Differential sphingosine-1-phosphate receptor-1 protein expression in the dorsolateral prefrontal cortex between schizophrenia Type 1 and Type 2

Abstract

There is growing evidence that there are subtypes of schizophrenia (Bowen et al., 2019; Chand et al., 2020). Specifically, messenger ribonucleic acid (mRNA) gene expression findings on postmortem dorsolateral prefrontal cortex (DLPFC) suggest that schizophrenia patients can be divided into two groups, those with a relatively normal DLPFC transcriptome (Type 1) and those with hundreds of differentially expressed genes (Type 2). The clinical relevance of that finding is limited by the fact that autopsy tissue is required to distinguish Type 1 from Type 2 patients, however the PET target sphingosine-1-phosphate receptor-1 (S1PR1) is among the genes whose mRNA expression is upregulated in Type 2 compared to Type 1 patients (Bowen et al., 2019). As a preliminary study to validate this PET target, S1PR1 protein expression was assessed by receptor autoradiography and immunohistochemistry in the DLPFC from schizophrenic patients classified as Type 1 or Type 2 based on their DLPFC transcriptomes and from controls. S1PR1 protein expression is upregulated in Type 2 compared to Type 1 (p < 0.05) supporting the possibility that positron emission tomography (PET) can be used as a clinical test to distinguish these subgroups of schizophrenic patients during life.