Clinical and Genetic Analysis of Psychosis in Parkinson’s Disease

Article type: Research Article

Authors: Radojević, Branislava^{a; *} | Dragašević-Mišković, Nataša T.^b | Marjanović, Ana^b | Branković, Marija^b | Dobričić, Valerija^c | Milovanović, Andona^b | Tomić, Aleksandra^b | Svetel, Marina^b | Petrović, Igor^b | Jančić, Ivan^d | Stanisavljević, Dejana^e | Savić, Miroslav M.^d | Kostić, Vladimir S.^{b; *}

Affiliations: [a] Special Hospital for Cerebrovascular Disorders Saint Sava, Belgrade, Serbia | [b] Clinic of Neurology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia | [c] Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), Institutes of Neurogenetics & Cardiogenetics, University of Lübeck, Lübeck, Germany | [d] Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia | [e] Institute Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

Correspondence: [*] Correspondence to: Branislava Radojević, Special Hospital for Cerebrovascular Disorders Saint Sava, Belgrade, Serbia. Tel.: +381 69 1007230; E-mail: [email protected] and Vladimir S. Kostić, Clinic of Neurology, CCS, Faculty of Medicine, University of Belgrade, Serbia. Tel.: +381 66 8301263; E-mail: [email protected].

Abstract: Background:Recent studies explored polymorphisms of multiple genes as contributing to genetic susceptibility to psychosis in Parkinson’s disease (PDP). Objective:We aimed to examine the association of seven selected polymorphisms of genes related to dopamine pathways with PDP development. At the same time, demographic and clinical correlates of PDP were assessed. Methods:PD patients (n = 234), treated with levodopa for at least two years, were genotyped for the rs4680 in COMT, rs6277, rs1076560, and rs2283265 in DRD2, and rs1800497 and rs2734849 polymorphisms in ANKK1 genes. Also, variable number of tandem repeats polymorphism in the DAT gene was examined. Each patient underwent comprehensive neurological examination, assessment of psychosis, as defined by the NINDS/NIMH criteria, as well as screening of depression, anxiety, and cognitive status. Results:Diagnostic criteria for PDP were met by 101 (43.2%) patients. They had longer disease duration, were taking higher doses of dopaminergic agents, and had higher scores of the motor and non-motor scales than the non-PDP group. Multivariate regression analysis revealed LEDD≥900 mg, Unified Parkinson’s Disease Rating Scale III part score, the Hamilton Depression Rating Scale score≥7, the Hamilton Anxiety Rating Scale score > 14,and GG homozygotes of rs2734849 ANKK1 as independent predictors of the onset of PDP. Conclusion:Besides previous exposure to dopaminergic drugs, impairment of motor status, depression and anxiety, as well-established clinical risk factors for the development of PDP, GG rs2734849 ANKK1 could also be a contributing factor, which requires addressing by future longitudinal studies.

Keywords: COMT Val158Met , DAT1 SLC6A3 , DRD2 , genetic polymorphisms, hallucinations, Parkinson’s disease, psychosis

DOI: 10.3233/JPD-212716

Journal: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1973-1980, 2021