Differential DNA Methylation Is Associated With Hippocampal Abnormalities in Pediatric Posttraumatic Stress Disorder.
Biological pathways
Child and adolescent psychiatry
Epigenetics
Imaging
Methylation
Posttraumatic stress disorder
Journal
Biological psychiatry. Cognitive neuroscience and neuroimaging
ISSN: 2451-9030
Titre abrégé: Biol Psychiatry Cogn Neurosci Neuroimaging
Pays: United States
ID NLM: 101671285
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
19
01
2021
revised:
01
04
2021
accepted:
26
04
2021
pubmed:
9
5
2021
medline:
19
11
2021
entrez:
8
5
2021
Statut:
ppublish
Résumé
Recent findings in neuroimaging and epigenetics offer important insights into brain structures and biological pathways of altered gene expression associated with posttraumatic stress disorder (PTSD). However, it is unknown to what extent epigenetic mechanisms are associated with PTSD and its neurobiology in youth. In this study, we combined a methylome-wide association study and structural neuroimaging measures in a Dutch cohort of youths with PTSD (8-18 years of age). We aimed to replicate findings in a similar independent U.S. cohort. We found significant methylome-wide associations for pediatric PTSD (false discovery rate p < .05) compared with non-PTSD control groups (traumatized and nontraumatized youths). Methylation differences on nine genes were replicated, including genes related to glucocorticoid functioning. In both cohorts, methylation on OLFM3 gene was further associated with anterior hippocampal volume. These findings point to molecular pathways involved in inflammation, stress response, and neuroplasticity as potential contributors to neural abnormalities and provide potentially unique biomarkers and treatment targets for pediatric PTSD.
Sections du résumé
BACKGROUND
Recent findings in neuroimaging and epigenetics offer important insights into brain structures and biological pathways of altered gene expression associated with posttraumatic stress disorder (PTSD). However, it is unknown to what extent epigenetic mechanisms are associated with PTSD and its neurobiology in youth.
METHODS
In this study, we combined a methylome-wide association study and structural neuroimaging measures in a Dutch cohort of youths with PTSD (8-18 years of age). We aimed to replicate findings in a similar independent U.S. cohort.
RESULTS
We found significant methylome-wide associations for pediatric PTSD (false discovery rate p < .05) compared with non-PTSD control groups (traumatized and nontraumatized youths). Methylation differences on nine genes were replicated, including genes related to glucocorticoid functioning. In both cohorts, methylation on OLFM3 gene was further associated with anterior hippocampal volume.
CONCLUSIONS
These findings point to molecular pathways involved in inflammation, stress response, and neuroplasticity as potential contributors to neural abnormalities and provide potentially unique biomarkers and treatment targets for pediatric PTSD.
Identifiants
pubmed: 33964519
pii: S2451-9022(21)00123-3
doi: 10.1016/j.bpsc.2021.04.016
pmc: PMC8568739
mid: NIHMS1727898
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1063-1070Subventions
Organisme : NIMH NIH HHS
ID : K08 MH100267
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH115910
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH117141
Pays : United States
Informations de copyright
Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Références
Depress Anxiety. 2008;25(6):514-26
pubmed: 17598145
BMC Bioinformatics. 2015 Apr 28;16:131
pubmed: 25928765
Nat Commun. 2020 Nov 24;11(1):5965
pubmed: 33235198
Brain Behav Immun. 2021 Jan;91:429-436
pubmed: 33152445
J Mol Biol. 2019 Apr 19;431(9):1830-1842
pubmed: 30878483
Am J Psychiatry. 2015 Jun;172(6):543-52
pubmed: 25982659
Neuropsychopharmacology. 2006 Aug;31(8):1822-31
pubmed: 16482088
Transl Psychiatry. 2017 Jul 11;7(7):e1169
pubmed: 28696412
Arch Gen Psychiatry. 2007 May;64(5):577-84
pubmed: 17485609
Front Cell Neurosci. 2018 Aug 03;12:243
pubmed: 30123114
Front Psychiatry. 2019 Nov 08;10:808
pubmed: 31780969
Mol Neurobiol. 2019 Feb;56(2):1421-1436
pubmed: 29948944
Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 Feb;4(2):171-179
pubmed: 30343133
Neuropsychopharmacology. 2015 Feb;40(3):537-45
pubmed: 25212487
Psychoneuroendocrinology. 2019 Nov;109:104380
pubmed: 31352130
Genome Biol. 2017 Jan 27;18(1):19
pubmed: 28129774
Nat Neurosci. 2014 Jan;17(1):131-43
pubmed: 24316888
Schizophr Bull. 2018 Feb 15;44(2):443-452
pubmed: 28521044
Schizophr Res. 2015 Dec;169(1-3):447-452
pubmed: 26381449
Bioinformatics. 2012 Apr 15;28(8):1109-13
pubmed: 22368244
J Pediatr Psychol. 2010 Jun;35(5):559-69
pubmed: 19995868
Depress Anxiety. 2006;23(1):17-25
pubmed: 16247760
Psychoneuroendocrinology. 2019 Aug;106:233-243
pubmed: 31005044
Mol Psychiatry. 2021 Aug;26(8):3884-3895
pubmed: 31811260
J Am Acad Child Adolesc Psychiatry. 2013 Aug;52(8):815-830.e14
pubmed: 23880492
Soc Psychiatry Psychiatr Epidemiol. 2015 Apr;50(4):525-37
pubmed: 25398198
Br J Psychiatry. 2014;204:335-40
pubmed: 24785767
Brain Sci. 2020 Mar 14;10(3):
pubmed: 32183256
Stress. 2017 Sep;20(5):449-464
pubmed: 28436309
Front Cell Dev Biol. 2014 Feb 26;2:6
pubmed: 25364714
Biol Psychiatry. 2021 Jan 15;89(2):144-151
pubmed: 32709416
Neurosci Biobehav Rev. 2020 May;112:392-409
pubmed: 32081689