with ASD from children with other developmental disorders. The aim of the present study was to identify behavioural patterns that could facilitate this differentiation. Prior to diagnostic assessment, 2- and 3-year-old children (n=30), all referred to a clinic for "possible autism", were observed in a semi-structured play interaction, and their parents were interviewed about the children's early development from 0 to 24 months. Following diagnostic assessment, the 17 children fulfilling the ICD-10 criteria for ASD were compared to the 13 children diagnosed with other developmental disorders (outside the autism spectrum). On the basis of parent reports only a few distinguishing signs of ASD were found before 24 months of age. On the basis of professional observations in a semi-structured play interaction several distinguishing signs were found for the 2- and 3-year-olds; smiles in response, responds to name, follows pointing, looks to "read" faces, initiates requesting verbal and nonverbal behaviours, and functional play.

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J Neurovirol. 2005 Feb;11(1):1-10.
Autistic disorder and viral infections.
Libbey JE, Sweeten TL, McMahon WM, Fujinami RS.
Department of Neurology, University of Utah, Salt Lake City, Utah 84132-2305, USA.

Autistic disorder (autism) is a behaviorally defined developmental disorder with a wide range of behaviors. Although the etiology of autism is unknown, data suggest that autism results from multiple etiologies with both genetic and environmental contributions, which may explain the spectrum of behaviors seen in this disorder. One proposed etiology for autism is viral infection very early in development. The mechanism, by which viral infection may lead to autism, be it through direct infection of the central nervous system (CNS), through infection elsewhere in the body acting as a trigger for disease in the CNS, through alteration of the immune response of the mother or offspring, or through a combination of these, is not yet known. Animal models in which early viral infection results in behavioral changes later in life include the influenza virus model in pregnant mice and the Borna disease virus model in newborn Lewis rats. Many studies over the years have presented evidence both for and against the association of autism with various viral infections. The best association to date has been made between congenital rubella and autism; however, members of the herpes virus family may also have a role in autism. Recently, controversy has arisen as to the involvement of measles virus and/or the measles, mumps, rubella (MMR) vaccine in the development of autism. Biological assays lend support to the association between measles virus or MMR and autism whereas epidemiologic studies show no association between MMR and autism. Further research is needed to clarify both the mechanisms whereby viral infection early in development may lead to autism and the possible involvement of the MMR vaccine in the development of autism.

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Res Dev Disabil. 2005 Jan-Feb;26(1):87-97.
Secretin is an ineffective treatment for pervasive developmental disabilities: a review of 15 double-blind randomized controlled trials.
Sturmey P.
Department of Psychology, Queens College and The Graduate Center, The City University of New York, CUNY, Flushing, NY 112367, USA. psturmey@aol.com

In 1998, Horvath et al. [Horvath, K., Stefanatos, G., Sokolski, K. N., Wachtel, R., Nabors, L., & Tildon, J. T. (1998). Improved social and language skills after secretin administration in patients with autism spectrum disorders. Journal of the Association of the Academy of Minority Physicians, 9, 9-15] reported an uncontrolled trial of secretin with three participants with autism, which apparently resulted in significant behavioral improvement. Subsequently, secretin was widely used. Sandler et al. [Sandler, A. D., Sutton, K. A., SeWeese, J., Girardi, M. A., Sheppard, V., & Bodfish, J. W. (1999). Lack of benefit of a single dose of synthetic human secretin in the treatment of autism and pervasive and developmental disorder. The New England Journal of Medicine, 341, 1801-1806] reported the first double-blind trial of secretin with negative results. This article is a review of 15 double-blind trials of secretin. Almost none of the studies reported any significant effects and none concluded that secretin was effective. Transient effects of secretin, including both minor benefits and behavioral deterioration were reported, probably due to multiple statistical tests. Four papers reported data on differential responding in sub-groups of participants, including those with gastrointestinal symptoms. These effects were not replicable. At this time there is no robust evidence that secretin is an effective treatment for pervasive developmental disorders.

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J Altern Complement Med. 2004 Dec;10(6):1033-9.
Pilot study of a moderate dose multivitamin/mineral supplement for children with autistic spectrum disorder.
Adams JB, Holloway C.
Arizona State University, Tempe, AZ.

Objective: Determine the effect of a moderate dose multivitamin/mineral supplement on children with autistic spectrum disorder. Design: Randomized, double-blind, placebo-controlled 3-month study. Subjects: Twenty (20) children with autistic spectrum disorder, ages 3-8 years. Results: A Global Impressions parental questionnaire found that the supplement group reported statistically significant improvements in sleep and gastrointestinal problems compared to the placebo group. An evaluation of vitamin B(6) levels prior to the study found that the autistic children had substantially elevated levels of B6 compared to a control group of typical children (75% higher, p < 0.0000001). Vitamin C levels were measured at the end of the study, and the placebo group had levels that were significantly below average for typical children, whereas the supplement group had near-average levels. Discussion: The finding of high vitamin B(6) levels is consistent with recent reports of low levels of pyridoxal-5-phosphate and low activity of pyridoxal kinase (i.e., pyridoxal is only poorly converted to pyridoxal- 5-phosphate, the enzymatically active form). This may explain the functional need for high-dose vitamin B(6) supplementation in many children and adults with autism.

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Neuropsychopharmacology. 2004 Dec 15; [Epub ahead of print]
A Placebo Controlled Crossover Trial of Liquid Fluoxetine on Repetitive Behaviors in Childhood and Adolescent Autism.
Hollander E, Phillips A, Chaplin W, Zagursky K, Novotny S, Wasserman S, Iyengar R.
[1] 1Seaver and New York Autism Center of Excellence, New York, USA [2] 2Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, USA.

Repetitive behaviors are a core symptom domain in autism that has been linked to alterations in the serotonin system. While the selective serotonin-receptive inhibitor fluvoxamine has been shown to be effective in adults with autism, as yet no published placebo controlled trials with these agents document safety and efficacy in children with autism. This study examines the selective serotonin reuptake inhibitor liquid fluoxetine in the treatment of repetitive behaviors in childhood and adolescent autism spectrum disorders (ASDs). In total, 45 child or adolescent patients with ASD were randomized into two acute 8-week phases in a double-blind placebo-controlled crossover study of liquid fluoxetine. Study design included two randomized 8-week fluoxetine and placebo phases separated by a 4-week washout phase. Outcome measures included measures of repetitive behaviors and global improvement. Low-dose liquid fluoxetine (mean final dose: 9.9+/-4.35 mg/day) was superior to placebo in the treatment of repetitive behaviors by CY-BOCS compulsion scale. The effect size was in the moderate to large range, and the doses used were low. Liquid fluoxetine was only slightly, and not significantly, superior to placebo on CGI autism score partially due to a phase order effect. However, fluoxetine was marginally superior to placebo on a composite measure of global effectiveness. Liquid fluoxetine did not significantly differ from placebo on treatment emergent side effects. Liquid fluoxetine in low doses is more effective than placebo in the treatment of repetitive behaviors in childhood autism. Limitations include small sample size and the crossover design of the study. Further replication and long-term maintenance trials are needed.Neuropsychopharmacology advance online publication, 15 December 2004; doi:10.1038/sj.npp.1300627.

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J Child Adolesc Psychopharmacol. 2004 Fall;14(3):426-32.
A retrospective assessment of topiramate in children and adolescents with pervasive developmental disorders.
Hardan AY, Jou RJ, Handen BL.
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. hardanay@msx.upmc.edu

An open-label retrospective study was conducted to assess the effectiveness and tolerability of topiramate in children and adolescents with pervasive developmental disorders (PDD). Topiramate is a novel antiepileptic drug approved as an adjunctive treatment for seizure disorders. A retrospective chart review was conducted in an outpatient clinic specialized in treating individuals with developmental disabilities, to identify all children and adolescents with PDD who received topiramate. Patients were included if concomitant medications remained unchanged. Treatment response was assessed using the Global Improvement item of the Clinical Global Impressions scale (CGI-GI), based on a review of medical records and the Conners Parent Scale (CPS), as completed by parents. Fifteen patients were identified (12 male, 3 female; age = 14.7 +/- 3.3 years), including 11 patients with autistic disorder, 2 patients with Asperger's disorder, and 2 patients with PDD not otherwise specified (PDD, NOS). Eight patients (4 patients with autistic disorder, 2 patients with Asperger's disorder, and 2 patients with PDD, NOS) were judged to be responders, as defined by a score of 1 or 2 on the CGI-GI. Treatment duration was 25 +/- 16 weeks, and the mean dose was 235 +/- 88 mg. Differences between baseline and the end-of-trial period were observed in the following CPS subscales: conduct, hyperactivity, and inattention. No differences were noted in the psychosomatic, learning, and anxiety subscales. Three patients discontinued topiramate because of side effects, with 2 patients experiencing cognitive difficulties and 1 patient a skin rash. Topiramate may be beneficial for treating secondary symptoms of PDD, and prospective openlabel studies and double-blind, placebo-controlled studies to assess its efficacy and safety are needed.

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Ment Retard Dev Disabil Res Rev. 2004;10(3):193-200.
Self-injurious behavior and the efficacy of naltrexone treatment: a quantitative synthesis.
Symons FJ, Thompson A, Rodriguez MC.
Department of Educational Psychology, University of Minnesota, Minneapolis, Minnesota 55455, USA. symon007@umn.edu

People with mental retardation, autism, and related developmental disabilities who self-injure are treated with a wide array of behavioral techniques and psychotropic medications. Despite numerous reports documenting short-term and some long-term changes in self-injury associated with the opiate antagonist naltrexone hydrochloride, no quantitative review of its efficacy has been reported. We conducted a quantitative synthesis of the peer-reviewed published literature from 1983 to 2003 documenting the use of naltrexone for the treatment of self-injurious behavior (SIB). Individual-level results were analyzed given subject and study characteristics. A sample of 27 research articles involving 86 subjects with self-injury was reviewed. Eighty percent of subjects were reported to improve relative to baseline (i.e., SIB reduced) during naltrexone administration and 47% of subjects SIB was reduced by 50% or greater. In studies reporting dose levels in milligrams, males were more likely than females to respond. No significant relations were found between treatment outcomes and autism status or form of self-injury. Results are discussed with respect to future efficacy work related to study outcomes and the pharmacological treatment of self-injury. (c) 2004 Wiley-Liss, Inc.

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J Clin Psychiatry. 2004;65 Suppl 15:35-44.
Diagnosing and treating comorbid (complicated) bipolar disorder.
McElroy SL.
Department of Psychiatry, University of Cincinnati College of Medicine, OH 45267, USA. susan.mcelroy@uc.edu

Comorbidity is the rule, not the exception, in bipolar disorder. The most common mental disorders that co-occur with bipolar disorder in community studies include anxiety, substance use, and conduct disorders. Disorders of eating, sexual behavior, attention-deficit/hyperactivity, and impulse control, as well as autism spectrum disorders and Tourette's disorder, co-occur with bipolar disorder in clinical samples. The most common general medical comorbidities are migraine, thyroid illness, obesity, type II diabetes, and cardiovascular disease. Bipolarity is a marker for comorbidity, and comorbid disorders, especially multiple conditions occurring when a patient is young, may be a marker for bipolarity. Relatively few controlled clinical studies have examined the treatment of bipolar disorder in the context of comorbid conditions (i.e., complicated or comorbid bipolar disorder). However, the first step in treating any type of complicated bipolar disorder--stabilizing a patient's mood--may be associated with improving the comorbid disorder. Standard mood stabilizers, atypical antipsychotics, and non-antimanic antiepileptic agents are emerging as potentially useful treatments for several of the disorders that frequently co-occur with bipolar disorder, and therefore may be useful treatments for comorbid bipolar disorder.

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Semin Pediatr Neurol. 2004 Sep;11(3):225-8.
Management of hyperactivity and other acting-out problems in patients with autism spectrum disorder.
Aman MG.
Nisonger Center, Ohio State University, Columbus, OH 43210-1296, USA.

Hyperactivity/impulsivity, aggression, self injury, and irritability are disruptive behaviors that frequently accompany autism spectrum disorders (ASD). The psychostimulants and atypical antipsychotics have been used with some success to manage hyperactivity, but neither drug group is fully satisfactory and clinical response to the stimulants varies. For other disruptive symptoms (irritability, aggression, self injury), both older antipsychotics and newer atypical antipsychotics have been shown to have helpful effects. Because of potential side effects, atypical antipsychotics should ordinarily be preferred over older agents. A small group of studies suggests that selective serotonin reuptake inhibitors may be helpful in managing symptoms related to aggression, self injury, and the like. A small and largely imperfect literature suggests that beta blockers, mood stabilizers, and alpha-2 agonists may also have some role for treating such symptoms. More research is needed on the management of all of these target symptoms, both for new agents (e.g., atomoxetine) and for established psychoactive medicines.

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Pediatrics. 2004 Nov;114(5):e634-41. Epub 2004 Oct 18.
Risperidone in the treatment of disruptive behavioral symptoms in children with autistic and other pervasive developmental disorders.
Shea S, Turgay A, Carroll A, Schulz M, Orlik H, Smith I, Dunbar F.
IWK Health Centre, and Dalhousie University, Halifax, Nova Scotia, Canada. sarah.shea@iwk.nshealth.ca

OBJECTIVE: To investigate the efficacy and safety of risperidone for the treatment of disruptive behavioral symptoms in children with autism and other pervasive developmental disorders (PDD). METHODS: In this 8-week, randomized, double-blind, placebo-controlled trial, risperidone/placebo solution (0.01-0.06 mg/kg/day) was administered to 79 children who were aged 5 to 12 years and had PDD. Behavioral symptoms were assessed using the Aberrant Behavior Checklist (ABC), Nisonger Child Behavior Rating Form, and Clinical Global Impression-Change. Safety assessments included vital signs, electrocardiogram, extrapyramidal symptoms, adverse events, and laboratory tests. RESULTS: Subjects who were taking risperidone (mean dosage: 0.04 mg/kg/day; 1.17 mg/day) experienced a significantly greater mean decrease on the irritability subscale of the ABC (primary endpoint) compared with those who were taking placebo. By study endpoint, risperidone-treated subjects exhibited a 64% improvement over baseline in the irritability score almost double that of placebo-treated subjects (31%). Risperidone-treated subjects also exhibited significantly greater decreases on the other 4 subscales of the ABC; on the conduct problem, insecure/anxious, hyperactive, and overly sensitive subscales of the Nisonger Child Behavior Rating Form (parent version); and on the Visual Analog Scale of the most troublesome symptom. More risperidone-treated subjects (87%) showed global improvement in their condition compared with the placebo group (40%). Somnolence, the most frequently reported adverse event, was noted in 72.5% versus 7.7% of subjects (risperidone vs placebo) and seemed manageable with dose/dose-schedule modification. Risperidone-treated subjects experienced statistically significantly greater increases in weight (2.7 vs 1.0 kg), pulse rate, and systolic blood pressure. Extrapyramidal symptoms scores were comparable between groups. CONCLUSIONS: Risperidone was well tolerated and efficacious in treating behavioral symptoms associated with PDD in children.

