TY - JOUR
T1 - Investigation of MORC1 DNA methylation as biomarker of early life stress and depressive symptoms
AU - Thomas, Mara
AU - Coope, Andressa
AU - Falkenberg, Carolin
AU - Dunlop, Boadie W.
AU - Czamara, Darina
AU - Provencal, Nadine
AU - Craighead, W. Edward
AU - Mayberg, Helen S.
AU - Nemeroff, Charles B.
AU - Binder, Elisabeth B.
AU - Nieratschker, Vanessa
N1 - Funding Information:
WEC is a board member of Hugarheill ehf, an Icelandic company dedicated to the prevention of depression, and he receives book royalties from John Wiley & Sons. His research is also supported by the Mary and John Brock Foundation and the Fuqua family foundations . He is a consultant to the George West Mental Health Foundation and is a member of the Scientific Advisory Boards of the ADAA and AIM for Mental Health.
Funding Information:
We thank the patients, staff, and faculty of the Grady Trauma Project and the PReDICT study for sharing their data. We also thank the study participants of the Tuebingen cohort and the medical staff of the University Hospital Tuebingen for their support. We thank all funding agencies for their financial support of this study.
PY - 2020/1
Y1 - 2020/1
N2 - Early life stress (ELS) is associated with an increased risk of depression and this association may be mediated by epigenetic mechanisms. A previous epigenome-wide DNA methylation (DNAm) study investigating human newborns and two animal models of ELS suggested that the epigenetic regulator MORC1 is differentially methylated following ELS. The ELS-induced DNAm alterations were long-lasting in the animal models. However, whether this finding is also transferable to humans experiencing ELS in childhood was not investigated. Further, MORC1 may provide a link between ELS and adult depression, as MORC1 DNAm and genetic variants were found to be associated with depressive symptoms in humans. In the present study, we investigated the validity of MORC1 DNAm as a biomarker of ELS in humans and its role in linking ELS to depression later in life by studying childhood maltreatment. We analyzed whole blood MORC1 DNAm in an adult cohort (N = 151) that was characterized for both the presence of depressive symptoms and childhood maltreatment. Further, we investigated the association between MORC1 DNAm, depressive symptoms and childhood maltreatment in two additional cohorts (N = 299, N = 310). Overall, our data do not indicate an association of MORC1 DNAm with childhood maltreatment. An association of MORC1 DNAm with depressive symptoms was present in all cohorts, but was inconsistent in the specific CpG sites associated and the direction of effect (Tuebingen cohort: standardized β = 0.16, unstandardized β = 0.01, 95% CI [-0.0004, −0.0179], p = 0.061, PReDICT cohort: standardized β = −0.12, unstandardized β = −0.01, 95% CI [-0.0258, −0.0003], p = 0.045), Grady cohort: standardized β = 0.16, unstandardized β = 0.008, 95% CI [0.0019, 0.0143], p = 0.01). Our study thus suggests that peripheral MORC1 DNAm cannot serve as biomarker of childhood maltreatment in adults, but does provide further indication for the association of MORC1 DNAm with depressive symptoms.
AB - Early life stress (ELS) is associated with an increased risk of depression and this association may be mediated by epigenetic mechanisms. A previous epigenome-wide DNA methylation (DNAm) study investigating human newborns and two animal models of ELS suggested that the epigenetic regulator MORC1 is differentially methylated following ELS. The ELS-induced DNAm alterations were long-lasting in the animal models. However, whether this finding is also transferable to humans experiencing ELS in childhood was not investigated. Further, MORC1 may provide a link between ELS and adult depression, as MORC1 DNAm and genetic variants were found to be associated with depressive symptoms in humans. In the present study, we investigated the validity of MORC1 DNAm as a biomarker of ELS in humans and its role in linking ELS to depression later in life by studying childhood maltreatment. We analyzed whole blood MORC1 DNAm in an adult cohort (N = 151) that was characterized for both the presence of depressive symptoms and childhood maltreatment. Further, we investigated the association between MORC1 DNAm, depressive symptoms and childhood maltreatment in two additional cohorts (N = 299, N = 310). Overall, our data do not indicate an association of MORC1 DNAm with childhood maltreatment. An association of MORC1 DNAm with depressive symptoms was present in all cohorts, but was inconsistent in the specific CpG sites associated and the direction of effect (Tuebingen cohort: standardized β = 0.16, unstandardized β = 0.01, 95% CI [-0.0004, −0.0179], p = 0.061, PReDICT cohort: standardized β = −0.12, unstandardized β = −0.01, 95% CI [-0.0258, −0.0003], p = 0.045), Grady cohort: standardized β = 0.16, unstandardized β = 0.008, 95% CI [0.0019, 0.0143], p = 0.01). Our study thus suggests that peripheral MORC1 DNAm cannot serve as biomarker of childhood maltreatment in adults, but does provide further indication for the association of MORC1 DNAm with depressive symptoms.
KW - Childhood trauma
KW - DNA methylation
KW - Depression
KW - Early life stress
KW - Epigenetics
UR - http://www.scopus.com/inward/record.url?scp=85074235287&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074235287&partnerID=8YFLogxK
U2 - 10.1016/j.jpsychires.2019.10.019
DO - 10.1016/j.jpsychires.2019.10.019
M3 - Article
C2 - 31683097
AN - SCOPUS:85074235287
VL - 120
SP - 154
EP - 162
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
SN - 0022-3956
ER -