Hyperarousal Symptom Severity in Women with Posttraumatic Stress Disorder Might Be Associated with LINE-1 Hypomethylation in Childhood Sexual Abuse Victims

Carolina Muniz Carvalho; Bruno Messina Coimbra; Amanda Bugiga; Diogo Ferri Marques; Vanessa Kiyomi Ota; Andrea Feijó Mello; Marcelo Feijó Mello; Sintia Iole Belangero

doi:10.1159/000529698

Hyperarousal Symptom Severity in Women with Posttraumatic Stress Disorder Might Be Associated with LINE-1 Hypomethylation in Childhood Sexual Abuse Victims

Complex Psychiatry. 2023 Feb 15;9(1-4):44-56. doi: 10.1159/000529698. eCollection 2023 Jan-Dec.

Authors

Carolina Muniz Carvalho^{1

2}, Bruno Messina Coimbra^{1

3}, Amanda Bugiga^{2

4}, Diogo Ferri Marques^{1

2

5}, Vanessa Kiyomi Ota^{2

4}, Andrea Feijó Mello¹, Marcelo Feijó Mello¹, Sintia Iole Belangero^{2

4}

Affiliations

¹ Department of Psychiatry of Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
² LiNC - Laboratory of Integrative Neuroscience of Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
³ Department of Psychiatry, Amsterdam Public Health Research Institute and Amsterdam Neuroscience Research Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
⁴ Genetics Division of Department of Morphology and Genetics of Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
⁵ Department of Medical Genetics, University of Calgary, Calgary, AB, Canada.

Abstract

Introduction: Sexual assault and a history of childhood sexual abuse (CSA) are related to posttraumatic stress disorder (PTSD) development. Long interspersed nuclear elements (LINE-1) are transposable elements, and their methylation is used to infer DNA global methylation. DNA methylation can be affected by trauma exposition which in turn would be associated with PTSD. Thus, we investigated if the LINE-1 methylation pattern is related to PTSD symptoms in females with a history of CSA.

Methods: This is a case-control study that examined, at baseline (W1), 64 women victims of sexual assault diagnosed with PTSD and 31 patients with PTSD who completed the 1-year follow-up (W2). Participants were categorized into two groups according to the presence of CSA (PTSDCSA+: NW1 = 19, NW2 = 10; PTSDCSA-: NW1 = 45, NW2 = 21). PTSD symptoms (re-experiencing, avoidance, hyperarousal, alterations in cognition/mood) were assessed using the Clinician-Administered PTSD Scale, and the history of CSA was assessed by the Childhood Trauma Questionnaire. LINE-1 methylation was measured in three sites (CpG1, CpG2, CpG3) located in the 5'UTR region using bisulfite conversion followed by pyrosequencing. Linear regression models were performed to test the relation between LINE-1 CpG sites methylation and PTSD symptoms.

Results: We found a negative association between CpG2 methylation and hyperarousal symptoms among those in the PTSDCSA+ group in W1 (adjusted p = 0.003) compared to the PTSDCSA- group (p > 0.05). Still, no association was observed between other PTSD symptoms and other CpG sites. Further, in the longitudinal analysis, LINE-1 hypomethylation was no longer observed in PTSD participants exposed to CSA.

Conclusion: Our findings suggest that LINE-1 methylation may help understand the relationship between trauma and PTSD. However, more studies are needed to investigate LINE-1 as an epigenetic marker of psychiatric disorders.

Keywords: Childhood sexual abuse; Hyperarousal symptom; LINE-1 methylation; Posttraumatic stress disorder.

Grants and funding

This work was supported by a research grant from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP2014/12559-5). CMC was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2015/26473-8). BMC was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/Brasil) – Finance-Code-001. Additional grant support came from CNPq 303389/2016-8 and CNPq 312464/2018-5.