Unraveling the Etiology of Schizophrenia: A Review of Genetic, Epigenetic, and Environmental Evidence

This review explores schizophrenia as a complex mental disorder that affects about ۱% of people worldwide and cannot be explained by a single cause. Instead, it is understood as the result of a continuous interaction between genetic vulnerability, environmental exposures, and epigenetic regulation.To gather evidence, the authors reviewed studies from major scientific databases such as PubMed, Scopus, Web of Science, and Google Scholar. The focus was on research from family and twin studies, genome-wide association studies (GWAS), and recent findings in epigenetics to better understand how biological and environmental factors come together in schizophrenia.The findings show that genetics play a major role, with heritability estimated at around ۸۰–۸۵%. Risk increases significantly among close relatives, and in identical twins the chance of both being affected approaches ۵۰%. Large-scale genetic studies have identified hundreds of risk loci, including single-nucleotide polymorphisms (SNPs) and copy number variations (CNVs), such as the well-known ۲۲q۱۱.۲ deletion, which is strongly linked to the disorder.However, genetic risk alone is not enough to explain schizophrenia. Environmental factors such as prenatal complications, maternal infections, childhood trauma, cannabis use, migration stress, and urban living conditions also contribute significantly. These factors can influence brain development through biological pathways involving inflammation and hormonal imbalance.Epigenetics provides the missing link between genes and environment. Mechanisms like DNA methylation, histone modification, and non-coding RNA activity can regulate gene expression without changing DNA itself. Environmental stressors may trigger these changes, altering the activity of genes involved in brain development and neurotransmission. Importantly, because epigenetic changes are potentially reversible, they offer promising targets for future treatments.In conclusion, schizophrenia emerges from the dynamic interaction of genetic susceptibility, environmental factors, and epigenetic regulation. Understanding this complicated model improves prediction, early detection, and opens new possibilities for more targeted and potentially reversible treatment approaches.

کلیدواژه ها:

schizophrenia ، epigenetics ، environmental factors ، DNA sequence variations