Major Depressive Disorder and Hypothalamic-Pituitary-Adrenal Axis Activity Results From a Large Cohort Study

S.A. Vreeburg, W.J.G. Hoogendijk, J. Pelt, R.H. DeRijk, R. van Dyck, J.H. Smit, F. G. Zitman, B.W.J.H. Penninx

    Research output: Contribution to JournalArticleAcademicpeer-review

    Abstract

    Context: There is a central belief that depression is associated with hyperactivity of the hypothalamic-pituitaryadrenal axis, resulting in higher cortisol levels. However, results are inconsistent. Objective: To examine whether there is an association between depression and various cortisol indicators in a large cohort study. Design, Setting, and Participants: Data are from 1588 participants of the Netherlands Study of Depression and Anxiety who were recruited from the community, general practice care, and specialized mental health care. Three groups were compared: 308 control subjects without psychiatric disorders, 579 persons with remitted (no current) major depressive disorder (MDD), and 701 persons with a current MDD diagnosis, as assessed using the DSM-IV Composite International Diagnostic Interview. Main Outcome Measures: Cortisol levels were measured in 7 saliva samples to determine the 1-hour cortisol awakening response, evening cortisol levels, and cortisol suppression after a 0.5-mg dexamethasone suppression test. Results: Both the remitted and current MDD groups showed a significantly higher cortisol awakening response compared with control subjects (effect size [Cohen d] range, 0.15-0.25). Evening cortisol levels were higher among the current MDD group at 10 PM but not at 11 PM. The postdexamethasone cortisol level did not differ between the MDD groups. Most depression characteristics (severity, chronicity, symptom profile, prior childhood trauma) were not associated with hypothalamic-pituitary-adrenal axis activity except for comorbid anxiety, which tended to be associated with a higher cortisol awakening response. The use of psychoactive medication was generally associated with lower cortisol levels and less cortisol suppression after dexamethasone ingestion. Conclusions: This large cohort study shows significant, although modest, associations between MDD and specific hypothalamic-pituitary-adrenal axis indicators. Because a higher cortisol awakening response was observed among both subjects with current MDD and subjects with remitted MDD, this may be indicative of an increased biological vulnerability for depression. ©2009 American Medical Association. All rights reserved.
    Original languageEnglish
    Pages (from-to)617-626
    JournalArchives of General Psychiatry
    Volume66
    Issue number6
    DOIs
    Publication statusPublished - 2009

    Bibliographical note

    J English Article Penninx, BWJH, Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, AJ Ernststr 887, NL-1081 HL Amsterdam, Netherlands [email protected] 64 3 AMER MEDICAL ASSOC CHICAGO 515 N STATE ST, CHICAGO, IL 60610-0946 USA ARCH GEN PSYCHIAT JUN Discipline: Psychiatry 452UN

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