Connecting Genes to Brain in the Autism Spectrum Disorders

Neurogenetics Program, Neurology Department, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1769, USA.
Archives of neurology (Impact Factor: 7.01). 04/2010; 67(4):395-9. DOI: 10.1001/archneurol.2010.47
Source: PubMed

ABSTRACT The autism spectrum disorders (ASDs) are a complex group of neuropsychiatric conditions involving language, social communication, and mental flexibility. Here, we attempt to place recent genetic advances within a developmental and anatomical context. Recent progress in identifying ASD candidate genes supports involvement of multiple brain regions, including the frontal lobes, anterior temporal lobes, caudate, and cerebellum. Understanding genetic data within an anatomical context will be critical to explain how individual risk factors operate to shape phenotypic presentation in patients.

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    ABSTRACT: Autism is a heritable disorder, with over 250 associated genes identified to date, yet no single gene accounts for 41–2% of cases. The clinical presentation, behavioural symptoms, imaging and histopathology findings are strikingly heterogeneous. A more complete understanding of autism can be obtained by examining multiple genetic or behavioural mouse models of autism using magnetic resonance imaging (MRI)-based neuroanatomical phenotyping. Twenty-six different mouse models were examined and the consistently found abnormal brain regions across models were parieto-temporal lobe, cerebellar cortex, frontal lobe, hypothalamus and striatum. These models separated into three distinct clusters, two of which can be linked to the under and overconnectivity found in autism. These clusters also identified previously unknown connections between Nrxn1α, En2 and Fmr1; Nlgn3, BTBR and Slc6A4; and also between X monosomy and Mecp2. With no single treatment for autism found, clustering autism using neuroanatomy and identifying these strong connections may prove to be a crucial step in predicting treatment response.
    Molecular Psychiatry 09/2014; DOI:10.1038/mp.2014.98 · 15.15 Impact Factor


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