Serum homocysteine showed potential association with cognition and abnormal gut microbiome in major depressive disorder.

Background: Cognitive impairment is one of the common clinical manifestations of depression, causing negative distress to patients. Elevated homocysteine (Hcy) concentrations and gut microbiome dysfunction may be observed in patients with depression.

Aim: To investigate the relationship between Hcy, microbiome, and cognition in depressive patients.

Methods: We recruited 67 patients with major depressive disorder (MDD) (MDD group) and 94 healthy controls (HCs) individuals (HCs group). Serum Hcy levels were determined using the enzyme circulation method. 16s rRNA sequencing was used to classify and identify the fecal bacteria. 17 Hamilton depression rating scale and MATRICS consensus cognitive battery were used to evaluate mood states and cognition in patients with MDD. Correlation analysis was performed to explore the correlation between fecal flora, Hcy, and depressive cognitive function.

Results: Elevated serum levels of Hcy were seen in patients with MDD compared to healthy individuals. Patients with MDD indicated significant decreases in cognitive scores (P < 0.001) in six modules: Speed of processing, working memory, visual learning, reasoning and problem-solving, social cognition, and total scores. Hcy levels showed a negative correlation with processing speed, social cognition, and total MDD scores (P < 0.05). Hcy was also significantly negatively correlated with Alistipes, Ruminococcae, Tenericides, and Porphyromonas (P < 0.05).

Conclusion: Our results highlight that Hcy was correlated with cognition and gut microbiome in MDD. This interaction may be related to the physiological and pathological mechanisms underlying cognitive deficits in depression.