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. 2014 Jun:44:47-59.
doi: 10.1016/j.psyneuen.2014.02.014. Epub 2014 Mar 12.

Prospective associations between the cortisol awakening response and first onsets of anxiety disorders over a six-year follow-up--2013 Curt Richter Award Winner

Emma K Adam  1 , Suzanne Vrshek-Schallhorn  2 , Ashley D Kendall  2 , Susan Mineka  2 , Richard E Zinbarg  3 , Michelle G Craske  4
Affiliations

Prospective associations between the cortisol awakening response and first onsets of anxiety disorders over a six-year follow-up--2013 Curt Richter Award Winner

Emma K Adam et al. Psychoneuroendocrinology. 2014 Jun.

Abstract

Cross-sectional associations have been found between anxiety disorders (ADs) and hypothalamic-pituitary-adrenal (HPA) axis functioning, as measured by levels of salivary cortisol, but prospective data are lacking, as are studies examining specific ADs. We have previously shown that one aspect of the diurnal rhythm of cortisol, the cortisol awakening response (CAR), prospectively predicts both new onsets and recurrences of major depressive disorder (MDD). Here we sought to examine whether it also predicts ADs. Participants (N=232) were drawn from the larger Northwestern-UCLA Youth Emotion Project, a two-site, longitudinal study of older adolescents, which aims to identify common and specific risk factors for mood and anxiety disorders. After baseline interviews for mental health diagnoses, a subset of adolescents completed a three-day cortisol sampling protocol measuring the CAR and other diurnal rhythm indices. Participants with past or current anxiety disorders at the time of cortisol measurement were excluded and Cox regression (survival analysis) was used to predict first onsets of ADs over the subsequent six years. AD onsets (N=25), the largest subset of which were social anxiety disorder (SAD) onsets (N=11), were observed over six annual follow up diagnostic interviews. Even when statistically adjusting for past and prospective MDD onsets and other covariates, a higher CAR significantly predicted increased first onsets of ADs (HR=2.20, p<.05). A higher CAR was also a strong and significant predictor of the subset of SAD onsets (HR=5.37, p<.005). Implications for the etiology of ADs, with a focus on SAD, are discussed.

Keywords: Adolescence; Anxiety disorders; Cortisol; Cortisol awakening response; Diurnal rhythms; Hypothalamic pituitary adrenal axis; Non-proportional hazard models; Prospective; Social anxiety disorder; Social phobia.

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Conflict of interest statement

Conflict of Interest: None of the authors have any conflicts of interest to declare with respect to this research.

Figures

Figure 1
Figure 1
Timeline of study procedures. SCID = Structured Clinical Interview for DSM-IV, non-patient edition (SCID; First et al., 2001). Average ages at time of assessments are provided in parentheses.
Figure 2
Figure 2
Model-estimated hazard ratios illustrate the observed CAR × Time interaction predicting social anxiety disorder onsets. Bars represent HRs for z-scored baseline natural log transformed CAR in year intervals after baseline. * = p < .05, ** = p < .01, NS = not significant, p > .05.
Figure 3
Figure 3
Baseline 3-day averages of raw salivary cortisol level (μg/dl) across the day for never anxiety-disordered participants and participants who experience a first onset of social anxiety disorder within the six-year follow-up.
See this image and copyright information in PMC

References

    1. Adam EK, Doane LD, Zinbarg RE, Mineka S, Craske MG, Griffith JW. Prospective prediction of major depressive disorder from cortisol awakening responses in adolescence. Psychoneuroendocrinology. 2010;35:921–931. - PMC - PubMed
    1. Adam EK, Hawkley LC, Kudielka BM, Cacioppo JT. Day-to-day dynamics of experience-cortisol associations in a population-based sample of older adults. Proceedings of the National Academy of Sciences. 2006;103:17058–17063. - PMC - PubMed
    1. Adam EK, Kumari M. Assessing salivary cortisol in large-scale, epidemiological research. Psychoneuroendocrinology. 2009;34:1423–1436. - PubMed
    1. Adam EK, Sutton JM, Doane LD, Mineka S. Incorporating hypothalamic– pituitary–adrenal axis measures into preventive interventions for adolescent depression: Are we there yet? Development and Psychopathology. 2008;20:975–1001. - PubMed
    1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th. American Psychiatric Publishing; Washington, D.C: 2000. text rev.

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