Cell-Type Specific Reductions in Interneuron Gene Expression within Subregions of the Anterior and Posterior Cingulate Gyrus of Schizophrenia and Bipolar Disorder Subjects

Abstract

AbstractSchizophrenia (SZ) and bipolar disorder (BP) patients share overlapping and distinct neurocognitive deficits. Neuroimaging of these patients and postmortem gene expression analyses suggest that compromised cingulate gyrus GABA-ergic interneurons may contribute to cognitive impairments in SZ and BP. Therefore, we investigated potential gene expression signatures for SZ and BP using interneuron cell-type specific markers including glutamic acid decarboxylase (GAD67), parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP) within cingulate Brodmann’s areas (BA). We report reduced GAD67 mRNA in anterior midcingulate cortex (aMCC) of SZ and BP subjects with BA24c’ being most dysregulated across disorders, demonstrating reduced PV (SZ), SST (BP), and VIP mRNA (SZ and BP). Dorsal posterior cingulate (dPCC) displayed decreased SST (BP) whereas retrosplenial cortex (RSC) showed reduced PV (SZ and BP) and SST mRNA (BP). Our results show shared and unique transcription signatures of two disorders in specific cingulate gyrus regions and cell types. SZ and BP show a similar profile of aMCC gene expression reductions suggesting subregional dysregulation within areas associated with error/action monitoring and the saliency network. In dPCC/RSC, transcriptional changes are associated with disease-specific gene/subregion signatures, possibly underlying differential effects on allocation of attentional resources and visuospatial memory processing unique to each disorder.