Cognitive impairment in schizophrenia is associated with prefrontal–striatal functional hypoconnectivity and striatal dopaminergic abnormalities

Abstract

Background: A better understanding of the mechanisms underlying cognitive impairment in schizophrenia is imperative, as it causes poor functional outcomes and a lack of effective treatments. Aims: This study aimed to investigate the relationships of two proposed main pathophysiology of schizophrenia, altered prefrontal–striatal connectivity and the dopamine system, with cognitive impairment and their interactions. Methods: Thirty-three patients with schizophrenia and 27 healthy controls (HCs) who are right-handed and matched for age and sex were recruited. We evaluated their cognition, functional connectivity (FC) between the dorsolateral prefrontal cortex (DLPFC)/middle frontal gyrus (MiFG) and striatum, and the availability of striatal dopamine transporter (DAT) using a cognitive battery investigating attention, memory, and executive function, resting-state functional magnetic resonance imaging with group independent component analysis and single-photon emission computed tomography with 99mTc-TRODAT. Results: Patients with schizophrenia exhibited poorer cognitive performance, reduced FC between DLPFC/MiFG and the caudate nucleus (CN) or putamen, decreased DAT availability in the left CN, and decreased right–left DAT asymmetry in the CN compared to HCs. In patients with schizophrenia, altered imaging markers are associated with cognitive impairments, especially the relationship between DLPFC/MiFG–putamen FC and attention and between DAT asymmetry in the CN and executive function. Conclusions: This study is the first to demonstrate how prefrontal–striatal hypoconnectivity and altered striatal DAT markers are associated with different domains of cognitive impairment in schizophrenia. More research is needed to evaluate their complex relationships and potential therapeutic implications.