Resolving the heterogeneity of dopamine subsystems dysfunction in schizophrenia: a PET meta-analysis

Abstract

The “dopamine hypothesis” of schizophrenia suggests the imbalance of the brain dopamine system plays a crucial role in the development of this disorder. Although this hypothesis has been partly supported by early studies, the brain region-specific abnormalities of different dopamine subsystems, and the influential factors on the heterogeneity of dopamine dysfunction of schizophrenia are still unknown. To address these issues, we carried out random-effect meta-analyses by collecting 49 in vivo PET studies (692 patients and 730 controls). Patients exhibited significant regional and population heterogeneity in D2/3 receptor availability, primarily manifesting as a moderate increased in the striatum of only drug-off patients (Cohen’s d = 0.56, 95%CI [0.16; 0.97]), whereas only drug-on patients showed a large decrease in D2/3 receptor availability in the thalamus, limbic lobe, substantia nigra, and temporal lobe (Cohen’s d