The underlying neurobiological basis of gray matter volume alterations in schizophrenia with auditory verbal hallucinations: A meta-analytic investigation

Abstract

Schizophrenia patients with auditory verbal hallucinations (AVH) frequently exhibit brain structural alterations, particularly reductions in gray matter volume (GMV).Understanding the neurobiological mechanisms underlying the changes is essential for advancing treatment strategies. To address this, a meta-analysis was conducted to identify GMV changes in schizophrenia patients with AVH and their associations with gene expression and neurotransmitter receptor profiles. The results indicated significant GMV reductions in the left and the right insula, as well as the left anterior cingulate cortex. Ontology analysis of genes associated with GMV alternations revealed enrichment in biological processes related to ion transport and synaptic transmission. Hub genes from the KCN, SCN, GN, and PRK families, along with neurotransmitter receptors such as D2, VAChT, and mGluR5, showed significant correlations with GMV changes. Furthermore, multivariate linear regression analysis demonstrated that GNB2, GNB4, PRKCG, D2, and mGluR5 significantly predicted GMV alternations. These findings suggest that GMV reductions in schizophrenia with AVH are linked to disruptions in neurobiological processes involving specific genes and neurotransmitter systems, highlighting the potential targets for therapeutic intervention.