Autism spectrum disorder (ASD) is a heterogeneous disease where efforts to define subtypes behaviorally have met with limited success. Hypothesizing that genetically based subtype identification may prove more productive, we resequenced the ASD-associated gene CHD8 in 3,730 children with developmental delay or ASD. We identified a total of 15 independent mutations; no truncating events were identified in 8,792 controls, including 2,289 unaffected siblings. In addition to a high likelihood of an ASD diagnosis among patients bearing CHD8 mutations, characteristics enriched in this group included macrocephaly, distinct faces, and gastrointestinal complaints. chd8 disruption in zebrafish recapitulates features of the human phenotype, including increased head size as a result of expansion of the forebrain/midbrain and impairment of gastrointestinal motility due to a reduction in post-mitotic enteric neurons. Our findings indicate that CHD8 disruptions define a distinct ASD subtype and reveal unexpected comorbidities between brain development and enteric innervation.

The development of language, social interaction and communicative skills is remarkably different in the child with autism spectrum disorder (ASD). Atypical brain connectivity has frequently been reported in this patient population. However, the neural correlates underlying their disrupted language development and functioning are still poorly understood. Using resting state fMRI, we investigated the functional connectivity properties of the language network in a group of ASD patients with clear comorbid language impairment (ASD-LI; N = 19) and compared them to the language related connectivity properties of 23 age-matched typically developing children. A verb generation task was used to determine language components commonly active in both groups. Eight joint language components were identified and subsequently used as seeds in a resting state analysis. Interestingly, both the interregional and the seed-based whole brain connectivity analysis showed preserved connectivity between the classical intrahemispheric language centers, Wernicke's and Broca's areas. In contrast however, a marked loss of functional connectivity was found between the right cerebellar region and the supratentorial regulatory language areas. Also, the connectivity between the interhemispheric Broca regions and modulatory control dorsolateral prefrontal region was found to be decreased. This disruption of normal modulatory control and automation function by the cerebellum may underlie the abnormal language function in children with ASD-LI.

Objective-This study examined whether neighbourhood level socioeconomic variables have an independent eVect on reported child behaviour problems over and above the eVect of individual level measures of socioeconomic status. 45).Conclusions-Living in a more deprived neighbourhood is associated with higher levels of child problem behaviour, irrespective of individual level socioeconomic status. The additional eVect of the neighbourhood may be attributable to contextual variables such as the level of social cohesion among residents. (J Epidemiol Community Health 2001;55:246-250) As it is known that behaviour problems in children increase the risk for later psychopathology, 1 unravelling the aetiology of early problem behaviour may provide possibilities for prevention of adult mental disorder. Many studies have shown that individual level variables, such as exposure to marital discord or coming from a low income family, are associated with behaviour problems in children. [2][3][4] In addition, behaviour problems occur more frequently in children living in deprived urban areas than in children living in rural communities.5 6 However, whether neighbourhood level socioeconomic variables have an independent eVect on child behaviour problems over and above the eVect of individual level variables has scarcely been studied. Duncan and colleagues have demonstrated that neighbourhood economic conditions and poverty status are powerful correlates of the behaviour of children even after accounting for family structure and maternal education.7 However, most studies on the eVects of neighbourhood on child behaviour have been hampered by the absence of data combining information at the individual, family, and neighbourhood levels in the appropriate statistical model. Thus, most studies on neighbourhood diVerences on child behaviour problems have not taken into account the hierarchical fashion in which such data are organised. Data that are grouped according to neighbourhood are, in statistical terms, part of a multilevel structure, with level one units (individuals) being clustered into level two units (neighbourhoods). Individuals from the same neighbourhood are more similar to each other than individuals from diVerent areas, implying that the variation of reported child behaviour problems is smaller than if it were completely random. A conventional regression technique cannot take into account the variance components of two diVerent levels, thus underestimating the standard errors of regression coeYcients.