Sex differences in the association between Hcy levels and cognitive deficits among individuals with first-episode and drug-naive major depressive disorder.
6 affiliations
- 1The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, 510370, China.
- 2School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, China.
- 3The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, 510370, China. [email protected].
- 4The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, 510370, China. [email protected].
- 5Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, 510370, China. [email protected].
- 6Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, 510370, China. [email protected].
Abstract
Objective
Previous studies have shown that elevated homocysteine (Hcy) levels are associated with cognitive deficits in first-episode and drug-naive individuals with major depressive disorder (MDD). However, research on sex differences in this context is limited. This study aimed to evaluate sex differences in the association between Hcy levels and cognitive deficits among individuals with first-episode and drug-naive MDD.Methods
We recruited 85 MDD patients and 100 healthy controls. The MATRICS Consensus Cognitive Battery (MCCB) was used to assess cognitive function, and serum Hcy levels were measured in all participants. Clinical features, including affective and psychotic symptom dimensions, were evaluated using the Hamilton Depression Rating Scale (HAMD), the Hamilton Anxiety Rating Scale (HAMA), and the Positive and Negative Syndrome Scale (PANSS).Results
Hcy levels were significantly higher in male patients with MDD than in female patients (Z = 3.58, P = 0.001). Female patients had significantly higher PANSS positive symptoms (F = 2.06, P = 0.043) and speed of processing (SOP) scores (F = 2.02, P = 0.047) than male patients. In male patients, higher Hcy levels were found to be positively correlated with the severity of positive symptoms (r = 0.477, P = 0.010) and correlated with working memory (WM) scores (r = -0.409, P = 0.030). Additionally, in male patients with MDD, multivariate regression analyses revealed that Hcy levels were independent predictors of WM scores (B = -0.43, t = 2.37, P = 0.026) and positive symptoms (B = 0.14, t = 2.42, P = 0.024).Conclusions
These findings highlight that Hcy levels differ between the sexes, and that in males, MDD Hcy levels were significantly associated with the severity of positive symptoms and cognitive deficits. These results support the potential of Hcy as a biomarker for cognitive deficits and positive psychotic symptoms, which provide a target for therapeutic intervention in male patients with MDD.Clinical trial number
Not applicable.
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BibTeX
@article{zhou2026differences,
title = {{Sex differences in the association between Hcy levels and cognitive deficits among individuals with first-episode and drug-naive major depressive disorder.}},
author = {Sumiao Zhou and Yuanyuan Huang and Shixuan Feng and Hehua Li and Ziyun Zhang and Chenyu Liu and Junhao Li and Wei Han and Kai Wu and Xingbing Huang and Fengchun Wu},
journal = {BMC psychiatry},
year = {2026},
month = aug,
doi = {10.1186/s12888-026-08486-z},
url = {https://europepmc.org/article/MED/42963750},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Sex differences in the association between Hcy levels and cognitive deficits among individuals with first-episode and drug-naive major depressive disorder.
AU - Sumiao Zhou
AU - Yuanyuan Huang
AU - Shixuan Feng
AU - Hehua Li
AU - Ziyun Zhang
AU - Chenyu Liu
AU - Junhao Li
AU - Wei Han
AU - Kai Wu
AU - Xingbing Huang
AU - Fengchun Wu
PY - 2026
DA - 2026/08/03
JO - BMC psychiatry
DO - 10.1186/s12888-026-08486-z
UR - https://europepmc.org/article/MED/42963750
AB - Objective Previous studies have shown that elevated homocysteine (Hcy) levels are associated with cognitive deficits in first-episode and drug-naive individuals with major depressive disorder (MDD). However, research on sex differences in this context is limited. This study aimed to evaluate sex differences in the association between Hcy levels and cognitive deficits among individuals with first-episode and drug-naive MDD.Methods We recruited 85 MDD patients and 100 healthy controls. The MATRICS Consensus Cognitive Battery (MCCB) was used to assess cognitive function, and serum Hcy levels were measured in all participants. Clinical features, including affective and psychotic symptom dimensions, were evaluated using the Hamilton Depression Rating Scale (HAMD), the Hamilton Anxiety Rating Scale (HAMA), and the Positive and Negative Syndrome Scale (PANSS).Results Hcy levels were significantly higher in male patients with MDD than in female patients (Z = 3.58, P = 0.001). Female patients had significantly higher PANSS positive symptoms (F = 2.06, P = 0.043) and speed of processing (SOP) scores (F = 2.02, P = 0.047) than male patients. In male patients, higher Hcy levels were found to be positively correlated with the severity of positive symptoms (r = 0.477, P = 0.010) and correlated with working memory (WM) scores (r = -0.409, P = 0.030). Additionally, in male patients with MDD, multivariate regression analyses revealed that Hcy levels were independent predictors of WM scores (B = -0.43, t = 2.37, P = 0.026) and positive symptoms (B = 0.14, t = 2.42, P = 0.024).Conclusions These findings highlight that Hcy levels differ between the sexes, and that in males, MDD Hcy levels were significantly associated with the severity of positive symptoms and cognitive deficits. These results support the potential of Hcy as a biomarker for cognitive deficits and positive psychotic symptoms, which provide a target for therapeutic intervention in male patients with MDD.Clinical trial number Not applicable.
SN - 1471-244X
ER -