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PubMed1999

Risperidone in the treatment of two very young children with autism.

This report describes the use of risperidone in the treatment of two very young children with autistic disorder, a 29-month-old boy and a 23-month-old boy, respectively. These children presented with severe and persistent symptoms of aggression and irritability that had not responded to previous treatment. In both cases, risperidone significantly reduced aggression and improved social relatedness. One patient's treatment with risperidone was complicated by persistent tachycardia and QTc interval prolongation that was dose-related. Consideration should be given to the appropriate use of medication in the treatment of very young children with autism when other interventions do not prove helpful.

Antipsychotic Agents↗

PubMed1989

After diagnosis, what? Some of the possible problems around diagnostic assessments.

Psychopathologies of low frequency of occurrence, such as autistic disorder, constitute a challenge because of the diagnosticians' relatively low familiarity with both the presenting symptoms and, particularly, effective intervention strategies for them. This paper highlights the key potential pitfalls in the assessment of such rare conditions as autism. It then offers some suggestions as to what should be included in a diagnostic assessment of severely and chronically dysfunctional individuals. As well it discusses the need to coordinate the effects of different professionals on behalf of the dysfunctional child and his/her family. Such efforts should take into account the considerable stress and vulnerability of the families across the affected individual's lifespan.

Autistic Disorder↗

PubMed2000

Motion processing in autism: evidence for a dorsal stream deficiency.

We report that motion coherence thresholds in children with autism are significantly higher than in matched controls. No corresponding difference in form coherence thresholds was found. We interpret this as a specific deficit in dorsal stream function in autism. To examine the possibility of a neural basis for the perceptual and motor related abnormalities frequently cited in autism we tested 23 children diagnosed with autistic disorder, on two tasks specific to dorsal and ventral cortical stream functions. The results provide evidence that autistic individuals have a specific impairment in dorsal stream functioning. We conclude that autism may have common features with other developmental disorders and with early stages of normal development, perhaps reflecting a greater vulnerability of the dorsal system.

Adult↗

PubMed2002

Normal P50 gating in children with autism.

BACKGROUND: An important characteristic of children with autism is their unusual reaction to stimuli, which may be related to problems in the filtering of sensory input. For this reason, sensory filtering was measured in children with autism using the P50 gating paradigm. METHOD: Twelve non-mentally retarded children with autism (i.e., having a DSM-IV diagnosis of either autistic disorder or pervasive developmental disorder not otherwise specified) and 11 healthy control children were tested for their ability to suppress P50, measured at the Cz electrode. RESULTS: No differences were found between the children with autism and the control children with regard to absolute P50 amplitudes and P50 suppression. CONCLUSION: The excitability of the neuronal substrate that causes P50 is normal in children with autism, as are the early, inhibitory processes related to P50 gating. These results distinguish between subjects with autism and subjects with schizophrenia, in whom sensory gating is abnormal.

Acoustic Stimulation↗

PubMed1999

Dynamics of self-injurious behaviors.

Self-injurious behavior was examined in a case study of head-banging by an 8-year-old girl with profound mental retardation and an autistic disorder. Trajectories of the arm movements and impact forces of the head blows were determined from a dynamic analysis of videotapes. Results revealed a high degree of cycle-to-cycle consistency in the qualitative dynamics of the limb motions, with one hand motions being faster than those with two hands (inphase and antiphase) and the motions with the helmet about 25% faster than those without the helmet. The impact force of SIBs as a percentage of body weights are near the low end of forces generated in boxing blows and karate hits.

Adolescent↗

PubMed2005

Clinical efficacy of fluvoxamine and functional polymorphism in a serotonin transporter gene on childhood autism.

