The effect of childhood trauma on blood transcriptome expression in major depressive disorder

Alessandra Minelli, Chiara Magri, Edoardo Giacopuzzi, Massimo Gennarelli

Research output: Contribution to journalArticle

Abstract

Childhood trauma (CT) increases the likelihood of developing severe mental illnesses, such as major depressive disorder (MDD), during adulthood. Several studies have suggested an inflammatory immune system dysregulation as a biological mediator; however, the molecular mechanisms underlying this relationship remain largely undetermined. Moreover, different types of CT, in particular, emotional abuse and neglect, confer a higher risk of developing MDD, and recent meta-analyses showed that each CT can be associated with different pro-inflammatory biomarkers. However, no studies using a hypothesis-free approach have been performed. For this reason, we carried out a reanalysis of transcriptome data from a large mRNA sequencing dataset to investigate different types of CT in MDD patients. Gene expression analysis followed by principal component and gene-set enrichment analyses were carried out to identify genes and pathways differentially expressed in 368 patients who experienced four different types of CT (sexual abuse, physical abuse, emotional abuse and neglect). Expression analysis of single genes revealed a significant association between the neglect CT and the MED22 gene (p = 1.11 × 10−6; FDR = 0.016). Furthermore, analyses of the principal components of expression data support a dysregulation of cytokine system pathways, such as interferon (IFN) α/β and γ signaling, as a consequence of emotional abuse in depressed patients. Our results corroborate the hypothesis that specific types of CT affect distinct molecular pathways, and in particular, emotional abuse and neglect exert the strongest impact on gene expression in MDD.

Original languageEnglish
Pages (from-to)50-54
Number of pages5
JournalJournal of Psychiatric Research
Volume104
DOIs
Publication statusPublished - Sep 1 2018

Fingerprint

Major Depressive Disorder
Transcriptome
Wounds and Injuries
Principal Component Analysis
Genes
Gene Expression
Sex Offenses
Interferons
Meta-Analysis
Immune System
Biomarkers
Cytokines
Messenger RNA

Keywords

  • Childhood trauma
  • Inflammation
  • Major depressive disorder
  • MED22
  • RNA-seq
  • Transcriptomic

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

The effect of childhood trauma on blood transcriptome expression in major depressive disorder. / Minelli, Alessandra; Magri, Chiara; Giacopuzzi, Edoardo; Gennarelli, Massimo.

In: Journal of Psychiatric Research, Vol. 104, 01.09.2018, p. 50-54.

Research output: Contribution to journalArticle

@article{68931ca6c52f4135bf16c9a06bb7b18d,
title = "The effect of childhood trauma on blood transcriptome expression in major depressive disorder",
abstract = "Childhood trauma (CT) increases the likelihood of developing severe mental illnesses, such as major depressive disorder (MDD), during adulthood. Several studies have suggested an inflammatory immune system dysregulation as a biological mediator; however, the molecular mechanisms underlying this relationship remain largely undetermined. Moreover, different types of CT, in particular, emotional abuse and neglect, confer a higher risk of developing MDD, and recent meta-analyses showed that each CT can be associated with different pro-inflammatory biomarkers. However, no studies using a hypothesis-free approach have been performed. For this reason, we carried out a reanalysis of transcriptome data from a large mRNA sequencing dataset to investigate different types of CT in MDD patients. Gene expression analysis followed by principal component and gene-set enrichment analyses were carried out to identify genes and pathways differentially expressed in 368 patients who experienced four different types of CT (sexual abuse, physical abuse, emotional abuse and neglect). Expression analysis of single genes revealed a significant association between the neglect CT and the MED22 gene (p = 1.11 × 10−6; FDR = 0.016). Furthermore, analyses of the principal components of expression data support a dysregulation of cytokine system pathways, such as interferon (IFN) α/β and γ signaling, as a consequence of emotional abuse in depressed patients. Our results corroborate the hypothesis that specific types of CT affect distinct molecular pathways, and in particular, emotional abuse and neglect exert the strongest impact on gene expression in MDD.",
keywords = "Childhood trauma, Inflammation, Major depressive disorder, MED22, RNA-seq, Transcriptomic",
author = "Alessandra Minelli and Chiara Magri and Edoardo Giacopuzzi and Massimo Gennarelli",
year = "2018",
month = "9",
day = "1",
doi = "10.1016/j.jpsychires.2018.06.014",
language = "English",
volume = "104",
pages = "50--54",
journal = "Journal of Psychiatric Research",
issn = "0022-3956",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - The effect of childhood trauma on blood transcriptome expression in major depressive disorder

