In a prospective, one-year longitudinal study of a normative, healthy sample of pre-adolescent children, we found modest support for a link between psychological well-being and immune function and illness. The strongest link, observed in the entire cohort of children, was a negative association between self-efficacy and IL-6. Two further associations were also detected, but only in older girls: depression was associated with increased NK cell function and with higher rates of illness.
The findings extend research on stress and health and allostatic load in children in several important ways. First, rather than rely on parent reports of stress, we included children’s self-reports of well-being, indexed by efficacy and depressive symptoms as predictors of immunity and health. These two indicators of psychological well-being are widely researched in the developmental and clinical psychology literature as causes and effects of psychosocial stress and as predictors of long-term behavioral adjustment. We provide some of the only evidence thus far that these psychological measures also predict health outcomes in normally developing children. The self-report data also provide an extension to the prior research on stress and children’s health, which has to date been dominated by parent reports of child stress exposure and, in some cases, inferred from parent self-report of their own psychological symptoms. The finding that children’s own views of their ability to cope with stress predicted lower levels of IL-6 extends a considerable adult literature on psychological outlook and immunity. For example, positive emotional style, assessed by measures of extraversion, agreeableness, and positive relationship style is associated with fewer colds following respiratory viral challenge (Cohen, Alper, Doyle, Treanor, & Turner, 2006
; Cohen, et al., 2003
). Also, increased optimism was inversely associated with an IL-6 response to acute psychosocial stress (Brydon, Walker, Wawrzyniak, Chart, & Steptoe, 2009
), whereas pessimism was associated with increased levels of IL-6, C reactive protein (CRP), and fibrinogen (Roy, et al., 2010
). Coping, appraisal and other psychological resources and dispositions need also to be incorporated into models of stress and health in pediatric samples. Significantly, the prediction from self-efficacy to IL-6 was independent of parental symptoms, providing further support for the need to consider psychological processes within the child as distinct from general markers of stress exposure as reported on by parents.
Second, results from the study begin to piece together a developmental model of psychoneuroimmunology. On one hand, children who report greater ability to achieve desired results in common situations showed a healthier, and presumably more adaptive immunological profile and reduced levels of IL-6; evidence of positive psychological appraisal and coping was associated with reduced generalized inflammation, a prediction that comports easily with existing animal and adult work. On the other hand, in older girls (only), we found that depression was associated with increased NK cell function or cytotoxicity. That is congruent with our earlier finding that psychosocial stress as reported by parents predicted increased NK cell function (Caserta, et al., 2008
). The extent to which the increased NK cell function associated with depression is compatible with or contradicts adult studies is confounded by the inconsistency across adult studies, with some reporting a decrease (Park, et al., 2006
) but others reporting an increase (Ravindran, Griffiths, Merali, & Anisman, 1998
; Seidel, et al., 1996
) in NK cells in depression. These discrepancies may be resolved by attention to depression subtypes (Ravindran, et al., 1998
), something that we were not able to investigate in our sample. In any event, it may be noteworthy that a link with NK cell function was found only in older girls, who may, by virtue of the age and sex effects on depression, present the most “adult-like” in terms of risk for depression. That a limited or focused effect of depression in older girls was also detected for illnesses also warrants consideration and implies, at a minimum, that age and sex may emerge as modifiers of the links between stress/psychological symptoms and immunity in pediatric samples. It is noteworthy that sex effects on the link between depression and immune markers have also been reported in adult studies (Brummett, et al., 2010
; Steptoe, O’Donnell, Badrick, Kumari, & Marmot, 2008
). Further work that incorporates the hormonal and neurophysiological changes associated with puberty (e.g., Dahl & Gunnar, 2009
) is needed to revise and expand a developmental model of psychoneuroimmunology.
A non-finding also deserves attention for what it may suggest about developmental influences and the detection of allostatic load in young people, namely, the lack of association between depression and IL-6. This lack of association in the current sample does contradict adult work that shows a reliable but small negative association between depressive symptoms and IL-6, as well as TNF-alpha, (Dowlati, et al., 2010
), which was not assessed in the current study. This raises the possibility that, for reasons not yet clear, associations between behavioral/psychological well-being and IL-6 either may be less robust in children or slower to develop, perhaps requiring chronic stress or depression, a possibility implicit in the adult work and in the allostatic load model but not yet adequately tested. In other words, our findings on a pre-adolescent sample do not mimic in every way the patterns so far reported in adults.
Finally, we did not find evidence that changes in immune markers mediated the effects of depression on health outcomes. In fact, we found, in older girls, depression leading to both increased NK cell function and increased illness. It may be that the impact on immunity and on observable health outcomes are under different time course constraints; it is also likely that health outcomes are multiply determined and that any specific immune marker may not carry sufficient impact to alter a systemic illness.
Several limits of the study should be noted. Detailed data on pubertal development were not available in this study; more precise measurement of pubertal changes may help clarify the moderating influence of sex and age on depression and IL-6 and illnesses. The young age of the sample may also confound interpretations of age and sex; indeed, we did not detect strong age and gender effects on levels of depressive symptoms that are found in pubertal or adolescent samples. Additionally, the interpretation of depression symptoms should be considered in light of the generally non-clinical nature of symptoms and impairment; arguably, a strength of this study, which would increase its generalizability, is that we detected associations within a healthy sample, outside of the clinical extremes. Also, a variety of other potential markers of immunity that could have been assessed were not included. We targeted those that had a sizable adult literature, and so had a limited focus; analyses of a wider array of pro- and anti-inflammatory markers will be needed to develop a comprehensive developmental model of psychoneuroimmunology. Furthermore, although the study sample size was adequately powered for main effects analyses and compares favorably with studies in the area, the power to detect multi-way interactions was limited and the reliability of interactions is notably less robust than main effects. Therefore, despite the strong a priori case for analyzing data by age and sex, replication of these findings is necessary before drawing firm conclusions. Finally, we proposed directional hypotheses concerning within-individual change, derived from adult and animal work, that changes in depression and self-efficacy would be associated with immune markers, the dependent variable. It is plausible that the direction of effects is reciprocal, and the time course for charting the dynamic interplay between psychological well-being and health and immune markers requires further study. These limitations are offset by several strengths of the paper, including the longitudinal design with multiple occasions of measurement of psychological and immune data, and detailed health diary data verified, to a considerable extent, by medical investigators on the project.
Clinical implications of the findings are not yet clear, but promising. Perhaps the most obvious is the need to consider physical well-being in those children who report psychological distress, in both assessment and intervention. If further research also endorses links between psychological well-being and physical health in children, then this would provide a conceptual-biological basis for instituting an inter-disciplinary model for child health assessment, something that is not now widely established.