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Hydrocortisone impairs working memory in healthy humans, but not in patients with major depressive disorder

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Abstract

Objective

Several studies have shown that stress or the administration of glucocorticoids can impair hippocampus-based declarative memory retrieval and prefrontal dependent working memory performance in healthy subjects. Major Depressive Disorder (MDD) is often characterized by memory impairment and increased cortisol secretion. Studies indicate that the impairing effects of glucocorticoids on declarative memory performance are missing in patients with MDD. The purpose of our study was to investigate whether the finding of missing effects of acute cortisol administration on memory performance in MDD is also seen when examining prefrontal-based working memory.

Methods

In a placebo-controlled study, 57 patients with MDD and 56 sex- and age-matched healthy control subjects received either placebo or 10 mg of hydrocortisone orally before memory testing. To test the verbal modality of working memory, the Word Suppression Test was applied with one negative and one neutral test part.

Results

After hydrocortisone intake, healthy subjects showed a significantly poorer working memory performance compared to placebo treatment when negative interference words were administered. In contrast, memory performance of MDD patients was not affected by hydrocortisone treatment.

Conclusions

The missing effects of glucocorticoid administration on working memory in MDD might be interpreted in the context of reduced central glucocorticoid receptor function.

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References

  • Arnsten AF (2000) Stress impairs prefrontal cortical function in rats and monkeys: role of dopamine D1 and norepinephrine alpha-1 receptor mechanisms. Prog Brain Res 126:183–192

    Article  PubMed  CAS  Google Scholar 

  • Baddeley (1995) Working Memory: the interface between memory and cognition. In: Schacter DL, Tulving E (eds) Memory systems. MIT, Cambridge, pp 351–368

    Google Scholar 

  • Baddeley (2001) Is working memory still working? Am Psychol 56(11):851–864

    Article  PubMed  CAS  Google Scholar 

  • Baddeley, Della Sala S (1996) Working memory and executive control. Philos Trans R Soc Lond B Biol Sci 351(1346):1397–1403, discussion 1403-1394

    Article  PubMed  CAS  Google Scholar 

  • Beck AT, Steer RA (1994) Beck-depressions-inventar: BDI. Testhandbuch. Huber, Bern

    Google Scholar 

  • Belanoff JK, Kalehzan M, Sund B, Fleming Ficek SK, Schatzberg AF (2001) Cortisol activity and cognitive changes in psychotic major depression. Am J Psychiatry 158(10):1612–1616

    Article  PubMed  CAS  Google Scholar 

  • Berton O, Nestler EJ (2006) New approaches to antidepressant drug discovery: beyond monoamines. Nat Rev Neurosci 7(2):137–151

    Article  PubMed  CAS  Google Scholar 

  • Brand AN, Jolles J, Gispen-de Wied C (1992) Recall and recognition memory deficits in depression. J Affect Disord 25(1):77–86

    Article  PubMed  CAS  Google Scholar 

  • Bremner JD, Vythilingam M, Vermetten E, Anderson G, Newcomer JW, Charney DS (2004) Effects of glucocorticoids on declarative memory function in major depression. Biol Psychiatry 55(8):811–815

    Article  PubMed  CAS  Google Scholar 

  • Buchanan TW, Tranel D, Adolphs R (2006) Impaired memory retrieval correlates with individual differences in cortisol response but not autonomic response. Learn Mem 13(3):382–387

    Article  PubMed  CAS  Google Scholar 

  • Burt DB, Zembar MJ, Niederehe G (1995) Depression and memory impairment: a meta-analysis of the association, its pattern, and specificity. Psychol Bull 117(2):285–305

    Article  PubMed  CAS  Google Scholar 

  • Cahill L, Prins B, Weber M, McGaugh JL (1994) Beta-adrenergic activation and memory for emotional events. Nature 371(6499):702–704

    Article  PubMed  CAS  Google Scholar 

  • Cerqueira JJ, Mailliet F, Almeida OF, Jay TM, Sousa N (2007) The prefrontal cortex as a key target of the maladaptive response to stress. J Neurosci 27(11):2781–2787

    Article  PubMed  CAS  Google Scholar 

  • Charles G, Wilmotte J, Quenon M, Mendlewicz J (1982) Reproducibility of the dexamethasone suppression test in depression. Biol Psychiatry 17(7):845–848

