Longitudinal hypothalamic-pituitary-adrenal axis trait and state effects in recurrent depression
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BACKGROUND: Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity has been observed in (recurrent) major depressive disorder (MDD), although inconsistently and mainly cross-sectional. Longitudinal studies clarifying state-trait issues are lacking. We aimed to determine whether HPA-axis (hyper)activity in recurrent MDD is: (I) reflecting a persistent trait; (II) influenced by depressive state; (III) associated with stress or previous episodes; (IV) associated with recurrence; and (V) influenced by cognitive therapy. METHODS: We included 187 remitted highly recurrent MDD-patients (mean number of previous episodes: 6.3), participating in a randomized-controlled-trial investigating the preventive effect of additional cognitive therapy on recurrence. In an add-on two-staged patient-control and prospective-cohort design, we first cross-sectionally compared patients' salivary morning and evening cortisol concentrations with 72 age- and sex-matched controls, and subsequently longitudinally followed-up the patients with repeated measures after three months and two years. RESULTS: Patients had higher cortisol concentrations than controls (p<.001), which did not change by MDD-episodes during follow-up. HPA-axis activity had no relation with daily hassles or childhood life events. Cortisol concentrations were lower in patients with more previous episodes (p=.047), but not associated with recurrence(s) during follow-up. Finally, randomly assigned cognitive therapy at study-entry enhanced cortisol declines over the day throughout the two-year follow-up (p=.052). CONCLUSIONS: Our results indicate that remitted recurrent MDD-patients have a persistent trait of increased cortisol concentrations, irrespective of stress. In combination with our finding that patients' cortisol concentrations do not change during new MDD-episodes (and thus not represent epiphenomenal or state-effects), our results support that hypercortisolemia fulfills the state-independence criterion for an endophenotype for recurrent depression.
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Longitudinal studies found that both higher and lower cortisol levels predicted recurrence of major depressive episodes in people with a history of major depressive disorder.
“Longitudinal studies have found that both enhanced and blunted cortisol levels predicted MDE recurrence amongst those with a prior history of MDD (72–74).”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [73]
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References 61 · Cited by 99
Research works printed but not linked: 1
- Starckmann, M.N., 2003. Psychiatric manifestations of hyperadre- nocorticism and hypoadrenocorticism, (Cushing's and Addeson's diseases). In: Wolkowitz, O.M., Rothschild, A.J. (Eds.), Psycho- neuroendocrinology. Americ Psychiatric Publishing, Inc., Washington, DC, pp. 165-188.
- Authors
- Lok, A., Mocking, R. J. T., Ruhé, H. G., Visser, I., Koeter, M. W. J., Assies, J., Bockting, C. L. H., Olff, M., & Schene, A. H.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- University of Groningen (NL)
- Corresponding author
- Lok, Anja
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 37
- Issue
- 7
- Pages
- 892-902
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W2168387026
- Cited by
- 99
- References
- 61
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 4 · 2019: 6 · 2018: 9 · 2017: 5 · 2016: 8 · 2015: 13 · 2014: 10 · 2013: 16 · 2012: 8
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Psychoneuroendocrinology (publishedVersion, other-oa)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- recurrent major depressive disorder, hypothalamic-pituitary-adrenal axis, HPA axis hyperactivity, salivary cortisol, endophenotypes, depression recurrence, cognitive therapy, daily hassles, remitted depression
- MeSH terms
- Adolescent, Adult, Aged, Cross-Sectional Studies, Depressive Disorder, Female, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Longitudinal Studies, Male, Middle Aged, Pituitary-Adrenal System, Recurrence, Cohort Studies, Cognitive Behavioral Therapy, Case-Control Studies, Young Adult
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