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

Summary & key facts

This paper describes a planned study that will test how ketamine affects people who have both posttraumatic stress disorder and major depression. The researchers will randomly give 42 people with both conditions either six ketamine infusions or a saline placebo over three weeks. They will take brain scans, give thinking tests, and ask about symptoms before and after. The goal is to see whether ketamine changes how brain regions communicate and whether those changes link to symptom improvement. The study is a test of a new, biology-based model of these combined conditions, not a finished proof that ketamine works for them yet.

Key facts:

• The study focuses on people who have both posttraumatic stress disorder and major depressive disorder, because this combination is the most common unhealthy response to trauma.
• Forty-two people with both conditions will be randomly assigned to receive either six ketamine infusions or six saline (placebo) infusions over three weeks.
• The researchers will measure brain function with neuroimaging, test thinking and memory with cognitive tasks, and collect self-reports about PTSD symptoms, depression symptoms, and rumination (repetitive negative thinking) before and after
• There will also be three comparison groups who are tested once: about 10 people with PTSD only, about 10 people who had trauma and now have depression only, and about 21 healthy people with no trauma-related diagnosis.
• The main idea being tested is that changes in symptoms are linked to changes in how brain regions communicate (called functional connectivity) and to thinking problems, and that ketamine might improve symptoms by fixing those communication
• This paper reports a planned experiment. It proposes a hypothesis and a design. It does not report results, so the study can show whether the idea is supported or not, but it does not yet prove ketamine is an effective treatment for these c

Abstract

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 (n = 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 (n = 10), trauma-exposed-MDD (TE-MDD; n = 10), and healthy controls (HC, n = 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.

Topics

Memory and Neural Mechanisms Treatment of Major Depression Tryptophan and brain disorders

Categories

Health Sciences Medicine Pharmacology

Tags

Clinical psychology Cognition Internal medicine Major depressive disorder Medicine Pathological Psychiatry Psychological intervention Psychology Rumination

Substances

Ketamine

Conditions & symptoms

Depression PTSD Anxiety or worry Difficulty focusing Lack of energy or motivation Poor sleep Sadness or low mood