Endocannabinoid and N-acylethanolamine concentrations in hair of female patients with posttraumatic stress disorder – associations with clinical symptoms and outcomes following multimodal trauma-focused inpatient treatment

Abstract While psychotherapeutic treatments for posttraumatic stress disorder (PTSD) show in general good responses in affected individuals, 30–40% of patients show limited improvement. On a biological level, the endocannabinoid system of the body may play a role in the aftermath of trauma, in PTSD,...

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Main Authors: L. Bergunde, M. L. Woud, L. Shkreli, L. Schindler-Gmelch, S. Garthus-Niegel, S. E. Blackwell, C. Kirschbaum, H. Kessler, S. Steudte-Schmiedgen
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Language:English
Published: Nature Publishing Group 2025-08-01
Series:Translational Psychiatry
Online Access:https://doi.org/10.1038/s41398-025-03476-3
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author L. Bergunde
M. L. Woud
L. Shkreli
L. Schindler-Gmelch
S. Garthus-Niegel
S. E. Blackwell
C. Kirschbaum
H. Kessler
S. Steudte-Schmiedgen
author_facet L. Bergunde
M. L. Woud
L. Shkreli
L. Schindler-Gmelch
S. Garthus-Niegel
S. E. Blackwell
C. Kirschbaum
H. Kessler
S. Steudte-Schmiedgen
author_sort L. Bergunde
collection DOAJ
description Abstract While psychotherapeutic treatments for posttraumatic stress disorder (PTSD) show in general good responses in affected individuals, 30–40% of patients show limited improvement. On a biological level, the endocannabinoid system of the body may play a role in the aftermath of trauma, in PTSD, and in extinction processes. This study is a secondary analysis of a randomized-controlled trial including patients with PTSD over the course of trauma-focused inpatient treatment. It aimed to investigate whether endocannabinoid system alterations are associated with symptom severity and treatment response. Fifty-four female inpatients with PTSD provided hair samples and completed psychometric questionnaires at pre-treatment, post-treatment, and 3-month follow-up. Endocannabinoid (EC: AEA, 1-AG/2-AG) and N-acylethanolamine (NAE: SEA, PEA, OEA) concentrations were measured in scalp-near 3-cm hair segments, reflecting cumulative concentrations in the 3 months prior to sampling. At pre-treatment, higher depressive and anxiety symptoms were significantly associated with lower hair AEA levels, whereas higher PTSD symptoms (when controlling for depressive symptoms) and more traumatic experiences were significantly associated with higher hair AEA and NAE levels respectively. PTSD symptoms improved across treatment, remaining stable at 3-month follow-up, but were predicted neither by pre-treatment hair ECs/NAEs nor their changes across treatment and follow-up, which was confirmed in subgroup analyses. Our findings suggest that hair ECs/NAEs may be distinctly linked with trauma-related and affective and anxiety symptoms, however, do not predict treatment response in PTSD. This challenges expectations and highlights the complexity of endocannabinoid system alterations in stress-related psychopathology. Given the study’s limitations, including a female-only sample and lack of a control group, larger studies with control groups and multiple biomarkers are needed to identify intervention-related biomarkers in PTSD.
