{
  "abstract": "Objective\n\nPrevious 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\n\nWe 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\n\nHcy 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\n\nThese 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\n\nNot applicable.",
  "abstract_shown": true,
  "affiliations": [
    "The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, 510370, China.",
    "School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, China.",
    "The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, 510370, China. hxbing2002@163.com.",
    "The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, 510370, China. 2018760372@gzhmu.edu.cn.",
    "Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, 510370, China. 2018760372@gzhmu.edu.cn.",
    "Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, 510370, China. 2018760372@gzhmu.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sumiao Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuanyuan Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Shixuan Feng"
    },
    {
      "affs": [
        0
      ],
      "name": "Hehua Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Ziyun Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Chenyu Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Junhao Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Wei Han"
    },
    {
      "affs": [
        1
      ],
      "name": "Kai Wu"
    },
    {
      "affs": [
        2
      ],
      "name": "Xingbing Huang"
    },
    {
      "affs": [
        3,
        4,
        5
      ],
      "name": "Fengchun Wu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/59m3mcdvkf690.bib",
  "cited_by": 0,
  "doi": "10.1186/s12888-026-08486-z",
  "fulltext_url": "https://europepmc.org/articles/PMC13721575",
  "id": "59m3mcdvkf690",
  "issns": [
    "1471-244X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42963750",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2736|Treatment of Major Depression"
    ]
  ],
  "openalex": "W4412887191",
  "pdf_url": "https://europepmc.org/articles/PMC13721575?pdf=render",
  "pmcid": "PMC13721575",
  "pmid": "42963750",
  "published": "2026-08-03",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/59m3mcdvkf690.ris",
  "sources": [
    {
      "first_seen": "2026-11-02T03:21:43Z",
      "native_id": "MED:42963750",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42963750"
    },
    {
      "first_seen": "2026-11-03T12:22:14Z",
      "native_id": "PMC13721575",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12888-026-08486-z"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Treatment of Major Depression",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Sex differences in the association between Hcy levels and cognitive deficits among individuals with first-episode and drug-naive major depressive disorder.",
  "title_text": "Sex differences in the association between Hcy levels and cognitive deficits among individuals with first-episode and drug-naive major depressive disorder.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:22:14Z",
  "url": "https://research.draconitic.com/paper/59m3mcdvkf690",
  "venue": "BMC psychiatry",
  "versions": []
}