Lost in translation. The quest for definitions of treatment-resistant depression with a focus on inflammation-related gene expression

Approximately one third of individuals with major depressive disorder (MDD) do not respond to antidepressant treatments; but what does treatment-resistant depression (TRD) mean? With this article, I aim to provide an overview of the clinical and operational criteria currently used to define TRD, highlighting core gaps in knowledge and open questions to be addressed in order to drive future research in the field. Importantly, a better definition of TRD must include a better characterization of the biological and molecular correlates of non-response. Among these potential biomarkers, compelling evidence reveals a potential role of inflammation-related gene expression signatures. A more accurate clinical and etiopathological characterization of TRD subjects may help to identify biologically based MDD clinical phenotypes to be targeted in future research and finally achieve better outcomes.