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J Child Psychol Psychiatry. 2004 Nov;45(8):1420-30.
A new social communication intervention for children with autism: pilot randomised controlled treatment study suggesting effectiveness.
Aldred C, Green J, Adams C.
Human Communication and Deafness Group, University of Manchester, UK.

BACKGROUND: Psychosocial treatments are the mainstay of management of autism in the UK but there is a notable lack of a systematic evidence base for their effectiveness. Randomised controlled trial (RCT) studies in this area have been rare but are essential because of the developmental heterogeneity of the disorder. We aimed to test a new theoretically based social communication intervention targeting parental communication in a randomised design against routine care alone. METHODS: The intervention was given in addition to existing care and involved regular monthly therapist contact for 6 months with a further 6 months of 2-monthly consolidation sessions. It aimed to educate parents and train them in adapted communication tailored to their child's individual competencies. Twenty-eight children with autism were randomised between this treatment and routine care alone, stratified for age and baseline severity. Outcome was measured at 12 months from commencement of intervention, using standardised instruments. RESULTS: All cases studied met full Autism Diagnostic Interview (ADI) criteria for classical autism. Treatment and controls had similar routine care during the study period and there were no study dropouts after treatment had started. The active treatment group showed significant improvement compared with controls on the primary outcome measure--Autism Diagnostic Observation Schedule (ADOS) total score, particularly in reciprocal social interaction--and on secondary measures of expressive language, communicative initiation and parent-child interaction. Suggestive but non-significant results were found in Vineland Adaptive Behaviour Scales (Communication Sub-domain) and ADOS stereotyped and restricted behaviour domain. CONCLUSIONS: A Randomised Treatment Trial design of this kind in classical autism is feasible and acceptable to patients. This pilot study suggests significant additional treatment benefits following a targeted (but relatively non-intensive) dyadic social communication treatment, when compared with routine care. The study needs replication on larger and independent samples. It should encourage further RCT designs in this area.

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Ment Retard Dev Disabil Res Rev. 2004;10(2):135-8.
AEDs and psychotropic drugs in children with autism and epilepsy.
Tuchman R.
Department of Neurology, Dan Marino Center, Miami Children's Hospital, University of Miami, Miami, Florida, USA. tuchman@att.net

The efficacy of antiepileptic drugs (AEDs) and psychotropic medications in children with autism is limited to the treatment of seizures or to specific behaviors such as irritability, impulsivity, hyperactivity, repetitive behaviors, or aggression. The reliability and value of the available data--to determine the efficacy of these medications in autism--are limited by lack of controlled clinical trials, the small number of subjects, the heterogeneity of the population studied, and the brief duration of most drug trials. Indeed, few controlled clinical trials using AEDs in autism, with or without seizures, have been conducted. Because some AEDs also have a positive effect on mood, the benefits that children with autism sometimes obtain from these medications may not be due to the treatment of the abnormal electrical activity or the seizures per se but to an effect on common neuronal systems responsible for both behavior and epilepsy. The relationship between epilepsy and autism, and specifically the effects that abnormal electrical activity may have on the developing brain, may provide some valuable insights into the type of studies that are needed to help us understand the pathophysiology of autism.

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Autism. 2004 Sep;8(3):319-33.
Comparison of behavioural and natural play interventions for young children with autism.
Bernard-Opitz V, Ing S, Kong TY.
National University of Singapore, Singapore. verabernard@cox.net

The article reports the results of a pilot study comparing traditional behavioural approaches and natural play interventions for young children with autism over a 10 week period. Two matched groups of eight young children with autism participated. Using a crossover design, children in both groups showed positive gains in compliance, attending, play and communication with their therapists and parents. Improvements in attending and compliance were higher following the behavioural condition compared with the natural play condition. Seven participants had reduced autism scores after the intervention. The findings suggest that behavioural and play approaches affect behaviour in different ways and that autistic symptomatology of young children may be amenable to treatment. The discussion focuses on the active ingredients of treatments and the need to base efficacy research on well-planned treatment comparisons.

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J Sleep Res. 2004 Sep;13(3):265-8.
Sleep problems in children with autism.
Gail Williams P, Sears LL, Allard A.
Weisskopf Center for the Evaluation of Children, University of Louisville, Louisville, KY 40202, USA. pgwill@iegwise.louisville.edu

Autism is a developmental disability characterized by severe deficits in social interaction and communication, and the presence of repetitive-ritualistic behaviors. Sleep problems are frequently reported by parents of children with autism with prevalence estimates of 44-83% for sleep disorders in this population. To better understand sleep in autism, we surveyed sleep problems in 210 children with autism using a Likert-based questionnaire for parent report. The most frequently reported sleep problems included difficulty in falling asleep, restless sleep, not falling asleep in own bed, and frequent wakenings. Least frequently reported sleep problems were sleep walking, morning headaches, crying during sleep, apnea, and nightmares. When surveys were divided into mental retardation (MR)/not MR categories, no significant differences were identified in frequencies of reported sleep problems except for waking at night which occurred much more frequently in the MR group. There was also no difference in sleep problems related to age of the child other than nocturnal enuresis. An association was noted between certain medical problems and sleep problems. Vision problems, upper respiratory problems, and runny nose were associated with decreased nighttime sleep. Vision problems, poor appetite, and poor growth were associated with increased nighttime waking. Poor appetite and poor growth were associated with decreased willingness to fall asleep. This study confirms a high prevalence of sleep problems reported by parents of children with autism and points to the need for more systematic research as an initial step in developing treatment strategies.

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Ann Pharmacother. 2004 Sep;38(9):1515-9. Epub 2004 Aug 03.
Treating functional impairment of autism with selective serotonin-reuptake inhibitors.
Moore ML, Eichner SF, Jones JR.
Drug Information Center, University of Tennessee Health Science Center, Memphis, TN 38163-0001, USA. mmoore31@utmem.edu

OBJECTIVE: To review literature describing use of selective serotonin-reuptake inhibitors (SSRIs) in the management of functional impairments associated with autistic disorder. DATA SOURCES: EMBASE (1980-3rd quarter of 2003), International Pharmaceutical Abstracts (1970-August 2003), and MEDLINE (1966-August 2003) were searched. Search terms included autism, autistic disorder, citalopram, fluoxetine, fluvoxamine, paroxetine, selective serotonin-reuptake inhibitors, and sertraline. DATA SYNTHESIS: Studies and case reports evaluating treatment outcomes associated with the use of SSRIs in managing impairments of autism were reviewed. Multiple SSRI dosing ranges were evaluated in autistic patients of different ages with various functional impairments. No specific SSRI or dose range has been shown to improve a specific autistic symptom although some patients have demonstrated improvements. CONCLUSIONS: Benefits with SSRIs in treating functional impairments in autism have been observed. Response to therapy and adverse effects are individualized. Current evidence does not support selection of one SSRI over another for any impairment associated with autism.

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J Speech Lang Hear Res. 2004 Aug;47(4):848-62.
Effects of speech and print feedback on spelling by children with autism.
Schlosser RW, Blischak DM.
Department of Speech-Language Pathology & Audiology, Northeastern University, Boston, MA 02115, USA. r.schlosser@neu.edu

In this systematic replication of a previous study (R. W. Schlosser, D. M. Blischak, P. J. Belfiore, C. Bartley, and N. Barnett, 1998), the effects of speech and print feedback on spelling performance were evaluated. Four children with autism and no functional speech were taught to spell words with a speech-generating device under 3 feedback conditions. In the auditory-visual condition, children received both speech and print feedback, whereas in the auditory and visual conditions, only 1 type of feedback was provided. An adapted alternating treatments design was used. All 4 children reached criterion across conditions. Although 3 children reached criterion first with print or speech-print feedback, 1 child was most efficient with speech-print followed by speech feedback. Based on the findings of both studies, 2 distinct profiles of feedback efficiency are proposed. Children that exemplify the primarily visual profile spell words most efficiently when feedback involves print. Children that fit the auditory profile spell words most efficiently when feedback involves speech. The implications for understanding the learning characteristics of children with autism, as well as those for practice and further research are derived.

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J Child Adolesc Psychopharmacol. 2004 Summer;14(2):287-94.
Quetiapine in nine youths with autistic disorder.
Findling RL, McNamara NK, Gracious BL, O'Riordan MA, Reed MD, Demeter C, Blumer JL.
Departments of Psychiatry and Pediatrics, University Hospitals of Cleveland/Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106-5080, USA. Robert.Findling@uhhs.com

OBJECTIVE: The aim of this study was to examine the effectiveness of quetiapine in adolescents suffering from autistic disorder (AD). METHODS: This was a 12-week, open-label study, for which medically healthy patients with AD between the ages of 10 and 17 years were eligible. Quetiapine treatment was gradually increased over the first 6 weeks of the study, to a total daily dose of 300 mg/day. Doses could then be increased to a maximum daily dose of 750 mg/day. Outcome measures included the Children's Psychiatric Rating Scale (CPRS) and the Clinical Global Impressions (CGI) scale. RESULTS: Nine (9) males were enrolled. Six (6) patients had previously been treated with other psychotropic agents. Although improvements in several symptom domains were observed on quetiapine, only 2 patients met a priori criteria for response ("much" or "very much improved" on the Clinical Global Impressions-Improvement Scale). In addition, only these same 2 patients' parents/guardians chose to continue quetiapine pharmacotherapy after study participation. CONCLUSIONS: These data suggest that quetiapine may not be a particularly effective agent in the treatment of adolescent patients with AD. However, should future studies be performed, it seems reasonable that they be conducted with more rigor, less treatment-resistant cohorts, and, possibly, a different dosing strategy.

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Ann Pharmacother. 2004 Aug 3 [Epub ahead of print]
Treating Functional Impairment of Autism with Selective Serotonin-Reuptake Inhibitors (September).
Moore ML, Eichner SF, Jones JR.
Drug Information Center, University of Tennessee Health Science Center, Memphis, TN.

OBJECTIVE: To review literature describing use of selective serotonin-reuptake inhibitors (SSRIs) in the management of functional impairments associated with autistic disorder. DATA SOURCES: EMBASE (1980-3rd quarter of 2003), International Pharmaceutical Abstracts (1970-August 2003), and MEDLINE (1966-August 2003) were searched. Search terms included autism, autistic disorder, citalopram, fluoxetine, fluvoxamine, paroxetine, selective serotonin-reuptake inhibitors, and sertraline. DATA SYNTHESIS: Studies and case reports evaluating treatment outcomes associated with the use of SSRIs in managing impairments of autism were reviewed. Multiple SSRI dosing ranges were evaluated in autistic patients of different ages with various functional impairments. No specific SSRI or dose range has been shown to improve a specific autistic symptom although some patients have demonstrated improvements. CONCLUSIONS: Benefits with SSRIs in treating functional impairments in autism have been observed. Response to therapy and adverse effects are individualized. Current evidence does not support selection of one SSRI over another for any impairment associated with autism.

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Zh Nevrol Psikhiatr Im S S Korsakova. 2004;104(6):35-9.
[Use of cholinomimetics in the treatment of endogenous autism in children]
[Article in Russian]
[Authors not listed]

Twenty children with endogenous autism of mild and moderate severity (30-44.5 scores according to the CARS), aged 3-8 years, were treated with choline alfoscerate (CA), 400 mg/day, during 8 weeks in the presence of maintenance therapy with neuroleptics (17 cases). Positive therapeutic effect was observed in 89% of the patients: significant improvement--in 61% and minimal efficacy--in 28%. Statistically significant positive changes in the patient's state were observed in the general improvement of behavior (p<0.001), development of social and communicative skills, as well as self-service, reduction of marked speech disturbances (p<0.001) and motor sphere (p<0.001), enhancement of learning activity and productivity (p<0.05). Good tolerability to the therapy, without patient's state worsening was registered. Some patients exhibited strengthening of affective lability in the first weeks of the treatment which attenuated to the 4th week as the CA dosages decreased to 400 mg every other day. CA may be recommended for combined therapy with neuroleptics as an effective and safe medicine for the treatment of cognitive and behavioral disorders in patients with children's autism.

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No To Hattatsu. 2004 Jul;36(4):289-95.
[Efficacy of secretin for the treatment of autism]
[Article in Japanese]
Toda Y, Mori K, Hashimoto T, Miyazaki M, Kuroda Y.
Department of Pediatrics, School of Medicine, University of Tokushima, Tokushima.

We administered secretin intravenously to 14 patients with autism (9 to 14 years, 10 males; 4 females), and evaluated its clinical effect. We also measured cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) and 5-hydroxy-indole-3-acetic acid (5HIAA) before and after 4 weeks treatment, and compared them with the grade of improvement of the clinical symptoms assessed by the scores of Autism Diagnostic Interview-Revised (ADI-R). After injection of secretin, the ADI-R score increased in 8 patients, but declined in 3. Improvement was observed in functions such as sociability (interpersonal relationships), communication and speech improved, whereas in the others. symptoms such as hyperkinesias and stereotyped behavior became worse. The CSF levels of HVA was significantly increased in all of the patients showing an improvement in the ADI-R score. SHIAA levels also tended to increase, although this increase was not significant. These findings suggest that secretin promotes the metabolism of serotonin and dopamine in the central nervous system, which may contribute to improvement in clinical symptoms of autism.

