Should Glutamatergic Modulators Be Considered Preferential Treatments for Adults with Major Depressive Disorder and A Reported History of Trauma? Conceptual and Clinical Implications

Abstract

<p>Major depressive disorder (MDD) is a chronic, highly prevalent and debilitating mental disorder associated with significant illness and economic burden globally. Exposure to trauma (e.g., physical, sexual, emotional abuse, and/or physical and emotional neglect) is common amongst individuals with MDD. Persons with MDD and a history of trauma often exhibit an attenuated response to conventional serotonergic antidepressants compared to those with non-traumatized depression. Emerging evidence indicates that exposure to trauma is associated with increased inflammatory markers [e.g., C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-a (TNF-a)] as well as glutamatergic dysregulation in the central nervous system (CNS). It is hypothesized that individuals with MDD and a history of trauma may be conceptualized as a distinct bio-phenotype compared to non-traumatized depression. Furthermore, preliminary evidence positions select glutamatergic modulators as potential novel, mechanistically-informed therapeutic strategies that may provide benefit to persons with elevated inflammation and glutamatergic dysregulation.</p>