Women who drank two to three cups of coffee per day were 15% less likely to develop depression than those who drank one or fewer, researchers found.

“These findings are consistent with earlier observations that suicide risk is lower among persons with higher consumption of coffee,” Alberto Aschiero, MD, DrPH, of the Harvard School of Public Health in Boston, and colleagues wrote in Archives of Internal Medicine.

The researchers analyzed coffee consumption and depression rates among 50,739 depression-free women who participated in the Nurses Health Study between 1996 and June 1, 2006.

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They measured caffeine consumption — including caffeine from coffee — and self reported physician-diagnosed depression using validated questionnaires. A total of 2,607 new cases of depression were identified during the study period.

Data indicated an inverse dose-response association between depression and both coffee intake and caffeine consumption. Specifically, women who drank two or three cups of coffee per day had a 0.85 relative risk for depression compared with those who consumed one cup or less (95% CI: 0.75-0.95).

Furthermore, relative risk for depression was lower as women consumed more coffee. Compared with those who consumed the least amount of coffee (less than 100 mg per day), women who consumed the most (at least 500 mg per day) had a 0.80 multivariate relative risk for depression (95% CI: 0.68-0.95; P for trend=0.02).

There was no association between decaffeinated coffee and depression risk, suggesting that caffeine and not some other component of coffee, is responsible for the relationship.

Interestingly, among current smokers, each two-cup increase in caffeinated coffee consumption was associated with a 0.78 multivariate relative risk for depression (95% CI: 0.68-0.95; P for trend=0.02) vs. 0.95 relative risk among never and former smokers (95% CI: 0.89-1.01).

This finding “was unexpected and may be due to chance,” the researchers wrote, noting that reverse causation may be to blame, with lower caffeine consumption among those with mild depressive symptoms accounting for these findings.

The researchers emphasized that because the study is observational in design, the data only suggest the possibility of a protective effect and do not definitively prove that the consumption of caffeine or caffeinated coffee truly reduces women’s risk for depression.

In an editor’s note, Seth A. Berkowitz, MD, of Department of Internal Medicine at the University of California San Francisco, wrote that while the findings are reassuring that coffee is not harmful, “it seems premature to recommend coffee consumption until studies with methodologies better able to determine causality are conducted.”

Lucas M et al. Arch Intern Med. 2011;171:1571-1578.