Mounting evidence indicates that children who are raised in risky families environments are vulnerable to chronic disease when they reach the later decades of life (Repetti et al., 2002
; Shonkoff et al., 2009
). While the mechanisms underlying this phenomenon are not well understood, one attractive hypothesis is that harsh family climates engender a pro-inflammatory phenotype, which over time takes an allostatic toll on the body (Cicchetti & Toth, 2005
; Miller et al., 2009b
; Zhang et al., 2006
). Our data provide support for this notion by showing that over a 1.5-year period, young women who were raised in risky families display increased IL-6 responses to 2 different types of threatening stimuli, an in vitro
challenge with bacterial products and a real-life psychological stressor. Over this period they also show progressive desensitization of the glucocorticoid receptor, such that their immune cells exhibit increasing resistance to anti-inflammatory signals from cortisol.
These findings converge with other studies that have observed greater inflammatory activity in adults who were reared in unfavorable circumstances (Danese et al., 2007
; Miller et al., 2009b
; Miller & Chen, 2007
; Taylor et al., 2006b
). They also extend previous research by showing that the magnitude of this disparity grows with time, such that youth from harsh families are set upon a trajectory of exaggerated pro-inflammatory responding and partial resistance to glucocorticoid signaling. It is not clear why the disparities were not apparent at study entry, but gradually accumulated as the follow-up progressed. Because the women in our sample were aged 15-18 at study entry, menarche-induced changes in immune functions are unlikely to be responsible. However, puberty sets into motion hormonal cascades that continue to promote maturation throughout adolescence (Dahl, 2004
), and it is conceivable that they underlie the findings observed herein. Identifying these cascades and how they modulate immunity needs to be a focus of future research.
This work also highlights glucocorticoid receptor desensitization as one mechanism potentially underlying the pro-inflammatory phenotype. Cortisol is a powerful regulator of the transcriptional-control pathways that orchestrate immune responses to infection and injuries (Webster et al., 2002
). To the extent that familial harshness impairs the immune system’s capacity to transduce cortisol-mediated signals, e.g., through glucocorticoid receptor desensitization, it would be expected to mount larger inflammatory responses to challenge and be slower to terminate them. In the short term, this pattern might benefit health by protecting against infectious threats. However, over the long term it would foster a low-grade inflammatory state (Miller et al., 2002
; Raison & Miller, 2003
) that contributes to aging-related conditions like the metabolic syndrome, autoimmune disorders, and cardiovascular disease (Nathan, 2002
The study also extends previous research by showing that even normative variations in the early family climate can shape the evolution of response tendencies in the immune system. We assessed harshness on a 5-point continuum. For each one-half point increment in harshness, there was a 10 percent increase in stimulated IL-6 production over time, and a 4 percent decline in sensitivity to cortisol. These patterns suggest that there is a good deal of plasticity in the response tendencies of monocytes (the cells that engage LPS and secrete IL-6) and that even mild exposure to a risky family in early life can shift the developmental trajectory towards a pro-inflammatory phenotype.
Though a harsh family climate presaged changes in stimulated cytokine production and sensitivity to cortisol, there was no evidence that it associated with the degree of ongoing inflammatory activity, as marked by serum IL-6. These findings suggest that harshness affects leukocytes’ response to microbial challenges, but not their production of cytokines under quiescent conditions. This discrepancy may reflect the fact that in young people, the immune system’s response to inhibitory molecules like cortisol is relatively intact, which prevents it from the kind of overshooting that fosters ongoing inflammation. However, our data suggest that as they age, women from harsh families will show larger cytokine responses to challenge, and become progressively more resistant to cortisol-mediated inhibition. Over time such tendencies could tip the balance in favor of the kinds of ongoing inflammatory activity seen in adults who faced early-life maltreatment (Danese et al., 2007
; Taylor et al., 2006b
Several limitations of this study need to be considered. First, it used retrospective self-reports of early family climate, whose veridicality was not ascertained through collateral sources. Thus, it is possible that our measure captured something different than what it was intended to, like participants’ reconstructed memories of their early family lives, or descriptions of them that had been enhanced to be more socially desirable. However, even if it did, this work would still be valuable, because reports like this have been linked to excess morbidity and mortality (Anda et al., 2009
; Dong et al., 2004
; Dube et al., 2009
). Thus, the phenomena that they are capturing, whether accurate reflections of early life or reconstructed versions of it, seem to be important for long-term health. Second, the observational design makes it impossible to derive causal inferences about the effects of early family climate. Although we used covariance analyses to eliminate the most plausible alternative explanations, other (unassessed) factors may have contributed to the observed associations. Third, our findings come from young women at risk for affective disorders, who are more likely than the general population to be reared in a harsh family climate, and are probably more sensitive to its effects. Thus, further research is needed to determine how generalizable the findings are to the broader population. Fourth, the study focused on a narrow window of time in the life course, 1.5 years of adolescence, and it is unclear how representative the trajectories we observed are of other periods. Collectively, these limitations suggest that our results should be considered preliminary until they have been substantiated in studies with representative samples, long-term prospective designs, and more thorough assessment of potential confounders.
Despite these limitations, the study provides insights into mechanisms through which early family climate might come to shape later risk for chronic disease. In future research it will be important to further characterize the elements of the phenotype we observed, and ascertain how they might together influence habitual patterns of responding to threatening stimuli. Particularly relevant to this endeavor are data showing that children from riskier families are vigilant for cues that connote anger and threat (Chen et al., 2004
; Pollak, 2008
), and seem to remain so into adulthood, perhaps as a result of experience-dependent remodeling of the amygdala and/or prefrontal circuitry that regulates it (Gianaros et al., 2008
; Taylor et al., 2006a
). Research that explicates how these tendencies modulate the function of other bodily systems, e.g., metabolic, cardiovascular, immune, and what implications that has for disease, would be especially valuable. With data like these in hand, we should soon be able to construct multi-level models that depict how the social context a child is reared in “gets under” the skin to shape long-term health.