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Related Experiment Video

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Association Between Sleep Quality and Cognitive Symptoms in Patients with Major Depressive Disorder

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Published on: April 26, 2024

Homocysteine and cognitive function in depression: a systematic review and meta-analysis.

Xiaotong Liu¹, Qingsong Liu¹, Jili Xu¹

¹Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.

Frontiers in Psychiatry

|May 29, 2026

Summary

Elevated homocysteine (Hcy) levels are linked to poorer cognitive function in depression patients. This systematic review and meta-analysis confirms a significant inverse association between Hcy and cognitive performance.

Keywords:

cognition cognitive impairment depression homocysteine meta-analysis

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Area of Science:

Neuroscience
Biochemistry
Psychiatry

Background:

Homocysteine (Hcy) is an amino acid linked to various health conditions.
Cognitive impairment is a common symptom in patients with depression.
Understanding the relationship between Hcy and cognitive function in depression is crucial for potential therapeutic strategies.

Purpose of the Study:

To systematically review and meta-analyze the association between homocysteine levels and cognitive function in individuals diagnosed with depression.
To quantify the relationship between Hcy levels and cognitive performance in this patient population.

Main Methods:

A comprehensive literature search was conducted across multiple databases (PubMed, Web of Science, EMBASE, etc.) up to December 2025.
Methodological quality was assessed using the AHRQ checklist, and evidence certainty was evaluated using the GRADE approach.
Random-effects models were employed for meta-analysis using Stata 17.0.

Main Results:

Thirteen studies involving 1,269 patients with depression were included in the analysis.
A significant inverse association was found between Hcy levels and cognitive scores (r = -0.41, p < 0.001).
Higher Hcy levels correlated with poorer cognitive performance (SMD = -0.37, p = 0.003) and were observed in patients with cognitive impairment (SMD = 2.44, p = 0.003).

Conclusions:

Homocysteine levels are significantly associated with cognitive impairment in patients with depression.
Subgroup and sensitivity analyses confirmed the consistency of this association.
Further prospective studies are warranted to elucidate the clinical relevance of Hcy in assessing cognitive impairment in depression.