Parkinson disease psychosis: from phenomenology to neurobiological mechanisms.

Summary

Psychosis in Parkinson disease (PDP) includes illusions, hallucinations, and delusions that can appear even early in the disease. While once thought to be solely a side effect of dopaminergic drugs, evidence now shows PDP results from the disease's own brain changes combined with medication. Dysfunction in attentional control, sensory processing, limbic structures, the default mode network, and thalamocortical connections leads to incorrect categorization of stimuli and false percepts. This review covers recent clinical, neuroimaging, and neurochemical findings that may help identify psychotic phenomena early and guide new treatments.

Study at a glance

Abstract

Parkinson disease (PD) psychosis (PDP) is a spectrum of illusions, hallucinations and delusions that are associated with PD throughout its disease course. Psychotic phenomena can manifest from the earliest stages of PD and might follow a continuum from minor hallucinations to structured hallucinations and delusions. Initially, PDP was considered to be a complication associated with dopaminergic drug use. However, subsequent research has provided evidence that PDP arises from the progression of brain alterations caused by PD itself, coupled with the use of dopaminergic drugs. The combined dysfunction of attentional control systems, sensory processing, limbic structures, the default mode network and thalamocortical connections provides a conceptual framework to explain how new incoming stimuli are incorrectly categorized, and how aberrant hierarchical predictive processing can produce false percepts that intrude into the stream of consciousness. The past decade has seen the publication of new data on the phenomenology and neurobiological basis of PDP from the initial stages of the disease, as well as the neurotransmitter systems involved in PDP initiation and progression. In this Review, we discuss the latest clinical, neuroimaging and neurochemical evidence that could aid early identification of psychotic phenomena in PD and inform the discovery of new therapeutic targets and strategies.