Investigation of MORC1 DNA methylation as biomarker of early life stress and depressive symptoms

Mara Thomas, Andressa Coope, Carolin Falkenberg, Boadie W. Dunlop, Darina Czamara, Nadine Provencal, W. Edward Craighead, Helen S. Mayberg, Charles B. Nemeroff, Elisabeth B. Binder, Vanessa Nieratschker

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)154-162
Number of pages9
JournalJournal of Psychiatric Research
Volume120
DOIs
StatePublished - Jan 2020
Externally publishedYes

Fingerprint

DNA Methylation
Psychological Stress
Biomarkers
Depression
Epigenomics
Animal Models
Newborn Animals
Cohort Effect

Keywords

  • Childhood trauma
  • Depression
  • DNA methylation
  • Early life stress
  • Epigenetics

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Thomas, M., Coope, A., Falkenberg, C., Dunlop, B. W., Czamara, D., Provencal, N., ... Nieratschker, V. (2020). Investigation of MORC1 DNA methylation as biomarker of early life stress and depressive symptoms. Journal of Psychiatric Research, 120, 154-162. https://doi.org/10.1016/j.jpsychires.2019.10.019

Investigation of MORC1 DNA methylation as biomarker of early life stress and depressive symptoms. / Thomas, Mara; Coope, Andressa; Falkenberg, Carolin; Dunlop, Boadie W.; Czamara, Darina; Provencal, Nadine; Craighead, W. Edward; Mayberg, Helen S.; Nemeroff, Charles B.; Binder, Elisabeth B.; Nieratschker, Vanessa.

In: Journal of Psychiatric Research, Vol. 120, 01.2020, p. 154-162.

Research output: Contribution to journalArticle

Thomas, M, Coope, A, Falkenberg, C, Dunlop, BW, Czamara, D, Provencal, N, Craighead, WE, Mayberg, HS, Nemeroff, CB, Binder, EB & Nieratschker, V 2020, 'Investigation of MORC1 DNA methylation as biomarker of early life stress and depressive symptoms', Journal of Psychiatric Research, vol. 120, pp. 154-162. https://doi.org/10.1016/j.jpsychires.2019.10.019
Thomas, Mara ; Coope, Andressa ; Falkenberg, Carolin ; Dunlop, Boadie W. ; Czamara, Darina ; Provencal, Nadine ; Craighead, W. Edward ; Mayberg, Helen S. ; Nemeroff, Charles B. ; Binder, Elisabeth B. ; Nieratschker, Vanessa. / Investigation of MORC1 DNA methylation as biomarker of early life stress and depressive symptoms. In: Journal of Psychiatric Research. 2020 ; Vol. 120. pp. 154-162.
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abstract = "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.",
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AU - Provencal, Nadine

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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.

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