Blunted arginine vasopressin secretion in individuals experiencing a major depressive episode with comorbid post-traumatic stress disorder: Results from an exploratory study using copeptin as a surrogate marker.
Hiroe Hu, Yoojin Lee, Alaina N Tillman, Elizabeth D. Ballard, Laura Waldman, Peixiong Yuan, Jenessa N Johnston, Shiyong Peng, Mark D Kvarta, Joseph G Verbalis, Carlos A. Zarate
Journal of Neuroendocrinology 2026 DOI: 10.1111/jne.70133 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort with experimental component Peer reviewed |
|---|---|
| Population | Individuals experiencing a major depressive episode with and without PTSD, and healthy volunteers |
| Intervention | Ketamine |
| Dose | subanesthetic-dose |
| Duration | Single infusion, acute changes measured post-infusion |
| Topics | Depression Ketamine PTSD |
| Keywords | Copeptin Vasopressin |
| Citations | 1 |
| Registration | NCT02543983 |
| Key findings | Participants with co-occurring major depressive episode and PTSD exhibited significantly lower baseline copeptin levels and a blunted reduction in copeptin after ketamine compared to those with depression alone. |
Abstract
Arginine vasopressin (AVP) modulates stress responsivity and social-affective behaviors, but its role in mood and trauma-related disorders remains poorly defined due to challenges in peripheral measurement. This study used copeptin, a stable, reliable, and well-validated surrogate marker of AVP secretion, to assess vasopressinergic function in a transdiagnostic sample of individuals experiencing a major depressive episode (MDE) with and without post-traumatic stress disorder (PTSD), as well as healthy volunteers (HVs). Baseline levels of copeptin, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and urine cortisol were compared across groups and examined in relation to clinical symptoms and behavioral traits. Acute changes in copeptin and other hypothalamic-pituitary-adrenal axis markers following a single subanesthetic-dose ketamine infusion were also investigated in a subset of patients. Participants with MDE + PTSD exhibited significantly lower baseline copeptin levels and a blunted reduction in copeptin levels post-ketamine compared to MDE-only participants. Copeptin was unrelated to primary mood diagnosis and to symptom severity of depression, anxiety, post-traumatic stress, anhedonia, suicidal ideation, childhood trauma history, or behavioral traits other than aggression. Higher baseline copeptin levels were associated with verbal aggression, and PTSD comorbidity attenuated these associations. Collectively, these findings suggest a possible biological subtype of attenuated AVP secretion in the dual diagnostic subgroup of co-occurring MDE and PTSD that is independent of symptom burden. Plasma copeptin might therefore serve not only as a peripheral biomarker but also as a proxy for central neuromodulatory changes relevant to AVP-driven circuits in the study of neuropsychiatric disorders. Future studies integrating the temporal dynamics of copeptin with neuroimaging, genetic, and stress-challenge paradigms are needed to delineate the potential neural pathways through which AVP contributes to the pathophysiology and treatment responsiveness of mood and trauma-related disorders. Clinical Trial Registration: www.clinicaltrials.gov (NCT02543983).
Comparable studies
Other experimental studies on PTSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A PILOT STUDY OF GROUP MINDFULNESS-BASED COGNITIVE THERAPY (MBCT) FOR COMBAT VETERANS WITH POSTTRAUMATIC STRESS DISORDER (PTSD) Veterans with chronic combat posttraumatic stress disorder seeking treatment at a VA... | 2013 | Quasi-experimental with treatment-as-usual comparison group | n = 37 |
| Resting‐state functional connectivity of the bed nucleus of the stria terminalis in post‐traumatic stress disorder and its dissociative subtype Adults with PTSD (n = 70), its dissociative subtype (n = 41), and healthy controls (n =... | 2017 | Cross-sectional resting-state fMRI study | n = 161 |
| Sensory overload and imbalance: Resting-state vestibular connectivity in PTSD and its dissociative subtype. Adults with PTSD, PTSD dissociative subtype, and healthy controls | 2017 | Cross-sectional, seed-based resting-state fMRI study | n = 141 |
| Altered Sense of Body Ownership and Agency in Posttraumatic Stress Disorder and Its Dissociative Subtype: A Rubber Hand Illusion Study Adults with PTSD (n=4), PTSD with dissociative subtype (n=6), and healthy controls (n=7) | 2018 | Case-control experimental study | n = 17 |
| Superior colliculus resting state networks in post‐traumatic stress disorder and its dissociative subtype Adults with PTSD (n = 67), its dissociative subtype (n = 41), and healthy controls (n =... | 2017 | Observational cross-sectional resting-state fMRI study | n = 158 |
Citations in the library
Cites 3
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder. American Journal of Psychiatry January 5, 2021
- Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials Pharmacological Reports April 16, 2020