HPA-axis reactivity interacts with stage of pubertal development to predict the onset of depression
Introduction
Major depressive disorder (MDD) affects nearly 20% of all Americans and is the most common of all psychiatric disorders (Kessler et al., 2014). One of the most striking features of MDD is the gender difference in incidence that emerges in early adolescence, when females begin to be twice as likely as males to develop the disorder (Stroud et al., 2004, Hilt and Nolen-Hoeksema, 2014). Importantly, the age at which this gender divergence arises corresponds to the complex transition through puberty. Pubertal development involves a host of biological, psychological, and social changes that researchers posit contribute to the increase in rates of MDD in adolescent girls; in fact, investigators have found pubertal stage to be a stronger predictor of the onset of depression than is chronological age (Angold et al., 1998). Thus, puberty is a critical period during which to examine factors that increase the risk of young adolescents, particularly females, for developing MDD.
In this context, investigators have implicated stress and stress responsivity in females’ pubertal development as a potential mechanism that underlies the gender difference in rates of MDD. For example, starting in early adolescence, girls report experiencing higher overall levels of stress than do boys (Brooks-Gunn, 1991, Ge et al., 2001). Moreover, sex-specific changes in the responsivity of the hypothalamic–pituitary–adrenal (HPA) axis, as assessed by levels of the stress hormone cortisol, have also been noted during puberty (Young and Altemus, 2004, Romeo, 2010, Young and Korszun, 2010). For example, in a cross-sectional study of stress reactivity across pubertal development, Gunnar et al. (2009) found not only that baseline cortisol levels and cortisol response to a laboratory stress-induction task (Trier Social Stress Task) increased as a function of level of pubertal development, but that around age 13, this increase in response to a stressor was more pronounced in girls than boys. Similarly, Stroud et al. (2009) found that with greater pubertal maturation, girls, but not boys, exhibited an increase in cortisol secretion following a corticotropin releasing hormone challenge. More recently, Blumenthal et al. (2014) found a positive association between cortisol response to a novel social setting and pubertal stage in adolescent girls, controlling for chronological age. Taken together, therefore, these findings document increases in cortisol responsivity in girls through puberty, which may underlie the elevated risk for depression in females that begins at this developmental period.
Consistent with this formulation, higher levels of cortisol over the transition through puberty have been found to be related to a greater vulnerability to depression in adolescence (Dahl and Gunnar, 2009, Stroud et al., 2009). For example, several investigators have found that higher levels of morning cortisol predict the subsequent onset of depression in adolescence (Adam et al., 2010, Vrshek-Schallhorn et al., 2013, Owens et al., 2014). Importantly, however, findings regarding cortisol stress responsivity as a predictor of subsequent changes in depressive symptoms are less consistent. For example, Susman et al. (1997) found that 9- to 15-year-old adolescents who had a greater cortisol response to a novel and challenging situation reported higher levels of depressive symptoms one year later. In contrast, however, Keenan et al. (2013) found that younger, 10- to 12-year-old, girls who exhibited a blunted cortisol response to a laboratory stressor and who had low absolute levels of cortisol secretion at age 12 experienced a subsequent increase in depressive symptoms. Given the changes in cortisol functioning that accompany pubertal development, it is possible that inconsistencies in previous findings are due, in part, to the different developmental stages at which participants were assessed across studies; that is, it appears that increases in depressive symptoms are predicted by blunted cortisol reactivity in younger girls, but by elevated cortisol reactivity in older girls.
The present study was designed to examine this formulation by assessing whether cortisol stress reactivity measured across puberty predicts the subsequent onset of MDD. We recruited 9- to 15-year-old never-disordered girls who spanned the full range of pubertal development, examined their patterns of cortisol stress reactivity, and followed them regularly through age 18 to assess the subsequent onset of depression. Specifically, we tested whether pubertal status at the time of cortisol assessment moderated the relation between cortisol reactivity and the subsequent development of MDD. To maximize the likelihood that a significant proportion of the girls would develop an episode of depression, we included in our sample girls at familial risk for the disorder by virtue of having a mother with a history of depressive episodes. Given the documented increase in cortisol secretion in girls across the transition through puberty (Gunnar et al., 2009, Blumenthal et al., 2014), combined with the increase in females’ rates of depression during and after this period, we hypothesized that girls at later stages of pubertal development who exhibit greater cortisol reactivity to a laboratory stressor would be more likely to experience a subsequent depressive episode than would comparable girls at earlier stages of pubertal development. Thus, we tested the prediction that cortisol reactivity would be a more sensitive marker of risk for the onset of MDD at later than at earlier stages of puberty.
