Altered Stress-Induced Regulation of Genes in Monocytes in Adults with a History of Childhood Adversity.
Exposure to serious or traumatic events early in life can lead to persistent alterations in physiological stress response systems, including enhanced cross talk between the neuroendocrine and immune system. These programming effects may be mechanistically involved in mediating the effects of adverse childhood experience on disease risk in adulthood. We investigated hormonal and genome-wide mRNA expression responses in monocytes to acute stress exposure, in a sample of healthy adults (n=30) with a history of early childhood adversity, and a control group (n=30) without trauma experience. The early adversity group showed altered hypothalamus-pituitary-adrenal axis responses to stress, evidenced by lower ACTH and cortisol responses. Analyses of gene expression patterns showed that stress-responsive transcripts were enriched for genes involved in cytokine activity, cytokine-cytokine receptor interaction, chemokine activity, and G-protein coupled receptor binding. Differences between groups in stress-induced regulation of gene transcription were observed for genes involved in steroid binding, hormone activity, and G-protein coupled receptor binding. Transcription factor binding motif analysis showed an increased activity of pro-inflammatory upstream signaling in the early adversity group. We also identified transcripts that were differentially correlated with stress-induced cortisol increases between the groups, enriched for genes involved in cytokine-cytokine receptor interaction and glutamate receptor signaling. We suggest that childhood adversity leads to persistent alterations in transcriptional control of stress-responsive pathways, which-when chronically or repeatedly activated-might predispose individuals to stress-related psychopathology.
Department of Genetic Psychology, Faculty of Psychology, Ruhr-University Bochum, Bochum, Germany.
Marion
M
Schwaiger
Department of Statistics, TU Dortmund University, Dortmund, Germany.
Marianna
M
Grinberg
Department of Genetic Psychology, Faculty of Psychology, Ruhr-University Bochum, Bochum, Germany.
Dirk
D
Moser
Department of Genetic Psychology, Faculty of Psychology, Ruhr-University Bochum, Bochum, Germany.
Johannes C S
JC
Zang
Department of Psychology, Laboratory for Biological and Personality Psychology, University of Freiburg, Freiburg, Germany.|Freiburg Brain Imaging Center, University Medical Center, University of Freiburg, Freiburg, Germany.
Markus
M
Heinrichs
Leibniz Research Centre for Working Environment and Human Factors at the Technical University of Dortmund (IfADo), Dortmund, Germany.
Jan G
JG
Hengstler
Department of Statistics, TU Dortmund University, Dortmund, Germany.
Jörg
J
Rahnenführer
David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Steve
S
Cole
Department of Genetic Psychology, Faculty of Psychology, Ruhr-University Bochum, Bochum, Germany.
Robert
R
Kumsta
D000324:Adrenocorticotropic Hormone / Q000097:blood; D002648:Child; D002649:Child Abuse / Q000523:psychology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D018709:Statistics, Nonparametric; D013315:Stress, Psychological / Q000097:blood / Q000473:pathology* / Q000503:physiopathology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D016207:Cytokines; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D014157:Transcription Factors; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone