VTA-insula Connectivity and Avolition in Subjects with Schizophrenia

Abstract

Introduction

Avolition represents an important domain of negative symptoms in schizophrenia with a strong impact on functional outcome. Primary and persistent avolition is refractory to available pharmacological and psychological treatments. A better understanding of its pathophysiological mechanisms is fundamental to promote development of new treatments. Recent models of avolition converge on dopaminergic circuits involved in motivation and its translation in goal-directed behavior. Deficits in task-related activation or connectivity within mesolimbic and mesocortical dopamine circuits were reported in schizophrenia but the relationship with avolition was not fully established.

Aims

The present study aimed to investigate resting-state functional connectivity (RS-FC) within the motivation circuits in schizophrenia patients and its relationships with primary and persistent avolition.

Methods

RS-FC, using VTA as a seed region, was investigated in 22 healthy controls (HC) and in 26 schizophrenia patients (SCZ) divided in high (HA) and low avolition (LA) subgroups. Avolition was assessed using the Schedule for the Deficit Syndrome.

Results

HA, in comparison to LA and HC, showed significantly reduced RS-FC with the right ventrolateral prefrontal cortex (R-VLPFC), right insula (R-INS) and right lateral occipital cortex (R-LOC). The RS-FC of these regions was negatively correlated to avolition.

Conclusions

Our findings demonstrate that avolition in schizophrenia is linked to dysconnection of VTA from key cortical regions involved in retrieval of outcome values of instrumental actions to motivate behavior.

Disclosure of interest

AM received honoraria or advisory board/consulting fees from the following companies: Janssen Pharmaceuticals, Otsuka, Pfizer and Pierre Fabre. SG received honoraria or advisory board/consulting fees from the following companies: Lundbeck, Janssen Pharmaceuticals, Hoffman-La Roche, Angelini-Acraf, Otsuka, Pierre Fabre and Gedeon-Richter. All other Authors declare no potential conflict of interest.