Cortisol in the morning and dimensions of anxiety, depression, and aggression in children from a general population and clinic-referred cohort: An integrated analysis. The TRAILS study
Introduction
Psychosocial stress is an important factor in the development and course of mental disorders. However, there is substantial intra-individual variability with regard to the impact of psychosocial stress on mental health. This may be related to differences in hypothalamic–pituitary–adrenal (HPA)-axis activity, being one of the major physiological stress-related bodily systems. The overall goal of the present study was to shed more light on the relationship between cortisol (the major stress-related hormone) and different dimensions of psychopathology in children. We studied the role of both basal morning cortisol levels and the cortisol awakening response (CAR). The CAR plays an important role in preparing the body for action and in dealing with the challenges of the upcoming day (see e.g., Klimes-Dougan et al., 2001, Fries et al., 2009). Theoretical assumptions point to the upregulation of the HPA-axis due to the experience of stress and the notion of hypersensitivity to stress in relation to internalizing problems on the one hand (Klimes-Dougan et al., 2001, Fries et al., 2009, Lopez-Duran et al., 2009a, Slavich et al., 2010) and to the notion of hyposensitivity to stress, hypoarousal, or fearlessness in relation to externalizing problems on the other hand (Van Goozen et al., 2007, Alink et al., 2008, Shirtcliff et al., 2009). Indeed, higher activity of the HPA-axis, as reflected in higher basal morning cortisol levels or a higher CAR, has been related to anxiety and depressive (internalizing) symptoms not only in adults (Vreeburg et al., 2009, Vreeburg et al., 2010, Knorr et al., 2010, Stetler and Miller, 2011) but also in children and adolescents (Lopez-Duran et al., 2009a, Ruttle et al., 2011, Stetler and Miller, 2011, Garcia de Miguel et al., 2012), albeit relationships in children are less well-established and investigated than in adults. In contrast, lower HPA-axis activity has been found to be associated with externalizing problems in youth (for reviews see Van Goozen et al., 2007, Alink et al., 2008, Shirtcliff et al., 2009).
In the past years, however, it has been increasingly recognized that associations between cortisol and internalizing and externalizing problems are weaker and more inconsistent than previously assumed (Birmaher and Heydl, 2001, Klimes-Dougan et al., 2001, Feder et al., 2004, Hawes et al., 2009, Garcia de Miguel et al., 2012). Two interesting suggestions to better understand inconsistent findings have been offered in recent studies from a population sample of 10-to-12-year-old children, as part of our cohort study Tracking Adolescents’ Individual Lives Survey (TRAILS; Huisman et al., 2008). First, sex differences have been suggested to modify the relation between HPA-axis activity and internalizing and externalizing problems (Sondeijker et al., 2007, Marsman et al., 2008, Bosch et al., 2009) and second, a differential relationship has been proposed between HPA-axis activity and specific depressive subdimensions (such as a distinction between cognitive-affective and somatic depressive symptoms; Bosch et al., 2009). Thus, associations in mixed-sex samples or with respect to overall depression problems might go undetected.
We aimed to investigate these aspects further in an independent cohort as part of TRAILS. Replication of findings could substantiate the possible importance of sex differences and of differential associations between cortisol and specific subdimensions of externalizing and internalizing problems. So far, each of the published TRAILS papers in the baseline population cohort had focused on specific domains of psychopathology in their relation with cortisol assessed in the morning (Greaves-Lord et al., 2007, Sondeijker et al., 2007, Marsman et al., 2008, Bosch et al., 2009), using various analytical approaches and cortisol indices. Therefore, we believed it would be timely to provide an integrated analysis of the TRAILS behavioral data (including all three problem dimensions of anxiety, depression, and aggression) in one overarching analytical model investigating all available cortisol indices assessed in the morning (basal morning cortisol levels and CAR), and to try to replicate findings in an independent sample. We used Structural Equation Modeling (SEM) to distinguish between higher-order (broad) versus lower-order (specific) problem dimensions of anxiety (cognitive versus somatic anxiety), depression (cognitive-affective versus somatic depression), and aggression (reactive versus proactive aggression) and focused on the sex-specificity of relationships by investigating boys and girls separately. Our independent sample, the TRAILS clinic-referred cohort consisted of children of the same age who had at least once been referred to our mental health outpatient clinic. A priori we assumed a higher level of psychopathology in the clinic-referred cohort and therefore expected to find stronger associations in the clinic-referred than in the population cohort.
