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

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.