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spelling doaj-art-b58eec94187d4d4ead913de204276df32025-08-24T11:51:42ZengNature Publishing GroupTranslational Psychiatry2158-31882025-08-0115111210.1038/s41398-025-03476-3Endocannabinoid and N-acylethanolamine concentrations in hair of female patients with posttraumatic stress disorder – associations with clinical symptoms and outcomes following multimodal trauma-focused inpatient treatmentL. Bergunde0M. L. Woud1L. Shkreli2L. Schindler-Gmelch3S. Garthus-Niegel4S. E. Blackwell5C. Kirschbaum6H. Kessler7S. Steudte-Schmiedgen8Institute and Policlinic of Occupational and Social Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of TechnologyDepartment of Clinical Psychology and Experimental Psychopathology, Georg-Elias-Mueller-Institute of Psychology, Georg-August-Universität GöttingenDepartment of Psychiatry, University of OxfordDepartment of Clinical Psychology and Psychotherapy, Friedrich-Alexander-Universität Erlangen-NürnbergInstitute and Policlinic of Occupational and Social Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of TechnologyDepartment of Clinical Psychology and Experimental Psychopathology, Georg-Elias-Mueller-Institute of Psychology, Georg-August-Universität GöttingenInstitute of Biological Psychology, Faculty of Psychology, Technische Universität DresdenDepartment of Psychosomatic Medicine and Psychotherapy, Campus Fulda, University of MarburgDepartment of Psychotherapy and Psychosomatic Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of TechnologyAbstract While psychotherapeutic treatments for posttraumatic stress disorder (PTSD) show in general good responses in affected individuals, 30–40% of patients show limited improvement. On a biological level, the endocannabinoid system of the body may play a role in the aftermath of trauma, in PTSD, and in extinction processes. This study is a secondary analysis of a randomized-controlled trial including patients with PTSD over the course of trauma-focused inpatient treatment. It aimed to investigate whether endocannabinoid system alterations are associated with symptom severity and treatment response. Fifty-four female inpatients with PTSD provided hair samples and completed psychometric questionnaires at pre-treatment, post-treatment, and 3-month follow-up. Endocannabinoid (EC: AEA, 1-AG/2-AG) and N-acylethanolamine (NAE: SEA, PEA, OEA) concentrations were measured in scalp-near 3-cm hair segments, reflecting cumulative concentrations in the 3 months prior to sampling. At pre-treatment, higher depressive and anxiety symptoms were significantly associated with lower hair AEA levels, whereas higher PTSD symptoms (when controlling for depressive symptoms) and more traumatic experiences were significantly associated with higher hair AEA and NAE levels respectively. PTSD symptoms improved across treatment, remaining stable at 3-month follow-up, but were predicted neither by pre-treatment hair ECs/NAEs nor their changes across treatment and follow-up, which was confirmed in subgroup analyses. Our findings suggest that hair ECs/NAEs may be distinctly linked with trauma-related and affective and anxiety symptoms, however, do not predict treatment response in PTSD. This challenges expectations and highlights the complexity of endocannabinoid system alterations in stress-related psychopathology. Given the study’s limitations, including a female-only sample and lack of a control group, larger studies with control groups and multiple biomarkers are needed to identify intervention-related biomarkers in PTSD.https://doi.org/10.1038/s41398-025-03476-3
spellingShingle L. Bergunde
M. L. Woud
L. Shkreli
L. Schindler-Gmelch
S. Garthus-Niegel
S. E. Blackwell
C. Kirschbaum
H. Kessler
S. Steudte-Schmiedgen
Endocannabinoid and N-acylethanolamine concentrations in hair of female patients with posttraumatic stress disorder – associations with clinical symptoms and outcomes following multimodal trauma-focused inpatient treatment
Translational Psychiatry
title Endocannabinoid and N-acylethanolamine concentrations in hair of female patients with posttraumatic stress disorder – associations with clinical symptoms and outcomes following multimodal trauma-focused inpatient treatment
title_full Endocannabinoid and N-acylethanolamine concentrations in hair of female patients with posttraumatic stress disorder – associations with clinical symptoms and outcomes following multimodal trauma-focused inpatient treatment
title_fullStr Endocannabinoid and N-acylethanolamine concentrations in hair of female patients with posttraumatic stress disorder – associations with clinical symptoms and outcomes following multimodal trauma-focused inpatient treatment
title_full_unstemmed Endocannabinoid and N-acylethanolamine concentrations in hair of female patients with posttraumatic stress disorder – associations with clinical symptoms and outcomes following multimodal trauma-focused inpatient treatment
title_short Endocannabinoid and N-acylethanolamine concentrations in hair of female patients with posttraumatic stress disorder – associations with clinical symptoms and outcomes following multimodal trauma-focused inpatient treatment
title_sort endocannabinoid and n acylethanolamine concentrations in hair of female patients with posttraumatic stress disorder associations with clinical symptoms and outcomes following multimodal trauma focused inpatient treatment
url https://doi.org/10.1038/s41398-025-03476-3
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