1. Campbell DB, Warren D, Sutcliffe JS, Lee EB, Levitt P. {{Association of MET with social and communication phenotypes in individuals with autism spectrum disorder}}. {Am J Med Genet B Neuropsychiatr Genet} (Mar 5);153B(2):438-446.
Autism is a complex neurodevelopmental disorder diagnosed by impairments in social interaction, communication, and behavioral flexibility. Autism is highly heritable, but it is not known whether a genetic risk factor contributes to all three core domains of the disorder or autism results from the confluence of multiple genetic risk factors for each domain. We and others reported previously association of variants in the gene encoding the MET receptor tyrosine kinase in five independent samples. We further described enriched association of the MET promoter variant rs1858830 C allele in families with co-occurring autism and gastrointestinal conditions. To test the contribution of this functional MET promoter variant to the domains of autism, we analyzed its association with quantitative scores derived from three instruments used to diagnose and describe autism phenotypes: the Autism Diagnostic Interview-Revised (ADI-R), the Autism Diagnostic Observation Schedule (ADOS), and both the parent and the teacher report forms of the Social Responsiveness Scale (SRS). In 748 individuals from 367 families, the transmission of the MET C allele from parent to child was consistently associated with both social and communication phenotypes of autism. Stratification by gastrointestinal conditions revealed a similar pattern of association with both social and communication phenotypes in 242 individuals with autism from 118 families with co-occurring gastrointestinal conditions, but a lack of association with any domain in 181 individuals from 96 families with ASD and no co-occurring gastrointestinal condition. These data indicate that the MET C allele influences at least two of the three domains of the autism triad. (c) 2009 Wiley-Liss, Inc.
2. Koenig K, White SW, Pachler M, Lau M, Lewis M, Klin A, Scahill L. {{Promoting Social Skill Development in Children With Pervasive Developmental Disorders: A Feasibility and Efficacy Study}}. {J Autism Dev Disord} (Mar 5)
A randomized controlled design was employed to evaluate a social skills intervention for children with pervasive developmental disorders. Aims included evaluating the acceptability of the program and gathering preliminary evidence on efficacy. Forty-four children, ages 8-11 years, were randomly assigned to treatment or wait list. Treatment consisted of a 16-week group intervention designed to teach appropriate social behavior. Between group comparisons showed that children in treatment were rated as improved on the primary outcome measure, (unblinded parent report), but not on the secondary outcome measure, a parent questionnaire. Parents reported a high level of satisfaction with the intervention. The study supports the feasibility of this intervention to families and highlights challenges for future research in social skills intervention.
3. Ma DQ, Rabionet R, Konidari I, Jaworski J, Cukier HN, Wright HH, Abramson RK, Gilbert JR, Cuccaro ML, Pericak-Vance MA, Martin ER. {{Association and gene-gene interaction of SLC6A4 and ITGB3 in autism}}. {Am J Med Genet B Neuropsychiatr Genet} (Mar 5);153B(2):477-483.
Autism is a heritable neurodevelopmental disorder with substantial genetic heterogeneity. Studies point to possible links between autism and two serotonin related genes: SLC6A4 and ITGB3 with a sex-specific genetic effect and interaction between the genes. Despite positive findings, inconsistent results have complicated interpretation. This study seeks to validate and clarify previous findings in an independent dataset taking into account sex, family-history (FH) and gene-gene effects. Family-based association analysis was performed within each gene. Gene-gene interactions were tested using extended multifactor dimensionality reduction (EMDR) and MDR-phenomics (MDR-P) using sex of affecteds and FH as covariates. No significant associations with individual SNPs were found in the datasets stratified by sex, but associations did emerge when we stratified by family history. While not significant in the overall dataset, nominally significant association was identified at RS2066713 (P = 0.006) within SLC6A4 in family-history negative (FH-) families, at RS2066713 (P = 0.038) in family-history positive (FH+) families but with the opposite risk allele as in the FH- families. For ITGB3, nominally significant association was identified at RS3809865 overall (P = 0.040) and within FH+ families (P = 0.031). However, none of the associations survived the multiple testing correction. MDR-P confirmed gene-gene effects using sex of affecteds (P = 0.023) and family history (P = 0.014, survived the multiple testing corrections) as covariates. Our results indicate the extensive heterogeneity within these two genes among families. The potential interaction between SLC6A4 and ITGB3 may be clarified using family history as an indicator of genetic architecture, illustrating the importance of covariates as markers of heterogeneity in genetic analyses. (c) 2009 Wiley-Liss, Inc.