We studied the correlation between response to fluvoxamine and serotonin transporter gene promoter region polymorphism (5-HTTLPR). Eighteen children with autistic disorder completed a 12-week double-blind, placebo-controlled, randomized crossover study of fluvoxamine. Behavioral assessments were obtained before and at 12 weeks of treatment. 5-HTTLPR (long (l) or short(s)), was analyzed by the PCR method. Ten out of 18 patients responded to fluvoxamine treatment; allele type analysis revealed that clinical global effectiveness was noted significantly more in the l allele than in the s allele. However, with respect to language use, a significant effectiveness was noted in the s allele. 5-HTTLPR may influence the individual responses to fluvoxamine administration.

Alleles↗

PubMed2002

FOXP2 is not a major susceptibility gene for autism or specific language impairment.

The FOXP2 gene, located on human 7q31 (at the SPCH1 locus), encodes a transcription factor containing a polyglutamine tract and a forkhead domain. FOXP2 is mutated in a severe monogenic form of speech and language impairment, segregating within a single large pedigree, and is also disrupted by a translocation in an isolated case. Several studies of autistic disorder have demonstrated linkage to a similar region of 7q (the AUTS1 locus), leading to the proposal that a single genetic factor on 7q31 contributes to both autism and language disorders. In the present study, we directly evaluate the impact of the FOXP2 gene with regard to both complex language impairments and autism, through use of association and mutation screening analyses. We conclude that coding-region variants in FOXP2 do not underlie the AUTS1 linkage and that the gene is unlikely to play a role in autism or more common forms of language impairment.

Alleles↗

PubMed2006

Oral human immunoglobulin for children with autism and gastrointestinal dysfunction: a prospective, open-label study.

Immunoglobulin secretion onto mucosal surfaces is a major component of the mucosal immune system. We hypothesized that chronic gastrointestinal (GI) disturbances associated with autistic disorder (AD) may be due to an underlying deficiency in mucosal immunity, and that orally administered immunoglobulin would be effective in alleviating chronic GI dysfunction in these individuals. In this pilot study, twelve male subjects diagnosed with AD were evaluated using a GI severity index (GSI) while receiving daily dosing with encapsulated human immunoglobulin. Following eight weeks of treatment, 50% of the subjects met prespecified criteria for response in GI signs and symptoms and showed significant behavioral improvement as assessed by the Autism Behavior Checklist and parent and physician rated Clinical Global Impression of Improvement.

Administration, Oral↗

PubMed1996

Autism in immigrants: a population-based study from Swedish rural and urban areas.

In a population study, 55 children aged 13 years and under were diagnosed as suffering from autistic disorder according to DSM-III-R criteria. Fifteen of these children (27%) were born to parents, at least one of whom had migrated to Sweden. These 15 cases were analysed in some detail with a view to finding possible background factors that could account for the relatively high prevalence of autism among some immigrant populations. In a few cases, autism or Asperger syndrome had been diagnosed in a native Swedish parent who went abroad in order to find a spouse. In several other cases, the child was the first child born in Sweden after the mother had moved there. The contribution of genetic and other prenatal factors to autism in immigrant populations is discussed.

Adolescent↗

PubMed2006

Adults with autism show increased sensitivity to outcomes at low error rates during decision-making.

Decision-making is an important function that can be quantified using a two-choice prediction task. Individuals with Autistic Disorder (AD) often show highly restricted and repetitive behavior that may interfere with adaptive decision-making. We assessed whether AD adults showed repetitive behavior on the choice task that was unaffected by changing task demands, by examining the influence of experimenter-determined error rates on decision-making. Sixteen AD adults and 14 typically developed subjects were administered a two-choice task using three error rate conditions. Although AD subjects showed occurrences of stereotyped responding, their decision-making behavior was strongly affected by changes in task demands, especially when they experienced frequent success. Thus, behavioral paradigms that provide frequent reinforcement may be helpful in modifying decision-making abilities in AD.

Adult↗

PubMed2002

Autism, macrocrania and epilepsy: how are they linked?

