title: Sequence variations in CREB1 cosegregate with depressive disorders in women.
abstract: Major depressive disorder (MDD) constitutes a major public health problem worldwide and affects women twice as frequently as men. Previous linkage studies have identified a 451 kb region of 2q33-35 that exhibited significant evidence of linkage to Mood Disorders among women (but not men) from families with recurrent, early-onset MDD (RE-MDD), a severe and strongly familial subtype of MDD. This 451 kb region includes CREB1, an attractive susceptibility gene for MDD and related disorders. Sequence variations in the CREB1 promoter and intron 8 have been detected that cosegregate with Mood Disorders, or their absence, in women from these families, identifying CREB1 as a sex-limited susceptibility gene for unipolar Mood Disorders. These findings implicate the cAMP signaling pathway in the pathophysiology of Mood Disorders and related conditions.
authors.affiliation: Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. zubenkog@pitt.edu
authors.forename: G S
authors.initials: GS
authors.lastname: Zubenko
authors.forename: H B
authors.initials: HB
authors.lastname: Hughes
authors.forename: J S
authors.initials: JS
authors.lastname: Stiffler
authors.forename: A
authors.initials: A
authors.lastname: Brechbiel
authors.forename: W N
authors.initials: WN
authors.lastname: Zubenko
authors.forename: B S
authors.initials: BS
authors.lastname: Maher
authors.forename: M L
authors.initials: ML
authors.lastname: Marazita
mesh_terms: D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008297:Male; D010375:Pedigree; D012737:Sex Factors; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D014157:Transcription Factors; D000242:Cyclic AMP