The association between serum homocysteine and depression: A systematic review and meta‐analysis of observational studies

Hyperhomocysteinaemia is known to interfere with neurological functions; however, there is a controversy regarding the relationship between homocysteine and depression.Science Direct, MEDLINE and ISI Web of Science were searched to find relevant articles, published up to August 2020. Studies were included if they compared homocysteine levels in healthy subjects with subjects with depression. Also, articles that reported the association between hyperhomocysteinaemia and risk of depression were included. Odds ratios of depression and means of homocysteine were used to ascertain the overall effect size.Homocysteine level was higher in subjects with depression in comparison with healthy controls (weight mean difference = 2.53 µmol/L, 95% confidence interval: 1.77, 3.30), and the depression diagnostic tool was a source of heterogeneity. Homocysteine level was significantly higher in subjects with depression in studies that used Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV), Geriatric Depression Scale (GDS), Zung Self-Rating Depression Scale (ZDRS) and Beck Depression Index II (BDI-II) as depression diagnostic tools. Also, participants with hyperhomocysteinaemia had a higher chance of depression (Pooled risk = 1.34, 95% confidence interval: 1.19, 1.52), where the depression diagnostic tool was a source of heterogeneity. In contrast to ZDRS and Patient Health Questionnaire (PHQ) subgroups, hyperhomocysteinaemia yielded a significantly higher risk of depression in DSM-IV, GDS and 'other' subgroups.Homocysteinemia level is higher in individuals with depression. However, the depression diagnostic tool used is instrumental in influencing their association, and thus, future studies should focus on the tools for depression assessment.