Abstract
PD comorbid with schizophrenia has been considered rare because these diseases associate with opposite alterations in the brain dopamine system. The objective of this study was to investigate the risk of PD after a diagnosis of a schizophrenia spectrum disorder. Regionally, this was a retrospective record-based case-control study. The cohort included 3045 PD patients treated 2004-2019 in southwestern Finland. Nationally this was a nested case-control study using registers to examine Finnish patients who received a clinically confirmed PD diagnosis 1996-2015 (n=22,189). PD patients with previously diagnosed schizophrenia spectrum disorder (separate analysis for schizophrenia) were included. Comparable non-PD control groups were derived from both data sets. All PD diagnoses were based on individual clinical examinations by certified neurologists. In PD patients, the prevalence of earlier schizophrenia spectrum disorder was 0.76% in regional data and 1.50% in nationwide data. In age-matched controls, the prevalence in the regional and national data was 0.16% and 1.31%, respectively. The odds ratio for PD after schizophrenia spectrum disorder diagnosis was 4.63 (95% CI, 1.76-12.19; P < 0.01) in the regional data and 1.17 (95% CI, 1.04-1.31; P < 0.01) in the national data. Schizophrenia spectrum disorder increases the risk of PD later in life. This association was observed in both individual patient data and nationwide register data. Therefore, despite the opposite dopaminergic disease mechanisms, schizophrenia spectrum disorder increases rather than decreases the risk of PD. The increased PD risk could be related to risk-altering effects of dopamine receptor antagonists or to the increased vulnerability of the dopamine system induced by illness phase-dependent dopamine dysregulation in schizophrenia/schizophrenia spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Highlights
In part I of the present study, case by case we investigated individual patients who first developed spectrum disorder (SCD) and later were diagnosed with Parkinson’s disease (PD), and we took into account misdiagnoses and drug treatments
After identifying all patients with comorbidities, we manually reviewed each patient’s electronic health records (EHRs) to exclude diagnosis coding errors and to confirm that the diagnoses were based on valid clinical symptoms and signs of PD and SCD
The results of this study indicate that SCD increases the risk of PD later in life
Summary
The study population consisted of all PD patients who were treated between January 1, 2004, and July 31, 2019, at Turku University Hospital district in southwestern Finland. After identifying all patients with comorbidities, we manually reviewed each patient’s electronic health records (EHRs) to exclude diagnosis coding errors and to confirm that the diagnoses were based on valid clinical symptoms and signs of PD and SCD. The age limit of 60 years was used to exclude very-late-onset SCD because psychotic symptoms among aged people are more likely to be associated with a prodromal phase of another neurodegenerative disease, such as Alzheimer’s disease, frontotemporal degeneration, or Lewy body dementia (very late onset: onset after age 60).[38] To verify the results, we performed an additional analysis using the same exclusion criteria otherwise but excluding patients diagnosed with SCD/SCZ after age 45 years. Because the study did not involve patient contacts, approval from the Ethics Committee was not required
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