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Pituitary-Adrenal and Sympathetic Nervous System Responses to Stress in Women Remitted From Recurrent Major Depression

From the Departments of Psychiatry and Psychotherapy (T.A., M.D., F.L.) and Biostatistics (B.K.), Central Institute of Mental Health, Mannheim, Germany; and Section of Biological Psychiatry (G.v.d.P., J.A.d.B.), Department of Psychiatry, University Medical Centre Groningen, Groningen, Netherlands.

Address correspondence and reprint requests to Florian Lederbogen, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, J5, 68159 Mannheim, Germany. E-mail: florian.lederbogen{at}zi-mannheim.de

Objective: To better understand the changes in hypothalamus-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) function after remission of depression. We characterized these systems at baseline and in response to a psychosocial stressor in a cohort of women remitted from recurrent major depression as well as in never-depressed healthy female controls.

Methods: Baseline HPA function was measured via saliva cortisol sampling at 8 AM and 4 PM over 7 days as well as quantification of urinary overnight cortisol secretion. The HPA system response to a psychosocial stressor was assessed by measuring serum cortisol and adrenocorticotropic hormone (ACTH) levels and SNS reactivity by determining serum epinephrine (E) and norepinephrine (NE) concentrations as well as autonomic nervous system changes by analysis of heart rate variability (HRV). The stressor included a speech task, mental arithmetic, and a cognitive challenge.

Results: In all, we studied 22 women remitted from recurrent major depression (age = 51.0 ± 1.7 years) and 20 healthy controls (age = 54.2 ± 1.6 years). Morning saliva cortisol concentrations were lower in remitted patients, paralleled by lower serum cortisol concentrations before stress testing. This group also displayed a blunted cortisol and ACTH response to the stressor, as compared with healthy controls. No between-group differences in HRV parameters were observed.

Conclusion: In this group of women remitted from recurrent major depressive disorder, we found evidence of HPA system hypoactivity, both in the basal state and in response to a psychosocial stressor.

Key Words: depression • remission • stress • cortisol • ACTH • norepinephrine • heart rate variability

Abbreviations: ACTH = adrenocorticotropic hormone; E = epinephrine; HAM-D = Hamilton Depression Scale; HPA = hypothalamus-pituitary-adrenal; HF = high frequency; HRV = heart rate variability; HR = heart rate; LF = low frequency; NE = norepinephrine; rm-ANOVA = repeated-measures analysis of variance; SNS = sympathetic nervous system; VAS = visual analogous scale.