Relationship between serum homocysteine levels and depressive symptoms: The Cooper Center longitudinal study

Objective: Elevated serum levels of the amino acid homocysteine (HCY) are associated with a variety of diseases. To resolve conflicting findings in studies that suggest a relationship between elevated serum HCY levels and depression, we examined the relationship between HCY levels and depressive symptoms in the largest sample studied to date. Method: We conducted a cross-sectional study of 11,757 participants (68.9% men) aged 20 to 90 years who completed preventive health examinations at the Cooper Clinic, Dallas, Texas, from 2007 to 2010. Currently experiencing depression was defined as a 10-item Center for Epidemiologic Studies Depression Scale (CES-D) score of ≥ 10. Serum HCY levels were obtained. Data were analyzed in a multiple logistic regression model of CES-D score of ≥ 10. Results: When controlling for age, sex, body mass index, exercise, education, smoking, antidepressant use, creatinine level, alcohol use, and chronic medical conditions, elevated HCY was associated with 26% greater odds of currently experiencing depressive symptoms (P = .007) as defined by CES-D score. Conclusions: In the largest sample examined to date, we found a significant positive relationship between elevated serum HCY levels and currently experiencing depressive symptoms. Given the cross-sectional nature of the study, it is not possible to determine the direction of the relationship or whether lowering HCY levels will ameliorate depressive symptoms. Thus, longitudinal studies are needed.