Hostname: page-component-76fb5796d-qxdb6 Total loading time: 0 Render date: 2024-04-26T19:42:04.900Z Has data issue: false hasContentIssue false
  • English
  • Français

Association between cortisol awakening response and memory function in major depression

Published online by Cambridge University Press:  27 February 2013

K. Hinkelmann ,
C. Muhtz ,
L. Dettenborn ,
A. Agorastos ,
S. Moritz ,
K. Wingenfeld ,
C. Spitzer ,
S. M. Gold ,
K. Wiedemann  and
C. Otte
K. Hinkelmann*
Affiliation:
Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany
C. Muhtz
Affiliation:
Department of Psychosomatic Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
L. Dettenborn
Affiliation:
Department of Medical Psychology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
A. Agorastos
Affiliation:
Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
S. Moritz
Affiliation:
Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
K. Wingenfeld
Affiliation:
Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany
C. Spitzer
Affiliation:
Asklepios Fachklinikum Tiefenbrunn, Rosdorf, Germany
S. M. Gold
Affiliation:
Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, Germany
K. Wiedemann
Affiliation:
Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
C. Otte
Affiliation:
Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Berlin, Germany
*
*Address for correspondence: K. Hinkelmann, M.D., Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany. (Email: kim.hinkelmann@charite.de)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

While impaired memory and altered cortisol secretion are characteristic features of major depression, much less is known regarding the impact of antidepressant medication. We examined whether the cortisol awakening response (CAR) is increased in depressed patients with and without medication compared with healthy controls (HC) and whether CAR is associated with memory function in each group.

Method

We examined 21 patients with major depression without medication, 20 depressed patients on antidepressant treatment, and 41 age-, sex- and education-matched healthy subjects. We tested verbal (Auditory Verbal Learning Task) and visuospatial (Rey figure) memory and measured CAR on two consecutive days.

Results

Patient groups did not differ in severity of depression. We found a significant effect of group (p = 0.03) for CAR. Unmedicated patients exhibited a greater CAR compared with medicated patients (p = 0.04) with no differences between patient groups and HC. We found a significant effect of group for verbal (p = 0.03) and non-verbal memory (p = 0.04). Unmedicated patients performed worse compared with medicated patients and HC in both memory domains. Medicated patients and HC did not differ. Regression analyses revealed a negative association between CAR and memory function in depressed patients, but not in HC.

Conclusions

While in unmedicated depressed patients the magnitude of CAR is associated with impaired memory, medicated patients showed a smaller CAR and unimpaired cognitive function compared with HC. Our findings are compatible with the idea that antidepressants reduce CAR and partially restore memory function even if depressive psychopathology is still present.

