Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Vukojevic V

PROVIDER: S-EPMC7474665 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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

Vukojevic Vanja V Coynel David D Ghaffari Navid R NR Freytag Virginie V Elbert Thomas T Kolassa Iris-Tatjana IT Wilker Sarah S McGaugh James L JL Papassotiropoulos Andreas A de Quervain Dominique J-F DJ

Proceedings of the National Academy of Sciences of the United States of America 20200817 35

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 ...[more]

PMID: 32817534

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Project description:Background: Network analysis has gained increasing attention as a new framework to study complex associations between symptoms of post-traumatic stress disorder (PTSD). A number of studies have been published to investigate symptom networks on different sets of symptoms in different populations, and the findings have been inconsistent. Objective: We aimed to extend previous research by testing whether differences in PTSD symptom networks can be found in survivors of type I (single event; sudden and unexpected, high levels of acute threat) vs. type II (repeated and/or protracted; anticipated) trauma (with regard to their index trauma). Method: Participants were trauma-exposed individuals with elevated levels of PTSD symptomatology, most of whom (94%) were undergoing assessment in preparation for PTSD treatment in several treatment centres in Germany and Switzerland (n = 286 with type I and n = 187 with type II trauma). We estimated Bayesian Gaussian graphical models for each trauma group and explored group differences in the symptom network. Results: First, for both trauma types, our analyses identified the edges that were repeatedly reported in previous network studies. Second, there was decisive evidence that the two networks were generated from different multivariate normal distributions, i.e. the networks differed on a global level. Third, explorative edge-wise comparisons showed moderate or strong evidence for specific 12 edges. Edges which emerged as especially important in distinguishing the networks were between intrusions and flashbacks, highlighting the stronger positive association in the group of type II trauma survivors compared to type I survivors. Flashbacks showed a similar pattern of results in the associations with detachment and sleep problems (type II > type I). Conclusion: Our findings suggest that trauma type contributes to the heterogeneity in the symptom network. Future research on PTSD symptom networks should include this variable in the analyses to reduce heterogeneity.

Dataset Information

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

Publications

<i>NTRK2</i> methylation is related to reduced PTSD risk in two African cohorts of trauma survivors.

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