Characterization of Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder Using Ketamine as an Experimental Medicine Probe

Oct 11, 2021Journal of psychiatry and brain science

Using Ketamine to Study Coexisting PTSD and Major Depression

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Abstract

Forty-two participants with comorbid PTSD and MDD will receive either ketamine infusions or saline placebo over three weeks.

Changes in clinical symptoms of PTSD and MDD may be linked to alterations in brain connectivity and cognitive function.
Ketamine infusions could improve clinical symptoms by correcting these functional connectivity changes and enhancing cognitive performance.
Functional imaging may reveal distinct patterns associated with the neurobiological mechanisms of PTSD and MDD.
The study aims to unify the understanding of PTSD and MDD beyond separate diagnoses to a common biological framework.
Outcomes may lead to more targeted interventions for managing the symptoms of PTSD and MDD.

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Comorbid posttraumatic stress disorder and major depressive disorder (PTSD + MDD) is the most common pathological response to trauma, yet despite their synergistic detriment to health, knowledge regarding the neurobiological mechanism underlying PTSD + MDD is extremely limited. This study proposes a novel model of PTSD + MDD that is built on biological systems shown to underlay PTSD + MDD and takes advantage of ketamine's unique suitability to probe PTSD + MDD due to its rescue of stress-related neuroplasticity deficits. The central hypothesis is that changes in PTSD + MDD clinical symptoms are associated with functional connectivity changes and cognitive dysfunction and that ketamine infusions improve clinical symptoms by correction of functional connectivity changes and improvement in cognition. Participants with PTSD + MDD (= 42) will be randomized to receive a series of six ketamine infusions or saline-placebo over three weeks. Pre/post-measures will include: (1) neuroimaging; (2) cognitive functioning task performance; and (3) PTSD, MDD, and rumination self-report measures. These measures will also be collected once in a trauma-exposed group including PTSD-only (= 10), trauma-exposed-MDD (TE-MDD;= 10), and healthy controls (HC,= 21). Successful completion of the study will strongly support the concept of a biologically-based model of PTSD + MDD. The results will (1) identify functional imaging signatures of the mechanisms underpinning pathological responses to trauma, (2) shift focus from mono-diagnostic silos to unified biological and behavioral disease processes and, thus, (3) inform interventions to correct dysregulation of PTSD + MDD symptom clusters thereby supporting more precise treatments and better outcomes. n n n n

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Characterization of Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder Using Ketamine as an Experimental Medicine Probe

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