We formulated the following hypotheses regarding the relationships between cortisol (basal morning cortisol levels and CAR) and the different specific problem dimensions. First, we hypothesized a differential association of cortisol with the cognitive (reflecting worry, rumination, or anticipatory anxiety) versus the somatic (reflecting bodily, panic-related symptoms) anxiety dimension. This might explain the lack of a relationship between morning cortisol and current-only anxiety problems in the previous TRAILS study of Greaves-Lord et al. (2007). Specifically, we expected higher cortisol to be associated most strongly with somatic anxiety, based on the notion that stress-related physiological activation would be intimately connected with bodily arousal symptoms of anxiety (e.g., Craske et al., 2009). Second, we expected that somatic depressive problems would be related to higher cortisol (higher CAR), and cognitive-affective depressive problems to lower cortisol (lower CAR), as suggested by Kuehner et al. (2007), and, particularly in boys, by Bosch et al. (2009). The former study found a lower CAR to be associated with self-focused rumination, a cognitive vulnerability marker of depression. Authors suggested possible downregulation of the adrenergic system due to long-term perseverative dysphoric mood inducing and maintaining negative thoughts. Finally, we hypothesized that the higher cortisol in relation to externalizing problems in girls (Sondeijker et al., 2007, Marsman et al., 2008) could primarily be explained by the externalizing dimension of reactive aggression (i.e. emotional, impulsive, and anger-related), whereas we expected to find lower cortisol to be associated with proactive aggression (i.e. instrumental, cool, and deliberate), as suggested in the literature (McBurnett et al., 2005, Van Bokhoven et al., 2005, Hawes et al., 2009, Lopez-Duran et al., 2009b). Reactive (emotional) aggression has been proposed to involve greater stress sensitivity or reactivity and therefore higher HPA-axis activity than proactive (unemotional) aggression.
Section snippets
Participants
Subjects participated in TRAILS, a large cohort study of Dutch adolescents (Huisman et al., 2008). TRAILS aims to chart and explain the development of mental health from early adolescence into adulthood. The current paper concerns cross-sectional analyses of data derived from two TRAILS samples, the baseline population sample and the baseline clinic-referred sample. Detailed information about sample selection and nonresponse of both the population and clinic-referred cohort has been given
Sample descriptives
Table 2 presents the descriptive statistics of both cohorts regarding the measures used in this study.
Model fit
Our main analysis focused on specifically constructed (lower-order) problem dimensions of cognitive and somatic anxiety, cognitive-affective and somatic depression, and reactive and proactive aggression. Tested in a four-group analysis, without constraints on factor loadings or intercepts, this model yielded a model fit with Chi-square 732.08 with df = 480, CFI = .97, TLI = .96; RMSEA = .032. Taking
Discussion
This study aimed to investigate relationships between HPA-axis activity (basal morning cortisol levels and CAR) and psychopathological problems in 10-to-12-year-old children from a general population cohort in an overarching model that included dimensions of anxiety (cognitive versus somatic), depression (cognitive-affective versus somatic), and aggression (reactive versus proactive), using latent variable modeling. Analyses were repeated in an independent clinic-referred cohort attempting to
Role of funding source
There is no role of Funding Source
Conflict of interest
Jan K. Buitelaar has been a consultant to/member of advisory board of and/or speaker for Janssen Cilag BV, Eli Lilly, Bristol-Myer Squibb, Organon/Shering Plough, UCB, Shire, Medice and Servier in the past 3 years. He is not an employee of any of these companies. He is not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, or royalties. Frank C. Verhulst is a contributing author of the Achenbach System of
Acknowledgements
This research is part of the TRacking Adolescents’ Individual Lives Survey (TRAILS). Participating centres of TRAILS include various departments of the University Medical Center and University of Groningen, the Erasmus University Medical Center Rotterdam, the University of Utrecht, the Radboud Medical Center Nijmegen, and the Parnassia Bavo group, all in the Netherlands. TRAILS has been financially supported by various grants from the Netherlands Organization for Scientific Research NWO
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