Association between function and structure of the triple network and catechol-O-methyltransferase val158met polymorphism in the first episode schizophrenia

Abstract

The aberrant orchestration between the triple networks has been suggested as a backbone for some cognitive and clinical features of schizophrenia. The salience network (SN) plays a general role in switching between the central executive network (CEN) and the default mode network (DMN) mediated by dopamine activity. Whether the disease state and dopamine associated gene, catechol-O-methyltransferase (COMT), has an interactive effect on the function and structure of the triple network has not been understood. To this end, independent component analysis was used to identify the triple network. Then, cortical thickness and inter-regional resting state functional connectivity (RSFC) of the triple network was investigated in 55 first episode schizophrenia (FES) patients and 53 age-, gender-, and education- matched healthy controls. Finally, we investigated if there exist interactive effect between disease and COMT gene variation on the abnormal brain structure and function. Our results show that patients with FES exhibited significantly increased RSFC between anterior cingulate cortex and left dorsolateral prefrontal cortex (DLPFC) compared with healthy controls. The cortical thickness of the left DLPFC was thinner in FES patients. Significant interaction effect between COMT and disease was found in cortical thickness of the left DLPFC. Specifically, cortical thinning in this region was evident with the val homozygotes group of the COMT gene in FES. This findings suggest abnormal RSFC between CEN and SN and thinker cortical thickness in FES. And the val homozygotes of COMT may contribute to further cortical thinning in FES patients.

Keywords: Catechol-O-methyltransferase gene; Cortical thickness; First episode schizophrenia; Resting state functional connectivity; Triple network.