Original Research Article Are Cortisol Profiles a Stable Trait During Child Development? MARK V. FLINN* Department of Anthropology, University of Missouri, Columbia, Missouri 65211 ABSTRACT Exposure to stressful experiences can increase vulnerability to adverse health outcomes. A potential neuroendocrine mechanism mediating the link between stress and health is the hypothalamic-pituitary-adrenal (HPA) system, with a key role attributed to the glucocorticoid hormone cortisol. Retrospective and cross sectional clinical stud- ies of humans and experimental studies with nonhuman primates and rodents suggest that traumatic experiences dur- ing critical periods in development may have permanent effects on HPA regulation, which in turn can have deleterious effects on health. Here I report results from a continuous 20-year study (1988–2009) of children in a rural community on Dominica. Sequential data on cortisol levels, social stressors, and health in naturalistic, everyday conditions are examined to assess developmental trajectories of HPA functioning. Saliva aliquots were assayed for cortisol in concert with monitoring of growth, morbidity, and social environment. Analyses here include data from 1989 to 1999 for 147 children aged 3–16 years with >100 saliva samples each. Cortisol values were standardized by elapsed time since wake-up. Results do not support the hypothesis that traumatic stress during childhood causes permanent general elevation of cortisol levels. Am. J. Hum. Biol. 21:769–771, 2009. ' 2009 Wiley-Liss, Inc. Humans, like most animals, have complex physiological systems that are responsive to stimuli from the social environment. The sensitivity of the neuroendocrine stress system to social challenges presents an evolutionary puz- zle. We do not have good explanations for why natural selection favored links between the neuropsychological mechanisms involved with assessment of the social envi- ronment and the neuroendocrine mechanisms that regu- late stress hormones such as cortisol. Furthermore, we do not understand why these links are modifiable during on- togeny, such that early traumatic experiences may have long-term effects on neuroendocrine stress response (Anisman et al., 1998; Mirescu et al., 2004). This puzzle is accentuated by the apparent negative consequences of social stress and concomitant abnormal cortisol levels for health and psychological development (Sapolsky, 2005). The dominant model in stress research has targeted the homeostatic mechanisms of the hypothalamic-anterior pituitary-adrenal cortex (HPA) system, which are posited to be permanently affected by exposure to high levels of glucocorticoids during ontogeny. Glucocorticoid receptors (GRs) in the hippocampus that are part of the negative feedback loop regulating release of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) can be damaged by the neurotoxic levels of cortisol associ- ated with traumatic or chronic stressors. Hence early trauma is hypothesized to result in permanent HPA dysregulation and hypercortisolemia, with consequent deleterious effects on the hippocampus, thymus, and other neural, metabolic, and immune system components (McEwen, 2004; Sapolsky, 2005). These effects may have additional consequences resulting from the high density of GRs in the prefrontal cortex in primates (de Kloet et al., 2005). Other potential mechanisms include DNA methyla- tion (Cameron et al., 2008; McGowan et al., 2009; Weaver et al., 2004, 2006). The specific mechanisms affecting rela- tions between exposure to trauma during development and subsequent HPA system function in humans are not as well documented as in animal studies. Nonetheless, a similar causal linkage appears plausible (e.g., Heim et al., 2000; Lupien et al., 2000). The HPA pathology hypothesis is supported by a num- ber of clinical and laboratory studies establishing that exposure to traumatic or chronic stress during develop- ment is associated with subsequent high levels of cortisol during adulthood (Essex et al., 2002; Gunnar and Quevedo, 2007; Heim et al., 2000). Other studies, however, indicate that children exposed to early life stress may have normal or subnormal HPA reactivity to experimental stressors such as the Trier Social Stress Test (e.g., Gunnar et al., 2009; Tarullo and Gunnar, 2006). Studies of post- traumatic stress disorder (PTSD) also suggest subnormal cortisol levels (Yehuda et al., 2007). Attenuation of initial hypercortisolemia is often followed by reduction of cortisol levels associated with comorbid social withdrawal and depressive symptoms. Studies of children in school and naturalistic environments indicate a variable relation between exposure to stress during development and sub- sequent cortisol levels, suggestive of individual differences (Flinn, 2006; Lupien et al., 2000). Several key issues in regard to relations between stress during development and the HPA system remain unre- solved: (1) do permanent changes in HPA regulation occur? (2) If there are changes in HPA regulation and cor- tisol levels (as per no. 1), are there functional consequen- ces? (3) What specific mechanisms are affected by early stress (e.g., GRs, DNA methylation, neural circuits in amygdala, or something else)? (4) Are there ‘‘sensitive periods’’ during development in regard to HPA modifica- tion by exposure to stress? Here I present analyses of lon- gitudinal data that primarily address the first question above, but the results also have indirect relevance for the other issues. Contract grant sponsor: National Science Foundation, Contract grant numbers: BCS-SBE-0640442, SBR-0136023, SBR-9205373, BNS-8920569. *Correspondence to: Flinn V. Mark, Department of Anthropology, University of Missouri, Columbia, MO 65211, USA. E-mail: FlinnM@Missouri.edu Received 26 June 2009; Accepted 27 June 2009 DOI 10.1002/ajhb.20981 Published online 19 August 2009 in Wiley InterScience (www.interscience. wiley.com). AMERICAN JOURNAL OF HUMAN BIOLOGY 21:769–771 (2009) V V C 2009 Wiley-Liss, Inc.