Early trauma and inflammation: role of familial factors in a study of twins. Psychosom Med

Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Rd, Atlanta, GA 30322, USA.
Psychosomatic Medicine (Impact Factor: 3.47). 02/2012; 74(2):146-52. DOI: 10.1097/PSY.0b013e318240a7d8
Source: PubMed


Although early trauma (trauma in childhood) has been linked to adult inflammation and adult disease of inflammatory origin, it remains unknown whether this relationship is due to long-term consequences of early life stress or other familial factors.
We examined 482 male middle-aged twins (241 pairs) born between 1946 and 1956 from the Vietnam Era Twin Registry. Childhood traumatic experiences, before the age of 18 years, were measured retrospectively with the Early Trauma Inventory and included physical, sexual, emotional abuse and general trauma. Lifetime major depressive disorder and posttraumatic stress disorder were assessed with the Structured Clinical Interview for DSM-IV. Traditional risk factors for cardiovascular disease were also assessed. Plasma C-reactive protein and interleukin 6 were measured to determine levels of inflammation. Mixed-effects regression models with a random intercept for pair were used to separate between- and within-twin pair effects.
When twins were analyzed as individuals, increasing levels of early trauma were positively related to C-reactive protein (p = .03) but not to interleukin 6 (p = .12). When estimating within- and between-pair effects, only the between-pair association of early trauma with the inflammatory markers remained significant.
The link between early trauma and inflammation is largely explained by familial factors shared by the twins because levels of inflammation were highest when both twins were exposed to trauma. Exposure to early trauma may be a marker for an unhealthy familial environment. Clarification of familial factors associated with early stress and adult inflammation will be important to uncover correlates of stress and disease.

