NTRK2 methylation is related to reduced PTSD risk in two African cohorts of trauma survivors

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 117; no. 35; pp. 21667 - 21672
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 01-09-2020
• Subjects: Activity recognition; Adult; Aged; Biological Sciences; Brain; Brain - metabolism; Brain mapping; Brain-derived neurotrophic factor; Cognitive ability; DNA Methylation - genetics; Epigenesis, Genetic - genetics; Epigenetics; Female; Functional magnetic resonance imaging; Gene regulation; Glucocorticoids; Glucocorticoids - metabolism; Humans; Kinases; Male; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Memory - physiology; Mental disorders; Methylation; Middle Aged; Polymorphism, Single Nucleotide - genetics; Populations; Post traumatic stress disorder; Psychological stress; Receptor, trkB - genetics; Receptor, trkB - metabolism; Receptors; Receptors, Glucocorticoid - metabolism; Risk; Risk Factors; Rwanda - epidemiology; Social Sciences; Stress Disorders, Post-Traumatic - genetics; Stress Disorders, Post-Traumatic - metabolism; Survival; Survivors; Trauma; Tropomyosin; Uganda - epidemiology; Uganda; Rwanda; PTSD; NTRK2; memory; glucocorticoids; epigenetics
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2008415117

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.