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Ned Tijdschr Geneeskd. 2004 May 22;148(21):1024-30.
[Sixty years of autism]
[Article in Dutch]
van Berckelaer-Onnes IA.
Universiteit Leiden, faculteit der Sociale Wetenschappen, Ambulatorium, Postbus 9555, 2300 RB Leiden. berck@fsw.leidenuniv.nl

The concept of autism has been broadened the last few years from 'early infantile autism' to 'an autistic spectrum'. Autism and related contact disorders are grouped together under 'pervasive developmental disorders' or 'autistic spectrum disorders'. The autistic disorder, Asperger's syndrome, pervasive developmental disorder not otherwise specified (PDD-NOS), Rett's disorder and the childhood disintegrative disorder all belong to this group. People with an autistic spectrum disorder have severe difficulties in the integration of perceived stimuli into a meaningful entity. More than two-thirds of the people with the autistic disorder (classical autism) are also mentally retarded. Although autism can still only be diagnosed at the behavioural level, there is considerable consensus regarding an underlying organic aetiology. Autism is clearly a multifactorial condition. Autism cannot be cured, but adequate intervention can significantly improve the quality of life of people with this disorder. Diagnosis and intervention are highly interrelated. In the intervention, a distinction is made between family-oriented and child-oriented strategies. Augmentative communication plays a key role in the treatment. People with autism need a lot of structure, clarity and predictability, also when they have become adults.

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J Child Neurol. 2004 Mar;19(3):165-9.
Treating autistic spectrum disorders in children: utility of the cholinesterase inhibitor rivastigmine tartrate.
Chez MG, Aimonovitch M, Buchanan T, Mrazek S, Tremb RJ.
Autism and Epilepsy Specialty Services of Illinois, Ltd., USA. mchezmd@sbcglobal.net

Rivastigmine tartrate is a dual-action cholinesterase inhibitor shown to improve language, cognition, and global functioning in patients with Alzheimer's disease, likely via increased availability of cerebral acetylcholine. Because cholinergic receptor abnormalities can contribute to the neuropathology of autistic spectrum disorders, rivastigmine tartrate could prove to be an effective therapy for affected children. Observations of improved behavior and language output from prior open-label and double-blind treatment of autistic children with donepezil, another cholinesterase inhibitor, prompted this 12-week open-label study with rivastigmine tartrate of 32 autistic patients. Therapeutic indices were the Childhood Autistic Rating Scale, Gardner's Expressive and Receptive One-Word Picture Vocabulary tests, and the Conners' Parent Rating Scale. Testing administered at baseline, 6 weeks, and 12 weeks showed gains in both expressive speech and overall autistic behavior over baseline. These improvements were statistically significant and supported the hypothesis that treatment with cholinergic enhancing drugs in autistic spectrum disorders yields positive therapeutic effects.

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J Clin Pharm Ther. 2004 Apr;29(2):145-50.
Cyproheptadine in the treatment of autistic disorder: a double-blind placebo-controlled trial.
Akhondzadeh S, Erfani S, Mohammadi MR, Tehrani-Doost M, Amini H, Gudarzi SS, Yasamy MT.
Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, South Kargar Street, Tehran, Iran.

Summary Objective: Autism is a childhood-onset disorder of unknown, possibly of multiple aetiologies. The core symptoms of autism are abnormalities in social interaction, communication and behaviour. The involvement of neurotransmitters such as 5-HT has been suggested in neuropsychiatric disorders and particularly in autistic disorder. Increased platelet 5-HT levels were found in 40% of the autistic population, suggesting that hyperserotonaemia may be a pathologic factor in infantile autism. Therefore, it is of interest to assess the efficacy of cyproheptadine, a 5-HT2 antagonist in the treatment of autistic disorder. In this 8-week double-blind, placebo-controlled trial, we assessed the effects of cyproheptadine plus haloperidol in the treatment of autistic disorder. Methods: Children between the ages 3 and 11 years (inclusive) with a DSM IV clinical diagnosis of autism and who were outpatients from a specialty clinic for children at Roozbeh Psychiatric Teaching Hospital were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to cyproheptadine + haloperidol (Group A) or haloperidol + placebo (Group B) for an 8-week, double-blind, placebo-controlled study. The dose of haloperidol and cyproheptadine was titrated up to 0.05 and 0.2 mg/kg/day respectively. Patients were assessed by a third-year resident of psychiatry at baseline and after 2, 4, 6 and 8 weeks of starting medication. The primary measure of the outcome was the Aberrant Behaviour Checklist-Community (ABC-C) and the secondary measure of the outcome was the Childhood Autism Rating Scale (relating to people and verbal communication). Side effects and extrapyramidal symptoms were systematically recorded throughout the study and were assessed using a checklist and the Extrapyramidal Symptoms Rating Scale, administered by a resident of psychiatry during weeks 1, 2, 4, 6 and 8. Results: The ABC-C and the Childhood Autism Rating Scale scores improved with cyproheptadine. The behaviour of the two treatments was not homogeneous across time (groups-by-time interaction, Greenhouse-Geisser correction; F = 7.30, d.f. = 1.68, P = 0.002; F = 8.21, d.f. = 1.19, P = 0.004 respectively). The difference between the two treatments was significant as indicated by the effect of group, and the between-subjects factor (F = 4.17, d.f. = 1, P = 0.048; F = 4.29, d.f. = 1, P = 0.045 respectively). No significant difference was observed between the two groups in terms of extrapyramidal symptoms (P = 0.23). The difference between the two groups in the frequency of side effects was not significant. Conclusion: The results suggest that the combination of cyproheptadine with a conventional antipsychotic may be superior to conventional antipsychotic alone for children with autistic disorder. However the results need confirmation by a larger randomized controlled trial.

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Autism. 2004 Mar;8(1):101-9.
Psychoeducational treatment of children with autism and reactive attachment disorder.
Mukaddes NM, Kaynak FN, Kinali G, Besikci H, Issever H.
University of Istanbul, Istanbul, Turkey. nmotavalli@yahoo.com

The aim of the study was to evaluate and compare the efficacy of short-term psychoeducational treatment in children with autism and reactive attachment disorder (RAD). Ten boys with autism aged 24-66 months and 11 children with RAD (nine boys and two girls) aged 30-70 months were included in the study. The Ankara Developmental Screening Inventory was used to monitor progress following a 14-session psychoeducational programme. This focused on establishing a reciprocal-dyadic interaction between children and their caregivers and it also provided an educational programme for emotional, social, and language development. Although both groups showed significant changes on all scales of the ADSI, the children with RAD showed greater improvement than the autism group in their total development score, on the language-cognitive subscale, and in social/self-care abilities.

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J Speech Lang Hear Res. 2004 Feb;47(1):126-44.
Effects of peer training and written text cueing on social communication of school-age children with pervasive developmental disorder.
Thiemann KS, Goldstein H.
Juniper Gardens Children's Project, Kansas City, KS 66101-2800, USA. thiemann@ku.edu

This study consecutively examined the effects of 2 social interventions-- peer training and written text treatment--on the social communication of 5 elementary students with pervasive developmental disorder. Each child with autism was paired with 2 peers without disabilities to form 5 triads. In Intervention 1 (peer training), peers were taught to use 5 facilitative social skills over 5 days. After peer training, 4 children with autism increased or used more stable rates of initiations and contingent responses overall. However, all children continued to demonstrate deficits in specific social-communication skills. Once Intervention 2 (direct instruction using written text cues) was implemented, increased use of 3 different communication skills was observed across all 5 participants. In addition, social validity outcomes revealed improved quality of child-peer interactions, 2 teacher reports of improved social skill development, and improved acceptance and friendship ratings for the children with autism. Results support the use of written text cues to improve children's social communication with peers, and suggest that combining approaches may be necessary to improve the quality of children's relationships.

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J Clin Psychiatry. 2004 Jan;65(1):110-3.
The effect of a switch to ziprasidone in an adult population with autistic disorder: chart review of naturalistic, open-label treatment.
Cohen SA, Fitzgerald BJ, Khan SR, Khan A.
1315 1st Ave. N., Seattle, WA 98109, USA. sacohenmd@msn.com

BACKGROUND: The present investigation retrospectively assessed the effect of an open-label switch to ziprasidone from other atypical antipsychotics on behavior, weight, and lipid levels in an adult population with autistic disorder. METHOD: We conducted a chart review of 10 adults (mean +/- SD age = 43.8 +/- 6.0 years) with DSM-IV autistic disorder who were switched from other atypical antipsychotics to ziprasidone, primarily due to weight gain, but other reasons included hypercholesterolemia, maladaptive behaviors, drowsiness, and depression. They had been treated with ziprasidone for at least 6 months. Our review focused on frequency of maladaptive behaviors, weight, and lipid levels. RESULTS: The mean +/- SD daily dose of ziprasidone was 128 +/- 41 mg, and all 10 patients continued with this same treatment after completion of the 6-month trial. Seven patients were found to have an improvement or no change in their maladaptive behavior. Eight patients (80%) lost weight (mean change = -13.1 +/- 7.0 lb [-5.9 +/- 3.2 kg]), 4 (80%) of 5 patients had a decrease in total cholesterol level, and 3 (60%) of 5 had a decrease in triglyceride levels. Data on lipid levels were available for 5 of the 10 patients. Behavioral activation was not noted in this population. There were no significant adverse effects associated with ziprasidone. CONCLUSION: In adults with autism, a switch to ziprasidone from other atypical antipsychotics appears to have the potential for maintaining beneficial effect on behavior while improving major health indices including weight and lipid levels.

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No To Hattatsu. 2003 Nov;35(6):473-7.
[An open trial of risperidone in autistic children]
[Article in Japanese]
Nishimura M, Hashimoto T, Miyazaki M, Mori K, Kuroda Y.
Department of Pediatrics, Tokushima University School of Medicine, Tokushima.

Clinical effects of risperidone were evaluated in 9 young autistic children under informed consent of their parents. The patients were evaluated by the Children's Behavioral Checklist and Rutter's Autistic Behavioral Rating Scale. After the administration, two subjects (playing and adaptation to change) of the Children's Behavioral Checklist and four (anomalous autistic behavior, destructive behavior, developmental problem and activity level) of the Rutter's Autistic Behavioral Rating Scale were improved significantly. There were no serious side effects such as extrapyramidal symptoms except minor adverse effects including sedation, depression, increased appetite and constipation. Risperidone might be effective for serious behavioral disturbances in young autistic children.

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Neurol Clin. 2003 Nov;21(4):915-32, viii.
Autism.
Tuchman R.
Dan Marino Center, Department of Neurology, Miami Children's Hospital, 2900 South Commerce Parkway, Weston, FL 33331, USA. tuchman@att.net

Autism is a neurologic disorder with impairments in language, social communication, and behavior, which may improve over time, but which persist throughout the lifetime. The evaluation of autism requires a separation of clinical and research objectives and is done best in close cooperation with professionals in the fields of communication, education, and psychology. There are no biologic markers of autism. Regression in language and social communication is present in approximately 30% of children with autism and is most likely to occur between 18 and 24 months of age. Early deficits in social communication can be identified by the assessment of joint attention, affective reciprocity, and metacognition. Current evidence suggests that deficits in social cognition and communication in autism may be related to dysfunction in the amygdala, hippocampus, and related limbic and cortical structures. Other neuroanatomic structures, such as the cerebellum, also may form part of a distributed neuronal network responsible for social cognition and communication. Genetics play a major role in autism, but what is inherited and how broad the inheritable phenotype is remain unclear. At a neurochemical level, the principal neurotransmitter implicated in autism is serotonin. Seizures and epileptiform discharges are common in autism and are linked to cognitive dysfunction. The role of medication is to target specific symptoms and open windows of opportunity that allow implementation of a multimodal individualized educational plan.

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Med Sci (Paris). 2003 Nov;19(11):1152-9.
[Autism: toward a necessary cultural revolution]
[Article in French]
Chamak B, Cohen D.
Centre de Recherche Psychotropes, sante mentale, societe, Cesames-UMR 8136, Universite Rene Descartes, 45, rue des Saints-Peres, 75006 Paris, France. brigitte.chamak@paris5.sorbonne.fr

Autism is a pervasive developmental disorder of childhood characterised by disturbances in both social interactions and communication as well as stereotyped patterns of activities and behaviour. The increase in estimates of the prevalence of autism has raised the question of an "epidemic" of autism. More active case assessment and changes in diagnostic criteria probably account in large part for such increase. Investigators have attempted to define the neural pathophysiology of autism ever since the hypothesis of "refrigerator mother" as its cause was replaced by the view that it is a developmental disorder of the immature brain. However consensus is yet to be reached concerning the brain regions implicated. Psychoanalysis, cognitive psychology, neurophysiology, neuropharmacology, and genetics propose restricted view of the major issues leaving extensive areas unexplored. Therapeutic approaches induce only partial and uncertain results. There is no cure for autism but substantial evidence indicates that early, intensive, individualised education is beneficial for children. All modern intervention programs for autism affected children share a high degree of environmental structuring and predictability and an extensive individual approach. Autism being a behaviourally defined syndrome, it gave rise to a number of controversies concerning definition, classification, etiopathogenesis and therapeutics. In the 1990s a crisis has occurred in France with a loss of confidence between parents and psychiatrists with a problem concerning the means and ways of care of the autistic individual. The aim of this paper is to point out the different questions raised by autism in order to better understand this syndrome which touches upon essential behaviour-related aspects such as self consciousness, reality perception, the functioning of the thought and communication, as well as the role of hereditary and acquired influences in normal and pathological development.

