Sequence variations in CREB1 cosegregate with depressive disorders in women.
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.
Zubenko
G S
GS
Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. zubenkog@pitt.edu
Hughes
H B
HB
Stiffler
J S
JS
Brechbiel
A
A
Zubenko
W N
WN
Maher
B S
BS
Marazita
M L
ML
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*
C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D014157:Transcription Factors; D000242:Cyclic AMP