A Child's Tears, Future Fears: Stress and Autoimmunity
Abstract & Commentary
By Russell H. Greenfield, MD
Synopsis: Results of this large, retrospective cohort investigation suggest that cumulative significant childhood stress and trauma contribute to development of systemic inflammation and autoimmune disease during adulthood.
Source: Dube SR, et al. Cumulative childhood stress and autoimmune diseases in adults. Psychosom Med 2009;71: 243-250.
To determine whether cumulative childhood stress and trauma is associated with an increased risk of autoimmune disease (AD) as an adult, researchers studied members of the Kaiser Foundation Health Plan in San Diego who from 1995 to 1997 were enrolled in the Adverse Childhood Experiences Study (ACEs), and followed them until 2005. The original cohort numbered > 17,000 people, with final evaluable data available for 15,357 (mean age, 56 years; n = 7,064 men).
Members of the cohort were mailed an ACEs questionnaire that was to provide data on childhood (up to age 18 years) exposure to eight types of serious household dysfunction that included emotional, physical and/or sexual abuse; household substance abuse; family member with mental illness; witnessing of domestic violence; family member with record of criminal activity; and parental separation or divorce. The total number of ACEs was called the ACE score, and was deemed representative of cumulative childhood stress. The primary outcome of interest was hospitalization for any of 21 selected ADs. In addition, four different immunopathology groupings were examined: Th1 AD (cell-mediated type more prevalent in men, e.g., idiopathic myocarditis); Th2 AD (antibody-type more prevalent in women, e.g., myasthenia gravis); Th2 rheumatic AD (e.g., rheumatoid arthritis); and mixed Th1/Th2 AD (no clear difference in prevalence between women and men, e.g., autoimmune hemolytic anemia).
Within the cohort, 64% reported at least one ACE, with 37% reporting two or more ACEs. The prevalence of each of the eight individual ACEs was as follows: emotional abuse 10%; physical abuse 28%; sexual abuse 21%; household substance abuse 27%; mental illness in the home 19%; witnessed domestic violence 13%; criminal member of household 5%; parental separation or divorce 23%. A total of 372 hospitalizations for AD were identified with the five most common ADs being NIDDM (23%), RA (19%), autoimmune TTP (17%), idiopathic pulmonary fibrosis (9%), and SLE (8%). Unadjusted rates for AD hospitalization increased with increasing age, with women more likely to have the AD diagnosis younger in life, and men more likely to receive the diagnosis after age 65.
For every increase in the ACE score the likelihood of first hospitalization with any AD increased by 20% for women and 10% for men. In addition, and again for every increase in ACE score, there was a 20% increased risk for Th1-type AD, a 20% increased risk for Th2-type AD, and a 30% increased risk for rheumatic diseases (no significant relationship was identified between ACEs and hospitalizations for mixed Th1/Th2-type AD). Compared with people with no ACEs, those with two or more ACEs were at a 70% increased risk for hospitalizations with Th1 AD, an 80% increased risk for Th2 AD, and a 100% increased risk for rheumatic disorders. The authors conclude that cumulative childhood stress increases the likelihood of hospitalization for AD decades later due to alteration in the body's inflammatory responses.
Commentary
If there are still practitioners (anyone, for that matter) who question the primacy of the interrelationship between mind and body, studies like this should severely impact their frame of reference. Yes, there are holes in the methodology, including the omission of outpatient data, the lack of information about when an ACE occurred and age of onset of AD, problems with generalizability due to the largely white and highly educated subjects, and no examination of inflammatory markers as compared with ACE scores. Some would even point out the inherent problems with a retrospective design, although the authors counter that there is often under-, not over-reporting, of ACEs. Certainly attention must be paid to these flaws, but the conclusions reached by the study authors still hold.
Previous research suggests that different forms of childhood abuse and trauma are interrelated, typically co-occur, and increase the risk for later suicide attempts, substance abuse, and mental illness. Some data suggest that it is the still-developing limbic system that is most sensitive to childhood stress and trauma, the limbic system being a primary seat of emotions.
Data also suggest, however, that ACEs are associated with elevated C-reactive protein levels decades later, as well as an increased risk of cardiovascular disease. ADs, where the immune system damages bodily tissues, affect some 3-8% of the population and the prevalence is increasing. The etiology of ADs remains controversial, but it appears that ACEs may be either an independent risk factor for AD, or at least contribute to the pathophysiologic processes that result in autoimmunity.
This is an important article for all the reasons noted earlier, but there is more at stake. As if more sobering notes were necessary, the incidence of ACEs in this group of well-educated subjects is staggering28% experienced physical abuse, 21% sexual abuse, and 27% witnessed substance abuse in the home. As is often the case, these research data bring up not only medical issues but also societal ones requiring large-scale approaches that reach not only into communities but to every individual. Our role as practitioners is at least to help identify at-risk children and families, and then to ensure that they receive proper assistance and guidance to minimize the untoward and potentially lifelong consequences of ACEs. Then, too, to add our voices to those calling for greater efforts to help prevent severe household dysfunction in the first place.
Results of this large, retrospective cohort investigation suggest that cumulative significant childhood stress and trauma contribute to development of systemic inflammation and autoimmune disease during adulthood.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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