DefinePK

Abstract

Schizophrenia is a complex neuropsychiatric disorder with a multifactorial etiology involving both genetic and environmental risk factors. This study aimed to investigate the interaction between genetic predisposition—measured through polygenic risk scores (PRS) and copy number variations (CNVs)—and key environmental exposures in the development of schizophrenia. A total of 150 patients diagnosed with schizophrenia and 150 matched healthy controls were evaluated through genome-wide genotyping, CNV profiling, and structured assessments of environmental risk factors, including childhood trauma, prenatal infection exposure, urbanicity, social support, and cannabis use. A clear rise in polygenic risk scores was observed in individuals with a schizophrenia diagnosis (mean z-score = 1.35 versus -0.12 in controls) as well as an increase in the frequency of copy number variations involving neurodevelopmental genes such as NRXN1, GRIN2A,  Environmental assessments indicated significantly greater trauma scores, higher cannabis use (68% vs. 35%), more urban exposure, poorer social support, and a greater number of prenatal infections among schizophrenics than controls.  Genomic analysis of the gene-environment interaction showed that schizophrenia is increased by high PRS, CNVs, childhood traumatic stressors, the use of cannabis, and urban dwelling, with an odds ratio interval of 2.4–3.7, synergistically.  These findings substantiate the urgent need for integrated risk models that involve environmental and genetic data to allow early identification of risk individuals.  By accentuating the part played by genetic predisposition and modifiable environmental factors, the findings propose a change towards individualized preventive and treatment pathways in psychiatry.  Through showing how it is important to observe biological as well as psychological variables, along with social aspects, this research supports the application of the biopsychosocial approach to mental health studies and intervention and provides new insights on schizophrenia.