Elsevier

Psychoneuroendocrinology

Volume 36, Issue 2, February 2011, Pages 173-181
Psychoneuroendocrinology

Cortisol reactivity to social stress in adolescents: Role of depression severity and child maltreatment

https://doi.org/10.1016/j.psyneuen.2010.07.006Get rights and content

Summary

This study examined the hypothesis that depressed adolescents with a history of childhood maltreatment will show greater cortisol reactivity to psychological stress challenge than those without, and this relation will be moderated by level of depression severity. Seventy-one adolescents were exposed to the Trier Social Stress Test. Salivary cortisol was assessed at baseline, immediately before the challenge, after the challenge, and during an extended recovery period. Childhood maltreatment was assessed with a rigorous contextual interview and rating system. Adolescents with a history of maltreatment produced higher and more prolonged levels of cortisol in response to the challenge than did adolescents with no maltreatment, but only among those with a mild/moderate level of depression severity. Those with moderate/severe depression exhibited a blunted cortisol response regardless of child maltreatment history. These findings indicate that depression is a heterogeneous syndrome, and that both depression severity and child maltreatment history should be considered in studies examining biological stress reactivity.

Introduction

Forty years of research has consistently documented dysregulation of hypothalamic-pituitary-adrenal (HPA) axis functioning in the pathophysiology of adult major depressive disorder (MDD) (Carroll et al., 1981, Holsboer, 2000). Furthermore, a recent meta-analysis of HPA axis function in 41 studies employing primarily adolescent samples reported that adolescents with MDD show greater cortisol production (or less suppression) after the dexamethasone suppression test (DST; d = .57), as well as higher basal cortisol levels (d = .20), in comparison to non-depressed groups (Lopez-Duran et al., 2009).

However, the DST and basal cortisol have been criticized as indices of HPA axis functioning because they fail to assess the endogenous response of the HPA axis to psychological stress (Rao et al., 2008). Therefore, more recently investigators have used psychological challenge paradigms such as the Trier Social Stress Test (TSST) (Kirschbaum et al., 1993). The TSST is one of the few available stress protocols that combines elements of uncontrollability and high levels of social-evaluative threat. Stress tasks containing these two components are associated with the largest HPA axis stress responses and the longest recovery times (Dickerson and Kemeny, 2004).

Meta-analytic results in adults have indicated that depressed individuals show blunted cortisol reactivity in response to psychological challenge, particularly in older and more severely depressed individuals (Burke et al., 2005). Only one study to our knowledge has compared depressed versus non-depressed adolescents using the TSST (Rao et al., 2008), and it found elevated and prolonged cortisol secretion in response to the TSST in depressed adolescents. In younger children, studies have found blunted cortisol reactivity in depressed children relative to controls (Luby et al., 2003, Luby et al., 2004). Several investigators have argued, however, that a distinction needs to be made between child and adolescent MDD, particularly with respect to HPA axis function (Kaufman and Charney, 2003, Kaufman et al., 2001). Therefore, results across these two sets of studies may not be comparable. Nevertheless, what is consistent across most studies using challenge paradigms in adult and pediatric MDD is a much larger variability in cortisol response within the depressed group versus the non-depressed individuals (Lopez-Duran et al., 2009). It is this heterogeneity within MDD that may help to account for inconsistencies in results across studies.

Two important sources of individual variability that have consequences for the HPA axis system are (a) a history of childhood maltreatment, and (b) individual differences in depression severity. On the one hand, research in both adult and child/adolescent samples has found that childhood maltreatment is associated with increased cortisol reactivity in response to biological (e.g., corticotropin-releasing hormone [CRH]) and psychological stress challenge (De Bellis et al., 1994, Heim et al., 2000, Heim et al., 2001, Heim et al., 2002, Kaufman et al., 1997, Rao et al., 2008;). On the other hand, there is a literature in adults linking severe depression to blunted cortisol reactivity response to stress challenge (Burke et al., 2005). Severe melancholic depression, in particular, has been linked to biological markers in the HPA axis (e.g., nonsuppression on the DST), and HPA axis parameters appear to be among the strongest discriminators of melancholic versus non-melancholic depression (Akil et al., 1993, Carroll et al., 1980, Dinan and Scott, 2005, Tsigos and Chrousos, 2002, Zimmerman et al., 1985).

