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Objective <p>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.</p> Methods <p>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).</p> Results <p>Hcy levels were significantly higher in male patients with MDD than in female patients (Z = 3.58, <i>P</i> = 0.001). Female patients had significantly higher PANSS positive symptoms (F = 2.06, <i>P</i> = 0.043) and speed of processing (SOP) scores (F = 2.02, <i>P</i> = 0.047) than male patients. In male patients, higher Hcy levels were found to be positively correlated with the severity of positive symptoms (<i>r</i> = 0.477, <i>P</i> = 0.010) and correlated with working memory (WM) scores (<i>r</i> = -0.409, <i>P</i> = 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, <i>P</i> = 0.026) and positive symptoms (B = 0.14, t = 2.42, <i>P</i> = 0.024).</p> Conclusions <p>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.</p> Clinical trial number <p>Not applicable.</p>

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Sex differences in the association between Hcy levels and cognitive deficits among individuals with first-episode and drug-naive major depressive disorder

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月3日

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  • Sumiao Zhou,
  • Yuanyuan Huang,
  • Shixuan Feng,
  • Hehua Li,
  • Ziyun Zhang,
  • Chenyu Liu,
  • Junhao Li,
  • Wei Han,
  • Kai Wu,
  • Xingbing Huang,
  • Fengchun Wu

摘要

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.