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Cerebral cortical gray matter overgrowth and functional variation of the serotonin transporter gene in autism
Journal article   Open access   Peer reviewed

Cerebral cortical gray matter overgrowth and functional variation of the serotonin transporter gene in autism

Thomas H Wassink, Heather C Hazlett, Eric A Epping, Stephan Arndt, Stephen R Dager, Gerard D Schellenberg, Geraldine Dawson and Joseph Piven
Archives of general psychiatry, Vol.64(6), pp.709-717
06/2007
DOI: 10.1001/archpsyc.64.6.709
PMID: 17548752
url
https://doi.org/10.1001/archpsyc.64.6.709View
Published (Version of record) Open Access

Abstract

Autism is a heritable neurodevelopmental disorder characterized biologically by enlargement of the head and brain and abnormalities of serotonin neurotransmission. To evaluate whether 5-HTTLPR, a functional promoter polymorphism of the serotonin transporter gene SLC6A4, influences cerebral cortical structure volumes in young male children with autism. Association study of a genetic variant with quantitative traits. Autism research centers at the University of North Carolina (UNC), Chapel Hill, and the University of Washington (UW), Seattle. Forty-four male children, 2 to 4 years old, with autism participating in longitudinal brain magnetic resonance imaging studies. Cerebral cortical and cerebellar gray and white matter volumes. We found that 5-HTTLPR genotype influenced gray matter volumes of the cerebral cortex (F(2,23) = 7.29, P = .004) and of 3 lobe-based subregions in the UNC sample of 29 children (frontal lobe gray matter: F(2,23) = 6.36, P = .01). The 5-HTTLPR short allele appeared to be additively associated with increasing gray matter volumes, an observation affirmed by tests of linear genotype effects (cortical gray matter: F(1,24) = 14.11, P = .001; frontal lobe gray matter: F(1,24) = 13.20, P = .001). Genotype did not influence cerebellar volumes. Confirmation was pursued by means of the UW sample of 15 children. While effects were not significant in the UW sample alone, the patterns of adjusted means resembled those found in the UNC sample. Positive Cochran-Mantel-Haenszel test results supported the concordance of relationships across the 2 sites, and analyses of covariance of the combined sample that included a site covariate showed significant linear genotype effects on structure volumes (cortical gray matter: F(1,38) = 5.73, P = .02; frontal lobe gray matter: F(1,38) = 11.73, P = .002). Effect sizes of 5-HTTLPR genotype on total cortical and frontal lobe gray matter volumes were 10% and 16%, respectively. The SLC6A4 promoter polymorphism 5-HTTLPR influences cerebral cortical gray matter volumes in young male children with autism.
 Autistic Disorder - genetics Autistic Disorder - pathology Age Factors Humans Cerebral Cortex - pathology Child, Preschool Genotype Male Hypertrophy - pathology Cerebellum - pathology Polymorphism, Genetic Genetic Variation Magnetic Resonance Imaging Serotonin Plasma Membrane Transport Proteins - genetics Sex Factors Female Frontal Lobe - pathology

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