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

Abstract

Background: Hyperhomocysteinaemia is known to interfere with neurological functions; however, there is a controversy regarding the relationship between homocysteine and depression. Materials and methods: 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. Results: 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. Conclusion: 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.

Intrinsic Capacity Declines with Elevated Homocysteine in Community-Dwelling Chinese Older Adults

“… 13 , 14 At the psychological level, a meta-analysis summarized that subjects with hyperhomocysteinaemia had a higher probability of depression. 56 The result of our study shows that elevated Hcy is associated with impairments in cognition, sensory, vitality, and psychology, accordance with the studies described above. However, the heterogeneity of the diagnostic tools was non-negligible.…”

The role of BDNF exon I region methylation in the treatment of depression with sertraline and its clinical diagnostic value

“… 35 Serum Hcy concentrations are higher in individuals with depression than in healthy subjects. 36 In this study, we found that the serum Hcy concentrations in patients with depression decreased significantly after sertraline treatment. However, we found no correlation between the Hcy concentration and BDNF methylation in further analysis.…”

Maternal Mental Health in Late Pregnancy and Longitudinal Changes in Postpartum Serum Vitamin B-12, Homocysteine, and Milk B-12 Concentration Among Brazilian Women

“…The studies conducted prior to ours' had yielded conflicting conclusions about the relationship between depression and B-12 or homocysteine concentrations ( 15 ). Some studies, with adults and elderly individuals, have indicated hyperhomocysteinemia in patients with depression ( 51 , 52 ), while others did not find any association ( 53 ).…”

“…B-12 has hematological and neurological functions and is required for S-adenosylmethionine (SAM) synthesis ( 4 ), while SAM has anti-depressive properties, as it plays a role in synthesizing neurotransmitters ( 13 ). Some studies have demonstrated that B-12 deficiency status could impair SAM synthesis and raise homocysteine levels, thus being related to anxiety and depressive symptoms ( 14 , 15 ). Homocysteine is a sulfur-containing amino acid formed during the methionine metabolism that also plays a role in neurotransmitter synthesis ( 16 , 17 ).…”