Voided REM Sleep (V-REM): A Candidate Biomarker Linking Treatment-Resistant PTSD and Major Depressive Disorder
Mouhammad Ousmane Ndiaye
Preprints.org September 29, 2026 preprint DOI: 10.20944/preprints202609.2452.v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper |
|---|---|
| Topics | Depression PTSD |
| Key points | Proposes that treatment-resistant PTSD and MDD may involve "Voided REM sleep" (V-REM), in which REM sleep appears architecturally normal on polysomnography but is functionally incomplete, with abnormal connectivity between the ventromedial prefrontal cortex and amygdala during REM epochs. Argues that establishing V-REM as a biomarker would not require determining whether it causes or results from treatment resistance. |
Abstract
A substantial proportion of patients with posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) do not respond to first-line treatment. Approximately 40% of PTSD patients do not respond to first-line psychotherapy, and 30.9% of MDD patients meet criteria for treatment-resistant depression. Yet standard polysomnography in these patients frequently shows REM sleep that appears architecturally normal. I propose that this apparent normality may be masking a functional anomaly in which the ventromedial prefrontal cortex (vmPFC) node of the default mode network and the amygdala show abnormal connectivity during REM epochs, occurring despite intact brainstem-generated REM markers (muscle atonia, rapid eye movements, characteristic EEG activity). I term this pattern Voided REM sleep (V-REM), REM sleep that completes its brainstem-generated form without completing its forebrain-mediated emotional-processing function. I outline the anatomical and physiological rationale for distinguishing REM’s form from its function, review evidence consistent with the hypothesis in both PTSD and MDD, specify a falsifiability criterion, and propose a functional MRI protocol using four matched comparison groups to test the hypothesis directly. Establishing V-REM as a biomarker would not require resolving, at this stage, whether the anomaly is a cause or a consequence of treatment resistance. As history has shown with other biomarkers whose clinical value was established well before their causal role was understood, this would not diminish the potentially pivotal role such a discovery could play in identifying and treating this subgroup of patients.
In the evidence
This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.
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Proposes 'Voided REM sleep' as a candidate biomarker linking treatment-resistant PTSD and major depressive disorder, arguing it would not require determining whether the anomaly causes or results from treatment resistance.
Synthesized
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State of the evidence: PTSD Unclear
Proposes 'voided REM sleep' as a candidate biomarker of treatment-resistant PTSD and depression, with a falsifiable fMRI protocol to test it.
Synthesized
Comparable studies
Other theoretical and historical papers on PTSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Theorizing that Psychedelic Assisted Therapy May Play a Role in the Treatment of Trauma-Induced Personality Disorders. | 2024 | Theoretical or philosophical paper | |
| The potential use of N-methyl-3,4-methylenedioxyamphetamine (MDMA) assisted psychotherapy in the treatment of eating disorders comorbid with PTSD. | 2021 | Theoretical or philosophical paper | |
| MDMA-assisted psychotherapy for PTSD in adolescents: rationale, potential, risks, and considerations. Adolescents with PTSD | 2024 | Theoretical or philosophical paper | |
| Agency in Post-traumatic Stress Disorder: Implications for Therapy | 2023 | Theoretical or philosophical paper | |
| The Inner World in the Outer World: The Phenomenology of Posttraumatic Stress Disorder from a Psychoanalytic Perspective | 1996 | Theoretical or philosophical paper |