Preexisting Bipolar Disorder Influences the Subsequent Phenotype of Parkinson's Disease

Background: Patients with bipolar spectrum disorders (BSDs) exhibit an increased risk of Parkinson's disease (PD). Objective: The aim is to investigate whether a previous diagnosis of BSDs influences the phenotype of PD. Methods: Of 2660 PD patients followed for at least 6 years (6–27), 250 (BSD-PD) had BSDs, 6–20 years before PD diagnosis; 48%–43% had a PD or BSD family history, and 34 carried glucocerebrosidase (GBA) and Parkin (PRKN) mutations. The cohort was split into a subset of 213 BSD-PD patients, compared with 426 matched PD patients without BSDs, and a subset of 34 BSD-PD and 79 PD patients carrying GBA or PRKN mutations. Carriers of mutations absent in BSD-PD patients and of synuclein triplication were excluded. Structured clinical interviews and mood disorder questionnaires assessed BSDs. Linear mixed models evaluated the assessment scales over time. Thirteen BSD-PD patients underwent subthalamic nucleus deep brain stimulation (STN-DBS) and were compared with 27 matched STN-DBS-treated PD patients. Results: Compared to PD patients, BSD-PD showed (1) higher frequency of family history of PD (odds ratio [OR] 3.31; 2.32–4.71) and BSDs (OR 6.20; 4.11–9.35) 5); (2) higher incidence of impulse control disorders (hazard ratio [HR] 5.95, 3.89–9.09); (3) higher frequency of functional disorders occurring before PD therapy (HR, 5.67, 3.95–8.15); (4) earlier occurrence of delusions or mild dementia (HR, 7.70, 5.55–10.69; HR, 1.43, 1.16–1.75); and (5) earlier mortality (1.48; 1.11–1.97). Genetic BSD-PD subjects exhibited clinical features indistinguishable from nongenetic BSD-PD subjects. STN-DBS-treated BSD-PD patients showed no improvements in quality of life compared to the control group. Conclusions: BSDs as a prodrome to PD unfavorably shape their course and are associated with detrimental neuropsychiatric features and treatment outcomes. © 2021 International Parkinson and Movement Disorder Society.