Pathways to schizophrenia: Divergent effects of childhood trauma and polygenic risk on cognition and subcortical dynamics
- 1Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital, Central South University, China
- 2Department of Psychiatry, McGill University, Montreal, Canada
- 3Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Canada
Abstract
Background: Schizophrenia is often a persistent mental illness characterized by cognitive deficits and altered brain network dynamics especially affecting the cortico-subcortical salience processing system. Childhood trauma has been implicated in mechanisms contributing to schizophrenia, but the role of genetic vulnerability remains unclear.
Methods: A total of 164 schizophrenia patients and 114 healthy controls were included. First, a matched subsample of 117 patients (76 with and 41 without childhood trauma), and 59 healthy controls were compared on polygenic risk scores for schizophrenia (SczPRS). SczPRS was then correlated with neurocognitive performance using a comprehensive cognitive battery (n = 147 patients) and brain-wide static and dynamic functional connectivity (sFC and dFC) using resting-state fMRI (n = 117 patients). Patients were also stratified into high-SczPRS and low-SczPRS (n = 25 each) subgroups.
Results: Patients with childhood trauma had significantly lower SczPRS than those without. Higher Childhood Trauma Questionnaire (CTQ) scores related to lower cognitive PC score (r = −0.282, p < 0.001), but CTQ did not affect brain-wide dysconnectivity or subcortical/salience system among patients. Patients with the highest SczPRS showed lower dFC between the cingulo-opercular network and subcortical networks (F = 7.949, p = 0.007), but SczPRS did not affect cognitive performance.
Conclusions: Our findings reveal distinct effects of childhood trauma and polygenic risk in the neural and cognitive substrates of schizophrenia. Childhood trauma relates to poor cognitive function, while polygenic risk primarily affects salience/subcortical network dynamics. These patterns indicate that in genetically predisposed individuals who experience childhood trauma, a “double mechanistic hit” may influence the schizophrenia phenotype.
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BibTeX
@article{huang2026pathways,
title = {{Pathways to schizophrenia: Divergent effects of childhood trauma and polygenic risk on cognition and subcortical dynamics}},
author = {Danqing Huang and Yicheng Long and Zhening Liu and Wenjian Tan and Xiawei Liu and Yunzhi Pan and Feiwen Wang and Lena Palaniyappan},
journal = {European Psychiatry},
year = {2026},
month = jul,
doi = {10.1192/j.eurpsy.2026.12246},
url = {https://doi.org/10.1192/j.eurpsy.2026.12246},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pathways to schizophrenia: Divergent effects of childhood trauma and polygenic risk on cognition and subcortical dynamics
AU - Danqing Huang
AU - Yicheng Long
AU - Zhening Liu
AU - Wenjian Tan
AU - Xiawei Liu
AU - Yunzhi Pan
AU - Feiwen Wang
AU - Lena Palaniyappan
PY - 2026
DA - 2026/07/29
JO - European Psychiatry
DO - 10.1192/j.eurpsy.2026.12246
UR - https://doi.org/10.1192/j.eurpsy.2026.12246
AB - Background: Schizophrenia is often a persistent mental illness characterized by cognitive deficits and altered brain network dynamics especially affecting the cortico-subcortical salience processing system. Childhood trauma has been implicated in mechanisms contributing to schizophrenia, but the role of genetic vulnerability remains unclear. Methods: A total of 164 schizophrenia patients and 114 healthy controls were included. First, a matched subsample of 117 patients (76 with and 41 without childhood trauma), and 59 healthy controls were compared on polygenic risk scores for schizophrenia (SczPRS). SczPRS was then correlated with neurocognitive performance using a comprehensive cognitive battery (n = 147 patients) and brain-wide static and dynamic functional connectivity (sFC and dFC) using resting-state fMRI (n = 117 patients). Patients were also stratified into high-SczPRS and low-SczPRS (n = 25 each) subgroups. Results: Patients with childhood trauma had significantly lower SczPRS than those without. Higher Childhood Trauma Questionnaire (CTQ) scores related to lower cognitive PC score (r = −0.282, p < 0.001), but CTQ did not affect brain-wide dysconnectivity or subcortical/salience system among patients. Patients with the highest SczPRS showed lower dFC between the cingulo-opercular network and subcortical networks (F = 7.949, p = 0.007), but SczPRS did not affect cognitive performance. Conclusions: Our findings reveal distinct effects of childhood trauma and polygenic risk in the neural and cognitive substrates of schizophrenia. Childhood trauma relates to poor cognitive function, while polygenic risk primarily affects salience/subcortical network dynamics. These patterns indicate that in genetically predisposed individuals who experience childhood trauma, a “double mechanistic hit” may influence the schizophrenia phenotype.
SN - 0924-9338
SN - 1778-3585
ER -