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Plasma folate's association with depressive symptoms among US adults: the role of dietary intake and diet quality

Folate deficiency has been implicated in the etiology of unipolar depression. Using a population‐based study of 1,681 subjects aged 30–64 years (Healthy Aging in Neighborhoods of Diversity across the Lifespan Study) the association of folate with depressive symptoms, measured with the Center for Epidemiologic Studies Depression scale (CES‐D), was examined. Folate was measured by plasma levels and dietary intakes based on two 24‐hr recalls. The 2005‐Healthy Eating Index (HEI) was computed. Multivariate logistic regression and structural equation modeling (SM) were conducted. Compared to the lowest tertile, the middle and uppermost tertiles of plasma folate were associated with a 39–40% reduced odds of elevated CES‐D (≥16) among women [adjusted OR (T3 vs. T1)=0.60(95% CI=0.42–0.86), P=0.006]. Confounding of this association by HEItotal was noted, though dietary folate did not confound this association appreciably. In SM, plasma folate completely mediated the inverse HEItotal‐CES‐D association among men only, particularly in six HEI components. Among women, HEItotal and four components had an inverse direct effect on CES‐D score suggesting an independent mechanism from plasma folate. Depressive symptoms may be alleviated by improving dietary quality with plasma folate playing a potential mediating role only among men.