ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Behavioral and Psychiatric Genetics
BDNF Genetic Variants Modulate the Impact of Childhood Trauma on Symptom Dimensions in First-Episode Schizophrenia
Provisionally accepted
- 1Xi'an Jiaotong University Health Science Center, Xi'An, China
- 2Department of Psychiatry, Third People's Hospital of Zhongshan City, Zhongshan, China
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Background: Gene–environment interactions play a critical role in shaping phenotypic heterogeneity in complex psychiatric disorders. Brain-derived neurotrophic factor (BDNF) is a key genetic regulator of stress-sensitive neuroplasticity. Yet, how BDNF polymorphisms are associated with the effect and impact of childhood trauma on clinical phenotypes remains incompletely understood. Methods: We conducted a case–control study including 93 patients with first-episode schizophrenia (SZ) and 64 healthy controls. Childhood trauma exposure was assessed using the Childhood Trauma Questionnaire (CTQ), and symptom dimensions were evaluated with the Positive and Negative Syndrome Scale (PANSS). Three BDNF single-nucleotide polymorphisms (rs6265, rs2030324, and rs11030101) were genotyped. Generalized linear models were applied to examine gene–environment interaction effects while adjusting for demographic and clinical covariates. Results: Patients with SZ exhibited significantly higher CTQ scores across all trauma subtypes compared with controls (all P < 0.05). Childhood trauma was associated with increased severity of positive, excitement/hostility, and depression/anxiety symptom dimensions. Importantly, BDNF variants significantly moderated these associations. Rs6265 (CT/TT genotypes) interacted with physical neglect to predict lower depression/anxiety scores, whereas rs11030101 (TA genotype) interacted with sexual abuse to predict increased depression/anxiety and showed negative interactions with physical neglect and total CTQ scores in relation to negative symptoms. Conclusion: These findings demonstrate that BDNF polymorphisms act as genetic modifiers of trauma-related symptom expression, supporting a gene–environment interaction model underlying phenotypic heterogeneity in schizophrenia.
Keywords: BDNF, childhood trauma, clinical symptoms, gene polymorphism, Schizophrenia
Received: 17 Jan 2026; Accepted: 10 Feb 2026.
Copyright: © 2026 Ping, Wu, Luo, Zhang, Jiang and Dang. 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: Yonghui Dang
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