Purpose The purpose of this study was to investigate the effects of ageing, sex and body mass index (BMI) on translocator protein (TSPO) availability in healthy subjects using positron emission tomography (PET) and the radioligand [ 11 C]PBR28. Methods [ 11 C]PBR28 data from 140 healthy volunteers (72 males and 68 females; N = 78 with HAB and N = 62 MAB genotype; age range 19–80 years; BMI range 17.6–36.9) were acquired with High Resolution Research Tomograph at three centres: Karolinska Institutet (N = 53), Turku PET centre (N = 62) and Yale University PET Center (N = 25). The total volume of distribution (V T ) was estimated in global grey matter, frontal, temporal, occipital and parietal cortices, hippocampus and thalamus using multilinear analysis 1. The effects of age, BMI and sex on TSPO availability were investigated using linear mixed effects model, with TSPO genotype and PET centre specified as random intercepts. Results There were significant positive correlations between age and V T in the frontal and temporal cortex. BMI showed a significant negative correlation with V T in all regions. Additionally, significant differences between males and females were observed in all regions, with females showing higher V T . A subgroup analysis revealed a positive correlation between V T and age in all regions in male subjects, whereas age showed no effect on TSPO levels in female subjects. Conclusion These findings provide evidence that individual biological properties may contribute significantly to the high variation shown in TSPO binding estimates, and suggest that age, BMI and sex can be confounding factors in clinical studies. Electronic supplementary material The online version of this article (10.1007/s00259-019-04403-7) contains supplementary material, which is available to authorized users.

A BS TRACT: Background: 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. Methods: Regionally, this was a retrospective recordbased 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 1996PD diagnosis -2015. 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. Results: 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. Conclusions: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 riskaltering 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.