{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T07:57:12Z","timestamp":1772697432192,"version":"3.50.1"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Gene\u2013environment 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\n                      <jats:italic>BDNF<\/jats:italic>\n                      polymorphisms are associated with the effect and impact of childhood trauma on clinical phenotypes remains incompletely understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a case\u2013control 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\n                      <jats:italic>BDNF<\/jats:italic>\n                      single-nucleotide polymorphisms (rs6265, rs2030324, and rs11030101) were genotyped. Generalized linear models were applied to examine gene\u2013environment interaction effects while adjusting for demographic and clinical covariates.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients with SZ exhibited significantly higher CTQ scores across all trauma subtypes compared with controls (all\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings demonstrate that\n                      <jats:italic>BDNF<\/jats:italic>\n                      polymorphisms act as genetic modifiers of trauma-related symptom expression, supporting a gene\u2013environment interaction model underlying phenotypic heterogeneity in schizophrenia.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpsyt.2026.1790184","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T06:58:22Z","timestamp":1772693902000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["BDNF genetic variants modulate the impact of childhood trauma on symptom dimensions in first-episode schizophrenia"],"prefix":"10.3389","volume":"17","author":[{"given":"Junjiao","family":"Ping","sequence":"first","affiliation":[{"name":"College of Medicine and Forensics, Xi\u2019an Jiaotong University Health Science Center","place":["Xi\u2019an, Shanxi, China"]},{"name":"Department of Psychiatry, The Third People\u2019s Hospital of Zhongshan","place":["Zhongshan, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, The Third People\u2019s Hospital of Zhongshan","place":["Zhongshan, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiali","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, The Third People\u2019s Hospital of Zhongshan","place":["Zhongshan, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, The Third People\u2019s Hospital of Zhongshan","place":["Zhongshan, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingyun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, The Third People\u2019s Hospital of Zhongshan","place":["Zhongshan, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonghui","family":"Dang","sequence":"additional","affiliation":[{"name":"College of Medicine and Forensics, Xi\u2019an Jiaotong University Health Science Center","place":["Xi\u2019an, Shanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.schres.2014.03.034","article-title":"Genetic underpinnings of white matter \u2018connectivity\u2019: heritability, risk, and heterogeneity in schizophrenia","volume":"161","author":"Voineskos","year":"2015","journal-title":"Schizophr Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2009.10.004","article-title":"Rare structural variants in schizophrenia: one disorder, multiple mutations; one mutation, multiple disorders","volume":"25","author":"Sebat","year":"2009","journal-title":"Trends Genet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-024-02749-5","article-title":"Schizophrenia is associated with altered DNA methylation variance","volume":"30","author":"Kiltschewskij","year":"2025","journal-title":"Mol Psychiatry"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s00406-013-0450-z","article-title":"Genetics of psychiatric disorders in the GWAS era: an update on schizophrenia","author":"Schwab","year":"2013","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-024-00731-z","article-title":"Gene-environment interactions in human health","volume":"25","author":"Herrera-Luis","year":"2024","journal-title":"Nat Rev Genet"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1578","article-title":"Gene-environment interactions in human diseases","volume":"6","author":"Hunter","year":"2005","journal-title":"Nat Rev Genet"},{"key":"B7","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.schres.2021.06.005","article-title":"Childhood adversity and psychotic disorders: Epidemiological evidence, theoretical models and clinical considerations","volume":"247","author":"Rosenfield","year":"2022","journal-title":"Schizophr Res"},{"key":"B8","doi-asserted-by":"publisher","first-page":"110612","DOI":"10.1016\/j.pnpbp.2022.110612","article-title":"Polygenic risk for schizophrenia as a moderator of associations between childhood trauma and schizotypy","volume":"119","author":"Tonini","year":"2022","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"B9","doi-asserted-by":"publisher","first-page":"29003","DOI":"10.1038\/s41598-025-14438-6","article-title":"Exposotypes in psychotic disorders","volume":"15","author":"Yassin","year":"2025","journal-title":"Sci Rep"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-023-00811-4","article-title":"Mechanisms underlying phenotypic variation in neurogenetic disorders","volume":"19","author":"Burgunder","year":"2023","journal-title":"Nat Rev Neurol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2024.1372620","article-title":"A network analysis of ICD-11 Complex PTSD, emotional processing, and dissociative experiences in the context of psychological trauma at different developmental stages","volume":"15","author":"Mohammadi","year":"2024","journal-title":"Front Psychiatry"},{"key":"B12","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.brainres.2007.05.071","article-title":"Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats","volume":"1162","author":"Xu","year":"2007","journal-title":"Brain Res"},{"key":"B13","doi-asserted-by":"publisher","first-page":"104304","DOI":"10.1016\/j.jtherbio.2025.104304","article-title":"Effects of heat environments on depressive