TCF4 and RBFOX1 as peripheral biomarkers for the differential diagnosis and treatment of major depressive disorder

Background: Recent genome-wide association studies on major depressive disorder (MDD) have indicated the involvement of LRFN5 and OLFM4; however, the expression levels and roles of these molecules in MDD remain unclear. The present study aimed to determine the serum levels of TCF4 and RBFOX1 in patients with MDD and to investigate whether these molecules could be used as biomarkers for MDD diagnosis.Methods: The study included 99 drug-naive MDD patients, 90 drug-treated MDD patients, and 81 healthy controls (HCs). Serum TCF4 and RBFOX1 levels were measured by ELISA. Pearson's correlation analysis was conducted to determine the association between TCF4/RBFOX1 and clinical variables. Linear support vector machine classifier was used to evaluate the diagnostic capabilities of TCF4 and RBFOX1.Results: Serum TCF4 and RBFOX1 levels were substantially higher in MDD patients than in HCs and significantly lower in drug-treated MDD patients than in drug-naive MDD patients. Moreover, serum TCF4 and RBFOX1 levels were associated with the Hamilton Depression Scale score, duration of illness, serum lipids levels, and hepatic function. Thus, both these molecules showed potential as biomarkers for MDD. TCF4 and RBFOX1 combination exhibited a higher diagnostic performance, with the mean area under the curve values of 0.9861 and 0.9936 in the training and testing sets, respectively.Limitations: Small sample size and investigation of only the peripheral nervous system.Conclusions: TCF4 and RBFOX1 may be involved in the pathogenesis of MDD, and their combination may serve as a diagnostic biomarker panel for MDD.