TY - JOUR

T1 - DNA methylation in blood cells is associated with cortisol levels in offspring of mothers who had prenatal post-traumatic stress disorder

AU - Fransquet, Peter Daniel

AU - Hjort, Line

AU - Rushiti, Feride

AU - Wang, Shr Jie

AU - Krasniqi, Sebahate Pacolli

AU - Çarkaxhiu, Selvi Izeti

AU - Arifaj, Dafina

AU - Xhemaili, Vjosa Devaja

AU - Salihu, Mimoza

AU - Leku, Nazmie Abullahu

AU - Ryan, Joanne

N1 - Publisher Copyright: © 2022 The Authors. Stress and Health published by John Wiley & Sons Ltd.

PY - 2022

Y1 - 2022

N2 - Maternal stress during pregnancy is associated with differential DNA methylation in offspring and disrupted cortisol secretion. This study aimed to determine methylation signatures of cortisol levels in children, and whether associations differ based on maternal post-traumatic stress disorder (PTSD). Blood epigenome-wide methylation and fasting cortisol levels were measured in 118 offspring of mothers recruited from the Kosovo Rehabilitation Centre for Torture Victims. Mothers underwent clinically administered assessment for PTSD using Diagnostic and Statistical Manual of Mental Disorders. Correlations between offspring methylation and cortisol levels were examined using epigenome-wide analysis, adjusting for covariates. Subsequent analysis focussed on a priori selected genes involved in the hypothalamic–pituitary–adrenal (HPA) axis stress signalling. Methylation at four sites were correlated with cortisol levels (cg15321696, r = −0.33, cg18105800, r = +0.33, cg00986889, r = −0.25, and cg15920527, r = −0.27). In adjusted multivariable regression, when stratifying based on prenatal PTSD status, significant associations were only found for children born to mothers with prenatal PTSD (p < 0.001). Several sites within HPA axis genes were also associated with cortisol levels in the maternal PTSD group specifically. There is evidence that methylation is associated with cortisol levels, particularly in offspring born to mothers with prenatal PTSD. However, larger studies need to be carried out to independently validate these findings.

AB - Maternal stress during pregnancy is associated with differential DNA methylation in offspring and disrupted cortisol secretion. This study aimed to determine methylation signatures of cortisol levels in children, and whether associations differ based on maternal post-traumatic stress disorder (PTSD). Blood epigenome-wide methylation and fasting cortisol levels were measured in 118 offspring of mothers recruited from the Kosovo Rehabilitation Centre for Torture Victims. Mothers underwent clinically administered assessment for PTSD using Diagnostic and Statistical Manual of Mental Disorders. Correlations between offspring methylation and cortisol levels were examined using epigenome-wide analysis, adjusting for covariates. Subsequent analysis focussed on a priori selected genes involved in the hypothalamic–pituitary–adrenal (HPA) axis stress signalling. Methylation at four sites were correlated with cortisol levels (cg15321696, r = −0.33, cg18105800, r = +0.33, cg00986889, r = −0.25, and cg15920527, r = −0.27). In adjusted multivariable regression, when stratifying based on prenatal PTSD status, significant associations were only found for children born to mothers with prenatal PTSD (p < 0.001). Several sites within HPA axis genes were also associated with cortisol levels in the maternal PTSD group specifically. There is evidence that methylation is associated with cortisol levels, particularly in offspring born to mothers with prenatal PTSD. However, larger studies need to be carried out to independently validate these findings.

KW - BDNF

KW - cortisol

KW - CRH

KW - CRHR1/2

KW - DNA methylation

KW - epigenetics

KW - FKBP5

KW - intergenerational

KW - maternal PTSD

KW - NR3C1/2

KW - offspring

KW - war

U2 - 10.1002/smi.3131

DO - 10.1002/smi.3131

M3 - Journal article

C2 - 35119793

AN - SCOPUS:85124591829

VL - 38

SP - 755

EP - 766

JO - Stress and Health

JF - Stress and Health

SN - 1532-2998

IS - 4

ER -