Opinion Review
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Sep 19, 2022; 12(9): 1127-1140
Published online Sep 19, 2022. doi: 10.5498/wjp.v12.i9.1127
Emerging role of psychosis in Parkinson's disease: From clinical relevance to molecular mechanisms
Shuo Zhang, Yan Ma
Shuo Zhang, Department of Neurology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
Yan Ma, Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
Author contributions: Zhang S and Ma Y conceived and designed the review; Zhang S wrote, reviewed, and edited the manuscript.
Supported by National Natural Science Foundation of China, No. 81801710; Technology Project Funds from Education Department of Liaoning Province of China; and 345 Talent Project, Shengjing Hospital of China Medical University.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yan Ma, MD, PhD, Associate Professor, Department of Ultrasound, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Shenyang 110004, Liaoning Province, China. mayan@cmu.edu.cn
Received: April 23, 2022
Peer-review started: April 23, 2022
First decision: May 30, 2022
Revised: June 12, 2022
Accepted: August 16, 2022
Article in press: August 16, 2022
Published online: September 19, 2022

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Psychosis is one of the common psychiatric presentations in the natural course of PD. PD psychosis is an important non-motor symptom, which is strongly correlated with a poor prognosis. Increasing attention is being given to PD psychosis. In this opinion review, we summarized and analyzed the identification, screening, epidemiology, mechanisms, risk factors, and therapeutic approaches of PD psychosis based on the current clinical evidence. PD psychosis tends to have a negative effect on patients' quality of life and increases the burden of family caregiving. Screening and identification in the early stage of disease is crucial for establishing tailored therapeutic strategies and predicting the long-term outcome. Development of PD psychosis is believed to involve a combination of exogenous and endogenous mechanisms including imbalance of neurotransmitters, structural and network changes, genetic profiles, cognitive impairment, and antiparkinsonian medications. The therapeutic strategy for PD psychosis includes reducing or ceasing the use of dopaminergic drug, antipsychotics, cholinesterase inhibitors, and non-pharmacological interventions. Ongoing clinical trials are expected to provide new insights for tailoring therapy for PD psychosis. Future research based on novel biomarkers and genetic factors may help inform individualized therapeutic strategies.

Keywords: Psychosis, Parkinson’s disease, Hallucinations, Delusions, Antipsychotics

Core Tip: Parkinson’s disease (PD) psychosis encompasses a variety of misperception symptoms including illusions, passage hallucinations, presence hallucinations, and delusions as well as formed visual hallucinations. PD psychosis is an independent predictor of mortality. A variety of risk factors for development of PD psychosis have been identified. Side effects of anti-Parkinsonism medications and patient-specific characteristics are both involved in the onset and progression of PD psychosis. Targeting the 5-hydroxytryptamine subtype 2A receptor is a promising pharmacological intervention.