Increased risk of bipolar disorder following Parkinson's disease: A nationwide population-based cohort study

Parkinson's disease (PD) is increasingly recognized as a multisystem disorder with significant neuropsychiatric involvement. However, the temporal association between PD and bipolar disorder (BD) remains unclear.

We conducted a nationwide retrospective cohort study using the Korean National Health Insurance Service database (2012-2023). Incident PD cases were identified with a 3-year washout period and matched to controls (1:5) using propensity scores. The primary outcome was incident BD based on repeated psychiatrist-assigned diagnoses. Incidence rates (IRs), incidence rate ratios (IRRs), and adjusted hazard ratios (aHRs) were estimated using time-stratified Cox models.

A total of 5158 PD patients and 25,790 matched controls were included. BD incidence was higher in the PD group (13.01 vs. 3.48 per 1000 person-years; IRR, 3.74; 95% CI, 3.18-4.41). The risk was highest within 0-3 years (aHR, 3.55; 95% CI, 2.75-4.59), decreased during 3-6 years (aHR, 2.12; 95% CI, 1.51-2.98), and increased again during 6-9 years (aHR, 2.62; 95% CI, 1.48-4.66), with consistent findings across subgroups.

PD was associated with an increased risk of BD, with the highest risk observed during the first 3 years after PD diagnosis and a sustained elevation thereafter. These findings support the need for early screening and ongoing psychiatric monitoring in patients with PD.