BDNF genetic variants modulate the impact of childhood trauma on symptom dimensions in first-episode schizophrenia

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.