Resting-state Functional Connectivity of the Ventral Tegmental Area and Negative Symptom Domains in Subjects with Schizophrenia

Introduction Negative symptoms (NS) represent a core aspect of schizophrenia with a huge impact on real life functioning. Dysfunctions within the dopaminergic cortico-striatal circuits have been documented in subjects with schizophrenia (SCZ) and hypothesized as possible neurobiological mechanisms underlying some domains of NS. Objectives We investigated relationships between the resting-state functional connectivity (RS-FC) of the ventro-tegmental area (VTA) and NS. Methods Resting-state fMRI data were recorded in 35 SCZ, recruited within the Italian Network for Research on Psychoses. We performed partial correlations between RS-FC and NS (evaluated with the Brief Negative Symptom Scale) controlling for possible sources of secondary negative symptoms. Results We found that the experiential domain correlated with the RS-FC of the VTA with the left ventro-lateral prefrontal cortex (lVLPFC) (r=0.372, p=0.039), while the Expressive deficit domain correlated with the RS-FC of the VTA with the left dorso-lateral prefrontal cortex (lDLPFC) (r= 0.470, p .008). Looking at subdomains, only the avolition (r= 0.418, p=0.019) and the blunted affect (r= 0.465, p=.008) showed the same correlations of the domains to which they belong. Conclusions According to our findings, separate dysfunctional neuronal circuits could underpin distinct negative symptom subdomains. A better understanding of neurobiological dysfunctions underlying NS could help to design new treatments, targeting different NS subdomains.