by Ela Doruk Korkmaz, Elif Everest

Objective: This narrative review examines clinical, genetic, and epidemiological evidence on schizophrenia (SCZ) to identify predictors of self-harm and violence, summarize genetic contributors to SCZ including pleiotropy and links between polygenic burden and negative/disorganized symptoms, and evaluate implications for early identification and predictive tools.
Method: We synthesized findings from large-scale genome-wide association studies, rare variant and polygenic risk research, gene–environment interplay, epidemiological studies on suicide and violence, and clinical trials of early-intervention programs for SCZ.
Results: SCZ involves a complex genetic architecture that includes hundreds of common risk variants and rarer coding and structural mutations. These genetic factors interact with environmental exposures, particularly childhood adversity and substance use, to shape vulnerability trajectories. Suicidality is a leading cause of excess mortality in SCZ, especially in early disease phases. Violence risk is modest overall but elevated in individuals with untreated psychosis or comorbid substance misuse. Emerging findings suggest that polygenic burden is linked to negative and disorganized symptoms, which in turn associate with worse clinical outcomes. Early, sustained, multicomponent intervention improves symptoms, functioning, and treatment adherence and may reduce self-harm and indirectly mitigate violence by addressing modifiable risk factors. Emerging machine learning models, though not yet widely validated, show promise in identifying individuals at higher risk of suicide or aggression by integrating clinical, demographic, and biological features.
Conclusions: Integrating genetic, clinical, and environmental data can enhance risk stratification and support precision prevention in SCZ. Polygenic risk scores are not yet clinically predictive alone but may add value when combined with symptom profiles and early-life adversity for early identification and detecting susceptibility to negative/disorganized symptoms. Near-term priorities include externally validating prediction tools, standardizing screening for trauma exposure and substance use within early-psychosis services to guide monitoring intensity and relapse-prevention planning, and scaling coordinated specialty care.

Key words: schizophrenia, polygenic risk, gene–environment interaction, suicide, violence, early intervention, precision psychiatry