Ketamine and epigenetic processes in depression, intersection between serotonergic and glutamatergic pathways

Depression involves a wide range of biological changes, from gene variations to epigenetic modifications, not only serotonergic mechanisms. Therapy response to antidepressants is linked to epigenetic regulation of genes in the serotonergic system. Persistent depressive symptoms may involve stable molecular adaptations in the brain at the epigenetic level. Responses to psychotherapy for mood disorders correlate with epigenetic alterations, including in genes regulating the serotonergic and glutamatergic systems and the HPA axis. Ketamine's antidepressant effects may be linked to epigenetic alterations, and further exploration of BDNF's relation with ketamine in epigenetic signaling is warranted. Understanding these mechanisms may help gauge therapy efficacy and duration.

Study at a glance

Abstract

Abstract Background Hypotheses surrounding the etiology of depressive disorders encompass a wide range of biological changes that can occur in a depressed individual, from gene variations to epigenetic modifications and not only serotonergic mechanisms. Once again, the therapy response of the patient to antidepressants is connected to modifications in the epigenetic regulation of genes within the serotonergic system. The persistence of depressive symptoms points to the possibility that stable molecular adaptations in the brain, particularly at the epigenetic level, may be involved. Methods Narrative review to first, discuss the historical evidence behind how serotonin (5-hydroxytryptamine, 5-HT) signaling and its associated actors are involved in various biological processes and second, examine the role of ketamine as one of the newer treatments for depression. Results There is increasing evidence that responses to psychotherapy for mood disorders are correlated with epigenetic alterations. Although therapy response appears to be associated with epigenetic changes in genes regulating the serotonergic system, there are multiple lines of research that provide additional data implicating epigenetic alterations in the glutamatergic system. Also, the epigenetic regulation of target genes along the HPA axis are becoming more intriguing in linking mood disorders with environmental stressors, and warrant a closer look. Recent research suggests that ketamine's antidepressant effects may be linked to epigenetic alterations. Considering the multiple studies linking BDNF with depression, further exploration of its relation with ketamine in the context of epigenetic signaling is warranted. Conclusion Understanding how and to what extent epigenetic mechanisms change gene expression and how these changes are influenced by environmental stressors may eventually allow mental health professionals to better understand the biological basis of depression as well as to gauge the efficacy, onset, durability and duration of therapies to treat mood disorders. Moreover, understanding the relation between serotonergic neurotransmission and epigenetic mechanisms of how these may be modified by ketamine should lead us to a greater knowledge of their therapeutic potential.