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High Homocysteine Levels Associated with Depression

Subjects given vitamin supplements had a significant overall improvement in their poor mental health, reported a study published in the journal Biologic Psychiatry in August 2006. Homocysteine levels were measured in this group. Forty two of the patients had homocysteine levels of greater than 15. Half of them were subsequently supplemented with vitamins B6, B12 and folic acid, or placebo, for three months in a study that was randomized, double-blinded and then crossed over. It was found that homocysteine levels declined with vitamin therapy.

BACKGROUND: Increased levels of homocysteine have been associated with anger and depression separately. We investigated the association of anger attacks in major depressive disorder (MDD) with serum levels of homocysteine.

METHODS: Homocysteine serum levels were measured in 192 outpatients with nonpsychotic MDD, mean age 39.9 +/- 10.7 (range 19-65), 53% women, at baseline of an open-trial antidepressant treatment. We used the Massachusetts General Hospital Anger Attacks Questionnaire to evaluate anger attacks, the Structured Clinical Interview for DSM-III-R Axis I Disorders-Patient Edition (SCID-I/P) to diagnose MDD and the 17-item Hamilton Rating Scale for Depression to measure depression severity.

RESULTS: In the multiple regression analysis split by anger attacks adjusted for parameters of depression, creatinine, vitamin B(12), folate, age, smoking, and alcohol consumption, serum levels of homocysteine were positively correlated with length of current major depressive episode (t value, 3.01; 95% confidence interval [CI], .09 to .43; p = .004) and HAM-D-17 scores (t value, 2.48; 95% CI, .07 to 0.64; p = .016) in patients with anger attacks but not in those without anger attacks.

CONCLUSIONS: Anger attacks in MDD may moderate the relationship of homocysteine serum levels with the severity and length of the depressive episode. Future studies are warranted to confirm and clarify the nature of this moderating effect.

Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.


Fraguas R Jr, Papakostas GI, Mischoulon D, Bottiglieri T, Alpert J, Fava M. Anger Attacks in Major Depressive Disorder and Serum Levels of Homocysteine. Biologial Psychiatry, Vol. 60, Issue 3, 1 Aug. 2006, p. 270-274.

Key concepts: homocysteine, depression, anger