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

Abstract

AbstractPURPOSEAberrant dopaminergic function is linked with motor, psychotic, and affective symptoms, but studies have typically compared a single patient group with healthy controls. METHODS: 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 Parkinson’s disease (PD), antipsychotic-naïve schizophrenia, severe violent behavior, pathological gambling, depression, and overweight. We analyzed regional group differences in D2R availability. We also analyzed the interregional correlation in D2R availability within each group. RESULTS: Subjects with PD showed the clearest decline in D2R availability. Overall, the groups showed high interregional correlation in D2R availability, while this pattern was weaker in violent offenders. Subjects with schizophrenia, pathological gambling, depression, or overweight did not show clear changes in either the regional receptor availability or the interregional correlation. CONCLUSION: 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 violence.HighlightsWe compared human striatal and thalamic type 2 dopamine receptor (D2R) availability between healthy controls, and subjects with Parkinson’s disease (PD), antipsychotic-naïve 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.Subjects with severe violent behavior had decreased correlation between the striatal and thalamic D2R availability.Altered regional D2R availability in the striatum and thalamus is linked with motor disorders, while lowered interregional connectivity in D2R might relate to violence.KEY POINTSQUESTION: Are there differences in the striatal (caudate nucleus, nucleus accumbens, and putamen), and thalamic D2R availability in a sample including healthy controls, and subjects with Parkinson’s disease, antipsychotic-naïve schizophrenia, severe violent behavior, pathological gambling, depression, and overweight?PERTINENT FINDINGS: Based on this register-based study of a large historical sample (n=437), Parkinson’s disease links to changes in the regional receptor availability, while in severe violent behavior, the correlation between regional receptor availabilities might be lowered. No clear receptor changes were observed in overweight.IMPLICATIONS FOR PATIENT CARE: Based on our data of striatal and thalamic type 2 dopamine receptors, region-specific changes are linked with motor disorders, while lowered between-region correlation might relate to violence.