    PubMed  CAS  Google Scholar 

  • de Kloet ER (2003) Hormones, brain and stress. Endocr Regul 37(2):51–68

    PubMed  Google Scholar 

  • de Quervain DJ, Roozendaal B, McGaugh JL (1998) Stress and glucocorticoids impair retrieval of long-term spatial memory. Nature 394(6695):787–790

    Article  PubMed  Google Scholar 

  • de Quervain DJ, Roozendaal B, Nitsch RM, McGaugh JL, Hock C (2000) Acute cortisone administration impairs retrieval of long-term declarative memory in humans. Nat Neurosci 3(4):313–314

    Article  PubMed  Google Scholar 

  • de Quervain DJ, Aerni A, Roozendaal B (2007) Preventive effect of beta-adrenoceptor blockade on glucocorticoid-induced memory retrieval deficits. Am J Psychiatry 164(6):967–969

    Article  PubMed  Google Scholar 

  • Diamond DM, Campbell AM, Park CR, Woodson JC, Conrad CD, Bachstetter AD et al (2006) Influence of predator stress on the consolidation versus retrieval of long-term spatial memory and hippocampal spinogenesis. Hippocampus 16(7):571–576

    Article  PubMed  Google Scholar 

  • Dolcos F, McCarthy G (2006) Brain systems mediating cognitive interference by emotional distraction. J Neurosci 26(7):2072–2079

    Article  PubMed  CAS  Google Scholar 

  • Dolcos F, Diaz-Granados P, Wang L, McCarthy G (2008) Opposing influences of emotional and non-emotional distracters upon sustained prefrontal cortex activity during a delayed-response working memory task. Neuropsychologia 46(1):326–335

    Article  PubMed  Google Scholar 

  • Eichenbaum H, Dudchenko P, Wood E, Shapiro M, Tanila H (1999) The hippocampus, memory, and place cells: is it spatial memory or a memory space? Neuron 23(2):209–226

    Article  PubMed  CAS  Google Scholar 

  • Heim C, Mletzko T, Purselle D, Musselman DL, Nemeroff CB (2008a) The dexamethasone/corticotropin-releasing factor test in men with major depression: role of childhood trauma. Biol Psychiatry 63(4):398–405

    Article  PubMed  CAS  Google Scholar 

  • Heim C, Newport DJ, Mletzko T, Miller AH, Nemeroff CB (2008b) The link between childhood trauma and depression: insights from HPA axis studies in humans. Psychoneuroendocrinology 33(6):693–710

    Article  PubMed  CAS  Google Scholar 

  • Hinkelmann K, Moritz S, Botzenhardt J, Riedesel K, Wiedemann K, Kellner M et al (2009) Cognitive impairment in major depression: association with salivary cortisol. Biol Psychiatry 66(9):879–885

    Article  PubMed  CAS  Google Scholar 

  • Holsboer F (2000) The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 23(5):477–501

    Article  PubMed  CAS  Google Scholar 

  • Holsboer F, Ising M (2010) Stress hormone regulation: biological role and translation into therapy. Annu Rev Psychol 61(81–109):C101–C111

    Google Scholar 

  • Holsboer F, Lauer CJ, Schreiber W, Krieg JC (1995) Altered hypothalamic-pituitary-adrenocortical regulation in healthy subjects at high familial risk for affective disorders. Neuroendocrinology 62(4):340–347

    Article  PubMed  CAS  Google Scholar 

  • Ising M, Kunzel HE, Binder EB, Nickel T, Modell S, Holsboer F (2005) The combined dexamethasone/CRH test as a potential surrogate marker in depression. Prog Neuropsychopharmacol Biol Psychiatry 29(6):1085–1093

    Article  PubMed  CAS  Google Scholar 

  • Kensinger EA, Corkin S (2003) Effect of negative emotional content on working memory and long-term memory. Emotion 3(4):378–393

    Article  PubMed  Google Scholar 

  • Kirschbaum C, Wolf OT, May M, Wippich W, Hellhammer DH (1996) Stress- and treatment-induced elevations of cortisol levels associated with impaired declarative memory in healthy adults. Life Sci 58(17):1475–1483

