Association of high-sensitivity C-reactive protein with de novo major depression

<b>Background:</b> Although there is cross-sectional evidence that changes in the immune system contribute to the pathophysiology of depression, longitudinal data capable of elucidating cause and effect relationships are lacking. <br /><br /><b>Aims: </b>We aimed to determine whether subclinical systemic inflammation, as measured by serum high-sensitivity C-reactive protein (hsCRP) concentration, is associated with an increased risk of de novo major depressive disorder. <br /><br /><b>Method:</b> Major depressive disorder was diagnosed using a clinical interview (SCID-I/NP). This is a retrospective cohort study; from a population-based sample of 1494 randomly selected women recruited at baseline during the period 1994-7, 822 were followed for a decade and provided measures of both exposure and outcome. Of these women, 644 (aged 20-84 years) had no prior history of depression at baseline and were eligible for analysis. <br /><br /><b>Results:</b> During 5827 person-years of follow-up, 48 cases of de novo major depressive disorder were identified. The hazard ratio (HR) for depression increased by 44% for each standard deviation increase in log-transformed hsCRP (ln-hsCRP) (HR = 1.44, 95% CI 1.04-1.99), after adjusting for weight, smoking and use of non-steroidal anti-inflammatory drugs. Further adjustment for other lifestyle factors, medications and comorbidity failed to explain the observed increased risk for depression. <br /><br /><b>Conclusions:</b> Serum hsCRP is an independent risk marker for de novo major depressive disorder in women. This supports an aetiological role for inflammatory activity in the pathophysiology of depression.