Keywords

Awakening responsecognitive functioncortisoldepressionhypothalamus–pituitary–adrenal axisneuropsychology
Type
Original Articles
Information
Psychological Medicine , Volume 43 , Issue 11 , November 2013 , pp. 2255 - 2263
Copyright
Copyright © Cambridge University Press 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adam, EK, Doane, LD, Zinbarg, RE, Mineka, S, Craske, MG, Griffith, JW (2010). Prospective prediction of major depressive disorder from cortisol awakening responses in adolescence. Psychoneuroendocrinology 35, 921–931.CrossRefGoogle ScholarPubMed
Adler, G, Jajcevic, A (2001). Post-dexamethasone cortisol level and memory performance in elderly depressed patients. Neuroscience Letters 298, 142–144.CrossRefGoogle ScholarPubMed
Aihara, M, Ida, I, Yuuki, N, Oshima, A, Kumano, H, Takahashi, K, Fukuda, M, Oriuchi, N, Endo, K, Matsuda, H, Mikuni, M (2007). HPA axis dysfunction in unmedicated major depressive disorder and its normalization by pharmacotherapy correlates with alteration of neural activity in prefrontal cortex and limbic/paralimbic regions. Psychiatry Research 155, 245–256.CrossRefGoogle ScholarPubMed
Aubry, JM, Jermann, F, Gex-Fabry, M, Bockhorn, L, Van der Linden, M, Gervasoni, N, Bertschy, G, Rossier, MF, Bondolfi, G (2010). The cortisol awakening response in patients remitted from depression. Journal of Psychiatric Research 44, 1199–1204.CrossRefGoogle ScholarPubMed
Belanoff, JK, Gross, K, Yager, A, Schatzberg, AF (2001). Corticosteroids and cognition. Journal of Psychiatric Research 35, 127–145.CrossRefGoogle ScholarPubMed
Bhagwagar, Z, Hafizi, S, Cowen, PJ (2003). Increase in concentration of waking salivary cortisol in recovered patients with depression. American Journal of Psychiatry 160, 1890–1891.CrossRefGoogle ScholarPubMed
Bhagwagar, Z, Hafizi, S, Cowen, PJ (2005). Increased salivary cortisol after waking in depression. Psychopharmacology 182, 54–57.CrossRefGoogle ScholarPubMed
Bremner, JD, Vythilingam, M, Vermetten, E, Vaccarino, V, Charney, DS (2004). Deficits in hippocampal and anterior cingulate functioning during verbal declarative memory encoding in midlife major depression. American Journal of Psychiatry 161, 637–645.CrossRefGoogle ScholarPubMed
Buchanan, TW, Kern, S, Allen, JS, Tranel, D, Kirschbaum, C (2004). Circadian regulation of cortisol after hippocampal damage in humans. Biological Psychiatry 56, 651–656.CrossRefGoogle ScholarPubMed
Burke, HM, Davis, MC, Otte, C, Mohr, DC (2005). Depression and cortisol responses to psychological stress: a meta-analysis. Psychoneuroendocrinology 30, 846–856.CrossRefGoogle ScholarPubMed
de Kloet, ER, Joels, M, Holsboer, F (2005 a). Stress and the brain: from adaptation to disease. Nature Reviews Neuroscience 6, 463–475.CrossRefGoogle ScholarPubMed
de Kloet, ER, Sibug, RM, Helmerhorst, FM, Schmidt, MV (2005 b). Stress, genes and the mechanism of programming the brain for later life. Neuroscience and Biobehavioural Reviews 29, 271–281.CrossRefGoogle ScholarPubMed
Dedovic, K, Engert, V, Duchesne, A, Lue, SD, Andrews, J, Efanov, SI, Beaudry, T, Pruessner, JC (2010). Cortisol awakening response and hippocampal volume: vulnerability for major depressive disorder? Biological Psychiatry 68, 847–853.CrossRefGoogle ScholarPubMed
Edwards, S, Clow, A, Evans, P, Hucklebridge, F (2001). Exploration of the awakening cortisol response in relation to diurnal cortisol secretory activity. Life Sciences 68, 2093–2103.CrossRefGoogle ScholarPubMed
Egeland, J, Lund, A, Landro, NI, Rund, BR, Sundet, K, Asbjornsen, A, Mjellem, N, Roness, A, Stordal, KI (2005). Cortisol level predicts executive and memory function in depression, symptom level predicts psychomotor speed. Acta Psychiatrica Scandinavica 112, 434–441.CrossRefGoogle ScholarPubMed
Fries, E, Dettenborn, L, Kirschbaum, C (2009). The cortisol awakening response (CAR): facts and future directions. International Journal of Psychophysiology 72, 67–73.CrossRefGoogle ScholarPubMed
Gomez, RG, Fleming, SH, Keller, J, Flores, B, Kenna, H, DeBattista, C, Solvason, B, Schatzberg, AF (2006). The neuropsychological profile of psychotic major depression and its relation to cortisol. Biological Psychiatry 60, 472–478.CrossRefGoogle ScholarPubMed
Gomez, RG, Posener, JA, Keller, J, DeBattista, C, Solvason, B, Schatzberg, AF (2009). Effects of major depression diagnosis and cortisol levels on indices of neurocognitive function. Psychoneuroendocrinology 34, 1012–1018.CrossRefGoogle ScholarPubMed
