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Working memory performance and cognitive flexibility after dexamethasone or hydrocortisone administration in healthy volunteers

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Abstract

Objective

Several studies have shown that glucocorticoids can impair declarative memory retrieval and working memory (WM) performance. The aim of the present study was to investigate the impact of a high dose of hydrocortisone on WM, as well as to examine the effects of cortisol suppression via treatment with a high dose of dexamethasone (DEX). We hypothesized that hydrocortisone treatment results in an impaired cognitive function compared with placebo. We further expected that dexamethasone treatment is also followed by cognitive impairment, due to the hypothesis that very low levels of cortisol are also associated with alterations in memory performance.

Methods

In a placebo-controlled study with a within-subject design, 16 healthy volunteers received placebo or 120 mg of hydrocortisone (two boluses of 60 mg) directly before neuropsychological testing or 4 mg of DEX the day before testing.

Results

We did not find any effect of hydrocortisone on WM and cognitive flexibility, even though cortisol levels were high at the time of testing. Furthermore, we did not find any effect of DEX treatment on WM and reaction time in a cognitive flexibility test. However, cognitive flexibility was negatively correlated with adrenocorticotropin (ACTH) in the DEX condition.

Conclusions

Our results found no clear effect of hydrocortisone and dexamethasone treatment on WM. These results emphasize the need for further research on the association between hypothalamic–pituitary–adrenal axis activity and cognition. These studies should investigate the hypotheses of dose-dependent associations in more detail and should also include analyses on ACTH and cognition.

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References

  • Abercrombie HC, Speck NS, Monticelli RM (2006) Endogenous cortisol elevations are related to memory facilitation only in individuals who are emotionally aroused. Psychoneuroendocrinology 31(2):187–196

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Belanoff JK, Gross K, Yager A, Schatzberg AF (2001) Corticosteroids and cognition. J Psychiatr Res 35(3):127–145

    Article  PubMed  CAS  Google Scholar 

  • Bitran D, Shiekh M, Dowd JA, Dugan MM, Renda P (1998) Corticosterone is permissive to the anxiolytic effect that results from the blockade of hippocampal mineralocorticoid receptors. Pharmacol Biochem Behav 60(4):879–887

    Article  PubMed  CAS  Google Scholar 

  • Buchanan TW (2007) Retrieval of emotional memories. Psychol Bull 133(5):761–779

    Article  PubMed  Google Scholar 

  • Carrasco GA, Van de Kar LD (2003) Neuroendocrine pharmacology of stress. Eur J Pharmacol 463(1–3):235–272

    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 

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

    PubMed  Google Scholar 

  • De Kloet ER, Vreugdenhil E, Oitzl MS, Joels M (1998) Brain corticosteroid receptor balance in health and disease. Endocr Rev 19(3):269–301

    Article  PubMed  Google Scholar 

  • de Kloet ER, Oitzl MS, Joels M (1999) Stress and cognition: are corticosteroids good or bad guys? Trends Neurosci 22(10):422–426

    Article  PubMed  Google Scholar 

  • de Kloet ER, Joels M, Holsboer F (2005) Stress and the brain: from adaptation to disease. Nat Rev Neurosci 6(6):463–475

    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 

  • Diorio D, Viau V, Meaney MJ (1993) The role of the medial prefrontal cortex (cingulate gyrus) in the regulation of hypothalamic–pituitary–adrenal responses to stress. J Neurosci 13(9):3839–3847

    PubMed  CAS  Google Scholar 

  • Elzinga BM, Roelofs K (2005) Cortisol-induced impairments of working memory require acute sympathetic activation. Behav Neurosci 119(1):98–103

    Article  PubMed  CAS  Google Scholar 

  • Elzinga BM, Bakker A, Bremner JD (2005) Stress-induced cortisol elevations are associated with impaired delayed, but not immediate recall. Psychiatry Res 134(3):211–223

    Article  PubMed  CAS  Google Scholar 

  • Het S, Ramlow G, Wolf OT (2005) A meta-analytic review of the effects of acute cortisol administration on human memory. Psychoneuroendocrinology 30(8):771–784

