Homocysteine and the risk of depression

Nutrition Research Newsletter, Jan, 2005

Low blood folate and cobalamin (vitamin B-12) concentrations have been found in patients with major depression, and this low blood folate concentrations have been associated with a poor response to antidepressant treatment.

A connection between vitamin B status and depression could be explained by direct effects of the vitamins on monoamine metabolism in the central nervous system. However, low vitamin B status leads to hyperhomocysteinemia, which has been linked to other neuropsychiatric disorders. So it has also been suggested the hyperhomocysteinemia itself could cause or aggravate depression. Since more research is needed to clarify the connection between B vitamins and depression, data from the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD Study) examined the relation between total homocysteine (tHcy) concentrations and depression among middle-aged Finnish men.

A cross-sectional study of 924 men aged 46 to 64 years who were without a history of psychiatric disorders was conducted as a part of the KIHD study. Depressive symptoms were assessed with the Human Population Laboratory Depression Scale. Those who scored >5 at baseline or at the four-year follow-up were considered to have a tendency toward depression, tHcy measurements were also taken. The subjects were ranked according to their blood tHcy concentration and divided into tertiles.

The serum tHcy concentration was elevated in 36.7% of the depressed men and in 26.4% of the non-depressed men. Those in the upper tertile for serum tHcy had a more than twofold 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.

In the current study, high serum tHcy is associated with depression in middle-aged Finnish men. It is not known whether these findings can be generalized to Finnish women, Finnish men of different ages or to subjects in other countries. An elevated serum tHcy concentration, rather than being an independent risk factor, may be an indicator of an unhealthy lifestyle, which in turn leads to an increased risk of depression. However, in this sample, many other well-known risk factors for depression were not associated with an increased serum tHcy concentration, and adjustment for those risk factors did not change the results.

Tommi Tolmunen, Jukka Hintikka, Sari Voutilainen, et al., Association between depressive symptoms and serum concentrations of homocysteine in men: a population study, Am J Clin Nutr 80:1574-1578 (December 2004) [Address reprint requests to S Voutilainen, Research Institute of Public Healht, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland. E-mail: sari.voutilainen@uku.fi]