Major Depressive Disorder: Current Advances and Paradigm Shifts
Yong‐Ku Kim
Abstract
Major depressive disorder (MDD) is a multi-etiological, multi-dimensional, heterogeneous disease with variable symptomatology and treatment efficacy. Although many biological factors have been considered as risk factors for depression, their causal links remain unclear. Because depression is more likely to be a syndrome caused by various risk factors rather than a single etiology, whether the various findings are risk factors for depression or results observed in depression is not always clear. Additionally, other biological factors, including inflammatory markers, neurophysiologic markers, and neuroimaging markers, might be associated with MDD. Current approaches such as gene-environment interactions and epigenetics have been used to identify potential biomarkers for MDD. Accumulating neuroimaging studies suggest potential biomarkers such as metabolic activity, structural, or functional connectivity within the limbic-cortical circuitries. Considering the different biological mechanisms of depressive subtypes (atypical, melancholic, psychotic, and so on), it would be helpful to understand the pathogenesis of each depressive disorder to more accurately predict an individual's response to a specific treatment for depression. However, MDD is still defined using a symptom-based classification, and its heterogeneity is of significant concern. Moreover, it is necessary to develop an etiology-based classification of