    Article  PubMed  CAS  Google Scholar 

  • Kuhlmann S, Kirschbaum C, Wolf OT (2005a) Effects of oral cortisol treatment in healthy young women on memory retrieval of negative and neutral words. Neurobiol Learn Mem 83(2):158–162

    Article  PubMed  CAS  Google Scholar 

  • Kuhlmann S, Piel M, Wolf OT (2005b) Impaired memory retrieval after psychosocial stress in healthy young men. J Neurosci 25(11):2977–2982

    Article  PubMed  CAS  Google Scholar 

  • Kunugi H, Ida I, Owashi T, Kimura M, Inoue Y, Nakagawa S et al (2006) Assessment of the dexamethasone/CRH test as a state-dependent marker for hypothalamic-pituitary-adrenal (HPA) axis abnormalities in major depressive episode: a Multicenter Study. Neuropsychopharmacology 31(1):212–220

    PubMed  CAS  Google Scholar 

  • Luethi M, Meier B, Sandi C (2008) Stress effects on working memory, explicit memory, and implicit memory for neutral and emotional stimuli in healthy men. Front Behav Neurosci 2:5

    Article  PubMed  Google Scholar 

  • Lupien SJ, Lepage M (2001) Stress, memory, and the hippocampus: can't live with it, can't live without it. Behav Brain Res 127(1–2):137–158

    Article  PubMed  CAS  Google Scholar 

  • Lupien SJ, Gaudreau S, Tchiteya BM, Maheu F, Sharma S, Nair NP et al (1997) Stress-induced declarative memory impairment in healthy elderly subjects: relationship to cortisol reactivity. J Clin Endocrinol Metab 82(7):2070–2075

    Article  PubMed  CAS  Google Scholar 

  • Lupien SJ, Gillin CJ, Hauger RL (1999) Working memory is more sensitive than declarative memory to the acute effects of corticosteroids: a dose-response study in humans. Behav Neurosci 113(3):420–430

    Article  PubMed  CAS  Google Scholar 

  • Matsubara T, Funato H, Kobayashi A, Nobumoto M, Watanabe Y (2006) Reduced glucocorticoid receptor alpha expression in mood disorder patients and first-degree relatives. Biol Psychiatry 59(8):689–695

    Article  PubMed  CAS  Google Scholar 

  • McGowan PO, Sasaki A, D'Alessio AC, Dymov S, Labonte B, Szyf M et al (2009) Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 12(3):342–348

    Article  PubMed  CAS  Google Scholar 

  • Mizoguchi K, Yuzurihara M, Ishige A, Sasaki H, Chui DH, Tabira T (2000) Chronic stress induces impairment of spatial working memory because of prefrontal dopaminergic dysfunction. J Neurosci 20(4):1568–1574

    PubMed  CAS  Google Scholar 

  • Modell S, Lauer CJ, Schreiber W, Huber J, Krieg JC, Holsboer F (1998) Hormonal response pattern in the combined DEX-CRH test is stable over time in subjects at high familial risk for affective disorders. Neuropsychopharmacology 18(4):253–262

    Article  PubMed  CAS  Google Scholar 

  • Monk CS, Nelson CA (2002) The effects of hydrocortisone on cognitive and neural function: a behavioral and event-related potential investigation. Neuropsychopharmacology 26(4):505–519

    Article  PubMed  CAS  Google Scholar 

  • Musselmann DL, DeBattista C, Nathan KI, Kilts CD, Schatzberg AF, Nemeroff CB (1998) Biology of mood disorders. In: Schatzberg AF, Nemeroff CB (eds) Textbook of psychopharmacology, 2nd edn. American Psychiatry Press, Arlington

    Google Scholar 

  • Nemeroff CB (1996) The corticotropin-releasing factor (CRF) hypothesis of depression: new findings and new directions. Mol Psychiatry 1(4):336–342

    PubMed  CAS  Google Scholar 

  • Oei NY, Everaerd WT, Elzinga BM, van Well S, Bermond B (2006) Psychosocial stress impairs working memory at high loads: an association with cortisol levels and memory retrieval. Stress 9(3):133–141

