Review Article

Psychosis in Parkinson’s disease and parkinsonism in antipsychotic-naive schizophrenia spectrum psychosis: clinical, nosological and pathobiological challenges

Authors: John L. Waddington1
1 School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, 2 Ireland and 2Jiangsu Key Laboratory of Translational Research & Therapy for Neuro-Psychiatric Disorders and Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
Correspondence to: John L. Waddington:,
DOI: 10.1038/s41401-020-0373-y
Received: 17 October 2019
Accepted: 27 January 2020
Advance online: 5 March 2020


Following the formulation of operational criteria for the diagnosis of psychosis in Parkinson’s disease, a neurodegenerative disorder, the past decade has seen increasing interest in such nonmotor psychopathology that appears to be independent of dopaminergic therapy. Similarly, there has been a resurgence of interest in motor aspects of the neurodevelopmental disorder of schizophrenia, including spontaneous parkinsonism that appears to be independent of antipsychotic treatment. This review first addresses the clinical and nosological challenges of these superficially paradoxical insights and then considers pathobiological challenges. It proposes that diverse modes of disturbance to one or more element(s) in a cortical-striatal-thalamocortical neuronal network, whether neurodegenerative or neurodevelopmental, can result in movement disorder, psychosis or both. It then proposes that time- and site-dependent dysfunction in such a neuronal network may be a generic substrate for the emergence of psychosis not only in Parkinson’s disease and schizophrenia-spectrum disorders but also in other neuropsychiatric disorders in which psychosis, and sometimes movement disorders, can be encountered; these include substance abuse, cerebrovascular disease, cerebral trauma, cerebral neoplasia, epilepsy, Huntington’s disease, frontotemporal dementia, Alzheimer’s disease and multiple sclerosis.
Keywords: Parkinson’s disease; psychosis; schizophrenia; parkinsonian movement disorder; cortical-striatal-thalamocortical network; neuronal network dysfunction

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