disorders: Neurogenesis-mediated mechanisms","volume":"134","author":"Kong","year":"2025","journal-title":"J Therm Biol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1038\/sj.mp.4001308","article-title":"Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia","volume":"8","author":"Weickert","year":"2003","journal-title":"Mol Psychiatry"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jpsychires.2011.09.022","article-title":"The role of BDNF in the pathophysiology and treatment of schizophrenia","volume":"46","author":"Favalli","year":"2012","journal-title":"J Psychiatr Res"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e1713","DOI":"10.1002\/wrna.1713","article-title":"Brain-derived neurotrophic factor-induced regulation of RNA metabolism in neuronal development and synaptic plasticity","volume":"13","author":"Costa","year":"2022","journal-title":"Wiley Interdiscip Rev RNA"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2217\/bmm.10.111","article-title":"Circulating levels of brain-derived neurotrophic factor: correlation with mood, cognition and motor function","volume":"4","author":"Teixeira","year":"2010","journal-title":"biomark Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.12.121","article-title":"Brain-derived neurotrophic factor and risk of schizophrenia: an association study and meta-analysis","volume":"353","author":"Qian","year":"2007","journal-title":"Biochem Biophys Res Commun"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000327605","article-title":"Influence of BDNF variants on diagnosis and response to treatment in patients with major depression, bipolar disorder and schizophrenia","volume":"65","author":"Pae","year":"2012","journal-title":"Neuropsychobiology"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-011-8159-5","article-title":"Association study of brain-derived neurotrophic factor gene polymorphisms and body weight change in schizophrenic patients under long-term atypical antipsychotic treatment","volume":"13","author":"Tsai","year":"2011","journal-title":"Neuromolecular Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"81","DOI":"10.3233\/JAD-140576","article-title":"Physical exercise improves peripheral BDNF levels and cognitive functions in mild cognitive impairment elderly with different bdnf Val66Met genotypes","volume":"43","author":"Nascimento","year":"2015","journal-title":"J Alzheimers Dis"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0639-2","article-title":"Neurobiology of BDNF in fear memory, sensitivity to stress, and stress-related disorders","volume":"25","author":"Notaras","year":"2020","journal-title":"Mol Psychiatry"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/13.2.261","article-title":"The positive and negative syndrome scale (PANSS) for schizophrenia","volume":"13","author":"Kay","year":"1987","journal-title":"Schizophr Bull"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.151.8.1132","article-title":"Initial reliability and validity of a new retrospective measure of child abuse and neglect","volume":"151","author":"Bernstein","year":"1994","journal-title":"Am J Psychiatry"},{"key":"B25","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.comppsych.2016.09.009","article-title":"The relationship between self-reported childhood adversities, adulthood psychopathology and psychological stress markers in patients with schizophrenia","volume":"72","author":"Seidenfaden","year":"2017","journal-title":"Compr Psychiatry"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1177\/00048674231177223","article-title":"Childhood trauma is prevalent and associated with co-occurring depression, anxiety, mania and psychosis in young people attending Australian youth mental health services","volume":"57","author":"Bendall","year":"2023","journal-title":"Aust N Z J Psychiatry"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.schbul.a006933","article-title":"Increased early life stress and depressive symptoms in patients with comorbid substance abuse and schizophrenia","volume":"28","author":"Scheller-Gilkey","year":"2002","journal-title":"Schizophr Bull"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e0160","DOI":"10.1097\/MD.0000000000010160","article-title":"Childhood trauma interacted with BDNF Val66Met influence schizophrenic symptoms","volume":"97","author":"Bi","year":"2018","journal-title":"Med (Baltimore)"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.849227","article-title":"A polymorphism in the BDNF gene (rs11030101) is associated with negative symptoms in chinese han patients with schizophrenia","volume":"13","author":"Ping","year":"2022","journal-title":"Front Genet"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00274","article-title":"Childhood trauma in schizophrenia: Current findings and research perspectives","volume":"13","author":"Popovic","year":"2019","journal-title":"Front Neurosci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.07.073","article-title":"A BDNF-mediated push-pull plasticity mechanism for synaptic clustering","volume":"24","author":"Niculescu","year":"2018","journal-title":"Cell Rep"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-024-04357-4","article-title":"BDNF-trkB signaling in mitochondria: implications for neurodegenerative diseases","volume":"62","author":"Soman S","year":"2025","journal-title":"Mol Neurobiol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2017.10.018","article-title":"Epigenetics and gene expression profile in first-episode psychosis: The role of childhood trauma","volume":"83","author":"Tomassi","year":"2017","journal-title":"Neurosci Biobehav Rev"}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2026.1790184\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T06:58:23Z","timestamp":1772693903000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2026.1790184\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,5]]},"references-count":33,"alternative-id":["10.3389\/fpsyt.2026.1790184"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2026.1790184","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,5]]},"article-number":"1790184"}}