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

• Published in: Movement disorders Vol. 36; no. 12; pp. 2840 - 2852
• Main Authors: Onofrj, Marco, Di Iorio, Angelo, Carrarini, Claudia, Russo, Mirella, Franciotti, Raffaella, Espay, Alberto J., Boylan, Laura S., Taylor, John‐Paul, Di Giannantonio, Massimo, Martinotti, Giovanni, Valente, Enza M., Thomas, Astrid, Bonanni, Laura, Delli Pizzi, Stefano, Dono, Fedele, Sensi, StefanoL
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-12-2021; Wiley Subscription Services, Inc
• Subjects: Bipolar disorder; Bipolar Disorder - complications; Bipolar Disorder - genetics; bipolar spectrum disorders; Deep brain stimulation; Deep Brain Stimulation - adverse effects; Dementia disorders; Diagnosis; Electrical stimuli; Family medical history; Glucosylceramidase; Humans; Impulsive behavior; Mental disorders; Movement disorders; Mutation; Neurodegenerative diseases; Parkinson Disease - complications; Parkinson Disease - genetics; Parkinson's disease; Parkinson's disease; glucocerebrosidase mutation; parkin mutation; Patients; Phenotype; Phenotypes; Quality of Life; Regular Issue; Solitary tract nucleus; Subthalamic nucleus; subthalamic nucleus deep brain stimulation; Synuclein; subthalamic nucleus deep brain stimulation; Parkinson's disease; glucocerebrosidase mutation; parkin mutation; bipolar spectrum disorders
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.28745

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