title: Association between serotonin transporter genotype, brain structure and adolescent-onset major depressive disorder: a longitudinal prospective study.
abstract: The extent to which brain structural abnormalities might serve as neurobiological endophenotypes that mediate the link between the variation in the promoter of the serotonin transporter gene (5-HTTLPR) and depression is currently unknown. We therefore investigated whether variation in hippocampus, amygdala, orbitofrontal cortex (OFC) and anterior cingulate cortex volumes at age 12 years mediated a putative association between 5-HTTLPR genotype and first onset of major depressive disorder (MDD) between age 13-19 years, in a longitudinal study of 174 adolescents (48% males). Increasing copies of S-alleles were found to predict smaller left hippocampal volume, which in turn was associated with increased risk of experiencing a first onset of MDD. Increasing copies of S-alleles also predicted both smaller left and right medial OFC volumes, although neither left nor right medial OFC volumes were prospectively associated with a first episode of MDD during adolescence. The findings therefore suggest that structural abnormalities in the left hippocampus may be present prior to the onset of depression during adolescence and may be partly responsible for an indirect association between 5-HTTLPR genotype and depressive illness. 5-HTTLPR genotype may also impact upon other regions of the brain, such as the OFC, but structural differences in these regions in early adolescence may not necessarily alter the risk for onset of depression during later adolescence.
authors.affiliation: 1] Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Victoria, Australia [2] Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia [3] Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Little
authors.affiliation: 1] Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia [2] School of Psychology, Deakin University, Geelong, Victoria, Australia.
authors.forename: C A
authors.initials: CA
authors.lastname: Olsson
authors.affiliation: 1] Orygen Youth Health Research Centre, Centre for Youth Mental Health, University of Melbourne, Melbourne, Victoria, Australia [2] Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Whittle
authors.affiliation: 1] Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Victoria, Australia [2] Monash Clinical and Imaging Neuroscience, School of Psychological Sciences and Monash Biomedical Imaging, Monash University, Melbourne, Victoria, Australia.
authors.forename: G J
authors.initials: GJ
authors.lastname: Youssef
authors.affiliation: Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: M L
authors.initials: ML
authors.lastname: Byrne
authors.affiliation: Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: J G
authors.initials: JG
authors.lastname: Simmons
authors.affiliation: Monash Clinical and Imaging Neuroscience, School of Psychological Sciences and Monash Biomedical Imaging, Monash University, Melbourne, Victoria, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Yücel
authors.affiliation: Orygen Youth Health Research Centre, Centre for Youth Mental Health, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: D L
authors.initials: DL
authors.lastname: Foley
authors.affiliation: 1] Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Victoria, Australia [2] Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia [3] Orygen Youth Health Research Centre, Centre for Youth Mental Health, University of Melbourne, Melbourne, Victoria, Australia [4] Department of Psychology, University of Oregon, Eugene, OR, USA.
authors.forename: N B
authors.initials: NB
authors.lastname: Allen
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping / Q000379:methods; D002648:Child; D003865:Major Depressive Disorder / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D011446:Prospective Studies; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins