Food and Behaviour Research

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Association between depressive symptoms and serum concentrations of homocysteine in men: a population study.

Tolmunen T, Hintikka J, Voutilainen S, Ruusunen A, Alfthan G, Nyyssonen K, Viinamaki H, Kaplan GA, Salonen JT. (2004) Am J Clin Nutr.  80(6) 1574-8. 

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BACKGROUND: Results of studies of the association between blood concentrations of homocysteine and depression in general populations and among psychiatric patients are inconsistent.

OBJECTIVE: The objective was to study the association between depression and serum concentrations of total homocysteine (tHcy).

DESIGN: A cross-sectional study of a sample of 924 men aged 46-64 y was conducted as a part of the Kuopio Ischaemic Heart Disease Risk Factor Study. Those who had a history of psychiatric disorder (6.0%) were excluded. Depressive symptoms were assessed with the 18-item Human Population Laboratory Depression Scale. Those who scored > or =5 at baseline or at the 4-y follow-up were considered to have a tendency toward depression.

RESULTS: The participants were ranked according to their blood tHcy concentration and divided into tertiles. Those in the upper tertile for serum tHcy had a more than twofold (odds ratio: 2.30; 95% CI: 1.35, 3.90; P=0.002) higher risk of being depressed than did those in the lowest tertile for serum tHcy. The results remained significant after adjustment for the month of study, history of ischemic heart disease, smoking habits, alcohol consumption, marital status, education, and socioeconomic status in adulthood (odds ratio: 2.23; 95% CI: 1.30, 3.83; P=0.004).

CONCLUSION: High serum concentrations of tHcy may be associated with depression in middle-aged men.


Homocysteine is a toxic by-product of normal metabolism, but it can normally be recycled provided there are sufficient levels of Vitamins B6, B12 and folate (B9), all of which can help to keep homocysteine levels low.

Elevated levels of homocysteine are associated with increased risks for both cardiovascular disease and dementia.

Here, high homocysteine levels in serum were found to predict depression in middle-aged men from a general population sample - adding to previous evidence reporting such a link in both general and clinical populations.

Association studies like this one cannot provide evidence of causal relationships, but these findings suggest that further investigation into possible links between homocysteine and depression are merited.