Neural substrates in Parkinson’s Disease psychosis: A systematic review

Neural underpinnings of Parkinson’s Disease psychosis (PDP) remain unclear to this day with relatively few studies and reviews available. Using a systematic review approach, here we aimed to qualitatively synthesize evidence from studies investigating PD psychosis-specific alterations in brain structure, function or chemistry using different neuroimaging modalities. PubMed, Web of Science and Embase databases were searched for fMRI, rsfMRI, DTI, PET, and SPECT studies comparing PDP patients with PD patients without psychosis (PDnP). We report findings from 18 studies (291 PDP patients, mean age ± SD = 68.65 ± 3.76 years; 48.5% males; 433 PDnP patients, mean age ± SD = 66.97 ± 3.80 years; 52% males). Qualitative synthesis revealed widespread patterns of altered brain function across task-based and resting-state fMRI studies in PDP compared to PDnP patients. Similarly, white matter abnormalities were reported in parietal, temporal, and occipital regions. Hypometabolism and reduced dopamine transporter binding were also reported whole brain and in subcortical areas. This suggests extensive alterations affecting regions involved in high order visual processing and attentional networks. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement SB, LV, DA, DF, KRC and CB are in receipt of funding from Parkinson's UK for a clinical trial in Parkinson's disease psychosis. SP PhD studentship is funded by Parkinson's UK. SB is supported by grants from the National Institute of Health Research (NIHR) Efficacy and Mechanism Evaluation scheme and Parkinson's UK. SB has participated in advisory boards for or received honoraria as a speaker from Reckitt Benckiser, EmpowerPharm/SanteCannabis and Britannia Pharmaceuticals. All of these honoraria were received as contributions toward research support through King's College London, and not personally. SB also has collaborated with Beckley Canopy Therapeutics/ Canopy Growth (investigator-initiated research) wherein they supplied study drug for free for charity (Parkinson's UK) and NIHR (BRC) funded research. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. LV has collaborated with Beckley Canopy Therapeutics/ Canopy Growth (investigator-initiated research) wherein they supplied study drug for free for charity (Parkinson's UK) and NIHR (BRC) funded research. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This publication is a systematic review, and as such it includes data that have already been published. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data availability statement: This publication is a systematic review, and as such it includes data that have already been published. The data that support the findings of this study are available from the corresponding author upon request.