Metabolite fingerprinting in posttraumatic stress disorder
2016, Koenig, Alexandra Maria, Karabatsiakis, Alexander, Wilker, Sarah, Hamuni, Gilava, Kolassa, Stephan, Renu, Durairaj, Kadereit, Suzanne, Schauer, Maggie, Hennessy, Thomas, Kolassa, Iris-Tatjana
Background: Posttraumatic stress disorder (PTSD) is associated with an increased risk for adverse physical health outcomes. However, the underlying biomolecular processes and associated pathways remain to be further elucidated. The metabolome represents all detectable small bioactive molecules (metabolites) in a given biological sample. Metabolites are the ultimate products of environmentally shaped gene expression and protein activity and are hence closely linked with the individual health status. The untargeted and holistic investigation of the metabolome (termed metabolite fingerprinting) in biological samples might lead to novel insights in PTSD pathophysiology.
Methods: Serum samples from 20 individuals with PTSD and 18 healthy controls were analyzed by liquid chromatography coupled to a Quadrupole/Time-Of-Flight (TOF) mass spectrometer. Groups were matched based on age and ethnicity. Univariate and multivariate approaches, namely Partial Least Square Discriminant Analysis (PLS-DA), were applied for statistical analyses.
Results: The group comparison revealed 13 metabolites, which were significantly altered in PTSD, including four glycerophospholipids and one metabolite involved in endocannabinoid signaling. In the multivariate approach, a metabolite profile of 19 biomolecules predicted PTSD status with an accuracy of 85%.
Conclusions: This study illustrates the potential of metabolite fingerprinting for the identification of novel, trauma and stress-associated pathophysiological underpinning and further provides the possibility to highlight associated biomolecular pathways, such as lipid-derived and endocannabinoid signaling in PTSD.
Effects of Psychotherapy on DNA Strand Break Accumulation Originating from Traumatic Stress
2014, Morath, Julia, Moreno-Villanueva, Maria, Hamuni, Gilava, Kolassa, Stephan, Ruf-Leuschner, Martina, Schauer, Maggie, Elbert, Thomas, Bürkle, Alexander, Kolassa, Iris-Tatjana
Background: Previous research reveals an association between traumatic stress and an increased risk for numerous diseases, including cancer. At the molecular level, stress may increase carcinogenesis via increased DNA damage and impaired DNA repair mechanisms. We assessed DNA breakage in peripheral blood mononuclear cells from individuals with post-traumatic stress disorder (PTSD) and measured the cellular capacity to repair single-strand breaks after exposure to ionizing X-radiation. We also investigated the effect of psychotherapy on both DNA breakage and DNA repair. Methods: In a first study we investigated DNA breakage and repair in 34 individuals with PTSD and 31 controls. Controls were subdivided into 11 trauma-exposed subjects and 20 individuals without trauma exposure. In a second study, we analysed the effect of psychotherapy (Narrative Exposure Therapy) on DNA breakage and repair. Thirty-eight individuals with PTSD were randomly assigned to either a treatment or a waitlist control condition. Follow-up was performed 4 months and 1 year after therapy. Results: In study 1 we found higher levels of basal DNA breakage in individuals with PTSD and trauma-exposed subjects than in controls, indicating that traumatic stress is associated with DNA breakage. However, single-strand break repair was unimpaired in individuals with PTSD. In study 2, we found that psychotherapy reversed not only PTSD symptoms, but also DNA strand break accumulation. Conclusion: Our results show - for the first time in vivo - an association between traumatic stress and DNA breakage; they also demonstrate changes at the molecular level, i.e., the integrity of DNA, after psychotherapeutic interventions.
Metabolite profiling in posttraumatic stress disorder
2015, Karabatsiakis, Alexander, Hamuni, Gilava, Wilker, Sarah, Kolassa, Stephan, Renu, Durairaj, Kadereit, Suzanne, Schauer, Maggie, Hennessy, Thomas, Kolassa, Iris-Tatjana
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.
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).
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%.
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.
Posttraumatic stress disorder is associated with an enhanced spontaneous production of pro-inflammatory cytokines by peripheral blood mononuclear cells
2013, Gola, Hannah, Engler, Harald, Sommershof, Annette, Adenauer, Hannah, Kolassa, Stephan, Schedlowski, Manfred, Gröttrup, Marcus, Elbert, Thomas, Kolassa, Iris-Tatjana
Posttraumatic stress disorder (PTSD) is associated with an enhanced risk for cardiovascular and other inflammatory diseases. Chronic low-level inflammation has been suggested as a potential mechanism linking these conditions. METHODS: We investigated plasma cytokine levels as well as spontaneous and lipopolysaccharide (LPS)-stimulated cytokine production by peripheral blood mononuclear cells (PBMCs) in a group of 35 severely traumatized PTSD patients compared to 25 healthy controls. RESULTS: Spontaneous production of interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha by isolated PBMCs was significantly higher in the PTSD compared to the control group and even correlated with PTSD symptom severity within the PTSD group. In contrast, circulating plasma levels of pro- and anti-inflammatory cytokines such as IL-6, IL-8, IL-10, TNF-alpha, or monocyte chemotactic protein (MCP)-1 were not significantly altered in PTSD patients compared to healthy controls.
Our findings indicate that PBMCs of PTSD patients are already pre-activated in vivo, providing further evidence for low-grade inflammation in PTSD. This might possibly represent one psychobiological pathway from PTSD to poor physical health.
Telomere shortening in leukocyte subpopulations in depression
2014, Karabatsiakis, Alexander, Kolassa, Iris-Tatjana, Kolassa, Stephan, Rudolph, K. Lenhard, Dietrich, Detlef E.
Telomere shortening is a normal age-related process. However, premature shortening of telomeres in leukocytes – as has been reported in depression – may increase the risk for age-related diseases. While previous studies investigated telomere length in peripheral blood mononuclear cells (PBMCs) as a whole, this study investigated specific changes in the clonal composition of white blood cells of the adaptive immune system (CD4+ helper and CD8+ cytotoxic T lymphocytes, and CD20+ B lymphocytes).
Forty-four females with a history of unipolar depression were investigated and compared to fifty age-matched female controls. Telomere lengths were compared between three groups: 1) individuals with a history of depression but currently no clinically relevant depressive symptoms, 2) individuals with a history of depression with relevant symptoms of depression, and 3) healthy age-matched controls. Telomere length was assessed using quantitative fluorescence in situ hybridization (qFISH).
Both groups with a history of unipolar depression (with and without current depressive symptoms) showed significantly shorter telomeres in all three lymphocyte subpopulations. The effect was stronger in CD8+ and CD20+ cells than in CD4+ cells. Individuals with a history of depression and with (without) current symptoms exhibited a CD8+ telomere length shortening corresponding to an age differential of 27.9 (25.3) years.
A history of depression is associated with shortened telomeres in the main effector populations of the adaptive immune system. Shorter telomeres seem to persist in individuals with lifetime depression independently of the severity of depressive symptoms. CD8+ cytotoxic T cells and CD20+ B cells seem to be particularly affected in depression. The total number of depressive episodes did not influence telomere length in the investigated adaptive immune cell populations.