title: DNA damage in lymphocytes of patients suffering from complex traumatization.
abstract: It has been shown that complex childhood traumatization (CCT) increases the risk for severe somatic and mental disorders. However, the somatic pathways linking maladaptive affect regulation and disease are not understood. Here we tested the hypothesis that traumatic stress is linked to the induction of DNA damage. We isolated peripheral lymphocytes (PBLCs) from blood of healthy donors and patients suffering from CCT. Cells were immobilised on slides and stained with anti-phosphohistone 2AX (γH2AX). The number of γH2AX foci, which are an accepted surrogate marker of DNA double-strand breaks (DSBs), was determined and set in relation to the patient characteristics. We show that CCT patients (HS) have higher levels of DSBs in PBLCs than healthy volunteers (CG) and psychiatric patients without CCT (LS) (HS: 0.88±0.46 foci/cell; LS: 0.31±0.23 foci/cell; CG: 0.15±0.10 foci/cell). The difference between HS and control group was highly significant (p<0.001). Insecure-dismissing attachment as a psychological marker was related to an increase in the γH2AX foci in all groups, but especially in the CCT patients. There was no significant correlation in the γH2AX level to potential external genotoxic influences such as smoking and alcohol consumption. In PBLCs, spontaneous occurring γH2AX foci partially colocalized with 53BP1 and pATM, supporting the notion they represent DSBs. Overall, our data indicate that complex traumatization is a source of genotoxic stress that can cause systemic DNA damage, pointing to the importance of emotional early life experiences for the genetically determined health status in later life periods. The finding of CCT to be interrelated to genomic instability opens new opportunities for a deeper understanding of the link between emotional stress, DNA damage and somatic disorders.
authors.affiliation: Institute of Toxicology, University Medical Center, Mainz, Germany; Clinic for Psychosomatic Medicine and Psychotherapy, University Medical Center, Mainz, Germany.
authors.forename: Liana M
authors.initials: LM
authors.lastname: Bergholz
authors.affiliation: Clinic for Psychosomatic Medicine and Psychotherapy, University Medical Center, Mainz, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Subic-Wrana
authors.affiliation: Institute of Toxicology, University Medical Center, Mainz, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Heylmann
authors.affiliation: Clinic for Psychosomatic Medicine and Psychotherapy, University Medical Center, Mainz, Germany.
authors.forename: Manfred E
authors.initials: ME
authors.lastname: Beutel
authors.affiliation: Clinic for Psychosomatic Medicine and Psychotherapy, University Medical Center, Mainz, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Wiltink
authors.affiliation: Institute of Toxicology, University Medical Center, Mainz, Germany. Electronic address: kaina@uni-mainz.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Kaina
mesh_terms: D000328:Adult; D000069586:Adult Survivors of Child Adverse Events; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013315:Stress, Psychological / Q000378:metabolism / Q000473:pathology*
keywords: DNA damage; DNA strand breaks; Emotional stress; Lymphocytes; Phosphorylated H2AX; Traumatization