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

Abstract

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 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; glucocerebrosidase mutation; parkin mutation; bipolar spectrum disorders; subthalamic nucleus deep brain stimulation.

FIG 1

Flowchart and design of the study. The flowchart depicts the cohort's enrollment and the subsequent distinction of the main groups for cross‐sectional (light blue) and longitudinal (green) analyses. The picture also identifies the genetic subsets of Parkinson's disease (PD)‐related genetic mutations. BSD‐PD, bipolar spectrum disorder‐Parkinson's disease; GBA, β‐glucocerebrosidase‐related PD; PRKN, Parkin 2‐related PD; SNCA, α‐synuclein triplication. [Color figure can be viewed at wileyonlinelibrary.com]