A theoretical framework is proposed to gain insight into the pathogenesis of major depressive disorder (MDD). Despite being a relatively weak argument, the neurogenesis theory is suggested to compensate for the limitations of the monoamine theory. In the adult hippocampus, neurogenesis is functionally related to regulation of the hypothalamic-pituitary-adrenal (HPA) axis, inflammatory processes, cognitive functions and other aspects that contribute to etiological factors that lead to MDD and promote recovery from MDD. Despite a lack of investigation into neurogenesis and antidepressant action, it is proposed that chronic administration of antidepressant(s) can induce the recruitment and integration of newborn neurons into the dentate gyrus and, ultimately, lead to the remission of MDD. The extant body of literature indicates that the suppression of neurogenesis per se may be associated with an impaired response to antidepressant treatment rather than with the induction of depressive-like behaviors. Moreover, recent studies have shown that increasing the survival rate and incorporation of new neurons can alleviate depressive-like behaviors and promote stress resilience. According to the neurogenic reserve hypothesis, hippocampal neurogenesis supports specific cortical functions, including executive functions, pattern separation and contextual information processing, control over the HPA axis and behavioral coping mechanisms in response to stressful situations. Therefore, hippocampal neurogenesis may be a promising biological indicator of stress resilience and antidepressant response in patients with MDD.
Keywords: Antidepressant; Biological indicator; Hippocampus; Major depressive disorder (MDD); Neurogenesis.