Relationship between somatostatin and death receptor expression in the orbital frontal cortex in schizophrenia: a postmortem brain mRNA study.

BACKGROUND

Recently, we provided evidence showing reductions in GAD67 and Dlx mRNAs in the orbital frontal cortex (OFC) in schizophrenia. It is unknown whether these reductions relate mainly to somatostatin (SST) or parvalbumin (PV) mRNA expression changes, and/or whether these reductions are related to decreased SST mRNA+ interneuron density.

AIMS

To determine whether inhibitory interneuron deficits in the OFC from people with schizophrenia are greatest for SST or PV mRNAs, and whether any such deficits relate to mRNAs encoding cell death signalling molecules.

METHODS

Inhibitory interneuron mRNAs (SST; PV: in situ hybridization, quantitative PCR (qPCR)) and death signaling mRNAs [FAS receptor (FASR); TNFSF13: qPCR] were measured in control and schizophrenia subjects (38/38). SST mRNA+ interneuron-like cells were quantified in layer II in the gyrus rectus. Gray matter SST and PV mRNAs were correlated with interstitial white matter neuron (IWMN) density (GAD65/67; NeuN) and death signaling mRNAs.

RESULTS

SST mRNA was reduced in OFC layers I-VI in schizophrenia (both in situ and qPCR), with greatest deficit in layer II (67%). Layer II SST mRNA+ neuron density was reduced in schizophrenia (~29%). PV mRNA was reduced in layers III (18%) and IV (31%) with no significant diagnostic difference in PV mRNA measured by qPCR. FASR mRNA was increased in schizophrenia (34%). SST, but not PV, expression correlated negatively with FASR and TNFSF13 expressions and with IWMN density.

CONCLUSIONS

Our study demonstrates that SST interneurons are predominantly linked to the inhibitory interneuron pathology in the OFC in schizophrenia and that increased death receptor signaling mRNAs relate to prominent laminar deficits in SST mRNA in the OFC in schizophrenia. We suggest that SST interneurons may be more vulnerable to increased death receptor signaling than PV interneurons.