It is noteworthy that these two lines of research reveal an opposing pattern of HPA function; that is, childhood maltreatment is associated with heightened reactivity, and high depression severity is associated with blunted reactivity. Childhood maltreatment and depression severity are, themselves, highly correlated (Harkness and Monroe, 2002). Therefore, it is possible that failure to take both of these sources of heterogeneity into account in research on the HPA axis in MDD may at least in part explain inconsistencies in findings across studies. To date, however, there have been no studies examining the relation of individual differences in depression severity to cortisol reactivity in adolescents, nor have there been any studies in either adults or adolescents examining the interaction of childhood maltreatment and depression severity on HPA axis function.

The goal of the present study was to examine the relation of childhood maltreatment, depression severity, and their interaction, to cortisol reactivity and total cortisol exposure in response to the TSST. We hypothesized that (a) consistent with the adult literature, adolescents with MDD will show blunted cortisol reactivity and lower total cortisol output in response to the TSST than non-depressed controls, particularly among those with a severe depression; (b) again, consistent with previous literature, adolescents with a history of childhood maltreatment will show greater cortisol reactivity and total cortisol exposure in response to the TSST than those without; and (c) depression severity will fully moderate the relation of childhood maltreatment to cortisol reactivity: heightened cortisol reactivity to the TSST in those with a history of child maltreatment will only be seen in the less severely depressed adolescents, whereas blunted cortisol reactivity will be seen in those with a history of child maltreatment in the context of severe depression. The latter hypothesis is tentative given the lack of previous research examining the relation of childhood maltreatment to HPA axis function moderated by depression severity.

Section snippets

Participants

Participants were 71 individuals (48 females) ages 12–21 years (M = 15.39, SD = 2.11) recruited from a mid-sized community in Ontario, Canada. The ethnic diversity of our sample was consistent with that of the community (89% European ancestry). Our depressed sample was drawn from community mental health agencies and community advertisements seeking adolescents with depression. Our non-depressed sample was recruited from local high schools and community advertisements seeking healthy adolescents.

Participant characteristics

Demographic and clinical characteristics of the three depression severity groups are presented in Table 1. There were no significant relations of depression severity group to sex (p = .42) or Tanner score (p = .19). However, groups differed in age, at a trend, F(2, 68) = 2.80, p = .07, η2 = .08, and parental Hollingshead index, F(2, 68) = 7.00, p < .005, η2 = .17. Among those with a diagnosis of a depressive disorder, there were no significant differences between those of moderate and severe BDI-II scores in

Discussion

The present study is the first to our knowledge to examine the effect of a history of childhood maltreatment on HPA axis reactivity as moderated by depression severity. Consistent with hypotheses, a history of childhood maltreatment was associated with significantly higher cortisol reactivity and total cortisol exposure (i.e., AUC) to a psychosocial stress challenge. However, an intriguing differential association between childhood maltreatment and HPA axis function emerged when the sample was

Role of funding sources

Funding for this study was provided by a grant from the Ontario Mental Health Foundation (Harkness, Wynne-Edwards). The OMHF had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Conflicts of interest

Dr. Harkness, Mr. Stewart, and Dr. Wynne-Edwards report no biomedical financial interests or potential conflicts of interest.

Contributions

Dr. Harkness designed the study, supervised data collection, and wrote the manuscript. Mr. Stewart aided in conducting the diagnostic and childhood maltreatment interviews and undertook the statistical analyses. Dr. Wynne-Edwards wrote the study protocol and supervised the cortisol assays.

Acknowledgements

We gratefully acknowledge the technical of Lea Bond in performing the cortisol assays. We would also like to acknowledge Eric Bulmash, Alexandra Sutherland, and Nazanin Alavi who performed the diagnostic and maltreatment interviews, and Shannon Coyle, Lindsey Lytle, Emma Dargie, and Lindsay Delima for their help with data coding and data management.

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