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J Clin Psychiatry. 2003 Sep;64(9):1039-47.
A 3-year naturalistic study of 53 preschool children with pervasive developmental disorders
treated with risperidone.
Masi G, Cosenza A, Mucci M, Brovedani P.
IRCCS Stella Maris, Scientific Institute of Child Neurology and Psychiatry, Calambrone, Pisa, Italy. gabriele.masi@inpe.unipi.it

BACKGROUND: Only sparse and short-term data are available on pharmacologic treatments in very young children with pervasive developmental disorders (PDD). The purpose of this 3-year naturalistic study (March 1999-April 2002) is to describe the clinical outcome of a consecutive sample of preschool children with PDD treated with risperidone monotherapy. METHOD: The sample consisted of 45 boys and 8 girls aged 3.6 to 6.6 years (mean +/- SD age = 4.6 +/- 0.7 years) with a DSM-IV diagnosis of autistic disorder or PDD, not otherwise specified. Outcome measures included the Children's Psychiatric Rating Scale (CPRS), Clinical Global Impressions-Improvement scale (CGI-I), Children's Global Assessment Scale (CGAS), and a checklist for risperidone side effects. RESULTS: Patients received risperidone for a period ranging from 1 to 32 months (7.9 +/- 6.8 months). Twenty-five patients (47.2%) continued to receive risperidone after the study was completed, while 28 (52.8%) discontinued due to side effects (22.6% [N = 12]), parents' choice (18.9% [N = 10]), lack of efficacy (5.7% [N = 3]), and decision of the treating psychiatrist (5.7% [N = 3]). The optimal dose was 0.55 +/- 0.2 mg/ day. Significant improvement at the last observation was found in CPRS (p < .0001) and CGAS (p < .0001) scores. On the basis of both an improvement of 25% in CPRS score and a score of 1 or 2 on the CGI-I, 46.8% (N = 22) of subjects were considered responders. Behavioral disorders and affect dysregulation were more sensitive to treatment than was interpersonal functioning. Responders received higher doses of medication for a longer period and had a greater weight gain than did nonresponders. Increased prolactin levels without clinical signs (65% [24 of 37]) and increased appetite (15% [8 of 531) were the most frequent side effects. CONCLUSION: These findings suggest that low-dose risperidone may positively affect the clinical outcome in young children with PDD not only in the short-term, but also in the long-term period.

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Novartis Found Symp. 2003;251:250-9; discussion 260-5, 281-97.
Can early interventions alter the course of autism?
Howlin P.
Department of Psychology, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK.

Interventions for autism have come a long way since the condition was described by Kanner in the 1940s. At that time, autism was considered to be closely linked to schizophrenia, and inadequate parenting was viewed as the principal cause. Psychoanalysis was often the therapy of choice, but there was also widespread use of the drugs and even electroconvulsive treatments that had been developed for use in schizophrenia. Over the years, as autism has come to be recognized as a developmental disorder, interventions have focused instead on enhancing developmental skills and on ways of ameliorating behavioural difficulties. Recognition of the role that language deficits in particular play in causing behaviour problems has led to a focus on the teaching of more effective communication skills. The need for early support for families and appropriate education is also widely acknowledged. Nevertheless, follow-up studies indicate that the prognosis for the majority of individuals with autism remains poor. And despite claims to the contrary, there is little evidence that very early, intensive interventions can significantly alter the long-term course of the disorder. The paper discusses findings from follow-up studies over the years and assess the impact of different intervention procedures on outcome.

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Novartis Found Symp. 2003;251:235-44; discussion 245-9, 281-97.
Why have drug treatments been so disappointing?
Buitelaar JK.
University of Medical Center Utrecht, Department of Child and Adolescent Psychiatry, B.01.324, PO Box 85500, 3508 GA Utrecht, The Netherlands.

The title of this contribution involves two consecutive questions: have the effects of medication in autism indeed been disappointing? And if so, why? The answer to the first question depends on whether one focuses on the core social and communicative deficits of autism, or on various complicating behaviour problems. Attempts over the past decades to develop drugs that specifically improve social and communicative functioning have failed. Among the most ambitious attempts were medical interventions in the endogenous opioid system that were motivated from animal models on the involvement of this system in various aspects of social behaviour. By contrast, medications such as the newer antipsychotics, psychostimulants, presynaptic noradrenergic blocking agents (clonidine and guanfacine) and selective serotonin reuptake inhibitors were shown to reduce impairing complicating symptoms of affective instability, irritability, hyperactivity and inattentiveness, aggression, self-injury and stereotypies. The explanation for the medication-refractory status of social and communicative deficits should be sought in at least two related factors: (1) the as yet unidentified neurochemical basis of autism, and (2) the obvious lack of involvement of the main neurotransmitter systems (dopamine, noradrenaline and serotonin) in the pathophysiology of social and communicative behaviour.

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Novartis Found Symp. 2003;251:112-22; discussion 122-8, 281-97.
The neuropathology of the autism spectrum disorders: what have we learned?
Bauman ML, Kemper TL.
Children's Neurology Service, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.

Autism is a behaviourally defined disorder, initially described by Kanner in 1943. By definition, symptoms are manifested by 36 months of age and are characterized by delayed and disordered language, impaired social interaction, abnormal responses to sensory stimuli, events and objects, poor eye contact, an insistence on sameness, an unusual capacity for rote memory, repetitive and stereotypic behaviour and a normal physical appearance. Relatively few neuropathological studies have been performed on the brains of autistic subjects. Of those reported, abnormalities have been described in the cerebral cortex, the brainstem, the limbic system and the cerebellum. Although those with the disorder present with a specific set of core characteristics, each individual patient is somewhat different from another. Thus, it should not be surprising that the brains of these subjects should show a wide range of abnormalities. However, it is important to delineate the anatomic features, which are common to all cases, regardless of age, sex and IQ, in order to begin to understand the central neurobiological profile of this disorder. The results of our systematic studies indicate that the anatomic features that are consistently abnormal in all cases include reduced numbers of Purkinje cells in the cerebellum, and small tightly packed neurons in the entorhinal cortex and in the medially placed nuclei of the amygdala. It is known that the limbic system is important for learning and memory, and that the amygdala plays a role in emotion and behaviour. Research in the cerebellum indicates that this structure is important as a modulator of a variety of brain functions and impacts on language processing, anticipatory and motor planning, mental imagery and timed sequencing. Defining the differences and similarities in brain anatomy in autism and correlating these observations with detailed clinical descriptions of the patient may allow us greater insight into the underlying neurobiology of this disorder.

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Zh Nevrol Psikhiatr Im S S Korsakova. 2003;103(6):15-8.
[The effect of cerebrolysin on cognitive functions in childhood autism and in Asperger syndrome]
[Article in Russian]
Krasnoperova MG, Bashina VM, Skvortsov IA, Simashkova NV.

Nineteen children with childhood autism and 8 with Asperger's syndrome aged 2-8 year, were treated with cerebrolysin (CL) in inpatient clinic. All the patients received 10 microinjections (intramuscularly and perinervously) of 0.1 ml CL daily during 5 days. Clinical study was combined with device estimation of cognitive functions and communicative skills. CL therapy resulted in improvement of cognitive functions (expressive and receptive speech, fine motoring, playing). Positive effects were revealed in all the patients with Asperger's syndrome and in 89% of the patients with childhood autism. Any negative effects were not found. With regard to cognitive functions development, therapeutic efficacy proved to be more pronounced in the patients with Asperger's syndrome as compared to childhood autistic group (p < 0.005).

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Lancet. 2003 Oct 4;362(9390):1133-41.
Autism.
Volkmar FR, Pauls D.
Child Study Center, Yale University, PO Box 207900, New Haven, CT 06520, USA. fred.volkmar@yale.edu

Autism is a disorder characterised by severe difficulties in social interaction and communication, and with unusual behaviours. Once thought of as rare, autism is now recognised as being common. The role of CNS factors in pathogenesis is suggested by high rates of seizure disorder; research has highlighted the role of several specific brain regions in syndrome pathogenesis. Autism is a strongly genetic disorder and probably arises because of multiple genes; recurrence rates in families with one child are high. Early intervention with various techniques is helpful in many cases. Some pharmacological agents may help with certain problematic behaviours but do not address the underlying cause of the disorder.

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Arch Dis Child. 2003 Aug;88(8):731-6.
Children with autistic spectrum disorders. I: comparison of placebo and single dose of human
synthetic secretin.
Levy SE, Souders MC, Wray J, Jawad AF, Gallagher PR, Coplan J, Belchic JK, Gerdes M, Mitchell R, Mulberg AE.
Division of Child Development and Rehabilitation, Children's Seashore House of The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. levys@email.chop.edu

AIMS: To examine the effect of a single dose of human synthetic secretin (HSS) on behaviour and communication in children with autism spectrum disorder (ASD) using an objective measure of communication and social reciprocity and standardised rating scales. METHODS: Randomised, crossover, double blind, and placebo controlled trial of a single intravenous dose of human synthetic secretin (HSS) 2 CU/kg. The 62 subjects (3-8 years) were assigned to group 1 (saline placebo/HSS) or group 2 (HSS/saline placebo). Diagnosis was confirmed by ADI-R (Autism Diagnostic Interview-Revised) algorithm. Severity of symptoms was rated using the CARS (Childhood Autism Rating Scale). Outcome measures included Communication and Symbolic Behavior Scale (CSBS), Ritvo Real-life Rating Scale, weekly Global Rating Scale (GBRS) by parents and teachers, and daily log of gastrointestinal symptoms. The communication subscale of the CSBS, specifying communication function, reciprocity, and social-affective signalling was videotaped and scored by a blinded, trained observer. RESULTS: Sixty one children completed the study. After randomisation, there were no significant differences in gender, race, age, and parent and teacher GBRS and Ritvo Scale between the two groups. Compared with placebo, secretin treatment was not associated with significant improvement of CSBS standard scores from baseline to 2 or 4 weeks post-infusion. Five children showed clinical improvement in standard scores: two after HSS and three after placebo. There were no significant changes in gastrointestinal symptoms after HSS or saline placebo. CONCLUSIONS: A single dose of intravenous human secretin is not effective in changing behaviour and communication in children with ASD when compared to placebo.

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Arch Dis Child. 2003 Aug;88(8):737-9.
Children with autistic spectrum disorders. II: parents are unable to distinguish secretin from placebo under double-blind conditions.
Coplan J, Souders MC, Mulberg AE, Belchic JK, Wray J, Jawad AF, Gallagher PR, Mitchell R, Gerdes M, Levy SE.
Division of Child Development and Rehabilitation, Children's Seashore House of The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

BACKGROUND: Standardised measures of behaviour have failed to detect short term improvement in children with autism following treatment with secretin. However, it is possible that standardised measures are insensitive to dimensions of child behaviour that are nonetheless detectable by parents. AIM: To determine the ability of parents of children with autism to guess, under double blind conditions, whether their child had received secretin or placebo. METHODS: 2x2 crossover randomised blinded study, comparing the effect of synthetic human secretin 2 U/kg to placebo (saline). Sixty two children with autism (aged 43-103 months) were randomly allocated to two groups: group 1 received placebo, followed six weeks later by secretin, and group 2 received secretin followed by placebo. At the conclusion of the study, parents were asked to guess their child's group assignment. RESULTS: Twenty seven families guessed their child's group assignment correctly and 27 guessed incorrectly. In 48 instances, parents based their guess on perceived improvement; in six cases, parents based their guess on perceived deterioration. Six families saw no difference after either infusion, and offered no guess. One family dropped out after the first infusion, and one family was lost to follow up after the second infusion. CONCLUSION: In a controlled setting, parents of young children with autism are unable to distinguish the short term behavioural effects of secretin from placebo.

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No To Hattatsu. 2003 May;35(3):233-7.
[Studies on the adverse effects of fluvoxamine treatment in children with autistic disorder: correlation with genetic polymorphism in serotonin related genes]
[Article in Japanese]
Sugie Y, Sugie H, Fukuda T, Ito M, Ohzeki T.
Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka. y-sugie@umin.ac.jp

Selective serotonin re-uptake inhibitors (SSRIs) have recently been applied to the children with autistic disorder. To create better treatment, we studied here clinical adverse effects of fluvoxamine and correlated them with genetic polymorphism of two genes, the promoter region of serotonin transporter gene (5-HTTLPR) and serotonin 2A receptor gene (5-HT2AR). Twenty-eight subjects, consisting of 23 boys and 5 girls, aged from 3 to 18 years old diagnosed as having autistic disorder were analyzed during fluvoxamine administration. The dosages and duration of fluvoxamine treatment are 1.5 to 3 mg/kg/day and 2 weeks to 17 months (mean 7.9 months), respectively. There were several clinical adverse effects such as sleep disturbance in 9 cases, climb up to high places in 8, gastrointestinal symptoms in 6, hyperactivities in 5, excitement in 4, general fatigability in 2 and urticaria in 1. Medication was discontinued in 2 patients with fatigability and 1 with sleep disturbance, diarrhea and poor appetite. There was no significant correlation between genetic polymorphism in 5-HTTLPR and the occurrence of clinical adverse effects of fluvoxamine. However hyperactivity was significantly more frequent in the subjects with 102T/102T polymorphism of 5-HT2AR, and patients with sleep disturbance were significantly less frequent in the subjects with 102C/102C polymorphism. We conclude that the clinical adverse effects such as climb up to high places and hyperactivity during fluvoxamine treatment may be relatively specific in children, and that genetic polymorphism of 5-HT2AR may be related to the appearance of clinical adverse effects.

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Issues Ment Health Nurs. 2003 Apr-May;24(3):273-95.
Effects of in-home training for culturally diverse fathers of children with autism.
Elder JH, Valcante G, Won D, Zylis R.
JHMHC UF College of Nursing, Gainesville, Florida 32610, USA. elderjh@nursing.ufl.edu

Recently there has been mounting interest in the role of fathers and the effect of their increasing involvement on child development. However, to date, little has been reported regarding the role of fathers with developmentally delayed children (e.g., autism, pervasive developmental delays) and cultural influences on father-child interactions. In this article we address this knowledge gap by reporting four cases representing the major ethnic groups. For each case, we (1) define the concept of fatherhood in its cultural context, (2) review and summarize related father-child research, and (3) present findings from our study evaluating the effects of an in-home intervention for autistic children. While variability is noted within and among the culturally diverse father-child dyads, there are also similarities across ethnic groups. Results of this study are promising, demonstrating the value of single subject experimental methods in characterizing and beginning to understand complex father-child interactions in autism and related child psychiatric disorders.

