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; Diego 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

Carolina Muniz Carvalho^*
, Bruno Messina Coimbra
, Amanda Bugiga
, Diego Ferri Marques
, Vanessa Kiyomi Ota
, Andrea Feijó Mello
, Marcelo Feijó Mello
, Sintia Iole Belangero

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	44-56
Number of pages	13
Journal	Complex Psychiatry
Volume	9
Issue number	1-4
DOIs	https://doi.org/10.1159/000529698
Publication status	Published - 15 Feb 2023
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2023 S. Karger AG, Basel. Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.

Funding

Funding Sources 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. 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.

Funders	Funder number
Brasil	Finance-Code-001
Fundação de Amparo à Pesquisa do Estado de São Paulo	2015/26473-8, FAPESP2014/12559-5
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Conselho Nacional de Desenvolvimento Científico e Tecnológico	303389/2016-8, 312464/2018-5

Keywords

Childhood sexual abuse
Hyperarousalsymptom
LINE-1 methylation
Posttraumaticstress disorder

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10.1159/000529698

Cite this

@article{f9ef352cb09e49ad8f761fba8f351ea6,

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

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, Hyperarousalsymptom, LINE-1 methylation, Posttraumaticstress disorder",

author = "Carvalho, \{Carolina Muniz\} and Coimbra, \{Bruno Messina\} and Amanda Bugiga and \{Ferri Marques\}, Diego and \{Kiyomi Ota\}, Vanessa and Mello, \{Andrea Feij{\'o}\} and Mello, \{Marcelo Feij{\'o}\} and Belangero, \{Sintia Iole\}",

note = "Publisher Copyright: {\textcopyright} 2023 S. Karger AG, Basel. Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.",

year = "2023",

month = feb,

day = "15",

doi = "10.1159/000529698",

language = "English",

volume = "9",

pages = "44--56",

journal = "Complex Psychiatry",

issn = "2673-3005",

publisher = "S. Karger AG",

number = "1-4",

}

Hyperarousal Symptom Severity in Women with Posttraumatic Stress Disorder Might Be Associated with LINE-1 Hypomethylation in Childhood Sexual Abuse Victims. / Carvalho, Carolina Muniz; Coimbra, Bruno Messina; Bugiga, Amanda et al.
In: Complex Psychiatry, Vol. 9, No. 1-4, 15.02.2023, p. 44-56.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Hyperarousal Symptom Severity in Women with Posttraumatic Stress Disorder Might Be Associated with LINE-1 Hypomethylation in Childhood Sexual Abuse Victims

AU - Carvalho, Carolina Muniz

AU - Coimbra, Bruno Messina

AU - Bugiga, Amanda

AU - Ferri Marques, Diego

AU - Kiyomi Ota, Vanessa

AU - Mello, Andrea Feijó

AU - Mello, Marcelo Feijó

AU - Belangero, Sintia Iole

N1 - Publisher Copyright: © 2023 S. Karger AG, Basel. Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.

PY - 2023/2/15

Y1 - 2023/2/15

N2 - 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.

AB - 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.

KW - Childhood sexual abuse

KW - Hyperarousalsymptom

KW - LINE-1 methylation

KW - Posttraumaticstress disorder

UR - https://www.scopus.com/pages/publications/85163869481

U2 - 10.1159/000529698

DO - 10.1159/000529698

M3 - Article

C2 - 37034826

SN - 2673-3005

VL - 9

SP - 44

EP - 56

JO - Complex Psychiatry

JF - Complex Psychiatry

IS - 1-4

ER -

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

Abstract

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Keywords

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