NTRK2 methylation is related to reduced PTSD risk in two African cohorts of trauma survivors
2020-09-01, Vukojevic, Vanja, Coynel, David, Ghaffari, Navid R., Freytag, Virginie, Elbert, Thomas, Kolassa, Iris-Tatjana, Wilker, Sarah, McGaugh, James L., Papassotiropoulos, Andreas, de Quervain, Dominique J.-F.
Extensive pharmacologic, genetic, and epigenetic research has linked the glucocorticoid receptor (GR) to memory processes, and to risk and symptoms of posttraumatic stress disorder (PTSD). In the present study we investigated the epigenetic pattern of 12 genes involved in the regulation of GR signaling in two African populations of heavily traumatized individuals: Survivors of the rebel war in northern Uganda (n = 463) and survivors of the Rwandan genocide (n = 350). The strongest link between regional methylation and PTSD risk and symptoms was observed for NTRK2, which encodes the transmembrane receptor tropomyosin-related kinase B, binds the brain-derived neurotrophic factor, and has been shown to play an important role in memory formation. NTRK2 methylation was not related to trauma load, suggesting that methylation differences preexisted the trauma. Because NTRK2 methylation differences were predominantly associated with memory-related PTSD symptoms, and because they seem to precede traumatic events, we next investigated the relationship between NTRK2 methylation and memory in a sample of nontraumatized individuals (n = 568). We found that NTRK2 methylation was negatively associated with recognition memory performance. Furthermore, fMRI analyses revealed NTRK2 methylation-dependent differences in brain network activity related to recognition memory. The present study demonstrates that NTRK2 is epigenetically linked to memory functions in nontraumatized subjects and to PTSD risk and symptoms in traumatized populations.
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.
Neurobiological Findings in Post-traumatic Stress Disorder
2015, Kolassa, Iris-Tatjana, Illek, Sonja, Wilker, Sarah, Karabatsiakis, Alexander, Elbert, Thomas
Post-traumatic stress disorder (PTSD) symptoms are present across cultures, with the only differences being the indigenous ways in which affected individuals deal with them. Hence, there must be a common underlying basis for these symptoms. The development of an intense memory for the traumatic experiences encountered, and associated neurobiological alterations, may explain the cross-cultural occurrence of similar PTSD symptoms.
This chapter presents selected neurobiological findings in post-traumatic stress disorder (PTSD) in the framework of a neurobiological model of PTSD, the fear network model, which explains the development of strong associative emotional-sensory memories for traumatic events. With repeated exposure to traumatic stressors, this associative network gets strengthened but at the same time detached from the corresponding contextual information. After introducing this theoretical background, we next review current knowledge on genetic risk factors for PTSD development, followed by epigenetic alterations found in trauma survivors with PTSD. This is followed by a section on physiological alterations associated with a diagnosis of PTSD. We elaborate on structural and functional alterations in the brain of trauma survivors with PTSD, which correspond well with the assumptions of the fear network model. Furthermore, we summarize evidence that trauma exposure and subsequent PTSD can have adverse physical health consequences, such as cardiovascular, cerebrovascular, gastrointestinal, musculoskeletal, inflammatory, and autoimmune diseases, and accelerate the aging process, increasing the risk for the earlier onset of age-related diseases. We illustrate on a molecular level which processes increase disease risk in traumatized populations. Finally, we show that at least some PTSD-associated molecular alterations might be reversible through treatment.