Striatal dopamine synthesis capacity and neuromelanin in the substantia nigra: A multimodal imaging study in schizophrenia and healthy controls

Abstract

[18F]F-DOPA PET is an established in-vivo method for investigating striatal dopamine synthesis capacity (DSC) and has demonstrated abnormalities in striatal DSC in schizophrenia. Neuromelanin-sensitive MRI (NM-MRI) is a promising, more accessible, tool that indirectly assesses dopaminergic functioning in the substantia nigra (SN). However, how [18F]F-DOPA PET and NM-MRI, as measures of nigrostriatal dopaminergic functioning, interrelate is still unknown. We hypothesize that NM-MRI signal in the SN is positively correlated with striatal DSC in patients with a schizophrenia spectrum disorder (SSD) and healthy controls (HC). We acquired NM-MRI and dynamic [18F]F-DOPA PET scans in 12 patients with SSD and 16 HC. In both groups, we assessed the correlation between nigral NM-MRI signal and DSC in the whole, associative, limbic, and sensorimotor striatum using voxelwise analyses within the SN. In HC, we found subsets of voxels within the SN where NM-MRI signal correlated negatively with DSC in the whole and limbic striatum. There were no significant associations between NM-MRI and DSC in the associative or sensorimotor striatum in HC and no significant associations in patients. These results show that NM-MRI signal and striatal DSC are negatively related in HC, but not in patients. Our results indicate that [18F]F-DOPA PET and NM-MRI reflect different aspects of dopaminergic functioning. The negative correlation in HC might be explained by vesicular monoamine transporter-2 (VMAT-2) functioning. A lack of a correlation in patients might be due to the small sample size, effects of symptom severity or antipsychotic medication.