title: Serotonin signaling modulates the effects of familial risk for depression on cortical thickness.
abstract: Depression is a highly familial and a heritable illness that is more prevalent in the biological offspring of the depressed individuals than in the general population. In a 3-generation, 30-year, longitudinal study of individuals at either a high(HR) or a low(LR) familial risk for depression, we previously showed cortical thinning in the right hemisphere was an endophenotype for the familial risk. In this study, we assessed whether the effects of familial risk were modulated by the serotonin-transporter-linked polymorphic region (5-HTTLPR). We measured cortical thickness using MRI of the brain and associated it with 5-HTTLPR polymorphism in 76 HR and 53 LR individuals. We studied the effects of genotype and gene-by-risk interaction on cortical thickness while controlling for the confounding effects of age and gender, and for the familial relatedness by applying a variance component model with random effects for genotype. The results showed significant effects of gene-by-risk interaction on thickness: The "s" allele was associated with thinner cortex in the LR individuals whereas with thicker cortex in the HR individuals. The opposing gene effects across the two risk groups were likely due to either epistatic effects and/or differing modulation of the neural plasticity by the altered 5-HT signaling in utero.
authors.affiliation: Department of Pediatrics, Keck School of Medicine, Los Angeles, CA 90033, United States; Institute for the Developing Mind, The Saban Research Institute, CHLA, CA 90027, United States. Electronic address: rabansal@chla.usc.edu.
authors.forename: Ravi
authors.initials: R
authors.lastname: Bansal
authors.affiliation: Department of Pediatrics, Keck School of Medicine, Los Angeles, CA 90033, United States; Institute for the Developing Mind, The Saban Research Institute, CHLA, CA 90027, United States.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Peterson
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, United States; New York State Psychiatric Institute, New York, NY 10032, United States.
authors.forename: Jay
authors.initials: J
authors.lastname: Gingrich
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, United States; New York State Psychiatric Institute, New York, NY 10032, United States.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Hao
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, United States; New York State Psychiatric Institute, New York, NY 10032, United States.
authors.forename: Zagaa
authors.initials: Z
authors.lastname: Odgerel
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, United States; New York State Psychiatric Institute, New York, NY 10032, United States.
authors.forename: Virginia
authors.initials: V
authors.lastname: Warner
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, United States; New York State Psychiatric Institute, New York, NY 10032, United States.
authors.forename: Priya J
authors.initials: PJ
authors.lastname: Wickramaratne
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, United States; New York State Psychiatric Institute, New York, NY 10032, United States.
authors.forename: Ardesheer
authors.initials: A
authors.lastname: Talati
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, United States; New York State Psychiatric Institute, New York, NY 10032, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Ansorge
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, United States; New York State Psychiatric Institute, New York, NY 10032, United States.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Brown
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, United States; Department of Child Psychiatry, University of Turku, Turku, Finland.
authors.forename: Andre
authors.initials: A
authors.lastname: Sourander
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, United States; New York State Psychiatric Institute, New York, NY 10032, United States.
authors.forename: Myrna M
authors.initials: MM
authors.lastname: Weissman
mesh_terms: D000293:Adolescent; D000328:Adult; D002540:Cerebral Cortex / Q000473:pathology*; D002648:Child; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic; D012306:Risk; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin
keywords: Familial Risk; Heritability; Imaging Genetics; Major Depressive Disorder; Serotonin; Structural MRI