Altered connectivity between striatal and extrastriatal regions in patients with schizophrenia on maintenance antipsychotics: an [F-18]fallypride PET and functional MRI study

Abstract

In addition to probing regional differences in receptor availability, molecular positron emission tomography (PET) is proving useful for investigating perturbations in neurotransmitter networks using interregional correlation analyses. In a multi-modal imaging study, we examined interregional correlationsof dopamine D-2/3 receptor availability between striatal and extrastriatal regions using [F-18]fallypride high-resolution PET in 11 patients with schizophrenia receiving low-dose maintenance atypical antipsychotics and 14 healthy control subjects, and investigated resting-state functional connectivity in the same subjects using seed-based functional magnetic resonance imaging (fMRI) analysis. In the healthy control group, there were no significant correlations of [F-18]fallypride binding potential (BPND) between striatal regions and any cortical areas, whereas the patient group showed significant and widespread inter-correlations. Correlations between BPND in striatum, amygdala and insula with cortex were significantly higher in patients than in controls. In seed-based resting-state fMRI analysis, the healthy controls revealed positive and negative functional connectivity patterns, while patients exhibited a pattern of exclusively positive connectivity. Functional connectivity was significantly higher between striatal regions and extrastriatal areas including cortical regions in patients compared to controls. In this first such report, molecular and functional connectivity between striatal and extrastriatal regions was primarily characterized by increased interregional relationships in treated patients with schizophrenia. The results suggest that the spatial organization of D-2/3 receptor availability and related functional connectivity are significantly perturbed in stable outpatients on maintenance antipsychotics. Future studies should include antipsychotic-naive patients to determine if these relationships are illness-related characteristics, or arising due to chronic antipsychotic treatment.