Hellhammer, J, Fries, E, Schweisthal, OW, Schlotz, W, Stone, AA, Hagemann, D (2007). Several daily measurements are necessary to reliably assess the cortisol rise after awakening: state- and trait components. Psychoneuroendocrinology 32, 80–86.CrossRefGoogle ScholarPubMed
Het, S, Ramlow, G, Wolf, OT (2005). A meta-analytic review of the effects of acute cortisol administration on human memory. Psychoneuroendocrinology 30, 771–784.CrossRefGoogle ScholarPubMed
Hinkelmann, K, Moritz, S, Botzenhardt, J, Muhtz, C, Wiedemann, K, Kellner, M, Otte, C (2012). Changes in cortisol secretion during antidepressive treatment and cognitive improvement in patients with major depression: a longitudinal study. Psychoneuroendocrinology 37, 685–692.CrossRefGoogle ScholarPubMed
Hinkelmann, K, Moritz, S, Botzenhardt, J, Riedesel, K, Wiedemann, K, Kellner, M, Otte, C (2009). Cognitive impairment in major depression: association with salivary cortisol. Biological Psychiatry 66, 879–885.CrossRefGoogle ScholarPubMed
Holsboer, F, Ising, M (2010). Stress hormone regulation: biological role and translation into therapy. Annual Review of Psychology 61, 81–109, C1–C11.CrossRefGoogle ScholarPubMed
Huber, TJ, Issa, K, Schik, G, Wolf, OT (2006). The cortisol awakening response is blunted in psychotherapy inpatients suffering from depression. Psychoneuroendocrinology 31, 900–904.CrossRefGoogle ScholarPubMed
Ising, M, Horstmann, S, Kloiber, S, Lucae, S, Binder, EB, Kern, N, Kunzel, HE, Pfennig, A, Uhr, M, Holsboer, F (2007). Combined dexamethasone/corticotropin releasing hormone test predicts treatment response in major depression – a potential biomarker? Biological Psychiatry 62, 47–54.CrossRefGoogle ScholarPubMed
Krogh, J, Videbech, P, Renvillard, SG, Garde, AH, Jorgensen, MB, Nordentoft, M (2012). Cognition and HPA axis reactivity in mildly to moderately depressed outpatients. A case–control study. Nordic Journal of Psychiatry 66, 414–421.CrossRefGoogle ScholarPubMed
Lezak, M (1995). Neuropsychological Assessment. Oxford University Press: New York.Google Scholar
Lupien, SJ, McEwen, BS, Gunnar, MR, Heim, C (2009). Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nature Reviews. Neuroscience 10, 434–445.CrossRefGoogle ScholarPubMed
Mannie, ZN, Barnes, J, Bristow, GC, Harmer, CJ, Cowen, PJ (2009). Memory impairment in young women at increased risk of depression: influence of cortisol and 5-HTT genotype. Psychological Medicine 39, 757–762.CrossRefGoogle ScholarPubMed
Manthey, L, Leeds, C, Giltay, EJ, van Veen, T, Vreeburg, SA, Penninx, BW, Zitman, FG (2011). Antidepressant use and salivary cortisol in depressive and anxiety disorders. European Neuropsychopharmacology 21, 691–699.CrossRefGoogle ScholarPubMed
McKinnon, MC, Yucel, K, Nazarov, A, MacQueen, GM (2009). A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder. Journal of Psychiatry and Neuroscience 34, 41–54.Google ScholarPubMed
Michopoulos, I, Zervas, IM, Pantelis, C, Tsaltas, E, Papakosta, VM, Boufidou, F, Nikolaou, C, Papageorgiou, C, Soldatos, CR, Lykouras, L (2008). Neuropsychological and hypothalamic–pituitary-axis function in female patients with melancholic and non-melancholic depression. European Archives of Psychiatry and Clinical Neuroscience 258, 217–225.CrossRefGoogle ScholarPubMed
O'Brien, JT, Lloyd, A, McKeith, I, Gholkar, A, Ferrier, N (2004). A longitudinal study of hippocampal volume, cortisol levels, and cognition in older depressed subjects. American Journal of Psychiatry 161, 2081–2090.CrossRefGoogle ScholarPubMed
Osterrieth, PA (1944). Le test de copie d'une figure complexe; contribution à l’étude de la perception et de la mémoire (Test of copying a complex figure; contribution to the study of perception and memory). Archives de Psychologie 30, 206–356.Google Scholar
Otte, C, Hinkelmann, K, Moritz, S, Yassouridis, A, Jahn, H, Wiedemann, K, Kellner, M (2010). Modulation of the mineralocorticoid receptor as add-on treatment in depression: a randomized, double-blind, placebo-controlled proof-of-concept study. Journal of Psychiatric Research 44, 339–346.CrossRefGoogle ScholarPubMed
Otte, C, Moritz, S, Yassouridis, A, Koop, M, Madrischewski, AM, Wiedemann, K, Kellner, M (2007). Blockade of the mineralocorticoid receptor in healthy men: effects on experimentally induced panic symptoms, stress hormones, and cognition. Neuropsychopharmacology 32, 232–238.CrossRefGoogle ScholarPubMed
Pariante, CM (2006). The glucocorticoid receptor: part of the solution or part of the problem? Journal of Psychopharmacology 20, 79–84.CrossRefGoogle ScholarPubMed
