Sequence variations in CREB1 cosegregate with depressive disorders in women

Mol Psychiatry. 2003 Jun;8(6):611-8. doi: 10.1038/


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cyclic AMP / metabolism
  • Cyclic AMP Response Element-Binding Protein
  • Depressive Disorder, Major / genetics*
  • Female
  • Genetic Linkage*
  • Genetic Predisposition to Disease
  • Humans
  • Introns
  • Male
  • Pedigree
  • Sex Factors
  • Signal Transduction
  • Transcription Factors / genetics*


  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • Transcription Factors
  • Cyclic AMP