SU82 - RNA SIGNATURE OF TREATMENT RESPONSE IN FIRST-EPISODE PSYCHOSIS

Abstract

Background Despite nearly fifty years of pharmacological research, the treatment of schizophrenia remains a challenge and clinical outcomes are still far from optimal. One of the major shortcomings in the current treatment of schizophrenia is that we have no valid criteria in clinical practice to predict who will respond to antipsychotic treatment and how long the treatment should be maintained before changing therapeutic strategy. The identification of blood-based biological markers of drug response with a good sensitivity and specificity would enable physicians to use these tests prior to choosing the antipsychotic treatment and therefore help the practitioner in his daily clinical practice. Methods Through a European consortium on Optimization of Treatment and Management of Schizophrenia in Europe (OPTiMiSE), we conducted a transcriptome analysis on 163 subjects with first episode psychosis. Patients were all treated for four weeks with amisulpride. Blood samples were collected at inclusion and after treatment and total RNA was analyzed by RNA-Seq for each patient before and after treatment as well as according to treatment outcome. After quality control, the detection of differentially expressed genes have been achieved using the DESeq. 2 package and in regards to biological processes and symptom improvement, with the aim of characterizing a biological signature of treatment response in first-episode psychosis. Results The transcription level of 10,683 expressed genes has been analyzed in peripheral blood mononuclear cells. We detected 499 and 84 genes that were differentially expressed after 4-week treatment with amisulpride in remitted and non-remitted patients, respectively, showing enrichment in differentially expressed genes in remitters when compared to non-remitters (p=0.02). We also found that for some of these genes, the expression level was significantly correlated with clinical outcome. A second analysis revealed that 39 of the 499 differentially expressed genes had a different expression level before amisulpride treatment between patients who will be in remission after 4-week treatment, suggesting these genes may help in predicting treatment response. Discussion We demonstrated here that amisulpride treatment affects gene expression in peripheral blood mononuclear cells, mainly in patients who will be in remission after four weeks of treatment, and that gene expression may be associated with symptom improvement. Further replications on independent samples are needed to confirm molecular mechanisms associated with clinical outcome and should help both in the identification of biological signatures of treatment response as well as in the development of new therapeutic strategies.