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J. Nutr. First published December 23, 2009; doi:10.3945/jn.109.113878
 Journal of Nutrition, doi:10.3945/jn.109.113878
Vol. 140, No. 2, 338-347, February 2010
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© 2010 American Society for Nutrition

Nutritional Epidemiology

The Sex-Specific Role of Plasma Folate in Mediating the Association of Dietary Quality with Depressive Symptoms1–3,

May A. Beydoun4,*, Marie T. Fanelli Kuczmarski5, Hind A. Beydoun6, Monal R. Shroff7, Marc A. Mason8, Michele K. Evans4 and Alan B. Zonderman4

4 National Institute on Aging, NIH/Intramural Research Program, Baltimore, MD 21224; 5 Department of Health, Nutrition and Exercise Sciences, University of Delaware, Newark, DE 19716; 6 Graduate Program in Public Health, Eastern Virginia Medical School, Norfolk, VA 23501; 7 Department of Epidemiology, Michigan State University, East Lansing, MI 48824; 8 Statistical Information Systems, MedStar Research Institute, Baltimore, MD 21224

Folate deficiency has been implicated in the etiology of unipolar depression. In this study, we attempted to cross-link plasma folate, depressive symptoms, and dietary quality (or dietary intake of folate) together in a comprehensive framework, while examining effect modification of those associations by sex. This was a cross-sectional, population-based study of 1681 participants aged 30–64 y (Healthy Aging in Neighborhoods of Diversity across the Lifespan Study). Participants were administered the Center for Epidemiologic Studies Depression scale (CES-D). Measures of plasma folate and dietary intakes (2 24-h recalls) from which the 2005-Healthy Eating Index (HEI) was computed were available. Multivariate logistic regression and structural equation modeling (SM) were conducted. Compared with 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 odds ratio (T3 vs. T1) = 0.60 (95% CI = 0.42–0.86); P = 0.006]. Confounding of this association by HEItotal was noted among both men and women, although dietary folate did not confound this association appreciably. In SM, plasma folate completely mediated the inverse HEItotal-CES-D association among men only, specifically for HEI2 (higher intakes of whole fruits), HEI3 (total vegetables), HEI5 (total grains), HEI6 (whole grains), HEI7 (milk), and HEI12 (lower discretionary energy). Among women, HEItotal and 4 components had an inverse direct effect on CES-D score, suggesting a mechanism that is independent of plasma folate. Depressive symptoms in our study may be alleviated by improving overall dietary quality, with plasma folate playing a potential mediating role only among men.

* To whom correspondence should be addressed. E-mail: baydounm{at}mail.nih.gov.

Manuscript received 30 July 2009. Initial review completed 9 September 2009. Revision accepted 24 November 2009.

Published online 23 December 2009.