Section snippets
Participants
Participants were 89 girls who, at entry into the study at Time 1 (T1), were between 9 and 15 years of age and had no past or current Axis I disorder. Forty-seven girls had mothers who also had no past or current Axis I disorder (low risk for depression; CTL), and 42 girls were at high risk for developing depression (RSK) by virtue of having mothers who had recurrent episodes of MDD during their daughters’ lifetime. As we noted above, given that maternal history of depression is a strong
Participant characteristics
Demographic and clinical characteristics of the MDD and no-MDD outcome groups are presented in Table 1. Girls who developed MDD did not differ from girls who did not develop MDD on most T1 variables, including time of day of cortisol collection, t(87) = 1.129, p = 0.262; pubertal stage, t(87) = 1.524, p = 0.146; ethnicity, χ2(1, N = 89) = 2.236, p = .135; medication use, χ2(1,89) = 0.425, p = .608; and body mass index (BMI), t(75) = .668, p = 0.506. Compared with girls who did not develop MDD, however, girls who
Discussion
This study was designed to examine the utility of cortisol response to stress and pubertal development, both alone and in interaction, in predicting the onset of MDD in young girls. We assessed cortisol reactivity and pubertal stage in a sample of 9- to 15-year-old girls who spanned the range of pubertal development and found a significant interaction between cortisol reactivity and pubertal stage in predicting the development of depression. For girls at the mean Tanner stage of the sample,
Conclusions
In conclusion, the findings of this study contribute to a literature documenting anomalous HPA-axis functioning in MDD. Importantly, the results reported here indicate that altered cortisol functioning precedes the onset of MDD and, therefore, may be a risk factor for this disorder. The present findings also underscore the importance of considering pubertal development when examining biological processes throughout adolescence and risk for psychopathology. Indeed, the association between girls’
Role of the funding sources
This work was supported by NIMH Grants MH074849 to IHG, F32 MH096385 to KK, and F32 MH090617 to LCFR, by NARSAD Young Investigator Awards 20814 to KK and 19018 to LCFR, and by a National Science Foundation Award to NLC.
Conflict of interest
None declared.
Acknowledgements
We thank Hannah Burley, Brooke Gilbert and Maria Lemus for their help in recruiting and running the participants.
References (37)
- et al.
Prospective prediction of major depressive disorder from cortisol awakening responses in adolescence
Psychoneuroendocrinology
(2010) - et al.
Pubertal maturation and cortisol level in response to a novel social environment among female adolescents
J. Adolesc.
(2014) - et al.
The measurement of puberty: a review
J. Adolesc.
(2002) - et al.
Hypothalamic–pituitary–adrenal axis dysregulation in dysphoric children and adolescents: cortisol reactivity to psychosocial stress from preschool through middle adolescence
Biol. Psychiatry
(2010) - et al.
K-SADS-PL: initial reliability and validity data
J. Am. Acad. Child Adolesc. Psychiatry
(1997) - et al.
Examining the development interface of cortisol and depression symptoms in young adolescent girls
Psychoneuroendocrinology
(2013) - et al.
Emotion regulation and cortisol reactivity to a social-evaluative speech task
Psychoneuroendocrinology
(2009) Pubertal maturation and programming of hypothalamic–pituitary–adrenal reactivity
Front. Neuroendocrinol.
(2010)- et al.
Puberty and depression: the roles of age, pubertal status, and pubertal timing
Psychol. Med.
(1998) - et al.
Hypocortisolism as a potential marker of allostatic load in children: associations with family risk and internalizing disorders
Dev. Psychopathol.
(2011)
How stressful is the transition to adolescence for girls?
Serotonin transporter polymorphism predicts waking cortisol in young girls
Psychoneuroendocrinology
Heightened stress responsiveness and emotional reactivity during pubertal maturation: implications for psychopathology
Dev. Psychopathol.
Measuring stress resilience and coping in vulnerable youth: the social competence interview
Psychol. Assess.
Social competence interview for assessing physiological reactivity in adolescents
Psychosom. Med.
Structured Clinical Interview for DSM-IV Axis I Disorders: Clinician Version
Pubertal transition, stressful life events and the emergence of gender differences in adolescent depressive symptoms
Dev. Psychol.
Children of depressed parents
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