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J Dev Behav Pediatr. 2003 Apr;24(2):104-8.
Use of citalopram in pervasive developmental disorders.
Namerow LB, Thomas P, Bostic JQ, Prince J, Monuteaux MC.
Department of Psychiatry, Hartford Hospital, University of Connecticut School of Medicine, Hartford, Connecticut 06106, USA.

This study assessed the effectiveness and tolerability of the selective serotonin reuptake inhibitor citalopram in the treatment of patients with pervasive developmental disorders (PDDs). The medical charts of 15 children and adolescents (aged 6-16 yr) with Asperger syndrome, autism, or PDD not otherwise specified treated with citalopram were retrospectively reviewed. The final dose of citalopram was 16.9 +/- 12.1 mg/day with a treatment duration of 218.8 +/- 167.2 days. Independent ratings of the Clinical Global Impression (CGI) Severity and Improvement scales allowed comparison between baseline and PDD symptoms at the last visit. Eleven adolescents (73%) exhibited significant improvement in PDD, anxiety, or mood CGI score (z = 2.95; p =.003). Anxiety symptoms associated with PDDs improved significantly in 66% of patients (z = 2.83, p =.005), and mood symptoms improved significantly in 47% of patients (z = 2.78, p =.005). Mild side effects were reported by five patients (33%). These data suggest citalopram may be effective, safe, and well tolerated as part of the treatment of PDDs.

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J Child Psychol Psychiatry. 2003 Mar;44(3):456-68.
Joint attention training for children with autism using behavior modification procedures.
Whalen C, Schreibman L.
Autism Spectrum Therapies, Los Angeles, CA 90034, USA. cdallaire@autismtherapies.com

BACKGROUND: Deficits in joint attention are considered by many researchers to be an early predictor of childhood autism (e.g., Osterling & Dawson, 1994) and are considered to be pivotal to deficits in language, play, and social development in this population (Mundy, 1995). Although many researchers have noted the importance of joint attention deficits in the development of children with autism (e.g., Mundy, Sigman, & Kasari, 1994) and have called for intervention strategies (e.g., Mundy & Crowson, 1997), few studies have attempted to target joint attention. In this study, joint attention behaviors were taught to children with autism using a behavior modification procedure. METHODS: A multiple-baseline design was implemented to evaluate intervention effects. The following target behaviors were included in the intervention: 1) Responding to showing, pointing, and gaze shifting of adult; 2) Coordinated gaze shifting (i.e., coordinated joint attention); and 3) Pointing (with the purpose of sharing, not requesting). Generalization to setting and parent, follow-up sessions, and social validation measures were also analyzed. RESULTS: Joint attention behaviors were effectively trained and targeted behaviors generalized to other settings. In addition, positive changes were noted by naive observers using social validation measures. CONCLUSIONS: Integrating joint attention training into existing interventions may be important for children with autism. In addition, training parents in these techniques may help to maintain joint attention skills outside of the treatment setting.

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J Child Neurol. 2003 Feb;18(2):113-8.
Application of a ketogenic diet in children with autistic behavior: pilot study.
Evangeliou A, Vlachonikolis I, Mihailidou H, Spilioti M, Skarpalezou A, Makaronas N, Prokopiou A, Christodoulou P, Liapi-Adamidou G, Helidonis E, Sbyrakis S, Smeitink J.
Department of Paediatrics, Medical School, University of Crete, Crete, Greece. evangeli@med.uoc.gr

A pilot prospective follow-up study of the role of the ketogenic diet was carried out on 30 children, aged between 4 and 10 years, with autistic behavior. The diet was applied for 6 months, with continuous administration for 4 weeks, interrupted by 2-week diet-free intervals. Seven patients could not tolerate the diet, whereas five other patients adhered to the diet for 1 to 2 months and then discontinued it. Of the remaining group who adhered to the diet, 18 of 30 children (60%), improvement was recorded in several parameters and in accordance with the Childhood Autism Rating Scale. Significant improvement (> 12 units of the Childhood Autism Rating Scale) was recorded in two patients (pre-Scale: 35.00 +/- 1.41[mean +/- SD]), average improvement (> 8-12 units) in eight patients (pre-Scale: 41.88 +/- 3.14[mean +/- SD]), and minor improvement (2-8 units) in eight patients (pre-Scale: 45.25 +/- 2.76 [mean +/- SD]). Although these data are very preliminary, there is some evidence that the ketogenic diet may be used in autistic behavior as an additional or alternative therapy.

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Cochrane Database Syst Rev. 2003;(1):CD003496.
Parent-mediated early intervention for young children with autism spectrum disorder.
Diggle T, McConachie HR, Randle VR.
Department of Child Health, The University of Newcastle, University of Newcastle, Newcastle upon Tyne, UK, NE2 4AE. T.J.Diggle@newcastle.ac.uk

BACKGROUND: Recent estimates concerning the prevalence of autistic spectrum disorder are much higher than those reported 30 years ago, with at least 1 in 400 children affected. This group of children and families have important service needs. The involvement of parents in implementing intervention strategies designed to help their autistic children has long been accepted as helpful. The potential benefits are increased skills and reduced stress for parents as well as children. OBJECTIVES: The objective of this review was to determine the extent to which parent-mediated early intervention has been shown to be effective in the treatment of children aged 1 year to 6 years 11 months with autistic spectrum disorder. In particular, it aimed to assess the effectiveness of such interventions in terms of the benefits for both children and their parents. SEARCH STRATEGY: A range of psychological, educational and biomedical databases were searched. Bibliographies and reference lists of key articles were searched, field experts were contacted and key journals were hand searched. SELECTION CRITERIA: Only randomised or quasi-randomised studies were included. Study interventions had a significant focus on parent-implemented early intervention, compared to a group of children who received no treatment, a waiting list group or a different form of intervention. There was at least one objective, child related outcome measure. DATA COLLECTION AND ANALYSIS: Appraisal of the methodological quality of included studies was carried out independently by two reviewers. Differences between the included studies in terms of the type of intervention, the comparison groups used and the outcome measures were too great to allow for direct comparison. MAIN RESULTS: The results of this review are based on data from two studies. Two significant results were found to favour parent training in one study: child language and maternal knowledge of autism. In the other, intensive intervention (involving parents, but primarily delivered by professionals) was associated with better child outcomes on direct measurement than were found for parent-mediated early intervention, but no differences were found in relation to measures of parent and teacher perceptions of skills and behaviours. REVIEWER'S CONCLUSIONS: This review has little to offer in the way of implications for practice: there were only two studies, the numbers of participants included were small, and the two studies could not be compared directly to one another. In terms of research, randomised controlled trials involving large samples need to be carried out, involving both short and long-term outcome information and full economic evaluations. Research in this area is hampered by barriers to randomisation, such as availability of equivalent services.

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J Child Neurol. 2002 Nov;17(11):833-7.
Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic
spectrum disorders.
Chez MG, Buchanan CP, Aimonovitch MC, Becker M, Schaefer K, Black C, Komen J.
Research Division, Autism and Epilepsy Specialty Services of Illinois, Ltd, Lake Bluff, IL 60044, USA. mchezmd@interaccess.com

L-Carnosine, a dipeptide, can enhance frontal lobe function or be neuroprotective. It can also correlate with gamma-aminobutyric acid (GABA)-homocarnosine interaction, with possible anticonvulsive effects. We investigated 31 children with autistic spectrum disorders in an 8-week, double-blinded study to determine if 800 mg L-carnosine daily would result in observable changes versus placebo. Outcome measures were the Childhood Autism Rating Scale, the Gilliam Autism Rating Scale, the Expressive and Receptive One-Word Picture Vocabulary tests, and Clinical Global Impressions of Change. Children on placebo did not show statistically significant changes. After 8 weeks on L-carnosine, children showed statistically significant improvements on the Gilliam Autism Rating Scale (total score and the Behavior, Socialization, and Communication subscales) and the Receptive One-Word Picture Vocabulary test (all P < .05). Improved trends were noted on other outcome measures. Although the mechanism of action of L-carnosine is not well understood, it may enhance neurologic function, perhaps in the enterorhinal or temporal cortex.

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Pediatr Nurs. 2002 Nov-Dec;28(6):573-8, 581.
Social interactions of children with autism in father-child and mother-child play sessions.
Elder JH, Valcante G, Groce S, Yarandi H, Carlton MS.
University of Florida, College of Nursing, Gainesville, FL, USA.

Autism, or the broader category of autistic spectrum disorder (ASD), is a complex developmental disability characterized by qualitative impairments in social interaction and communication and restricted repetitive patterns of behavior. Specific aims of the investigation reported here were to (a) compare autistic child behaviors in clinic versus home settings, (b) compare father and mother behaviors in clinic versus home settings, and (c) characterize interactions of fathers with their autistic children and compare these with mother-child interactions. While results indicated that there were no statistically significant group differences between child behaviors in clinic versus home settings or in father versus mother behaviors, there was wide behavioral variability in each setting and differences when comparing individual cases. These findings are consistent with the clinical impression that autism is a syndrome with various symptom configurations and individual differences in behaviors.

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J Autism Dev Disord. 2002 Dec;32(6):519-33.
Contextualized behavioral support in early intervention for children with autism and their families.
Moes DR, Frea WD.
University of California, Los Angeles, USA.

Parent education programs have become an effective mode of treatment delivery for teaching families effective behavioral strategies to manage challenging behavior in young children with autism. Functional assessment and functional communication training (FCT) are empirically validated procedures that have recently been introduced into parent education programming to help resolve challenging behaviors. The success of these procedures, however, is contingent on family members' ability to integrate them into the specific contexts in which challenging behaviors occur. Consequently, the application of these procedures in home settings necessitates consideration of the family context in the assessment and treatment planning process. A study is presented that investigated the use of information on family context (i.e., caregiving demands, family support, patterns of social interaction) to direct the assessment and intervention planning process. More specifically, information on family context was used to individualize behavioral support plans designed to support family use of functional communication training within important family routines. Through parent-investigator collaboration we individualized the manner in which functional communication training procedures were taught and implemented so they were contextually relevant. Utilizing a multiple baseline design, the challenging behaviors and functional communication of three children with autism were monitored across baseline, intervention (i.e., FCT, and contextulized FCT), and follow-up phases. Multiple routines for each participant were selected and monitored across all phases to evaluate changes in the dependent measures within training and generalization routines. A self-report questionnaire was administered intermittently to parents to determine if consideration of family context improved the "goodness of fit" of the functional communication training treatment packages across FCT and contextualized FCT intervention phases. Results from the study indicate that consideration of family context in the assessment and intervention planning process does not jeopardize and may contribute to the stability and durability of reductions in challenging behavior achieved with functional assessment and functional communication training procedures.

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Neuropsychopharmacology 2003 Jan;28(1):193-8
Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger's disorders.
Hollander E, Novotny S, Hanratty M, Yaffe R, DeCaria CM, Aronowitz BR, Mosovich S.
Department of Psychiatry, Seaver Autism Research Center, Mount Sinai School of Medicine, New York, NY 10029, USA. eric.hollander@mssm.edu

Autism is a neurodevelopmental disorder characterized by dysfunction in three core behavioral domains: repetitive behaviors, social deficits, and language abnormalities. There is evidence that abnormalities exist in peptide systems, particularly the oxytocin system, in autism spectrum patients. Furthermore, oxytocin and the closely related peptide vasopressin are known to play a role in social and repetitive behaviors. This study examined the impact of oxytocin on repetitive behaviors in 15 adults with autism or Asperger's disorder via randomized double-blind oxytocin and placebo challenges. The primary outcome measure was an instrument rating six repetitive behaviors: need to know, repeating, ordering, need to tell/ask, self-injury, and touching. Patients with autism spectrum disorders showed a significant reduction in repetitive behaviors following oxytocin infusion in comparison to placebo infusion. Repetitive behavior in autism spectrum disorders may be related to abnormalities in the oxytocin system, and may be partially ameliorated by synthetic oxytocin infusion.

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N Engl J Med 2002 Aug 1;347(5):314-21
Comment in: J Pediatr. 2003 Jan;142(1):86-7.
Risperidone in children with autism and serious behavioral problems.
McCracken JT, McGough J, Shah B, Cronin P, Hong D, Aman MG, Arnold LE, Lindsay R, Nash P, Hollway J, McDougle CJ, Posey D, Swiezy N, Kohn A, Scahill L, Martin A, Koenig K, Volkmar F, Carroll D, Lancor A, Tierney E, Ghuman J, Gonzalez NM, Grados M, Vitiello B, Ritz L, Davies M, Robinson J, McMahon D; Research Units on Pediatric Psychopharmacology Autism Network.
University of California, Los Angeles, USA.

