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.

2009, Kolassa, Iris-Tatjana, Jurisch, Florentine, Elbert, Thomas

2017-03-27, Heck, Angela, Milnik, Annette, Vukojevic, Vanja, Petrovska, Jana, Egli, Tobias, Singer, Jochen, Escobar, Pablo, Kolassa, Iris-Tatjana, Elbert, Thomas, Papassotiropoulos, Andreas

Many mental disorders represent the extremes of the normal distribution of traits, which are related to multiple cognitive and emotional dimensions. By performing whole-exome sequencing of healthy, young subjects with extremely high versus extremely low aversive memory performance, we identified TROVE2 as a gene implicated in emotional memory in health and disease. TROVE2 encodes Ro60, a broadly expressed RNA-binding protein implicated in the regulation of inflammatory gene expression and autoimmunity. A regulatory TROVE2 variant was linked to higher emotional memory capacity and higher emotional memory-related brain activation in healthy subjects. In addition, TROVE2 was associated with traumatic memory and the frequency of post-traumatic stress disorder in genocide survivors.

2006, Elbert, Thomas, Rockstroh, Brigitte, Kolassa, Iris-Tatjana, Schauer, Maggie, Neuner, Frank

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.