Exploring association between transcriptional characteristics of immune cells and antidepressant therapy response

Abstract Depression is a mental illness with significant heterogeneity, and its pathogenesis involves multiple aspects. At present, there are certain difficulties in clinical diagnosis and treatment of depression, and it is significant to develop biomarkers for depression treatment. We used available data from the GEO database and divided depressive patients into responders and non-responders according to different treatment outcomes. Through WGCNA and machine learning models, we screened out the key genes significantly related to treatment response, and delineated the genetic characteristics of depressive patients with different treatment outcomes, aiming to look for reliable biomarkers for predicting antidepressant treatment response. The top five module eigengenes in the core candidate gene set related to antidepressant therapy response are ZNF683, PPDPF, CLEC1B, GYPB and DPYSL5, among which ZNF683 has the highest contribution. As an important regulator of T cell functions, ZNF683 is critically involved in the immune response by regulating the proliferation, differentiation and effector functions of T cells. High levels of ZNF683 are associated with adverse therapeutic reactions, fully suggesting the important role of immune cells, especially T cells, in the antidepressant therapeutic response.