title: Linking the serotonin transporter gene, family environments, hippocampal volume and depression onset: A prospective imaging gene × environment analysis.
abstract: A single imaging gene-environment (IGxE) framework that is able to simultaneously model genetic, neurobiological, and environmental influences on psychopathology outcomes is needed to improve understanding of how complex interrelationships between allelic variation, differences in neuroanatomy or neuroactivity, and environmental experience affect risk for psychiatric disorder. In a longitudinal study of adolescent development we demonstrate the utility of such an IGxE framework by testing whether variation in parental behavior at age 12 altered the strength of an imaging genetics pathway, involving an indirect association between allelic variation in the serotonin transporter gene to variation in hippocampal volume and consequent onset of major depressive disorder by age 18. Results were consistent with the presence of an indirect effect of the serotonin transporter S-allele on depression onset via smaller left and right hippocampal volumes that was significant only in family environments involving either higher levels of parental aggression or lower levels of positive parenting. The previously reported finding of S-allele carriers' increased risk of depression in adverse environments may, therefore, be partly because of the effects of these environments on a neurobiological pathway from the serotonin transporter gene to depression onset that proceeds through variation in hippocampal volume.
authors.affiliation: Melbourne School of Psychological Sciences.
authors.forename: Keriann
authors.initials: K
authors.lastname: Little
authors.affiliation: School of Psychology, Deakin University.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Olsson
authors.affiliation: School of Psychology, Deakin University.
authors.forename: George J
authors.initials: GJ
authors.lastname: Youssef
authors.affiliation: Orygen Youth Health Research Centre, Centre for Youth Mental Health, University of Melbourne.
authors.forename: Sarah
authors.initials: S
authors.lastname: Whittle
authors.affiliation: Melbourne School of Psychological Sciences, University of Melbourne.
authors.forename: Julian G
authors.initials: JG
authors.lastname: Simmons
authors.affiliation: Monash Clinical and Imaging Neuroscience, School of Psychological Sciences and Monash Biomedical Imaging, Monash University.
authors.forename: Murat
authors.initials: M
authors.lastname: Yücel
authors.affiliation: Oregon Research Institute.
authors.forename: Lisa B
authors.initials: LB
authors.lastname: Sheeber
authors.affiliation: Orygen Youth Health Research Centre, Centre for Youth Mental Health, University of Melbourne.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Foley
authors.affiliation: Melbourne School of Psychological Sciences, Orygen Youth Health Research Centre, Centre for Youth Mental Health, University of Melbourne.
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Allen
mesh_terms: D000293:Adolescent; D000483:Alleles; D002648:Child; D003865:Major Depressive Disorder / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000523:psychology; D005190:Family / Q000523:psychology*; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009929:Organ Size; D010287:Parent-Child Relations; D016487:Parenting / Q000523:psychology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012931:Social Environment
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins