ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Mood Disorders
Neurocognitive Risk Markers in First-Episode Major Depressive Disorder with Positive Family History: A Large-Scale Case-Control Study
Provisionally accepted
- Clinical Psychiatry, Hefei Fourth People’s Hospital, Hefei, China
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Objective To identify specific neurocognitive risk markers in first-episode major depressive disorder (MDD) patients with positive family history (PFH). Methods Antipsychotic-naïve adults aged 18–60 were recruited across three groups:major depressive disorder patients with positive family history,PFH-MDD (n=171),major depressive disorder patients with negative family history,NFH-MDD (n=185),and healthy controls (HC, n=180).All patients met DSM-5 criteria for first-episode MDD (HAMD-24 ≥ 17).Neurocognition was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).Group differences were examined with Kruskal–Wallis and ANCOVA.Logistic regressions identified independent cognitive predictors;ROC curves evaluated discriminative validity. Results RBANS total and domain scores differed across groups (p<0.001).PFH-MDD performed worse than NFH-MDD in language function (p<0.001) and total score (p<0.001).In PFH group,Language function score was negatively correlated with HAMD score(r=-0.184, p=0.016).In NFH group,Language function score was positively correlated with HAMA score(r=0.402, p<0.001) and negatively correlated with HAMD score(r=-0.364, p<0.001),Total score was negatively correlated with HAMD score(r=-0.158, p=0.032).After adjustment,language function (OR=0.82, p=0.042) and total score (OR=0.90, p<0.001) independently predicted PFH-MDD;only total score predicted NFH-MDD (OR=0.77, p<0.001).ROC-AUC for PFH-MDD: language=0.967, total=0.991.Gender × group interactions were non-significant. Conclusions Language dysfunction and global cognitive impairment maybe independent markers of first-episode MDD with PFH.Early cognitive profiling may facilitate targeted prevention in high-risk relatives.
Keywords: Major Depressive Disorder, family history, RBANS, neurocognition, Risk marker
Received: 08 Jul 2025; Accepted: 02 Dec 2025.
Copyright: © 2025 Li, Min, Cheng, Zhang, Wang, Fang, Guan and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xialong Cheng
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