4. Munasinghe SA, Oliff C, Finn J, Wray JA. {{Digestive Enzyme Supplementation for Autism Spectrum Disorders: A Double-Blind Randomized Controlled Trial}}. {J Autism Dev Disord} (Mar 5)
To examine the effects of a digestive enzyme supplement in improving expressive language, behaviour and other symptoms in children with Autism Spectrum Disorder. Randomized, double-blind placebo-controlled trial using crossover design over 6 months for 43 children, aged 3-8 years. Outcome measurement tools included monthly Global Behaviour Rating Scales, Additional Rating Scales of other symptoms by parents and therapists, and monthly completion of the Rescorla Language Development Survey. Compared with placebo, treatment with enzyme was not associated with clinically significant improvement in behaviour, food variety, gastrointestinal symptoms, sleep quality, engagement with therapist, or the Language Development Survey Vocabulary or Sentence Complexity Scores. A small statistically significant improvement on enzyme therapy was seen for the food variety scores. No clinically significant effect improvement of autism symptoms with enzyme use was shown with this trial, however, possible effects on improvement in food variety warrants further detailed investigation.
5. Scheurich A, Fellgiebel A, Muller MJ, Poustka F, Bolte S. {{[Does the Fragmented Images Test measure locally oriented visual processing in autism spectrum disorders?]}}. {Z Kinder Jugendpsychiatr Psychother} (Mar);38(2):103-110.
Objective: The cognitive phenotype of autism spectrum disorders (ASD) is characterized among other things by local processing (weak central coherence). It was examined whether a test that measures identification of fragmented pictures (FBT) is able to seize this preference for local processing. Method: The FBT performance of 15 patients with ASD, 16 with depression, 16 with schizophrenia and of 16 control subjects was compared. In addition, two tests well known to be sensitive to local processing were assessed, namely the Embedded Figures Test (EFT) and the Block Design Test (BDT). Results: ASD patients demonstrated a preference for local processing. Difficulties in global processing, or more specifically in gestalt perception (FBT), were accompanied by good performance on the EFT and BDT as expected. Controlling for age and nonverbal intelligence (ANCOVA) reduced differences to trends. However, the calculation of difference scores (i.e., subtraction of FBT from EFT performance) resulted in significant differences between ASD and control groups even after controlling for of age and intelligence. Conclusions: The FBT is a suitable exploratory test of local visual processing in ASD. In particular, a difference criterion can be generated (FBT vs. EFT) that discriminates between ASD and clinical as well as healthy control groups.
6. Simon EW, Haas-Givler B, Finucane B. {{A longitudinal follow-up study of autistic symptoms in children and adults with duplications of 15q11-13}}. {Am J Med Genet B Neuropsychiatr Genet} (Mar 5);153B(2):463-467.
We completed a longitudinal follow-up of autistic symptoms in a cohort of children and young adults with duplications of chromosome 15q11-13. In our initial investigation of 29 individuals, tentative conclusions were drawn based on cross-sectional data suggesting that autistic symptoms increased with age, most specifically in the area of social interaction. We were able to re-assess 22 individuals from the original study an average of 7 years later using the same standardized autism screening measure. As predicted, autistic symptoms were found to increase for the younger children in the cohort but remained constant for the older participants. This global change in autistic symptoms among the younger children could not be ascribed to any particular autism subscale and reflects small but cumulatively significant increases across several domains. (c) 2009 Wiley-Liss, Inc.
7. Wermter AK, Kamp-Becker I, Hesse P, Schulte-Korne G, Strauch K, Remschmidt H. {{Evidence for the involvement of genetic variation in the oxytocin receptor gene (OXTR) in the etiology of autistic disorders on high-functioning level}}. {Am J Med Genet B Neuropsychiatr Genet} (Mar 5);153B(2):629-639.
An increasing number of animal studies advert to a substantial role of the neuropeptide oxytocin in the regulation of social attachment and affiliation. Furthermore, animal studies showed anxiety and stress-reduced effects of oxytocin. First human studies confirm these findings in animal studies and implicate a crucial role of oxytocin in human social attachment behavior and in social interactions. Thus, the oxytocin system might be involved in the impairment of social interaction and attachment in autism spectrum disorders (ASD). The human oxytocin receptor gene (OXTR) represents a plausible candidate gene for the etiology of ASD. To analyze whether genetic variants in the OXTR gene are associated with ASD we performed family-based single-marker and haplotype association analyses with 22 single nucleotide polymorphisms (SNPs) in the OXTR and its 5′ region in 100 families with autistic disorders on high-functioning level (Asperger syndrome (AS), high-functioning autism (HFA), and atypical autism (AA)). Single-marker and haplotype association analyses revealed nominally significant associations of one single SNP and one haplotype with autism, respectively. Furthermore, employing a « reverse phenotyping » approach, patients carrying the haplotype associated with autism showed nominally significant impairments in comparison to noncarriers of the haplotype in items of the Autism Diagnostic Interview-Revised algorithm describing aspects of social interaction and communication. In conclusion, our results implicate that genetic variation in the OXTR gene might be relevant in the etiology of autism on high-functioning level. (c) 2009 Wiley-Liss, Inc.
