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 use ketamine to learn how posttraumatic stress disorder and major depression often happen together. The researchers will give six ketamine or saline infusions over three weeks to people who have both conditions. They will take brain scans, run thinking tests, and ask about symptoms before and after treatment. The team wants to see whether changes in symptoms match changes in how brain areas talk to each other and in thinking skills. If the study works as planned, it could point to biological brain patterns that link trauma-related problems and help guide more precise treatments in the future. The study itself has not yet produced results.

Key facts:

• The study focuses on people who have both posttraumatic stress disorder and major depressive disorder at the same time, which the authors say is the most common harmful reaction after trauma.
• Forty-two people with both PTSD and depression will be randomly assigned to get six ketamine infusions or six saline placebo infusions over three weeks.
• Before and after the infusions, researchers will collect brain scans, tests of thinking and memory, and self-reported measures of PTSD, depression, and rumination (repetitive negative thinking).
• The main idea being tested is that symptom changes will be linked to changes in how different brain areas communicate with each other and to changes in cognitive performance, and that ketamine might improve symptoms by fixing those brain communication and thinking problems.
• The study also includes three comparison groups who will be measured once: about 10 people with PTSD only, about 10 people with trauma-exposed depression only, and about 21 healthy people without trauma-related problems.
• If the planned results appear, the authors say the study could identify brain imaging patterns tied to trauma-related illness and move research toward treating combined PTSD and depression based on shared biology rather than separate diagnoses.

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 Feeling disconnected from others Lack of energy or motivation Poor sleep Sadness or low mood