BACKGROUND: Atypical antipsychotic agents, which block postsynaptic dopamine and serotonin receptors, have advantages over traditional antipsychotic medications in the treatment of adults with schizophrenia and may be beneficial in children with autistic disorder who have serious behavioral disturbances. However, data on the safety and efficacy of atypical antipsychotic agents in children are limited. METHODS: We conducted a multisite, randomized, double-blind trial of risperidone as compared with placebo for the treatment of autistic disorder accompanied by severe tantrums, aggression, or self-injurious behavior in children 5 to 17 years old. The primary outcome measures were the score on the Irritability subscale of the Aberrant Behavior Checklist and the rating on the Clinical Global Impressions - Improvement (CGI-I) scale at eight weeks. RESULTS: A total of 101 children (82 boys and 19 girls; mean [SD] age, 8.82.7 years) were randomly assigned to receive risperidone (49 children) or placebo (52). Treatment with risperidone for eight weeks (dose range, 0.5 to 3.5 mg per day) resulted in a 56.9 percent reduction in the Irritability score, as compared with a 14.1 percent decrease in the placebo group (P<0.001). The rate of a positive response, defined as at least a 25 percent decrease in the Irritability score and a rating of much improved or very much improved on the CGI-I scale, was 69 percent in the risperidone group (34 of 49 children had a positive response) and 12 percent in the placebo group (6 of 52, P<0.001). Risperidone therapy was associated with an average weight gain of 2.72.9 kg, as compared with 0.82.2 kg with placebo (P<0.001). Increased appetite, fatigue, drowsiness, dizziness, and drooling were more common in the risperidone group than in the placebo group (P<0.05 for each comparison). In two thirds of the children with a positive response to risperidone at eight weeks (23 of 34), the benefit was maintained at six months. CONCLUSIONS: Risperidone was effective and well tolerated for the treatment of tantrums, aggression, or self-injurious behavior in children with autistic disorder. The short period of this trial limits inferences about adverse effects such as tardive dyskinesia. Copyright 2002 Massachusetts Medical Society

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J Dev Behav Pediatr 2002 Aug;23(4):225-30
Levetiracetam in autistic children: an open-label study.
Rugino TA, Samsock TC.
Department of Pediatrics, Marshall University Joan C Edwards School of Medicine, Huntington, West Virginia, USA. drtomrug@mac.com

The objectives of this study were to determine whether autistic children taking levetiracetam (1) showed improvement in the areas of aggression, impulsivity, hyperkinesis, and mood instability, and (2) showed a nootropic response. Ten white autistic boys ranging from 4 to 10 years were compared pretreatment and while taking levetiracetam for an average of 4.1 weeks. Inattention, hyperkinesis, and impulsivity were evaluated using the Achenbach Attention Problems scale, Conners DSM-IV Total scale, and the Conners Attention-Deficit Hyperactivity Disorder Index scale, all of which showed statistically significant improvements. Mood instability was measured with the Conners Global Index (CGI) Emotional Lability and CGI Total scales, both of which showed statistically significant improvements. Aggressive behavior, as measured with the Achenbach Aggression scale, showed statistically significant improvement only for subjects who were not recently weaned from medications that reduce aggression (e.g., risperidone, carbamazepine, desipramine). Levetiracetam may reduce hyperactivity, impulsivity, mood instability, and aggression in autistic children with these problems. No nootropic effect was observed.

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Int J Circumpolar Health 2002;61 Suppl 2:69-79
Some aspects of treatment and habilitation of children and adolescents with autistic disorder in Northern-Finland.
Kielinen M, Linna SL, Moilanen I.
Clinic of Child Psychiatry, University Hospital of Oulu, Oulu, Finland. marko.kielinen@autismiliitto.fi

Hospital records and data on the treatment/habilitation status of 187 children with autism aged 3-18 years were gathered from Northern Finland. The treatment programs and therapies varied, depending on the trained staff available. One-hundred and fifty-two (82.9%) children and adolescents with autism received more than one therapeutic intervention or specific training program. The most common therapies were physiotherapy as well as speech, occupational and music therapy. 43.9% of the children and adolescents with autism received specific training according to TEACCH (Treatment and Education of Autistic and related Communication-Handicapped Children), 10.2% according to Lovaas and 30.5% according to the Portage program. Antiepileptic medication had been prescribed to 23.9% and psychopharmacological interventions to 14.9% of the individuals with autistic disorder (AD). One hundred and seventy-eight subjects out of 187 showed some improvement on the Childhood Autism Rating Scale (CARS), even if no statistically significant difference was found between the outcome of the available habilitation methods.

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Int J Circumpolar Health 2002;61 Suppl 2:15-21
Do high functioning autistic individuals treated in a residential setting differ in divided attention abilities from those treated in an out-patient setting?
Bogte H, Flamma B, van der Meere J.
Workhome Zuidlaren, Stichting GGz Groningen, The Netherlands.

The goal of this current study was to test divided attention abilities of a group adults with autism and normal intellectual functioning, treated in a residential setting versus those treated in an out-patient setting. Both groups were compared with a control group using the Sternberg (1969) reaction time paradigm. It appeared that the in-patient group suffered from a divided attention deficit compared to a norm group. The patients treated in an out-patient setting scored in between the norm group and the in-patient group. Findings are discussed with respect to the relevance for the day to day clinical practice.

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Cochrane Database Syst Rev 2002;(4):CD003497
Combined vitamin B6-magnesium treatment in autism spectrum disorder.
Nye C, Brice A.
UCF Center for Autism & Related Disabilities, 12001 Science Dr, Suite 145, Orlando, Florida 32826, USA. cnye@mail.ucf.edu

BACKGROUND: The use of mega-vitamin intervention began in the early 1950's with the treatment of schizophrenic patients. Pyroxidine (vitamin B6) was first used with children diagnosed with "autism syndrome" when speech and language improvement was observed in some children as a result of large doses of B6. A number of published studies attempted to assess the effects of vitamin B6-Mg (Mg was found to reduce undesirable side effects from B6) on a variety of characteristics such as verbal communication, non-verbal communication, interpersonal skills, and physiological function, in individuals with autism. OBJECTIVES: To determine the efficacy of vitamin B6 and magnesium (B6-Mg) for treating social, communication and behavioural responses of children and adults with autism. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2002), MEDLINE (1966- January 2002), EMBASE (1980-January 2002), PsychINFO (1887 - January 2002), Dissertation Abstracts International (1861 - January 2002). The search engine FirstSearch was also used (January 2002). Reference lists for all the obtained studies and other review articles were examined for additional studies. SELECTION CRITERIA: All studies in which the participants were randomly allocated prior to intervention and in which outcomes were compared to either a placebo or non-treated group were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated all potential studies identified as indicated above for inclusion. MAIN RESULTS: Two trials were included in the review. Both studies used a double-blind crossover design. One study (Tolbert 1993) provided insufficient data to conduct an analysis. The senior author was contacted for supporting data but was unable to provide the needed information. The remaining study (Findling, 1997) yielded no significant differences between treatment and placebo group performances following the B6 intervention on measures of social interaction, communication, compulsivity, impulsivity, or hyperactivity. REVIEWER'S CONCLUSIONS: Due to the small number of studies, the methodological quality of studies, and small sample sizes, no recommendation can be advanced regarding the use of B6-Mg as a treatment for autism.

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Altern Med Rev 2002 Dec;7(6):472-99
Autism, an extreme challenge to integrative medicine. Part 2: medical management.
Kidd PM.

Autism and allied autistic spectrum disorders (ASD) present myriad behavioral, clinical, and biochemical abnormalities. Parental participation, advanced testing protocols, and eclectic treatment strategies have driven progress toward cure. Behavioral modification and structured education are beneficial but insufficient. Dietary restrictions, including removal of milk and other casein dairy products, wheat and other gluten sources, sugar, chocolate, preservatives, and food coloring are beneficial and prerequisite to benefit from other interventions. Individualized IgG or IgE testing can identify other troublesome foods but not non-immune mediated food sensitivities. Gastrointestinal improvement rests on controlling Candida and other parasites, and using probiotic bacteria and nutrients to correct dysbiosis and decrease gut permeability. Detoxification of mercury and other heavy metals by DMSA/DMPS chelation can have marked benefit. Documented sulfoxidation-sulfation inadequacies call for sulfur-sulfhydryl repletion and other liver p450 support. Many nutrient supplements are beneficial and well tolerated, including dimethylglycine (DMG) and a combination of pyridoxine (vitamin B6) and magnesium, both of which benefit roughly half of ASD cases. Vitamins A, B3, C, and folic acid; the minerals calcium and zinc; cod liver oil; and digestive enzymes, all offer benefit. Secretin, a triggering factor for digestion, is presently under investigation. Immune therapies (pentoxifyllin, intravenous immunoglobulin, transfer factor, and colostrum) benefit selected cases. Long-chain omega-3 fatty acids offer great promise. Current pharmaceuticals fail to benefit the primary symptoms and can have marked adverse effects. Individualized, in-depth clinical and laboratory assessments and integrative parent-physician-scientist cooperation are the keys to successful ASD management.

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World J Biol Psychiatry 2002 Jul;3(3):162-6
Treatment of late onset autism as a consequence of probable autommune processes related to
chronic bacterial infection.
Matarazzo EB.
Department of Psychiatry, School of Medicine, University of Sao Paulo, Brazil. eneidam_br@yahoo.com.br

Two cases are described of children who at first developed normally, but before the age of three developed autistic symptoms following the reactivation of a chronic oto-rhinolaryngologic infection. The clinical and laboratory data of the cases support the aetiological hypothesis of an autoimmune process. Adrenocorticotrophic hormone (ACTH), prescribed in the first months of the disease, cured one case. The other patient, who was two years old when autistic symptoms appeared and was treated only six years later, showed a partial but definitive improvement with the immunosuppressive treatment. This report proposes that reactivation of a chronic bacterial infection be included among the aetiologies of Late Onset Autism, and demonstrates that, when the aetiological hypothesis of an autoimmune process based on clinical and laboratory data is considered, an immunosuppressive treatment, particularly with ACTH, can be very effective and also safe.

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Z Kinder Jugendpsychiatr Psychother 2002 Nov;30(4):271-80
[Intervention in autistic disorders: status quo, evidence-based, questionable and doubtful techniques]
[Article in German]
Bolte S, Poustka F.
Klinik fur Psychiatrie und Psychotherapie des Kindes- und Jugendalters, Klinikums der Johann Wolfgang Goethe-Universitat. Boelte@em.uni-frankfurt.de

OBJECTIVE: We describe and critically discuss intervention methods that have been used to modify autistic behaviors. METHODS: Early intervention methods, training of social skills, pharmacological treatment and alternative approaches are reviewed in the light of the empirical evidence. RESULTS: Autism is a persistent and phenotypically heterogeneous disorder for which no cure has been found to date. However, individually composed care and therapies can lead to remarkable quantitative improvement. CONCLUSIONS: Further research is needed to evaluate the true impact of psychological and biological intervention techniques in autistic disorders. Among other things, the therapy studies carried out up to now often lack an adequate diagnostic assessment.

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Psychiatr Clin North Am 2002 Dec;25(4):811-36
The autistic spectrum: subgroups, boundaries, and treatment.
Willemsen-Swinkels SH, Buitelaar JK.
Department of Child and Adolescent Psychiatry, University Medical Center, PO Box 85500, 3508 GA Utrecht, The Netherlands. s.h.n.willemsen@psych.azu.nl

There is consensus about the disorders that comprise the autistic spectrum, with autistic disorder, Asperger's disorder, and PDD-NOS as the most typical examples and Rett's disorder and disintegrative disorder as the other components. Important controversies regarding the precise definitions of autistic spectrum disorders and the boundaries between the milder manifestations of those disorders, particularly PDD-NOS, and non-autistic conditions have not been and cannot be resolved fully as long as there is no known biologic cause or consistent biologic or psychological marker. This includes issues as basic as whether the autistic spectrum is a predominantly unitary entity or a collection of more or less similar phenotypes with multiple, varying etiologies. This is why the highest long-term priority in the area of definite diagnosis is the search for biologic marker(s) for autism and related autism spectrum disorders [91]. In the absence of a medical test to unequivocally diagnose autism, definitions of autism and related conditions are based only on manifestations in overt behavior, with all the unreliability this entails. In the future, the discovery of biologic correlates, causes, and pathogenetic pathways will undoubtedly change the way in which autism is diagnosed and lead to a new nosology [95]. Until that time the definitions in the current versions of the classification systems should be considered in a state of evolution. The key problem of the current classification systems is the fact that the boundaries between the various disorders are fuzzy. Instead of a categorical approach, a more useful description might be that of "autistic spectrum disorder," which reflects the range of severity of symptoms. Such a dimensional understanding of PDD is useful to clinicians, who may otherwise use nonspecific terms to avoid the categorical diagnosis of autism [31]. Rutter and Schopler [96] argued for separate clinical and research schemes because clinical and research needs are different. For research purposes it is desirable to have as much direct comparability across studies as possible. The focus is on a high degree of homogeneity within diagnostic groupings. A price must be paid for this detailed specification, and the main cost lies in the proportion of cases left undiagnosed. For example, there may be good scientific reasons for a narrowly defined categorical diagnosis that includes only individuals who definitely and clearly have a specifically defined condition and excludes individuals who may have the condition. For clinicians and educators, classification helps guide the selection of treatments for an individual. From this point of view, broader diagnostic concepts may be most appropriate [95].

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J Child Adolesc Psychopharmacol 2002 Fall;12(3):237-41
A retrospective open trial of adjunctive donepezil in children and adolescents with autistic disorder.
Hardan AY, Handen BL.
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. hardanay@msx.upmc.edu

In light of the recently reported neuropathologic and neurochemical abnormalities of the cholinergic pathways in autism, donepezil, a cholinesterase inhibitor, is a potentially useful agent in the treatment of cognitive and behavioral symptoms observed in this disorder. A retrospective pilot study was conducted to determine whether donepezil is effective in the treatment of children and adolescents with autism. Eight patients (mean age = 11.0 4.1 years; range 7-19 years) who met Diagnostic and Statistical Manual of Mental Disorders (4th edition) criteria for autistic disorder were openly treated with donepezil. All patients were on concomitant psychoactive medications. Four of these patients (50%) demonstrated significant improvement as assessed by the Aberrant Behavior Checklist and the Clinical Global Impression Scale. Decreases in the Irritability and Hyperactivity subscales were observed, but no changes in the Inappropriate Speech, Lethargy, and Stereotypies subscales were noted. Limited and transient side effects were reported, with one patient experiencing gastrointestinal disturbances and another reporting mild irritability. Double-blind, placebo-controlled investigations are needed to provide further evidence of the potential benefits of donepezil to patients with autistic disorder.

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Dev Med Child Neurol 2002 Oct;44(10):652-9
Fluoxetine response in children with autistic spectrum disorders: correlation with familial major affective disorder and intellectual achievement.
DeLong GR, Ritch CR, Burch S.
Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA. Delon006@mc.duke.edu

One hundred and twenty-nine children, 2 to 8 years old, with idiopathic autistic spectrum disorder diagnosed by standard instruments (Childhood Austim Ratings Scale and Autism Diagnostic Observation Schedule) were treated with fluoxetine (0.15 to 0.5mg/kg) for 5 to 76 months (mean 32 to 36 months), with discontinuation trials. Response criteria are described. Family histories were obtained using the family history method in repeated interviews. Fluoxetine response, family history of major affective disorder, and unusual intellectual achievement, pretreatment language, and hyperlexia were used to define a coherent subgroup of autistic spectrum disorder. Statistical analyses were post hoc. Of the children, 22 (17%) had an excellent response, 67 (52%) good, and 40 (31%) fair/poor. Treatment age did not correlate with response. Fluoxetine response correlated robustly with familial major affective disorder and unusual intellectual achievement, and with hyperlexia in the child. Family history of bipolar disorder and of unusual intellectual achievement correlated strongly. Five children developed bipolar disorder during follow-up. Fluoxetine response, family history of major affective disorder (especially bipolar), unusual achievement, and hyperlexia in the children appear to define a homogeneous autistic subgroup. Bipolar disorder, unusual intellectual achievement, and autistic spectrum disorders cluster strongly in families and may share genetic determinants.

