Preference for biological motion is reduced in ASD: implications for clinical trials and the search for biomarkers.

BACKGROUND: The neurocognitive mechanisms underlying autism spectrum disorder (ASD) remain unclear. Progress has been largely hampered by small sample sizes, variable age ranges and resulting inconsistent findings. There is a pressing need for large definitive studies to delineate the nature and extent of key case/control differences to direct research towards fruitful areas for future investigation. Here we focus on perception of biological motion, a promising index of social brain function which may be altered in ASD. In a large sample ranging from childhood to adulthood, we assess whether biological motion preference differs in ASD compared to neurotypical participants (NT), how differences are modulated by age and sex and whether they are associated with dimensional variation in concurrent or later symptomatology. METHODS: Eye-tracking data were collected from 486 6-to-30-year-old autistic (N = 282) and non-autistic control (N = 204) participants whilst they viewed 28 trials pairing biological (BM) and control (non-biological, CTRL) motion. Preference for the biological motion stimulus was calculated as (1) proportion looking time difference (BM-CTRL) and (2) peak look duration difference (BM-CTRL). RESULTS: The ASD group showed a present but weaker preference for biological motion than the NT group. The nature of the control stimulus modulated preference for biological motion in both groups. Biological motion preference did not vary with age, gender, or concurrent or prospective social communicative skill within the ASD group, although a lack of clear preference for either stimulus was associated with higher social-communicative symptoms at baseline. LIMITATIONS: The paired visual preference we used may underestimate preference for a stimulus in younger and lower IQ individuals. Our ASD group had a lower average IQ by approximately seven points. 18% of our sample was not analysed for various technical and behavioural reasons. CONCLUSIONS: Biological motion preference elicits small-to-medium-sized case-control effects, but individual differences do not strongly relate to core social autism associated symptomatology. We interpret this as an autistic difference (as opposed to a deficit) likely manifest in social brain regions. The extent to which this is an innate difference present from birth and central to the autistic phenotype, or the consequence of a life lived with ASD, is unclear

Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders.

International audienceSHANK3 (also known as ProSAP2) regulates the structural organization of dendritic spines and is a binding partner of neuroligins; genes encoding neuroligins are mutated in autism and Asperger syndrome. Here, we report that a mutation of a single copy of SHANK3 on chromosome 22q13 can result in language and/or social communication disorders. These mutations concern only a small number of individuals, but they shed light on one gene dosage-sensitive synaptic pathway that is involved in autism spectrum disorders

Animal model integration to AutDB, a genetic database for autism

<p>Abstract</p> <p>Background</p> <p>In the post-genomic era, multi-faceted research on complex disorders such as autism has generated diverse types of molecular information related to its pathogenesis. The rapid accumulation of putative candidate genes/loci for Autism Spectrum Disorders (ASD) and ASD-related animal models poses a major challenge for systematic analysis of their content. We previously created the Autism Database (AutDB) to provide a publicly available web portal for ongoing collection, manual annotation, and visualization of genes linked to ASD. Here, we describe the design, development, and integration of a new module within AutDB for ongoing collection and comprehensive cataloguing of ASD-related animal models.</p> <p>Description</p> <p>As with the original AutDB, all data is extracted from published, peer-reviewed scientific literature. Animal models are annotated with a new standardized vocabulary of phenotypic terms developed by our researchers which is designed to reflect the diverse clinical manifestations of ASD. The new Animal Model module is seamlessly integrated to AutDB for dissemination of diverse information related to ASD. Animal model entries within the new module are linked to corresponding candidate genes in the original "Human Gene" module of the resource, thereby allowing for cross-modal navigation between gene models and human gene studies. Although the current release of the Animal Model module is restricted to mouse models, it was designed with an expandable framework which can easily incorporate additional species and non-genetic etiological models of autism in the future.</p> <p>Conclusions</p> <p>Importantly, this modular ASD database provides a platform from which data mining, bioinformatics, and/or computational biology strategies may be adopted to develop predictive disease models that may offer further insights into the molecular underpinnings of this disorder. It also serves as a general model for disease-driven databases curating phenotypic characteristics of corresponding animal models.</p

The dopamine D2 receptor mediates approach-avoidance tendencies in smokers

Dopamine D2 receptors (DRD2) have been strongly implicated in reward processing of natural stimuli and drugs. By using the Approach-Avoidance Task (AAT), we recently demonstrated that smokers show an increased approach bias toward smoking-related cues but not toward naturally-rewarding stimuli. Here we examined the contribution of the DRD2 Taq1B polymorphism to smokers’ and non-smokers’ responsivity toward smoking versus naturally-rewarding stimuli in the AAT. Smokers carrying the minor B1 allele of the DRD2 Taq1B polymorphism showed reduced approach behavior for food-related pictures compared to non-smokers with the same allele. In the group of smokers, a higher approach-bias toward smoking-related compared to food-related pictures was found in carriers of the B1 allele. This pattern was not evident in smokers homozygous for the B2 allele. Additionally, smokers with the B1 allele reported fewer attempts to quit smoking relative to smokers homozygous for the B2 allele. This is the first study demonstrating that behavioral shifts in response to smoking relative to natural rewards in smokers are mediated by the DRD2 Taq1B polymorphism. Our results indicate a reduced natural-reward brain reactivity in smokers with a genetically determined decrease in dopaminergic activity (i.e., reduction of DRD2 availability). It remains to be determined whether this pattern might be related to a different outcome after psychological cessation interventions, i.e. AAT modification paradigms, in smokers

Genomic Regions Identified by Overlapping Clusters of Nominally-Positive SNPs from Genome-Wide Studies of Alcohol and Illegal Substance Dependence

Declaring “replication” from results of genome wide association (GWA) studies is straightforward when major gene effects provide genome-wide significance for association of the same allele of the same SNP in each of multiple independent samples. However, such unambiguous replication is unlikely when phenotypes display polygenic genetic architecture, allelic heterogeneity, locus heterogeneity and when different samples display linkage disequilibria with different fine structures. We seek chromosomal regions that are tagged by clustered SNPs that display nominally-significant association in each of several independent samples. This approach provides one “nontemplate” approach to identifying overall replication of groups of GWA results in the face of difficult genetic architectures. We apply this strategy to 1 M SNP GWA results for dependence on: a) alcohol (including many individuals with dependence on other addictive substances) and b) at least one illegal substance (including many individuals dependent on alcohol). This approach provides high confidence in rejecting the null hypothesis that chance alone accounts for the extent to which clustered, nominally-significant SNPs from samples of the same racial/ethnic background identify the same sets of chromosomal regions. It identifies several genes that are also reported in other independent alcohol-dependence GWA datasets. There is more modest confidence in: a) identification of individual chromosomal regions and genes that are not also identified by data from other independent samples, b) the more modest overlap between results from samples of different racial/ethnic backgrounds and c) the extent to which any gene not identified herein is excluded, since the power of each of these individual samples is modest. Nevertheless, the strong overlap identified among the samples with similar racial/ethnic backgrounds supports contributions to individual differences in vulnerability to addictions that come from newer allelic variants that are common in subsets of current humans