Gene expression: biomarker of antidepressant therapy?

Abstract

While antidepressant therapy is an essential treatment of major depression, a substantial group of treated patients do not respond to therapy, or suffer from severe side effects. Moreover, the time of onset of the clinical improvement is often delayed. Antidepressants as currently available usually enhance serotonergic, noradrenergic and dopaminergic neurotransmission and may contribute to the inadequate remission rates for major depression. Therefore biomarkers enabling the identification of subgroups of patients and also finding unprecedented targets would provide the basis for personalized medication and thus improve treatment efficacy and reduce side effects. Several pharmacogenetic studies on antidepressant treatment response using single nucleotide polymorphism (SNPs) mapping have been performed but provided only modest findings. Therefore the analysis of gene expression to integrate genomic activity and environmental effects promises a new approach to cope with the complexity of factors influencing antidepressant treatment. Here gene expression studies focusing on candidate genes and genome-wide approaches using RNA derived from peripheral blood cells are reviewed. The most promising findings exist for hypothalamic-pituitary-adrenal (HPA) axis, inflammation and neuroplasticity related genes. However, straightforward translation into tailored treatment is still unlikely. Contradictory results limit the clinical use of the findings. Future studies are necessary, which could include functional analysis and consider gene-environment interactions.