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J Am Acad Child Adolesc Psychiatry 2002 Nov;41(11):1315-21
Comment in: J Am Acad Child Adolesc Psychiatry. 2002 Nov;41(11):1322-3.
A randomized, double-blind, placebo-controlled trial of porcine versus synthetic secretin for reducing symptoms of autism.
Unis AS, Munson JA, Rogers SJ, Goldson E, Osterling J, Gabriels R, Abbott RD, Dawson G.
Department of Psychiatry and Behavioral Science, University of Washington, Seattle, WA 98195, USA.

OBJECTIVE: To compare the effects of a single dose of biologic and synthetic porcine secretin to placebo on a variety of autism symptoms. METHOD: Eighty-five children with autism without other medical conditions and not taking other psychotropic medications participated (ages between 3 and 12 years, mean IQ = 55). Children were grouped into trios matched by age and communication level and then randomly assigned to one of three treatment groups: biologic secretin (2 CU/kg), synthetic secretin (0.4 microg/kg), and placebo. Measures collected 1 week before and 4 weeks after infusion included autism symptoms, language skills, and problem behaviors, gathered from parents, teachers, and investigators, who were all blind to treatment. Two-factor, repeated-measures analyses of variance (3 treatment levels by 2 repeated measures, pre- and postinfusion) were used to examine efficacy. RESULTS: Direct observation measures did not show change over time related to secretin. Parent reports showed an overall reduction of symptom severity for all treatment groups, including the placebo group. One teacher-report measure showed decreases in autism symptoms in the placebo and synthetic secretin groups. CONCLUSIONS: No evidence that either biologic or synthetic secretin provided amelioration of symptoms beyond placebo was observed. This held true when children with and without gastrointestinal problems were examined separately.

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J Med Assoc Thai 2002 Aug;85 Suppl 2:S784-9
Risperidone in the treatment of autistic Thai children under 4 years of age.
Boon-Yasidhi V, Tarugsa J, Suwanwattana C, Soising L.
Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

The authors report five cases of very young children with autistic disorder, aged 2.1-3.7 years, treated with risperidone, as part of the comprehensive intervention. Treatment with risperidone 0.25-0.5 mg per day was associated with clinically meaningful decreases in problem behaviors including hyperactivity, irritability, and aggressiveness. There were also improvements in social relatedness and cooperation with developmental treatment. All of the children tolerated the medication well and experienced no untoward effects. The efficacy of risperidone in the treatment of very young children with autistic disorder reported here is consistent with findings in the limited number of cases previously reported in the literature. Controlled studies are needed to confirm the efficacy and safety of risperidone in the treatment of these children.

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Mol Neurobiol 2002 Aug;26(1):97-107
Secretin as a neuropeptide.
Ng SS, Yung WH, Chow BK.
Department of Zoology, University of Hong Kong, Hong Kong, PRC.

The role of secretin as a classical hormone in the gastrointestinal system is well-established. The recent debate on the use of secretin as a potential therapeutic treatment for autistic patients urges a better understanding of the neuroactive functions of secretin. Indeed, there is an increasing body of evidence pointing to the direction that, in addition to other peptides in the secretin/glucagon superfamily, secretin is also a neuropeptide. The purpose of this review is to discuss the recent data for supporting the neurocrine roles of secretin in rodents. By in situ hybridization and immunostaining, secretin was found to be expressed in distinct neuronal populations within the cerebellum and cerebral cortex, whereas the receptor transcript was found throughout the brain. In the rat cerebellum, secretin functions as a retrograde messenger to facilitate GABA transmission, indicating that it can modulate motor and other functions. In summary, the recent data support strongly the neuropeptide role of secretin, although the secretin-autism link remains to be clarified in the future.

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Res Dev Disabil 2002 Jul-Aug;23(4):285-92
Effects of single and repeated shock on perceived pain and startle response in healthy volunteers.
Duker PC, Douwenga H, Joosten S, Franken T.
Psychology Laboratory, University of Nijmegen and Plurijn Foundation, Netherlands. p.duker@ped.kun.nl

Contingent shock (CS) has been used in a number of studies to suppress health-threatening self-injurious behavior of individuals with mental retardation and autism. As sustained suppression is an issue of concern, research into procedural variables of CS is needed. In this study, clinical evidence was used to infer a variable that might be of relevance for the application of clinical contingent shock, that is, to assess the effect of single versus repeated shock at a specific location on the body. With pain intensity and startle response as dependent variables, shocks were administered to 48 healthy volunteers. Electric shocks were identical to those that used in clinical practice. The second shock in succession to the same location of the body produced higher pain intensity ratings than the first shock and that the third shock in succession to the same location of the body produced higher pain intensity ratings than the second shock in succession. Startle responses, however, failed to be affected in this direction. The latter result is consistent with a previous study. Our data suggest that repeated shock to the same location is likely to be more effective to establish suppression than repeated shock to different locations.

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J Clin Psychopharmacol 2002 Oct;22(5):455-60
Open-label study of olanzapine in children with pervasive developmental disorder.
Kemner C, Willemsen-Swinkels SH, de Jonge M, Tuynman-Qua H, van Engeland H.
University Medical Center Utrecht, Department of Child and Adolescent Psychiatry, The Netherlands. C.kemner@psych.azu.nl

The effects of olanzapine on the symptomatology of children with pervasive developmental disorder with emphasis on problems of communication and the safety of the drug were investigated in a 3-month open-label, open-dosage study. Participating in the study were 25 children age 6 to 16 years with a diagnosis of either autistic disorder or pervasive developmental disorder not otherwise specified. Psychometric measures included the Clinical Global Impression of Severity/Improvement, the Aberrant Behavior Checklist, and the TARGET (a checklist of five target symptoms). Communication skills were assessed during behavioral analysis of a playroom session. Safety measures included clinical chemistry variables, electrocardiography, the SimpsonAngus Neurological Rating Scale, the Barnes Akathisia Scale, and vital signs. Twenty-three children completed the study and showed significant improvement on three subscales of the Aberrant Behavior Checklist (Irritability, Hyperactivity, and Excessive Speech) and the TARGET. The final mean dose was 10.7 mg/day. Several aspects of communication were also improved after olanzapine treatment. However, only three children were considered responders in terms of the Clinical Global Impression of Severity/Improvement scores. The most important adverse events were weight gain, increased appetite, and loss of strength. Three children showed extrapyramidal symptoms that disappeared after the dose was lowered. Thus, while olanzapine was a relatively safe medication in children, its clinical relevance in children with pervasive developmental disorder may be limited.

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Curr Opin Investig Drugs 2002 Aug;3(8):1212-6
Risperidone: a potential treatment for autism.
Posey DJ, McDougle CJ.
Riley Hospital for Children, Indianapolis, IN 46202, USA. dposey@iupui.edu

Autistic disorder (autism) is a neuropsychiatric syndrome characterized by marked deficits in reciprocal social relatedness, communication impairment and a narrow range of interests and/or repetitive behaviors. Autism is frequently associated with, but distinct from, mental retardation. It is classified as a subtype of pervasive developmental disorder (PDD) along with 'PDD not otherwise specified' (NOS) and Asperger's disorder. These disorders have in common marked impairments in social relatedness. Individuals with autism may also have other symptoms that become the primary focus of psychiatric treatment. These associated symptoms include aggression, self-injury, irritability and anxiety.

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Med Hypotheses 2002 Sep;59(3):283-8
Live virus vaccination near a pregnancy: flawed policies, tragic results.
Yazbak FE, Yazbak K.
TL Autism Research, West Falmouth, Massachusetts 02574-0770, USA. tlautstudy@aol.com

Vaccination of women with live virus vaccines around conception has always been contraindicated by the Center for Disease Control and Prevention (CDC) and the vaccine manufacturer because of potential risks to the fetus. Nevertheless this dangerous practice occurs and is associated with maternal health problems and a very high incidence of early-onset autism in the children.Postpartum vaccination with live virus vaccines has been recommended by the CDC, and described as 'convenient' by the vaccine manufacturer. This 'routine practice' may lead to health and is also associated with many health and obstetrical problems in the recipient, and is frequently associated with autism in both current and future children. Re-vaccination often fails to produce immunity, the very reason for which it was recommended.

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Neuroendocrinol Lett 2002 Aug;23(4):303-8
Treatment of autism spectrum children with thiamine tetrahydrofurfuryl disulfide: a pilot study.
Lonsdale D, Shamberger RJ, Audhya T.
Preventive Medicine Group, 24700 Center Ridge Road, Westlake, OH 44145, USA. dlonsdale@pol.net

OBJECTIVES: In a Pilot Study, the clinical and biochemical effects of thiamine tetrahydrofurfuryl disulfide (TTFD) on autistic spectrum children were investigated. SUBJECTS AND METHODS: Ten children were studied. Diagnosis was confirmed through the use of form E2, a computer assessed symptom score. For practical reasons, TTFD was administered twice daily for two months in the form of rectal suppositories, each containing 50 mg of TTFD. Symptomatic responses were determined through the use of the computer assessed Autism Treatment Evaluation Checklist (ATEC) forms. The erythrocyte transketolase (TKA) and thiamine pyrophosphate effect (TPPE), were measured at outset and on completion of the study to document intracellular thiamine deficiency. Urines from patients were examined at outset, after 30 days and after 60 days of treatment and the concentrations of SH-reactive metals, total protein, sulfate, sulfite, thiosulfate and thiocyanate were determined. The concentrations of metals in hair were also determined. RESULTS: At the beginning of the study thiamine deficiency was observed in 3 out of the 10 patients. Out of 10 patients, 6 had initial urine samples containing arsenic in greater concentration than healthy controls. Traces of mercury were seen in urines from all of these autistic children. Following administration of TTFD an increase in cadmium was seen in 2 children and in lead in one child. Nickel was increased in the urine of one patient during treatment. Sulfur metabolites in urine did not differ from those measured in healthy children. CONCLUSIONS: Thiamine tetrahydrofurfuryl disulfide appears to have a beneficial clinical effect on some autistic children, since 8 of the 10 children improved clinically. We obtained evidence of an association of this increasingly occurring disease with presence of urinary SH-reactive metals, arsenic in particular.

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Nutr Neurosci 2002 Sep;5(4):251-61
A randomised, controlled study of dietary intervention in autistic syndromes.
Knivsberg AM, Reichelt KL, Hoien T, Nodland M.
Center for Reading Research, Stavanger University College, Norway. ann-mari.knivsberg@slf.his.no

Impaired social interaction, communication and imaginative skills characterize autistic syndromes. In these syndromes urinary peptide abnormalities, derived from gluten, gliadin, and casein, are reported. They reflect processes with opioid effect. The aim of this single blind study was to evaluate effect of gluten and casein-free diet for children with autistic syndromes and urinary peptide abnormalities. A randomly selected diet and control group with 10 children in each group participated. Observations and tests were done before and after a period of 1 year. The development for the group of children on diet was significantly better than for the controls.

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J Am Acad Child Adolesc Psychiatry 2002 Aug;41(8):921-7
Case series: use of ziprasidone for maladaptive symptoms in youths with autism.
McDougle CJ, Kem DL, Posey DJ.
Department of Psychiatry, Indiana University School of Medicine, Indianapolis 46202-4800, USA.

OBJECTIVE: To conduct a preliminary evaluation of the safety and effectiveness of ziprasidone in children, adolescents, and young adults with autism. METHOD: Twelve patients (mean age SD, 11.62 4.38 years; range, 8-20 years) with DSM-IV-defined autism (n = 9) or pervasive developmental disorder not otherwise specified (n = 3) received open-label treatment with ziprasidone (mean daily dose, 59.23 34.76 mg; range, 20-120 mg) for at least 6 weeks (mean duration, 14.15 8.29 weeks; range, 6-30 weeks). RESULTS: Six (50%) of the 12 patients were considered responders based on a Clinical Global Impression Scale rating of "much improved" or "very much improved." Transient sedation was the most common side effect. No cardiovascular side effects, including chest pain, tachycardia, palpitations, dizziness, or syncope, were observed or reported.The mean change in body weight for the group was -5.83 12.52 lb (range, -35 to lb). Five patients lost weight, five had no change, one gained weight, and one had no follow-up weight obtained beyond the baseline measurement. CONCLUSIONS: Ziprasidone appears to have the potential for improving symptoms of aggression, agitation, and irritability in children, adolescents, and young adults with autism. Significant weight gain was not observed in this short-term trial. Double-blind, placebo-controlled studies are needed to substantiate these preliminary findings.

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Med Hypotheses 2002 Jul;59(1):115-6
Use of a GABA-transaminase agonist for treatment of infantile autism.
Cohen BI.
ED Laboratories, S. Hackensack, New Jersey 07606, USA. EDS@Pipeline.com

This paper describes the use of a GABA-transaminase agonist for the treatment of infantile autism. An approximate one third reduction of GABA and ammonia levels for an autistic patient with noticeable improvement of verbal/language skills and a reduction of repetitious ritualistic self-stimulatory behavior (stimming) was observed. A reduction of the plasma GABA (by administrating a GABA-T agonist, Imipramine) probably results in more axon(s)-to-oligodendrocyte signaling in the corpus callosum and it is postulated that this could result in a reduction of the autistic features for the patient.

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J Hum Nutr Diet 2002 Aug;15(4):261-9
Gluten and casein free diets in autism: a study of the effects on food choice and nutrition.
Cornish E.
Community Nutrition Service, South Derbyshire Community Health NHS Trust, Dar es Salaam, Tanzania.

