Potential Clinical Utility of Niacin Skin Test and FACS-Based GPR109A Evaluation as a Combined Discriminatory Tool for Treatment-Resistant Schizophrenia

Several studies have suggested that an abnormal niacin-induced flush response may serve as a stable biomarker for schizophrenia.This response is mediated by the G-protein-coupled receptor 109A (GPR109A).Treatment-resistant schizophrenia (TRS) patients typically exhibit more severe psychopathology; however, the molecular mechanisms underlying niacinmediated signaling in TRS remain unclear.This study aimed to evaluate the potential of the niacin response and GPR109A as biomarkers for TRS.We examined 19 patients with TRS, 24 patients with non-TRS, and 37 healthy controls (HC).GPR109A expression on monocytes was measured using flow cytometry.Receiver operating characteristic (ROC) curve analysis and support vector machine (SVM) were used for evaluating the classified efficiency of the combined niacin flush response and GPR109A expression.TRS tended to have attenuated niacin flush response and lower levels of GPR109A expression than non-TRS and HC.In the ROC curve analysis based on logistic regression, the area under the curve (AUC) for the combined representative score of niacin flush response and GPR109A expression was 0.98 for TRS vs. HC, 0.88 for non-TRS vs. HC, and 0.76 for TRS vs. non-TRS.Using an SVM classifier, the AUC for the combined markers in distinguishing TRS from non-TRS was 0.86.Our findings indicate that the combined assessment of niacin flush response and GPR109A expression could discriminate between TRS and non-TRS cases.These markers may therefore serve as predictive tools for identifying schizophrenia patients in whom clinical assessment alone is inconclusive, thereby facilitating early recognition of those at risk of developing TRS.