lunes, 28 de noviembre de 2011

Longitudinal hypothalamic–pituitary–adrenal axis trait and state effects in recurrent depression

Anja Loka, Corresponding Author Contact Information, 1, E-mail The Corresponding Author, Roel J.T. Mockinga, 1, Henricus G. Ruhéa, Ieke Vissera, Maarten W.J. Koetera, Johanna Assiesa, Claudi L.H. Bocktingb, Miranda Olffc, Aart H. Schenea
a Program for Mood Disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
b Department of Clinical and Experimental Psychology, University of Groningen, Groningen, The Netherlands
c Center for Psychological Trauma, Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Available online 17 November 2011.

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.


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.


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).


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.

Keywords: Depressive disorder; Major; Recurrence; Hypothalamo-hypophyseal system; Pituitary–adrenal system; Glucocorticoids; Saliva; Cohort studies; Case–control studies; Randomized controlled trial; Cognitive therapy

Corresponding Author Contact InformationCorresponding author at: Department of Psychiatry, Academic Medical Center, Meibergdreef 5, Amsterdam 1105 AZ, The Netherlands. Tel.: +31 205669111.

Fuente: Psychoneuroendocrinology

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