De Maeyer, S. | Search bioRxiv

bioRxiv2023

Alterations in type 2 dopamine receptors across neuropsychiatric conditions: A large-scale PET cohort

Aberrant dopaminergic function is linked with motor, psychotic, and affective symptoms, but studies have typically compared a single patient group with healthy controls. Here, we investigated the variation in striatal (caudate nucleus, nucleus accumbens, and putamen) and thalamic type 2 dopamine receptor (D2R) availability using [11C]raclopride positron emission tomography (PET) data from a large sample of 437 humans including healthy controls and subjects with Parkinsons disease (PD), antipsychotic-naive schizophrenia, severe violent behavior, pathological gambling, depression, and overweight. We analyzed regional group differences in D2R availability using Bayesian mixed effects modeling. Subjects with PD showed clearest decline in D2R availability. Healthy controls and patients with PD showed high interregional correlation of D2R availability, while this pattern was weaker in schizophrenia, severe violent behavior, and depression. Subjects with pathological gambling or overweight did not show clear changes in either the regional receptor availability or the interregional correlation. We conclude that the dopaminergic changes in neuropsychiatric conditions might not only affect the overall receptor availability but also the connectivity between the regions. The region-specific receptor availability more profoundly links to the motor symptoms, while the between-region connectivity might be disrupted in affective symptoms. HighlightsWe compared human striatal and thalamic type 2 dopamine receptor (D2R) availability between healthy controls, and subjects with Parkinsons disease (PD), antipsychotic-naive schizophrenia, severe violent behavior, pathological gambling, depression, and overweight. We present the mean brain maps of group specific D2R availabilities in NeuroVault (https://neurovault.org; https://identifiers.org/neurovault.collection:12799). Dopamine type 2 receptor availability is lowered in PD in caudate nucleus, nucleus accumbens and thalamus. Antipsychotic-naive schizophrenia, severe violent behavior, and depression were associated with decreased connectivity between the striatal and thalamic D2R availability. Altered regional D2R availability in the striatum and thalamus is linked with motor disorders, while lowered regional connectivity in D2R might relate to affective disturbance.

neuroscience↗

bioRxiv2022

Brain glucose metabolism and ageing: A 5-year longitudinal study in a large PET cohort

BackgroundAgeing and clinical factors impact brain glucose metabolism. However, there is a substantial variation of the reported effects on brain glucose metabolism across studies due to the limited statistical power and cross-sectional study designs. MethodsWe retrospectively analyzed data from 441 healthy males (mean 42.8, range 38-50 years) who underwent health check-up program twice at baseline and 5-year follow-up. Health check-up program included 1) brain 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET), 2) anthropometric and body composition measurements, 3) blood samples, and 4) questionnaires for stress and depression. After spatial normalization of brain FDG PET scans, standardized uptake value ratio (SUVR) was measured from 12 region-of-interests. We used hierarchical clustering analysis to reduce their dimensionality before the Bayesian hierarchical modelling. Five clusters were established for predicting regional SUVR; 1) metabolic cluster (body mass index, waist-to-hip ratio, fat percentage, muscle percentage, homeostatic model assessment index-insulin resistance), 2) blood pressure (systolic, diastolic), 3) glucose (fasting plasma glucose level, HbA1c), 4): psychological cluster (stress, depression), and 5) heart rate. The effects of clinical variable clusters on regional SUVR were investigated using Bayesian hierarchical modelling with brms that applies the Markov-Chain Monte Carlo sampling tools. ResultsAll the clinical variables except depression changed during the 5-year follow-up. SUVR decreased in caudate, cingulate, frontal lobe and parietal lobe and increased in cerebellum, hippocampus, occipital lobe, pallidum, putamen, temporal lobe and thalamus. SUVRs of thalamus, pallidum, hippocampus, putamen and parietal lobe were negatively associated with metabolic cluster and the effects of glucose on SUVRs varied across regions. SUVRs of thalamus, hippocampus, cingulate, cerebellum increased and those with occipital lobe decreased with heart rate. The effects of blood pressure and psychological cluster markedly overlapped with zero across regions. ConclusionRegionally selective decline in brain glucose utilization begins already in the middle age, while individual differences in brain glucose metabolism remain stable. In addition to ageing, brain glucose utilization is also associated with metabolic cluster, blood glucose levels and heart rate. These effects are also consistent over the studied period of 5 years in the middle adulthood.

neuroscience↗