    Article  PubMed  CAS  Google Scholar 

  • Oei NY, Tollenaar MS, Spinhoven P, Elzinga BM (2009) Hydrocortisone reduces emotional distracter interference in working memory. Psychoneuroendocrinology 34(9):1284–1293

    Article  PubMed  CAS  Google Scholar 

  • Pariante CM, Lightman SL (2008) The HPA axis in major depression: classical theories and new developments. Trends Neurosci 31(9):464–468

    Article  PubMed  CAS  Google Scholar 

  • Pariante CM, Thomas SA, Lovestone S, Makoff A, Kerwin RW (2004) Do antidepressants regulate how cortisol affects the brain? Psychoneuroendocrinology 29(4):423–447

    Article  PubMed  CAS  Google Scholar 

  • Parker KJ, Schatzberg AF, Lyons DM (2003) Neuroendocrine aspects of hypercortisolism in major depression. Horm Behav 43(1):60–66

    Article  PubMed  CAS  Google Scholar 

  • Plotsky PM, Owens MJ, Nemeroff CB (1998) Psychoneuroendocrinology of depression. Hypothalamic-pituitary-adrenal axis. Psychiatr Clin North Am 21(2):293–307

    Article  PubMed  CAS  Google Scholar 

  • Porter RJ, Barnett NA, Idey A, McGuckin EA, O'Brien JT (2002) Effects of hydrocortisone administration on cognitive function in the elderly. J Psychopharmacol 16(1):65–71

    Article  PubMed  CAS  Google Scholar 

  • Quraishi S, Walshe M, McDonald C, Schulze K, Kravariti E, Bramon E et al (2009) Memory functioning in familial bipolar I disorder patients and their relatives. Bipolar Disord 11(2):209–214

    Article  PubMed  Google Scholar 

  • Robinson SJ, Sunram-Lea SI, Leach J, Owen-Lynch PJ (2008) The effects of exposure to an acute naturalistic stressor on working memory, state anxiety and salivary cortisol concentrations. Stress 11(2):115–124

    Article  PubMed  CAS  Google Scholar 

  • Rohleder N, Wolf JM, Wolf OT (2010) Glucocorticoid sensitivity of cognitive and inflammatory processes in depression and posttraumatic stress disorder. Neurosci Biobehav Rev 35(1):104–114

    Article  PubMed  CAS  Google Scholar 

  • Roozendaal B, McReynolds JR, McGaugh JL (2004) The basolateral amygdala interacts with the medial prefrontal cortex in regulating glucocorticoid effects on working memory impairment. J Neurosci 24(6):1385–1392

    Article  PubMed  CAS  Google Scholar 

  • Roozendaal B, Hui GK, Hui IR, Berlau DJ, McGaugh JL, Weinberger NM (2006a) Basolateral amygdala noradrenergic activity mediates corticosterone-induced enhancement of auditory fear conditioning. Neurobiol Learn Mem 86(3):249–255

    Article  PubMed  CAS  Google Scholar 

  • Roozendaal B, Okuda S, de Quervain DJ, McGaugh JL (2006b) Glucocorticoids interact with emotion-induced noradrenergic activation in influencing different memory functions. Neuroscience 138(3):901–910

    Article  PubMed  CAS  Google Scholar 

  • Schlosser N, Wolf OT, Fernando SC, Riedesel K, Otte C, Muhtz C et al (2010) Effects of acute cortisol administration on autobiographical memory in patients with major depression and healthy controls. Psychoneuroendocrinology 35(2):316–320

    Article  PubMed  CAS  Google Scholar 

  • Schoofs D, Preuss D, Wolf OT (2008) Psychosocial stress induces working memory impairments in an n-back paradigm. Psychoneuroendocrinology 33(5):643–653

    Article  PubMed  CAS  Google Scholar 

  • Schoofs D, Wolf OT, Smeets T (2009) Cold pressor stress impairs performance on working memory tasks requiring executive functions in healthy young men. Behav Neurosci 123(5):1066–1075

    Article  PubMed  Google Scholar 

  • Schule C, Baghai TC, Eser D, Rupprecht R (2009) Hypothalamic-pituitary-adrenocortical system dysregulation and new treatment strategies in depression. Expert Rev Neurother 9(7):1005–1019

