Common genetic vulnerability to depressive symptoms and coronary artery disease: a review and development of candidate genes related to inflammation and serotonin

Psychosom Med. 2006 Mar-Apr;68(2):187-200. doi: 10.1097/01.psy.0000208630.79271.a0.


Objective: Although it is well established that depressive symptoms are associated with recurrent cardiac events among cardiac patients and novel cardiac events among participants with no known coronary artery disease (CAD), the nature of this association remains unclear. In this regard, little attention has been paid to the possibility that common genetic vulnerability contributes to both depressive symptoms and CAD. In this paper, we review the existing evidence for common genetic contributions to depression and CAD, primarily using evidence from twin and family studies, followed by a review of two major pathophysiological mechanisms thought to underlie covariation between depressive symptoms and CAD: inflammation and serotonin. We conclude with an overview of select candidate genes within these pathways.

Methods: Literature review.

Results: In twin studies, both depression and CAD appear heritable. In the only twin study to consider depression and CAD jointly, the correlation across heritabilities was 0.42, suggesting that nearly 20% of variability in depressive symptoms and CAD was attributable to common genetic factors. In addition, although it is plausible that genetic variation related to inflammation and serotonin may be associated with both depression and CAD, genetic variation related to inflammation has been primary examined in relation to CAD, whereas genetic variation in the serotonin system has been primarily examined in relation to depression.

Conclusions: It appears that the covariation of depressive symptoms and CAD may be attributable, in part, to a common genetic vulnerability. Although several pathways may be involved, genes within the inflammation and serotonin pathways may serve as good candidates for the first steps in identifying genetic variation important for depression, CAD or both.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Coronary Artery Disease / complications
  • Coronary Artery Disease / genetics*
  • Cytokines / genetics
  • Cytokines / immunology
  • Depression / complications
  • Depression / genetics*
  • Diseases in Twins / genetics
  • Female
  • Genetic Linkage
  • Genetic Predisposition to Disease
  • Humans
  • Inflammation / genetics
  • Male
  • Serotonin / genetics


  • Cytokines
  • Serotonin