Background: Major Depressive Disorder (MDD) and its frequent partial response to antidepressants are a major health concern and therefore an important focus of research. Despite the efforts, MDD pathogenesis and the mechanisms of antidepressant action are only partially understood. In the last few years, the need of rethinking the classification of depressive disorders and psychiatric disorders in general has been suggested, in order to provide a nosology that reflects more closely the biological background associated with disease pathogenesis and its role/significance in treatment. The classification proposed by the National Institute of Mental Health (NIMH), namely the research domain criteria (RDoC), may represent a key framework to guide research in this direction. Methods: A literature search was performed on PubMed and Google Scholar databases in order to retrieve data regarding Antidepressants effects on specific RDoC constructs. Further, the targets of drugs of interest were identified through Drugbank database, and their possible function within RDoC constructs was discussed. Discussion: In this review we summarize and discuss the significance of the results of pre-clinical and clinical studies investigating specific RDoC paradigms relevant to depressive phenotypes and antidepressant effects.
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