AU - Minelli, Alessandra

AU - Magri, Chiara

AU - Giacopuzzi, Edoardo

AU - Gennarelli, Massimo

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Childhood trauma (CT) increases the likelihood of developing severe mental illnesses, such as major depressive disorder (MDD), during adulthood. Several studies have suggested an inflammatory immune system dysregulation as a biological mediator; however, the molecular mechanisms underlying this relationship remain largely undetermined. Moreover, different types of CT, in particular, emotional abuse and neglect, confer a higher risk of developing MDD, and recent meta-analyses showed that each CT can be associated with different pro-inflammatory biomarkers. However, no studies using a hypothesis-free approach have been performed. For this reason, we carried out a reanalysis of transcriptome data from a large mRNA sequencing dataset to investigate different types of CT in MDD patients. Gene expression analysis followed by principal component and gene-set enrichment analyses were carried out to identify genes and pathways differentially expressed in 368 patients who experienced four different types of CT (sexual abuse, physical abuse, emotional abuse and neglect). Expression analysis of single genes revealed a significant association between the neglect CT and the MED22 gene (p = 1.11 × 10−6; FDR = 0.016). Furthermore, analyses of the principal components of expression data support a dysregulation of cytokine system pathways, such as interferon (IFN) α/β and γ signaling, as a consequence of emotional abuse in depressed patients. Our results corroborate the hypothesis that specific types of CT affect distinct molecular pathways, and in particular, emotional abuse and neglect exert the strongest impact on gene expression in MDD.

AB - Childhood trauma (CT) increases the likelihood of developing severe mental illnesses, such as major depressive disorder (MDD), during adulthood. Several studies have suggested an inflammatory immune system dysregulation as a biological mediator; however, the molecular mechanisms underlying this relationship remain largely undetermined. Moreover, different types of CT, in particular, emotional abuse and neglect, confer a higher risk of developing MDD, and recent meta-analyses showed that each CT can be associated with different pro-inflammatory biomarkers. However, no studies using a hypothesis-free approach have been performed. For this reason, we carried out a reanalysis of transcriptome data from a large mRNA sequencing dataset to investigate different types of CT in MDD patients. Gene expression analysis followed by principal component and gene-set enrichment analyses were carried out to identify genes and pathways differentially expressed in 368 patients who experienced four different types of CT (sexual abuse, physical abuse, emotional abuse and neglect). Expression analysis of single genes revealed a significant association between the neglect CT and the MED22 gene (p = 1.11 × 10−6; FDR = 0.016). Furthermore, analyses of the principal components of expression data support a dysregulation of cytokine system pathways, such as interferon (IFN) α/β and γ signaling, as a consequence of emotional abuse in depressed patients. Our results corroborate the hypothesis that specific types of CT affect distinct molecular pathways, and in particular, emotional abuse and neglect exert the strongest impact on gene expression in MDD.

KW - Childhood trauma

KW - Inflammation

KW - Major depressive disorder

KW - MED22

KW - RNA-seq

KW - Transcriptomic

UR - http://www.scopus.com/inward/record.url?scp=85049305339&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049305339&partnerID=8YFLogxK

U2 - 10.1016/j.jpsychires.2018.06.014

DO - 10.1016/j.jpsychires.2018.06.014

M3 - Article

AN - SCOPUS:85049305339

VL - 104

SP - 50

EP - 54

JO - Journal of Psychiatric Research

JF - Journal of Psychiatric Research

SN - 0022-3956

ER -