Plasma concentrations of endocannabinoids and related primary Fatty Acid amides in patients with post-traumatic stress disorder.

Endocannabinoids (ECs) and related N-acyl-ethanolamides (NAEs) play important roles in stress response regulation, anxiety and traumatic memories. In view of the evidence that circulating EC levels are elevated under acute mild stressful conditions in humans, we hypothesized that individuals with traumatic stress exposure and post-traumatic stress disorder (PTSD), an anxiety disorder characterized by the inappropriate persistence and uncontrolled retrieval of traumatic memories, show measurable alterations in plasma EC and NAE concentrations. We determined plasma concentrations of the ECs anandamide (ANA) and 2-arachidonoylglycerol (2-AG) and the NAEs palmitoylethanolamide (PEA), oleoylethanolamide (OEA), stearoylethanolamine (SEA), and N-oleoyldopamine (OLDA) by HPLC-MS-MS in patients with PTSD (n = 10), trauma-exposed individuals without evidence of PTSD (n = 9) and in healthy control subjects (n = 29). PTSD was diagnosed according to DSM-IV criteria by administering the Clinician Administered PTSD Scale (CAPS), which also assesses traumatic events. Individuals with PTSD showed significantly higher plasma concentrations of ANA (0.48±0.11 vs. 0.36±0.14 ng/ml, p = 0.01), 2-AG (8.93±3.20 vs. 6.26±2.10 ng/ml, p<0.01), OEA (5.90±2.10 vs. 3.88±1.85 ng/ml, p<0.01), SEA (2.70±3.37 vs. 0.83±0.47, ng/ml, p<0.05) and significantly lower plasma levels of OLDA (0.12±0.05 vs. 0.45±0.59 ng/ml, p<0.05) than healthy controls. Moreover, PTSD patients had higher 2-AG plasma levels (8.93±3.20 vs. 6.01±1.32 ng/ml, p = 0.03) and also higher plasma concentrations of PEA (4.06±1.87 vs. 2.63±1.34 ng/ml, p<0.05) than trauma-exposed individuals without evidence of PTSD. CAPS scores in trauma-exposed individuals with and without PTSD (n = 19) correlated positively with PEA (r = 0.55, p = 0.02) and negatively with OLDA plasma levels (r = -0.68, p<0.01). CAPS subscores for intrusions (r = -0.65, p<0.01), avoidance (r = -0.60, p<0.01) and hyperarousal (r = -0.66, p<0.01) were all negatively related to OLDA plasma concentrations. PTSD appears to be associated with changes in plasma EC/NAE concentrations. This may have pathophysiological and diagnostic consequences but will need to be reproduced in larger cohorts

Metabolite profiling in posttraumatic stress disorder

Background Traumatic stress does not only increase the risk for posttraumatic stress disorder (PTSD), but is also associated with adverse secondary physical health outcomes. Despite increasing efforts, we only begin to understand the underlying biomolecular processes. The hypothesis-free assessment of a wide range of metabolites (termed metabolite profiling) might contribute to the discovery of biological pathways underlying PTSD. Methods Here, we present the results of the first metabolite profiling study in PTSD, which investigated peripheral blood serum samples of 20 PTSD patients and 18 controls. We performed liquid chromatography (LC) coupled to Quadrupole/Time-Of-Flight (QTOF) mass spectrometry. Two complementary statistical approaches were used to identify metabolites associated with PTSD status including univariate analyses and Partial Least Squares Discriminant Analysis (PLS-DA). Results Thirteen metabolites displayed significant changes in PTSD, including four glycerophospholipids, and one metabolite involved in endocannabinoid signaling. A biomarker panel of 19 metabolites classifies PTSD with 85% accuracy, while classification accuracy from the glycerophospholipid with the highest differentiating ability already reached 82%. Conclusions This study illustrates the feasibility and utility of metabolite profiling for PTSD and suggests lipid-derived and endocannabinoid signaling as potential biological pathways involved in trauma-associated pathophysiology

The effect of trauma-focused therapy on the altered T cell distribution in individuals with PTSD: Evidence from a randomized controlled trial

Morath J, Gola H, Sommershof A, et al. The effect of trauma-focused therapy on the altered T cell distribution in individuals with PTSD: Evidence from a randomized controlled trial. Journal of Psychiatric Research. 2014;54:1-10.Posttraumatic stress disorder (PTSD) is associated with a reduced ratio of naive cytotoxic T lymphocytes, an increased ratio of memory cytotoxic T lymphocytes, and a reduced proportion of FoxP3(+) regulatory T lymphocytes. This study investigated whether these immunological alterations are reversible through an evidence-based psychotherapeutic treatment. Therefore, 34 individuals with PTSD were randomly assigned to either a treatment condition of 12 sessions narrative exposure therapy (NET) or a waitlist control (WLC) group. PTSD symptoms were significantly reduced in the NET group, but not in the WLC group, four months post-therapy (effect size: Hedges' g = -1.61). One year after therapy, PTSD symptoms were improved even further in the NET group compared to baseline (Hedges' g = -1.96). This symptom improvement was mirrored in an increase in the originally reduced proportion of regulatory T cells (T-regs) in the NET group at the one-year follow-up, when comparing subgroups matched for baseline T-reg numbers. However, no changes were found for the initially reduced proportion of CD45RA(+)CCR7(+) naive T lymphocytes. In conclusion, NET was effective in reducing trauma-related PTSD symptoms and had a positive effect on the proportion of T-regs cells, thus demonstrating an effect of psychotherapy on an immunological level. Yet, the shift in the proportion of naive and memory T lymphocytes in individuals with PTSD, discussed in the literature as a correlate of premature immunosenescence, was not reversible and thus might render these patients permanently more susceptible to infectious diseases. (C) 2014 Elsevier Ltd. All rights reserved

Effect of comorbid depression or the use of antidepressants on plasma EC/NAE concentrations.

<p>Effect of comorbid depression or the use of antidepressants on plasma EC/NAE concentrations.</p

Relationship between OLDA plasma concentrations and CAPS scores.

<p>Panel A: CAPS sum score (r = −0.68, p<0.01, n = 19); Panel B: CAPS – intrusion subscore (r = −0.65, p<0.01); Panel C: CAPS – avoidance subscore (r = −0.59, p<0.01); Panel D: CAPS – hyperarousal subscore (r = −0.66, p<0.01). Solid line indicates regression line and dotted lines 95% confidence intervals.</p

Correlation between CAPS scores and PEA plasma levels in individuals after trauma exposure (n = 19).

<p>Panel A: CAPS sum score (r = 0.54, p = 0.02); Panel B: CAPS – intrusion subscore (r = 0.65, p<0.01); Panel C: CAPS – avoidance subscore (r = 0.21, p = 0.40); Panel D: CAPS - hyperarousal subscore (r = 0.29, p = 0.23). Solid line indicates regression line and dotted lines 95% confidence intervals.*marks significant correlations.</p

Correlation between the number of CAPS traumatic event types and OLDA plasma concentrations (r = −0.50, p = 0.03, n = 19).

<p>The solid line represents the regression line and dotted lines 95% confidence intervals.</p

Comorbidities (except depression) or medication use (except antidepressants) and plasma EC/NAE concentrations in individuals after trauma exposure.

a<p>Comorbidities were rheumatic disease (n = 1), hepatitis B (n = 1) and chronic gastritis (n = 2).</p>b<p>Medications were contraceptives (n = 2), mood stabilizers (n = 1) and antacids (n = 2).</p

EC/NAE concentrations in smokers vs. non-smokers.

<p>EC/NAE concentrations in smokers vs. non-smokers.</p