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Sex Differences in Endocannabinoid and Inflammatory Markers Associated with Posttraumatic Stress Disorder
Therese A Rajasekera1,2,3, Anna Joseph1, Hui Pan4
1Department of Psychiatry, Brigham and Women's Hospital, Boston, MA, USA.
Medrxiv : the Preprint Server for Health Sciences
|February 20, 2025
Summary
Sex differences in posttraumatic stress disorder (PTSD) are linked to distinct biological mechanisms. Men with PTSD show lower endocannabinoid levels, while women exhibit increased inflammation, suggesting varied pathophysiology.
Area of Science:
- Neuroscience
- Psychiatry
- Immunology
Background:
- Posttraumatic stress disorder (PTSD) disproportionately affects women, with biological underpinnings of this sex disparity remaining unclear.
- Altered endocannabinoid (eCB) system function and increased inflammation are implicated in PTSD pathophysiology and may explain sex differences in risk and severity.
- This study investigates sex-specific differences in circulating eCBs and peripheral inflammatory markers in individuals with PTSD compared to controls.
Purpose of the Study:
- To examine sex-based differences in endocannabinoid (eCB) and inflammatory marker levels in individuals with posttraumatic stress disorder (PTSD).
- To elucidate potential biological mechanisms contributing to the higher prevalence of PTSD in women.
- To explore whether these biological differences persist in individuals with comorbid major depressive disorder.
Main Methods:
- Retrospective analysis of serum samples from 88 individuals with PTSD and 85 healthy controls (HC).
- Quantification of circulating endocannabinoids (anandamide, 2-AG, OEA, AA) and inflammatory markers (IL-1β, IL-6, IL-8, IL-18, TNFα, CRP).
- Statistical analysis using linear regression and t-tests to identify differential abundance by disease state and sex, with adjustments for comorbid MDD and genotype.
Main Results:
- Male PTSD patients exhibited significantly lower levels of anandamide (AEA), arachidonic acid (AA), and oleoylethanolamide (OEA) compared to controls and female subgroups.
- Female PTSD patients showed elevated levels of interleukin-6 (IL-6) and interleukin-8 (IL-8).
- Both male and female PTSD patients displayed increased tumor necrosis factor-alpha (TNFα) concentrations compared to controls.
Conclusions:
- This study reveals, for the first time, that decreased endocannabinoid (eCB) levels are not observed in women with PTSD.
- Women with PTSD present with a broader range of elevated inflammatory markers, suggesting distinct biological pathways compared to men.
- These findings indicate that the biological mechanisms underlying PTSD may differ significantly between sexes.
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