To evaluate the possible association of autistic disorder (AD), macrocrania and epilepsy, we performed a retrospective study comparing epileptic and non-epileptic AD patients with macrocrania, and AD patients with macrocrania to age- and sex-matched AD controls without macrocrania. We found macrocrania in 17.3% of 121 patients with AD. Epilepsy was not significantly more frequent in AD patients with macrocrania than in those without macrocrania. There were no significant differences in the other clinical characteristics studied except for epileptiform EEG abnormalities which were more often found in AD patients with epilepsy. AD with macrocrania and epilepsy is not a syndrome but may be a marker for a group of subjects with AD. A role for familial macrocrania needs further assessment.

Adolescent↗

PubMed2005

Risperidone for the core symptom domains of autism: results from the study by the autism network of the research units on pediatric psychopharmacology.

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.

Adolescent↗

PubMed2005

Psychometric properties of the Chinese version of the Psycho-educational Profile-Revised (CPEP-R).

The purpose of this study was to examine the reliability and validity of the Chinese version of the Psycho-educational Profile-Revised (PEP-R). The Chinese PEP-R (CPEP-R) was administered to 63 preschool children with symptoms of autistic disorder recruited from special child-care centers in Hong Kong. Results showed that the scales of the CPEP-R were internally consistent, reliable across raters and temporally stable. Regarding the concurrent validity of the CPEP-R, the developmental score and developmental age assessed by the CPEP-R were significantly correlated with the Merrill-Palmer Scale of Mental Tests and the Hong Kong Based Adaptive Behavior Scale. The Behavioral Scale of the CPEP-R was also significantly related to the Childhood Autism Rating Scale. Besides replicating the findings in the Western context, the present study suggests that the psychometric properties of the PEP-R are stable across cultures and the related findings support the cross-cultural reliability of the tool.

Asian People↗

PubMed2003

Central coherence and cognitive shifting in relation to social improvement in high-functioning young adults with autism.

The objective of this prospective study was to evaluate the possible role of two cognitive styles--weak central coherence and poor cognitive shifting--in predicting social improvement in patients with autistic disorder. Thirty patients, largely similar in age (young adults), intelligence (high-functioning) and living conditions (residential treatment in the same unit) were assessed at two separate time points with a 3-year interval between pretest and posttest. At pretest central coherence, cognitive shifting and several aspects of social functioning--symptom severity, social intelligence and social competence--were measured. At posttest social functioning was reassessed. Unlike central coherence, cognitive shifting was identified as a significant prognostic marker. This differential outcome might be an indication that patients with poor cognitive shifting and patients with weak central coherence have different prognoses with the current, highly structured treatment milieu; it is unknown whether patients with poor cognitive flexibility might benefit more from treatments specifically designed to address this problem.

Adolescent↗

PubMed2001

Molecular genetic delineation of 2q37.3 deletion in autism and osteodystrophy: report of a case and of new markers for deletion screening by PCR.

We recently studied a patient who meets criteria for autistic disorder and has a 2q37 deletion. Molecular cytogenetic studies were carried out using DNA isolated from 22 different 2q37 mapped BACs to more precisely define the extent of the chromosome deletion. We also analyzed 2q37 mapped polymorphic markers. In addition DNA sequences of BACs in the deletion region were scanned to identify microsatellite repeats. We describe four new polymorphic microsatellite repeat markers in the 2q37.3 region. These markers enabled us to determine the parental origin of the deletion in our patient. DNA from 8-13 unrelated individuals was used to determine heterozygosity estimates for these markers. We review four genes deleted in our patient - genes whose known functions and sites of expression in the brain and/or bone make them candidates for involvement in autism and/or the osteodystrophy observed in patients with 2q37.3 deletions.

Adolescent↗

PubMed2005

Sleep disturbances in adolescents and young adults with autism and Asperger syndrome.