Download full-text


Available from: Viola Vaccarino,
    • "Affective disorders Depression CRP, IL-6 (after additional stress exposure) Rice et al. (2009), Fagundes et al. (2013) Anxiety disorders CRP, IL-6, TNFa, Duivis et al. (2013) Post Traumatic Stress Disorder CRP, TNFa, IL-4 Plantinga et al. (2013), Spitzer et al. (2010), Von Känel et al. (2007), Turner et al. (2013) Low socioeconomic status CRP, IL-6 (after additional stress exposure), sICAM, ET-1 Nazmi and Victora (2007), Brydon et al. (2004), Hong et al. (2006) Caregiver stress IL-6, CRP, D-dimer Nazmi and Victora (2007), Kiecolt-Glaser et al. (2003), Von Känel et al. (2006), Miller et al. (2008) Loneliness/social isolation IL-6, CRP, sICAM-1 Ford et al. (2006), Loucks et al. (2006), Heffner et al. (2011) Early life stress/childhood maltreatment CRP, fibrinogen Danese et al. (2007), Rooks et al. (2012) "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cardiovascular disease (CVD) remains a leading cause of death worldwide and identification and therapeutic modulation of all its risk factors is necessary to ensure a lower burden on the patient and on society. The physiological response to acute and chronic stress exposure has long been recognized as a potent modulator of immune, endocrine and metabolic pathways, however its direct implications for cardiovascular disease development, progression and as a therapeutic target are not completely understood. More and more attention is given to the bidirectional interaction between psychological and physical health in relation to cardiovascular disease. With atherosclerosis being a chronic disease starting already at an early age the contribution of adverse early life events in affecting adult health risk behavior, health status and disease development is receiving increased attention. In addition, experimental research into the biological pathways involved in stress-induced cardiovascular complications show important roles for metabolic and immunologic maladaptation, resulting in increased disease development and progression. Here we provide a concise overview of human and experimental animal data linking chronic and acute stress to CVD risk and increased progression of the underlying disease atherosclerosis. Copyright © 2015. Published by Elsevier Inc.
    Brain Behavior and Immunity 08/2015; DOI:10.1016/j.bbi.2015.08.007 · 5.89 Impact Factor
  • Source
    • "Bertone-Johnson et al., 2012 Subtotal Witek-Janusek et al., 2013 Tietjen et al., 2012 Bertone-Johnson et al., 2012 Rooks et al., 2012 Hartwell et al., 2013 Runsten et al., 2012 Tietjen et al., 2012 Kiecolt-Glaser et al., 2011 Zeugmann et al., 2013 Subtotal Frodl et al., 2012 Lu et al., 2013 McDade et al., 2012 Slopen et al., 2010 Hepgul et al., 2012 Danese et al., 2009 Lacey et al., 2013 Kiecolt-Glaser et al., 2011 Taylor et al., 2006 Di Nicola et al., 2012 Gouin et al., 2012 Frodl et al., 2012 Hartwell et al., 2013 Hartwell et al., 2013 Subtotal Gouin et al., 2012 Matthews et al., 2013 Dennison et al., 2012 Lu et al., 2013 Archer et al., 2012 Slopen et al., 2010 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Childhood trauma confers higher risk of adulthood physical and mental illness; however, the biological mechanism mediating this association remains largely unknown. Recent research has suggested dysregulation of the immune system as a possible biological mediator. The present paper conducted a meta-analysis to establish whether early-life adversity contributes to potentially pathogenic pro-inflammatory phenotypes in adult individuals. A systematic search of Pubmed, PsycINFO, EMBASE, Scopus and Medline identified 25 articles for the meta-analysis, including 18 studies encompassing a sample of 16 870 individuals for C-reactive protein (CRP), 15 studies including 3751 individuals for interleukin-6 (IL-6) and 10 studies including 881 individuals for tumour necrosis factor-α (TNF-α). Random-effects meta-analysis showed that individuals exposed to childhood trauma had significantly elevated baseline peripheral levels of CRP (Fisher's z=0.10, 95% confidence interval (CI)=0.05-0.14), IL-6 (z=0.08, 95% CI=0.03-0.14) and TNF-α (z=0.23, 95% CI=0.14-0.32). Subgroup analyses for specific types of trauma (sexual, physical or emotional abuse) revealed that these impact differentially the single inflammatory markers. Moreover, meta-regression revealed greater effect sizes in clinical samples for the association between childhood trauma and CRP but not for IL-6 or TNF-α. Age, body mass index (BMI) and gender had no moderating effects. The analysis demonstrates that childhood trauma contributes to a pro-inflammatory state in adulthood, with specific inflammatory profiles depending on the specific type of trauma.Molecular Psychiatry advance online publication, 2 June 2015; doi:10.1038/mp.2015.67.
    Molecular Psychiatry 06/2015; DOI:10.1038/mp.2015.67 · 14.50 Impact Factor
    • "Our heritability estimates for IL-6 in blood do contrast with some of the commonly held assumptions derived from other approaches. For example, it has been reported previously that both CRP and IL-6 levels are similar in twins, a finding that will emerge when the influence of adiposity is not taken into account, nor statistically considered as a contributing factor (Rooks et al., 2012; Wörns et al., 2006). In addition, there is a substantial literature reporting that allele polymorphisms affect IL-6 release, but that effect is most apparent in the context of inflammatory disorders, or when cells are activated in vitro by a proinflammatory stimulant (Bennermo et al., 2004; Brull et al., 2001; Burzotta et al., 2001; Shah et al., 2013). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Interleukin-6 and C-reactive protein are commonly assessed biomarkers linked to illness, obesity, and stressful life events. However, relatively little is known about their heritability. By comparing Caucasian twins from the Midlife in the US project (MIDUS), we estimated the heritability of IL-6, its soluble receptor, and CRP. Based on the hypothesis that adiposity might contribute more to IL-6 than to sIL-6r, we fit heritability models quantifying the extent to which each reflected genetic and environmental factors shared with obesity. Genetic influences on IL-6 and its receptor proved to be distinct. Further, the appearance of a heritable basis for IL-6 was mediated largely via shared paths with obesity. Supporting this conclusion, we confirmed that when unrelated adult controls are carefully matched to twin participants on BMI, age, gender and socioeconomic indices, their IL-6 is similar to the corresponding twins. In contrast, the effect of BMI on CRP was split between shared genetics and environmental influences. In conclusion, IL-6 is strongly affected by factors associated with obesity accounting for its lability and responsiveness to diet, life style and contemporaneous events. Copyright © 2015. Published by Elsevier Inc.
    Brain Behavior and Immunity 06/2015; 49. DOI:10.1016/j.bbi.2015.05.010 · 5.89 Impact Factor
Show more