title: The influence of 5-HTTLPR transporter genotype on amygdala-subgenual anterior cingulate cortex connectivity in autism spectrum disorder.
abstract: Social deficits in autism spectrum disorder (ASD) are linked to amygdala functioning and functional connection between the amygdala and subgenual anterior cingulate cortex (sACC) is involved in the modulation of amygdala activity. Impairments in behavioral symptoms and amygdala activation and connectivity with the sACC seem to vary by serotonin transporter-linked polymorphic region (5-HTTLPR) variant genotype in diverse populations. The current preliminary investigation examines whether amygdala-sACC connectivity differs by 5-HTTLPR genotype and relates to social functioning in ASD. A sample of 108 children and adolescents (44 ASD) completed an fMRI face-processing task. Youth with ASD and low expressing 5-HTTLPR genotypes showed significantly greater connectivity than youth with ASD and higher expressing genotypes as well as typically developing (TD) individuals with both low and higher expressing genotypes, in the comparison of happy vs. baseline faces and happy vs. neutral faces. Moreover, individuals with ASD and higher expressing genotypes exhibit a negative relationship between amygdala-sACC connectivity and social dysfunction. Altered amygdala-sACC coupling based on 5-HTTLPR genotype may help explain some of the heterogeneity in neural and social function observed in ASD. This is the first ASD study to combine genetic polymorphism analyses and functional connectivity in the context of a social task.
authors.affiliation: Department of Psychology, University of Michigan, United States. Electronic address: velasqfr@umich.edu.
authors.forename: Francisco
authors.initials: F
authors.lastname: Velasquez
authors.affiliation: Department of Psychology, University of Michigan, United States.
authors.forename: Jillian Lee
authors.initials: JL
authors.lastname: Wiggins
authors.affiliation: Department of Psychology, University of Michigan, United States.
authors.forename: Whitney I
authors.initials: WI
authors.lastname: Mattson
authors.affiliation: Department of Human Genetics, University of Michigan, United States.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Martin
authors.affiliation: Center for Autism and the Developing Brain, Weill Cornell Medicine, United States.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lord
authors.affiliation: Department of Psychology, Neuroscience Program, Department of Psychiatry, Center for Growth and Human Development, University of Michigan, United States.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Monk
mesh_terms: D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D005260:Female; D005838:Genotype; D006179:Gyrus Cinguli / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: 5-HTTLPR; Amygdala; Autism spectrum disorder; Connectivity; Face-processing; Heterogeneity; Serotonin; Subgenual anterior cingulate cortex