Dataset Information

Gene expression and response prediction to amisulpride in the OPTiMiSE first episode psychoses.

ABSTRACT: A fundamental shortcoming in the current treatment of schizophrenia is the lack of valid criteria to predict who will respond to antipsychotic treatment. The identification of blood-based biological markers of the therapeutic response would enable clinicians to identify the subgroup of patients in whom conventional antipsychotic treatment is ineffective and offer alternative treatments. As part of the Optimisation of Treatment and Management of Schizophrenia in Europe (OPTiMiSE) programme, we conducted an RNA-Seq analysis on 188 subjects with first episode psychosis, all of whom were subsequently treated with amisulpride for 4 weeks. We compared gene expression on total RNA from patients' blood before and after treatment and identified 32 genes for which the expression changed after treatment in good responders only. These findings were replicated in an independent sample of 24 patients with first episode psychosis. Six genes showed a significant difference in expression level between good and poor responders before starting treatment, allowing to predict treatment outcome with a predictive value of 93.8% when combined with clinical features. Collectively, these findings identified new mechanisms to explain symptom improvement after amisulpride medication and highlight the potential of combining gene expression profiling with clinical data to predict treatment response in first episode psychoses.

SUBMITTER: Troudet R

PROVIDER: S-EPMC7421408 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Gene expression and response prediction to amisulpride in the OPTiMiSE first episode psychoses.

Troudet Réjane R Ali Wafa Bel Haj WBH Bacq-Daian Delphine D Rossum Inge Winter van IWV Boland-Auge Anne A Battail Christophe C Barau Caroline C Rujescu Dan D McGuire Philip P Kahn René S RS Deleuze Jean-François JF Leboyer Marion M Jamain Stéphane S

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20200525 10

A fundamental shortcoming in the current treatment of schizophrenia is the lack of valid criteria to predict who will respond to antipsychotic treatment. The identification of blood-based biological markers of the therapeutic response would enable clinicians to identify the subgroup of patients in whom conventional antipsychotic treatment is ineffective and offer alternative treatments. As part of the Optimisation of Treatment and Management of Schizophrenia in Europe (OPTiMiSE) programme, we co ...[more]

PMID: 32450569

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Project description:BackgroundAntipsychotic-induced weight gain is a common and debilitating side effect of antipsychotics. Although genome-wide association studies of antipsychotic-induced weight gain have been performed, few genome-wide loci have been discovered. Moreover, these genome-wide association studies have included a wide variety of antipsychotic compounds.AimsWe aim to gain more insight in the genomic loci affecting antipsychotic-induced weight gain. Given the variable pharmacological properties of antipsychotics, we hypothesized that targeting a single antipsychotic compound would provide new clues about genomic loci affecting antipsychotic-induced weight gain.MethodsAll subjects included for this genome-wide association study (n=339) were first-episode schizophrenia spectrum disorder patients treated with amisulpride and were minimally medicated (defined as antipsychotic use <2 weeks in the previous year and/or <6 weeks lifetime). Weight gain was defined as the increase in body mass index from before until approximately 1 month after amisulpride treatment.ResultsOur genome-wide association analyses for antipsychotic-induced weight gain yielded one genome-wide significant hit (rs78310016; β=1.05; p=3.66 × 10-08; n=206) in a locus not previously associated with antipsychotic-induced weight gain or body mass index. Minor allele carriers had an odds ratio of 3.98 (p=1.0 × 10-03) for clinically meaningful antipsychotic-induced weight gain (⩾7% of baseline weight). In silico analysis elucidated a chromatin interaction with 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1. In an attempt to replicate single-nucleotide polymorphisms previously associated with antipsychotic-induced weight gain, we found none were associated with amisulpride-induced weight gain.ConclusionOur findings suggest the involvement of rs78310016 and possibly 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 in antipsychotic-induced weight gain. In line with the unique binding profile of this atypical antipsychotic, our findings furthermore hint that biological mechanisms underlying amisulpride-induced weight gain differ from antipsychotic-induced weight gain by other atypical antipsychotics.

Dataset Information

Gene expression and response prediction to amisulpride in the OPTiMiSE first episode psychoses.

Publications

Gene expression and response prediction to amisulpride in the OPTiMiSE first episode psychoses.

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