    Article  PubMed  CAS  Google Scholar 

  • Kirschbaum C, Kudielka BM, Gaab J, Schommer NC, Hellhammer DH (1999) Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus–pituitary–adrenal axis. Psychosom Med 61(2):154–162

    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 

  • Lorenzetti V, Allen NB, Fornito A, Yucel M (2009) Structural brain abnormalities in major depressive disorder: a selective review of recent MRI studies. J Affect Disord 117(1–2):1–17. doi:10.1016/j.jad.2008.11.021

    Article  PubMed  Google Scholar 

  • Luethi M, Meier B, Sandi C (2009) Stress effects on working memory, explicit memory, and implicit memory and emotional stimuli in healthy men. Frontiers Behav Neurosci 2:1–9

    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, 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 

  • Meaney MJ, Aitken DH (1985) [3H]Dexamethasone binding in rat frontal cortex. Brain Res 328(1):176–180. doi:10.1016/0006-8993(85)91340-X

    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 

  • 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 

  • 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. doi:10.1080/10253890600965773

    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 

  • Otte C, Moritz S, Yassouridis A, Koop M, Madrischewski AM, Wiedemann K et al. (2007). Blockade of the mineralocorticoid receptor in healthy men: effects on experimentally induced panic symptoms, stress hormones, and cognition. Neuropsychopharmacology, 32(1), 232-238.

    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 

  • 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(7):916–931

    Article  PubMed  CAS  Google Scholar 

  • Rimmele U, Meier F, Lange T, Born J (2010) Suppressing the morning rise in cortisol impairs free recall. Learn Mem 17(4):186–190. doi:10.1101/lm.172851017/4/186

    Article  PubMed  CAS  Google Scholar 

  • Roozendaal B (2002) Stress and memory: opposing effects of glucocorticoids on memory consolidation and memory retrieval. Neurobiol Learn Mem 78(3):578–595

    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 

  • Seckl JR, Dickson KL, Yates C, Fink G (1991) Distribution of glucocorticoid and mineralocorticoid receptor messenger RNA expression in human postmortem hippocampus. Brain Res 561(2):332–337. doi:10.1016/0006-8993(91)91612-5

    Article  PubMed  CAS  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. doi:10.1016/j.ijpsycho.2005.11.007

    Article  PubMed  Google Scholar 

  • Terfehr K, Wolf OT, Schlosser Fernando SC, Otte C, Muhtz C et al. (in press). Hydrocortisone impairs working memory in healthy humans, but not in patients with major depressive disorder. Psychopharmacology (Berl).

  • Tops M, van Peer JM, Wester AE, Wijers AA, Korf J (2006) State-dependent regulation of cortical activity by cortisol: an EEG study. Neurosci Lett 404(1–2):39–43. doi:10.1016/j.neulet.2006.05.038

    Article  PubMed  CAS  Google Scholar 

  • Wagner U, Born J (2008) Memory consolidation during sleep: interactive effects of sleep stages and HPA regulation. Stress 11(1):28–41. doi:10.1080/10253890701408822

    Article  PubMed  CAS  Google Scholar 

  • Wechsler D (1987) Wechsler memory scale—revised. Harcourt Brace Jovanovich, San Antonio

    Google Scholar 

  • Wolf OT (2009) Stress and memory in humans: twelve years of progress? Brain Res 1293:142–154

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Zimmerman P, Fimm B (1993) Testbatterie zur Aufmerksamkeitsprüfung (TAP), Handbuch. Psytest, Herzogenrath

    Google Scholar 

Download references

Acknowledgments

The present study was funded by the Wilhelm Sander-Stiftung (92.040.2).

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There were no conflicts of interest, financial or otherwise, to declare.

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Correspondence to Katja Wingenfeld.

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Wingenfeld, K., Wolf, S., Krieg, JC. et al. Working memory performance and cognitive flexibility after dexamethasone or hydrocortisone administration in healthy volunteers. Psychopharmacology 217, 323–329 (2011). https://doi.org/10.1007/s00213-011-2286-4

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  • DOI: https://doi.org/10.1007/s00213-011-2286-4

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