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

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.