title: Identification of a circuit-based endophenotype for familial depression.
abstract: Frontal and parietal lesions may cause depression, and cortical thinning of the right frontal and parietal lobes has been shown to be a marker of risk for familial major depression. We studied biological offspring within a three-generation cohort, in which risk was defined by the depression status of the first generation, to identify regional volume differences associated with risk for depression throughout the cerebrum. We found reduced frontal and parietal white matter volumes in the high-risk group, including in persons without any personal history of depression, suggesting that hypoplasia of frontal and parietal white matter is an endophenotype for familial depression. In addition, white matter volumes in these regions correlated with current severity of symptoms of depression, inattention, and impulsivity. White matter volumes also correlated strongly with the degree of thinning in the right parietal cortex. These findings support a model of pathogenesis in which hypoplasia within a neural network for attention and emotional processing predisposes to depression.
authors.affiliation: The New York State Psychiatric Institute, New York, NY 10032, USA. mrd9035@med.cornell.edu
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Dubin
authors.forename: Marc
authors.initials: M
authors.lastname: Dubin
authors.forename: Myrna M
authors.initials: MM
authors.lastname: Weissman
authors.forename: Myrna
authors.initials: M
authors.lastname: Weissman
authors.forename: Dongrong
authors.initials: D
authors.lastname: Xu
authors.forename: Ravi
authors.initials: R
authors.lastname: Bansal
authors.forename: Xuejun
authors.initials: X
authors.lastname: Hao
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Virginia
authors.initials: V
authors.lastname: Warner
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Peterson
authors.forename: Bradley
authors.initials: B
authors.lastname: Peterson
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D002648:Child; D003863:Depression / Q000473:pathology* / Q000503:physiopathology*; D058068:Endophenotypes; D005192:Family Health; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D013223:Statistics as Topic; D055815:Young Adult