Sleep problems are commonly reported in children with autistic disorders. Most studies are based on sleep questionnaires and sleep diaries, but polysomnographic and actigraphic data have also been used. In this study we investigated sleep in older individuals (aged 15-25 years) with autism and Asperger syndrome, using sleep questionnaires, sleep diaries and actigraphy. Although the sleep questionnaires completed by parents and caretakers revealed only a moderate degree of sleep problems, greater sleep disturbance was recorded with actigraphy. Using the latter method, low sleep efficiency (below 85 percent) or long sleep latency (more than 30 minutes) were found in 80 percent of the individuals. There was no early morning awakening, contrary to some earlier reports. This study suggests that even though subjective complaints of sleep disturbances are less common in adolescents and young adults with autism, this may be due to an adaptation process rather than an actual reduction in sleep disturbances.

Adolescent↗

PubMed2006

Serotonin transporter promoter variants: Analysis in Indian autistic and control population.

Serotonin transporter (5-HTT) is a transmembrane protein belonging to Na+/Cl- dependent membrane transporter family and transports 5-HT across the membranes of presynaptic neurons. 5-HTT-linked polymorphic region (5-HTTLPR) gained much interest because of the differential regulation of expression and activity of 5-HTT by its various genotypes. A population-based study has been conducted on 5-HTTLPR with 358 individuals, which included 79 autistic probands, 136 parents, and 143 controls from two subpopulations of east and northeast regions of India. The genotypic frequencies of all the groups conform to Hardy-Weinberg equilibrium. With the finding of efficacy of serotonin reuptake inhibitors in ameliorating ritualistic behavior in autistic disorder, 5-HTT emerged as a putative candidate gene for autism and association studies have been carried out in different ethnic populations. But these studies were inconclusive due to conflicting results on association. Because such a study has never been performed in the Indian population, we have tested the possible involvement of 5-HTTLPR polymorphism with autism. The present study failed to establish any association or linkage of 5-HTTLPR with autism in the Indian population by case-control studies (chi2 = 1.314, P = 0.63) and family-based approaches (TDT chi2 = 0.22, P = 0.64 and HHRR-chi2 = 0.25, P = 0.61). However, when a meta-analysis of all the available TDT data, inclusive of the present study is carried out, we observed a significant preferential transmission of S-allele from parents to the affected offspring (chi2 = 7.51, P = 0.006) indicating an association of 5-HTTLPR with autism.

Autistic Disorder↗

PubMed2006

5-HTTLPR Genotype-Specific Phenotype in Children and Adolescents With Autism.

OBJECTIVE: The serotonin transporter gene (SLC6A4) is a strong autism candidate gene because of its association with anxiety, aggression and attention, and the effectiveness of selective serotonin reuptake inhibitors (SSRIs) in treating certain behavioral symptoms. In families with individuals with autism, several reports of biased transmission of both alleles (short, long) at the serotonin transporter gene promotor polymorphism (5-HTTLPR) locus of SLC6A4 now exist. The heterogeneity in these reports may be due to clinical heterogeneity. The authors hypothesized that 5-HTTLPR genotypes would be related to variation in specific symptoms in children with autism. METHOD: The authors explored whether variants of two functional polymorphisms of SLC6A4 (5-HTTLPR, intron 2 variable number tandem repeat [2 VNTR]) were related to behavioral characteristics measured by the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. Subjects (N=73, age 3-19 years old) met diagnostic criteria for autistic disorder based on both measures. RESULTS: Evidence of genotype-phenotype interactions on the Autism Diagnostic Interview-Revised was found with the 5-HTTLPR short group of HTTLPR (S/L or S/S genotypes) being rated as more severe on the subdomain "failure to use nonverbal communication to regulate social interaction," and the long group (L/L genotype) being more severe on the subdomain "stereotyped and repetitive motor mannerisms" and on an aggression measure. In contrast, on the Autism Diagnostic Observation Schedule, the long group was associated with greater severity on directed facial expressions and unusual sensory interests. There were no significant relationships between the intron 2 VNTR genotypes and subdomains or domains of symptoms on the Autism Diagnostic Interview-Revised or the Autism Diagnostic Observation Schedule. CONCLUSIONS: These findings provide initial support for genotype-specific phenotypes for 5-HTTLPR in autism based on ratings from the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule.

Adolescent↗