Depressive symptoms, health behaviors, and subsequent inflammation in patients with coronary heart disease: prospective findings from the heart and soul study

Am J Psychiatry. 2011 Sep;168(9):913-20. doi: 10.1176/appi.ajp.2011.10081163. Epub 2011 Jul 1.


Objective: Depression has been associated with inflammation in patients with coronary heart disease. However, it is uncertain whether depressive symptoms lead to inflammation or vice versa.

Method: The authors evaluated 667 outpatients with established coronary heart disease from the Heart and Soul Study. Depressive symptoms were assessed annually with the 9-item Patient Health Questionnaire. Participants were categorized as having no significant depressive symptoms (score below 10 at all interviews), depressive symptoms (score of 10 or higher) at one interview, or depressive symptoms at two or more interviews. At baseline and 5-year follow-up, fasting blood samples were collected to measure three inflammatory biomarkers: fibrinogen, interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP).

Results: Of the 667 participants, 443 had no depressive symptoms, 86 had depressive symptoms at one assessment, and 138 had depressive symptoms at two or more annual assessments. Across the three groups, greater depressive symptoms were associated with higher subsequent log-transformed levels of IL-6 and hsCRP, and the association with higher fibrinogen levels approached significance. Baseline inflammation did not predict subsequent depressive symptoms. The association of depressive symptoms with subsequent inflammation levels was eliminated after adjustment for health behaviors associated with depression-physical inactivity, smoking, and higher body mass index.

Conclusions: Depressive symptoms predicted higher IL-6 and hsCRP levels among outpatients with coronary heart disease, but higher inflammation levels did not predict subsequent depressive symptoms. The association between depressive symptoms and inflammation was no longer significant after adjustment for health behaviors, which suggests these behaviors may mediate depressive effects.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Aged
  • Body Mass Index
  • C-Reactive Protein / metabolism
  • Coronary Disease / immunology*
  • Coronary Disease / psychology*
  • Depressive Disorder / immunology*
  • Depressive Disorder / psychology*
  • Exercise / psychology
  • Female
  • Fibrinogen / metabolism
  • Follow-Up Studies
  • Health Behavior
  • Humans
  • Inflammation Mediators / blood*
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Mind-Body Relations, Metaphysical*
  • Prospective Studies
  • Risk Factors
  • Smoking / adverse effects


  • Inflammation Mediators
  • Interleukin-6
  • Fibrinogen
  • C-Reactive Protein