Genomic Studies of Treatment Resistance in Major Depressive Disorder

Abstract

Treatment-resistant depression describes the subset of individuals with major depressive disorder who do not reach symptomatic remission despite multiple adequate treatment trials. While treatment resistance has a substantial impact on functioning, quality of life, and healthcare costs, little is known about the underlying neurobiology. While at least some treatment-resistant depression (TRD) risk is likely to be heritable, based primarily on evidence from antidepressant pharmacogenomics, studies to date have failed to reliably identify rare or common genetic variation associated with this phenotype. Challenges in the study of TRD include misclassifi cation arising from medication intolerance or inadequate treatment trials, the heterogeneity of the concept itself, and most notably the absence of well-characterized cohorts with DNA available for study. New strategies to identify large cohorts from biobanks or disease registries and efforts to meta-analyze multiple cohorts may facilitate the identifi cation of risk variants. In addition, further studies to understand the potential utility of pharmacogenomic testing among individuals with TRD or to stratify risk for TRD are needed. Background and MotivationAround 1/3 of individuals who receive initial antidepressant treatment for major depressive disorder will not reach symptomatic remission. A subset of these, perhaps approaching 50 %, will not remit despite additional antidepressant treatment [ 31 ]. Such nonremission in the face of adequate antidepressant trials is referred to as treatment-resistant depression [ 9 ], a concept fi rst characterized more than 40

Prioritization and comprehensive analysis of genes related to major depressive disorder

“…Most of these genes, such as PCDH9 , MDD1 , MDD2 , CREB1 and DISC1 , have been identified to be associated with MDD (Cacabelos, Torrellas, & Fernandez‐Novoa, ; Xiao et al, ), and some of them (e.g. TPH1, GRIN2B and MAOA) were also related to other mental disorders (van Donkelaar et al, ; Perlis, ; Tovilla‐Zarate et al, ). This indicated that our preferred solution designed was able to be utilized to get the expected data.…”