    Article  PubMed  Google Scholar 

  • Shansky RM, Rubinow K, Brennan A, Arnsten AF (2006) The effects of sex and hormonal status on restraint-stress-induced working memory impairment. Behav Brain Funct 2:8

    Article  PubMed  Google Scholar 

  • Smeets T, Jelicic M, Merckelbach H (2006) The effect of acute stress on memory depends on word valence. Int J Psychophysiol 62(1):30–37

    Article  PubMed  Google Scholar 

  • Squire LR (1992) Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychol Rev 99(2):195–231

    Article  PubMed  CAS  Google Scholar 

  • Terfehr K, Wolf OT, Schlosser N, Carvalho Fernando S, Otte C, Muhtz C et al (in press) Cortisol administration and memory in major depression. J Clin Psychiatry (in press)

  • Thomson F, Craighead M (2008) Innovative approaches for the treatment of depression: targeting the HPA axis. Neurochem Res 33(4):691–707

    Article  PubMed  CAS  Google Scholar 

  • Van Den Eede F, Van den Bossche B, Hulstijn W, Sabbe BG, Cosyns P, Claes SJ (2006) Combined dexamethasone/CRF test in remitted outpatients with recurrent major depressive disorder. J Affect Disord 93(1–3):259–263

    Google Scholar 

  • Veiel HO (1997) A preliminary profile of neuropsychological deficits associated with major depression. J Clin Exp Neuropsychol 19(4):587–603

    Article  PubMed  CAS  Google Scholar 

  • Webster MJ, Knable MB, O'Grady J, Orthmann J, Weickert CS (2002) Regional specificity of brain glucocorticoid receptor mRNA alterations in subjects with schizophrenia and mood disorders. Mol Psychiatry 7(9):985–994, 924

    Article  PubMed  CAS  Google Scholar 

  • Wechsler D (1987) Wechsler memory scale-revised manual. Psychological Corporation, San Antonio

    Google Scholar 

  • Wittchen HU, Zaudig M, Fydrich T (1997) Strukturiertes Klinisches Interview für DSM-IV. Achse I: Psychische Störungen. SKID-I.: Hogrefe. Göttingen, Bern, Toronto, Seattle

  • Wolf OT, Convit A, McHugh PF, Kandil E, Thorn EL, De Santi S et al (2001) Cortisol differentially affects memory in young and elderly men. Behav Neurosci 115(5):1002–1011

    Article  PubMed  CAS  Google Scholar 

  • Young AH, Sahakian BJ, Robbins TW, Cowen PJ (1999) The effects of chronic administration of hydrocortisone on cognitive function in normal male volunteers. Psychopharmacology (Berl) 145(3):260–266

    Article  CAS  Google Scholar 

  • 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(8):1538–1545

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The work of the authors is supported by grants from the German Research Foundation (DFG WI3396/2-1 and WO 733/6-2).

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Authors and Affiliations

  1. Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf & Schön Klinik Hamburg-Eilbek, Hamburg, Germany

    Kirsten Terfehr, Carsten Spitzer, Bernd Löwe & Katja Wingenfeld

  2. Department of Cognitive Psychology, University of Bochum, Bochum, Germany

    Oliver Tobias Wolf

  3. Department of Psychiatry and Psychotherapy Bethel, Ev. Hospital Bielefeld, Bielefeld, Germany

    Nicole Schlosser, Silvia Carvalho Fernando, Thomas Beblo & Martin Driessen

  4. Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Christian Otte & Christoph Muhtz

  5. Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    Katja Wingenfeld

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  1. Kirsten Terfehr
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  2. Oliver Tobias Wolf
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  3. Nicole Schlosser
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  4. Silvia Carvalho Fernando
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  5. Christian Otte
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  6. Christoph Muhtz
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  7. Thomas Beblo
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  8. Martin Driessen
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  9. Carsten Spitzer
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  10. Bernd Löwe
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  11. Katja Wingenfeld
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Correspondence to Katja Wingenfeld.

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Terfehr, K., Wolf, O.T., Schlosser, N. et al. Hydrocortisone impairs working memory in healthy humans, but not in patients with major depressive disorder. Psychopharmacology 215, 71–79 (2011). https://doi.org/10.1007/s00213-010-2117-z

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