Porter, RJ, Bourke, C, Gallagher, P (2007). Neuropsychological impairment in major depression: its nature, origin and clinical significance. Australian and New Zealand Journal of Psychiatry 41, 115–128.CrossRefGoogle ScholarPubMed
Pruessner, JC, Kirschbaum, C, Meinlschmid, G, Hellhammer, DH (2003). Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology 28, 916–931.CrossRefGoogle ScholarPubMed
Raison, CL, Capuron, L, Miller, AH (2006). Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends in Immunology 27, 24–31.CrossRefGoogle ScholarPubMed
Reppermund, S, Zihl, J, Lucae, S, Horstmann, S, Kloiber, S, Holsboer, F, Ising, M (2007). Persistent cognitive impairment in depression: the role of psychopathology and altered hypothalamic–pituitary–adrenocortical (HPA) system regulation. Biological Psychiatry 62, 400–406.CrossRefGoogle ScholarPubMed
Rubinow, DR, Post, RM, Savard, R, Gold, PW (1984). Cortisol hypersecretion and cognitive impairment in depression. Archives of General Psychiatry 41, 279–283.CrossRefGoogle ScholarPubMed
Schatzberg, AF, Posener, JA, DeBattista, C, Kalehzan, BM, Rothschild, AJ, Shear, PK (2000). Neuropsychological deficits in psychotic versus nonpsychotic major depression and no mental illness. American Journal of Psychiatry 157, 1095–1100.CrossRefGoogle ScholarPubMed
Schule, C (2007). Neuroendocrinological mechanisms of actions of antidepressant drugs. Journal of Neuroendocrinology 19, 213–226.CrossRefGoogle ScholarPubMed
Sheehan, DV, Lecrubier, Y, Sheehan, KH, Amorim, P, Janavs, J, Weiller, E, Hergueta, T, Baker, R, Dunbar, GC (1998). The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry 59 (Suppl. 20), 22–57.Google ScholarPubMed
Stetler, C, Miller, GE (2005). Blunted cortisol response to awakening in mild to moderate depression: regulatory influences of sleep patterns and social contacts. Journal of Abnormal Psychology 114, 697–705.CrossRefGoogle ScholarPubMed
Vreeburg, SA, Hartman, CA, Hoogendijk, WJ, van Dyck, R, Zitman, FG, Ormel, J, Penninx, BW (2010). Parental history of depression or anxiety and the cortisol awakening response. British Journal of Psychiatry 197, 180–185.CrossRefGoogle ScholarPubMed
Vreeburg, SA, Hoogendijk, WJ, van Pelt, J, Derijk, RH, Verhagen, JC, van Dyck, R, Smit, JH, Zitman, FG, Penninx, BW (2009). Major depressive disorder and hypothalamic–pituitary–adrenal axis activity: results from a large cohort study. Archives of General Psychiatry 66, 617–626.CrossRefGoogle ScholarPubMed
Vrshek-Schallhorn, S, Doane, LD, Mineka, S, Zinbarg, RE, Craske, MG, Adam, EK (2013). The cortisol awakening response predicts major depression: predictive stability over a 4-year follow-up and effect of depression history. Psychological Medicine 43, 483–493.CrossRefGoogle Scholar
Vythilingam, M, Vermetten, E, Anderson, GM, Luckenbaugh, D, Anderson, ER, Snow, J, Staib, LH, Charney, DS, Bremner, JD (2004). Hippocampal volume, memory, and cortisol status in major depressive disorder: effects of treatment. Biological Psychiatry 56, 101–112.CrossRefGoogle ScholarPubMed
Watson, S, Gallagher, P, Porter, RJ, Smith, MS, Herron, LJ, Bulmer, S; North-East Mood Disorders Clinical Research Group, Young, AH, Ferrier, IN (2012). A randomized trial to examine the effect of mifepristone on neuropsychological performance and mood in patients with bipolar depression. Biological Psychiatry 72, 943–949.CrossRefGoogle ScholarPubMed
Wilhelm, I, Born, J, Kudielka, BM, Schlotz, W, Wust, S (2007). Is the cortisol awakening rise a response to awakening? Psychoneuroendocrinology 32, 358–366.CrossRefGoogle Scholar
Wingenfeld, K, Wolf, OT (2011). HPA-axis alterations in mental disorders: impact on memory and its relevance for therapeutic interventions. CNS Neuroscience and Therapeutics 17, 714–722.CrossRefGoogle ScholarPubMed
Young, AH, Gallagher, P, Watson, S, Del-Estal, D, Owen, BM, Ferrier, IN (2004). Improvements in neurocognitive function and mood following adjunctive treatment with mifepristone (RU-486) in bipolar disorder. Neuropsychopharmacology 29, 1538–1545.CrossRefGoogle ScholarPubMed
Zobel, AW, Schulze-Rauschenbach, S, von Widdern, OC, Metten, M, Freymann, N, Grasmader, K, Pfeiffer, U, Schnell, S, Wagner, M, Maier, W (2004). Improvement of working but not declarative memory is correlated with HPA normalization during antidepressant treatment. Journal of Psychiatric Research 38, 377–383.CrossRefGoogle Scholar
Zunszain, PA, Anacker, C, Cattaneo, A, Carvalho, LA, Pariante, CM (2011). Glucocorticoids, cytokines and brain abnormalities in depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry 35, 722–729.CrossRefGoogle ScholarPubMed