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Am J Psychiatry. 2007 Jun;164(6):861-7.

The homocysteine hypothesis of depression.

Author information

  • 1FRiedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.

Erratum in

  • Am J Psychiatry. 2007 Jul;164(7):1123. Buel, Jennifer [corrected to Buell, Jennifer].


High levels of homocysteine are associated with cerebrovascular disease, monoamine neurotransmitters, and depression of mood. A plausible hypothesis for these associations is that high homocysteine levels cause cerebral vascular disease and neurotransmitter deficiency, which cause depression of mood. The homocysteine depression hypothesis, if true, would mandate inclusions of imaging studies for cerebrovascular disease and measures of homocysteine, folate, and B12 and B6 vitamins in the clinical evaluation of older depressed patients. Longitudinal studies and clinical trials should be designed to challenge the hypothesis.

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