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

Abstract

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.