BACKGROUND: There is growing interest in possible dietary involvement in the aetiology and treatment of Autistic Spectrum Disorders (ASD). Research has focused on the physiological and behavioural effects of dietary change but has not examined the effect of exclusion diets on nutritional intake. AIMS: The aim of this study was to examine whether the removal of major dietary staples placed children with autism at risk of nutrient deficiency and compares their food choice with ASD children not following gluten and/or casein free diets. METHODS: A postal questionnaire was sent to parents of children aged 3-16 years, diagnosed with ASD belonging to the National Autistic Society in Leicestershire and southern Derbyshire. Detailed dietary information and a 3-day food diary were collected. The sample size was small: those using gluten/casein free diets (n = 8) and those not following diet (n = 29). RESULTS: Nutrient intakes fell below the Lower Reference Nutrient Intake (LRNI) in 12 children (32%) for zinc, calcium, iron, vitamin A, vitamin B12 and riboflavin in the nondiet group and four children (50%) for zinc and calcium in the diet group. Fruit and vegetable intakes were higher and cereal, bread and potato consumption were lower in those children using gluten and/or casein free diets. CONCLUSION: No significant differences in the energy, protein and micronutrient intakes were found between the two groups of children. A longitudinal prospective study is suggested to examine whether differences in food choice are the result of dietary intervention or the prerequisite for the successful application of diet in this special group of children.

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Pharmacotherapy 2002 Jul;22(7):905-14
Secretin treatment for autistic disorder: a critical analysis.
Patel NC, Yeh JY, Shepherd MD, Crismon ML.
College of Pharmacy, The University of Texas at Austin, Austin State Hospital, Texas Department of Mental Health and Retardation, 78712, USA.

We assessed evidence of the effects of secretin on behavior in individuals with autistic disorder. Articles were obtained through a MEDLINE search of the English-language literature from January 1966-November 2001; all investigations and case reports on the topic were included. Press releases obtained from the World Wide Web also were included. Secretin, a gastrointestinal hormone, is suggested to improve autistic symptoms, particularly social function and communication. Two formulations, porcine and synthetic human secretin, were evaluated in humans. A small body of literature and popular belief in autistic disorder communities supported the agent's efficacy. A number of controlled clinical trials did not show improvement in autistic symptoms with secretin compared with placebo, possibly indicating no role for the drug in autistic disorder.

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Acta Paediatr 2002;91(5):540-5
Multiple doses of secretin in the treatment of autism: a controlled study.
Sponheim E, Oftedal G, Helverschou SB.
Centre for Child and Adolescent Psychiatry, University Hospital, Oslo, Norway. eili.sponheim@psykiatri.uio.no

Dramatic effects on autistic behaviour after repeated injections of the gastrointestinal hormone secretin have been referred in a number of case reports. In the absence of curative and effective treatments for this disabling condition, this information has created new hope among parents. Although controlled studies on the effect of mainly one single dose have not documented any effect, many children still continue to receive secretin. Six children enrolled in a double-blind, placebo-controlled crossover study in which each child was its own control. Human synthetic secretin, mean dose 3.4 clinical units, and placebo were administered intravenously in randomized order every 4th wk, on three occasions each. The measurement instruments were the visual analogue scale (VAS) and the aberrant behaviour checklist (ABC). Statistically significant differences were found for placebo in 3 out of 6 children and for secretin in one child, using parental ratings only (VAS scores). Differences were small and lacked clinical significance, which was in accordance with the overall impression of the parents and teachers and visual inspection of graphs. Conclusion: In this placebo-controlled study, multiple doses of secretin did not produce any symptomatic improvement.

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J Autism Dev Disord 2002 Jun;32(3):161-7
Double-blind placebo-controlled trial of secretin: effects on aberrant behavior in children with autism.
Carey T, Ratliff-Schaub K, Funk J, Weinle C, Myers M, Jenks J.
Department of Pediatrics, Medical College of Ohio, Toledo 43608, USA. TCarey@mc.edu

Secretin has been proposed as a treatment alternative for autistic spectrum disorders, but empirical support is lacking. A double-blind placebo-controlled study examined the effect of a single dose of synthetic human secretin on aberrant behavior. Parent and teacher data from the Aberrant Behavior Checklist for eight male children were analyzed for reliable change in a clinical replication series. By parent and teacher report, the majority of change occurred either on the placebo trial or reflected deterioration subsequent to secretin infusion. Repeated-measures multivariate analysis of variance results were similar. Results are consistent with other studies, suggesting that secretin may not be an effective treatment option.

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J Autism Dev Disord 2002 Jun;32(3):153-60
Efficacy of porcine secretin in children with autism and pervasive developmental disorder.
Kern JK, Van Miller S, Evans PA, Trivedi MH.
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas 75390-9101, USA. janet.kern@UTSouthwestern.edu

Secretin, a gastrointestinal (GI) hormone, was reported in a preliminary study to improve language and behavior in children with autism/pervasive developmental disorder (PDD) and chronic diarrhea. To determine the efficacy of secretin, we completed a double-blind, placebo-controlled, crossover (3 weeks) study in children with autism/PDD and various GI conditions using a single dose of intravenous porcine secretin. Children with chronic, active diarrhea showed a reduction in aberrant behaviors when treated with the secretin but not when treated with the placebo. Children with no GI problems are unaffected by either secretin or placebo. The improvement seen with secretin in children with autism/PDD and chronic diarrhea suggests that there may be a subtype of children with autism/PDD who respond to secretin.

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Encephale 2002 May-Jun;28(3 Pt 1):248-54
[Review of psychopharmacological treatments in adolescents and adults with autistic disorders]
[Article in French]
Baghdadli A, Gonnier V, Aussilloux C.
Praticien Hospitalier, Centre de Ressources Autisme, SMPEA Peyre Plantade, CHU de Montpellier, 291, avenue du Doyen Giraud, 34295 Montpellier cedex 5.

Autism is an early developmental disorder. It leads to severe and durable disturbances. Given this problem, no treatment can be excluded a priori. Thus, many approaches are used to deal with autistic disorders. In France, pharmacological treatments are, for instance, largely and mostly used in adults. In the USA, these treatments concern 50% of persons with autism of any age. Nevertheless, they are rarely based on controlled studies. At the present, however, prescriptions and expected effects appear to be hard to localize. Furthermore, only few controlled studies validate their use. Aim - We offer a review of studies about medical treatments used in adolescents and adults with autism. They are classified in 3 categories: the first (category I) includes drugs used for their neurochemical effects focusing on autistic signs. The second (category II) covers drugs used for treatment of behavioural disorders frequently associated with autism. The third (category III) corresponds to a wide range of drugs or vitamins for wich only few case studies exist reporting irregular positive effects. The main hypothesis of this review is that autism involves a dysfunction of the neuromediation systems. This hypothesis opens new perspectives in the research of medical treatments in autism by focusing on molecules, which are supposed to have an effect on neuromediation systems. Method - Our review is based on studies, which have been published during the past twenty years. For many studies, data are limited to adolescents and adults. So we expanded our review to data available in children. The data bases that we have used are medline and psyclit. Keywords have been chosen according to: pharmacological considerations (psychotropic, psychoactive drugs, psychopharmacology) and clinical symptoms (autism, automutilations, aggressive behavior, and hyperactivity). Hypothesis of a dysfunction in the neuromediation systems in autism - Many studies exist about biochemical abnormalities in autism. As in schizophrenia and mental retardation, dysfunctions of the neuromediation systems are considered to be etiological factors. In 30% of people with autism the most regular dysfunction is the increase of serotonine. This led to the serotoninergic hypothesis in autism and to the use of active drugs in the serotonine system. However, the presence of other neurometabolic abnormalities also motivates the use of drugs, supposed to be active in other neuromediation systems. Pharmacological treatments in autism - Category I section sign 1 Active drugs in the dopamine system. Haloperidol (Dopamine antagonist): The effects of this molecule have been broadly studied in autism. Results indicate high efficiency in some symptoms of autism (lack in social behaviour, stereotypical behaviour) and in behavioural impairments that may be associated with autism (aggressive behaviour, hyperactivity). Its side effects, particulary the risk of late dyskinesy, make atypical antipsychotics preferable because of their lower risks. Risperidone (Dopamine and serotonine antagonist): Among several studies only few have been controlled. They indicate that Risperidone has positive effects on the behaviour and is quite well tolerated. section sign 2 Active drugs in the serotonine system. Clomipramine: after promising results, the medium-term efficiency has decreased and severe side effects have limited its use. Fluvoxamine, Fluoxetine, Sertraline (Specific serotonine drugs): Their efficiency has been mainly tested through open studies and their results are contrasted. In some cases, social behaviours have improved and aggressiveness and stereotyped behaviours have decreased. Fenfluramine: At present, this drug is removed from the market. Yet, some studies have suggested that it improves behavioural disturbances as well as performances in autism. section sign 3 Active drugs in the opiate system. Naltrexone: Several controlled studies have indicated an improvement in social and aggressive behaviours. Nevertheless, these studies have used small size sample and have not been replicated. Category II. This category correspond to drugs supposed to be active on neurochemical disturbances found in autism but their target symptoms are not autism specific signs as defined by the ICD 10. Buspirone: This serotonine agonist may have a good impact on emotional disorders and sleeping confusions. Methylphenidate: Most of the current studies about this noradrenergic drug concern children. The results are variable. Paradoxical effects may exist in children with severe mental retardation. Propanolol: Some isolated studies habe reported its efficiency on behavioural disturbances. Clonidine: This adrenergic drug treats efficiently some cases of aggressive behaviour and hyperactivity. Category III. This category contains a wide range of drugs, vitamins or method used in autism after sporadic observations of their positive effects. Secretine: An important improvement has been reported in isolated cases. However, controlled studies in children do not confirm these results. Vitamines B6, B12 and Magnesium: An improvement in socialization and in behavioural disorders have been reported in some cases, but these results are not yet confirmed. Lithium, Carbamazepine, Valproate: Results of some case studies have found it to be efficient in cyclic disorders. Gluten and casein free diet: An improvement of social behaviour have been reported by some parents after these diets. No controlled study has validated this observation. Conclusion - There is no consensus on the use of psychopharmacological treatments in autism. Although there exist many clinical observations, only few controlled studies have validated the efficiency and safety of these treatments. At the present time and until having sufficient studies, drugs are generally limited to severe disorders, for which usual psycho-educational approaches are insufficient.

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Res Dev Disabil 2002 Jan-Feb;23(1):81-104
Progress and outcomes for children with autism receiving parent-managed intensive interventions.
Bibby P, Eikeseth S, Martin NT, Mudford OC, Reeves D.
Autism & Developmental Disorders Education Research, London, England, UK. peterjbibby@compuserve.com

Parent-managed behavioral interventions for young children with autism are under-researched. We analysed data from 66 children served by 25 different early intervention consultants. After a mean of 31.6 months of intervention, IQ scores had not changed (N = 22). Vineland adaptive behavior scores had increased significantly by 8.9 points (N = 21). No children aged >72 months attained normal functioning, i.e., IQ > 85 and unassisted mainstream school placement (N = 42). Progress for 60 children across 12 months was found for mental age (5.4 months), adaptive behavior (9.7 months), and language (5.1 months). The interventions did not reproduce results from clinic-based professionally directed programs. The effectiveness of the parent-managed intervention model as it has developed and the adequacy of professional services in that model are discussed.

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Med Hypotheses 2002 May;58(5):422-8
Enzyme-based therapy for autism spectrum disorders—is it worth another look?
Brudnak MA, Rimland B, Kerry RE, Dailey M, Taylor R, Stayton B, Waickman F, Waickman M, Pangborn J, Buchholz I.
Autism Research Institute, San Diego, CA, USA.

Autism is a developmental disease usually manifesting within the first three years of life. To date, no causative agent has been found. Similarly, treatment options have been limited. Of the treatment options available, a number of them have been nutritionally based in an attempt to address one or more of the theories regarding the etiology of the disease. An example would be enzyme therapy for the digestion of purported offending neuroactive peptides collectively known as exorphins. This paper discusses the exorphin theory of autism and subsequent treatment with dietary enzyme therapy. Novel data are presented in support of the theory that enzymes play a critical role in autism. Forty-six patients between the ages of 5 and 31 were selected for inclusion in the study based on a diagnosis placing them in the category of the autism spectrum disorders (ASD). The diets were supplemented with a novel dietary enzyme formulation, ENZYMAID, for a period of 12 weeks. Progress was tracked according to the Symptom Outcome Survey (SOS) (1) form method of symptom charting and presented in a table for further analysis. The novel enzyme formula, ENZYMAID, beneficially and safely affected all 13 of the parameters measured. Improvements ranged from 50-90%, depending on the parameter measured. Enzyme therapy to treat ASD may indeed a viable option in treatment protocols. These results indicate that further controlled studies are warranted. Copyright 2002 Published by Elsevier Science Ltd.

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Curr Gastroenterol Rep 2002 Jun;4(3):251-8
Autism and gastrointestinal symptoms.
Horvath K, Perman JA.
Department of Pediatrics, University of Maryland School of Medicine, 22 South Greene Street, N5W70, Box 140, Baltimore, MD 21201-1595, USA. E-mail: khorvath@umaryland.edu

Autism is a collection of behavioral symptoms characterized by dysfunction in social interaction and communication in affected children. It is typically associated with restrictive, repetitive, and stereotypic behavior and manifests within the first 3 years of life. The cause of this disorder is not known. Over the past decade, a significant upswing in research has occurred to examine the biologic basis of autism. Recent clinical studies have revealed a high prevalence of gastrointestinal symptoms, inflammation, and dysfunction in children with autism. Mild to moderate degrees of inflammation were found in both the upper and lower intestinal tract. In addition, decreased sulfation capacity of the liver, pathologic intestinal permeability, increased secretory response to intravenous secretin injection, and decreased digestive enzyme activities were reported in many children with autism. Treatment of digestive problems appears to have positive effects on autistic behavior. These new observations represent only a piece of the unsolved autism "puzzle" and should stimulate more research into the brain-gut connection.

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