Risk of Schizophrenia Spectrum Disorders Following Parkinson’s Disease: A Nationwide Population-Based Cohort Study

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OBJECTIVE: Psychotic symptoms are common in Parkinson's disease (PD), yet it remains unclear whether these manifestations reflect transient, medication-related phenomena or an increased risk of clinically diagnosed schizophrenia spectrum disorders (SSD). This study aimed to evaluate the long-term risk of incident SSD following PD using a nationwide population-based cohort and to assess whether this risk varies across demographic, lifestyle, and metabolic subgroups. METHODS: We conducted a retrospective cohort study using the Korean National Health Insurance Service database from 2012 to 2023. Individuals newly diagnosed with PD were identified using repeated International Classification of Diseases, 10th Revision (ICD-10) codes and matched 1:5 with controls using propensity scores. Incident SSD was defined by repeated ICD-10 diagnoses. Incidence rates, incidence rate ratios, Kaplan-Meier curves, and Cox proportional hazards models were used. RESULTS: Among 5,110 patients with PD and 25,550 matched controls, 128 and 177 incident cases of SSD were identified, respectively. The incidence rate of SSD was higher in the PD group than in controls (7.09 vs. 1.75 per 1,000 person-years), yielding an IRR of 4.06 (95% confidence interval [CI], 3.23-5.09). PD was associated with an increased risk of SSD after multivariable adjustment (adjusted hazard ratio 4.90; 95% CI, 3.52-6.81), with particularly elevated risk among individuals younger than 60 years. CONCLUSION: PD was associated with a substantially increased long-term risk of SSD. These findings suggest that psychotic manifestations following PD may reflect persistent psychiatric morbidity rather than transient symptoms alone.

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