Abstract
There have been proposals for REM to have a function of emotional memory consolidation, and also for REM sleep to be involved in the promotion of attachment behaviour. The hormones cortisol and oxytocin, respectively, may be involved in these proposed REM sleep functions. However, there are conflicting reports on whether levels of cortisol differ between sleep stages when time since sleep onset (SSO) is controlled, and virtually no literature on whether levels of oxytocin differ between sleep stages. This study thus investigated the changes in levels of oxytocin (OT) and cortisol (CT) across the night, and whether these levels differ between REM and N2 sleep when time SSO is controlled. 20 participants (10 males, 10 females, mean age = 20.45, SD = 2.01) were awakened 10 min into REM and N2 sleep periods in the sleep laboratory and gave saliva samples which were assayed for OT and CT. Levels of OT were relatively constant across the night, whereas CT increased significantly. REM and N2 did not differ significantly neither for OT nor for CT. The study has implications for models of sleep-dependent memory consolidation that incorporate the late sleep increase in cortisol as a functional component of memory consolidation, and also for the medical diagnostic assaying of OT during sleep.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Amico JA, Tenicela R, Johnston J, Robinson AG (1983) A time-dependent peak of oxytocin exists in cerebrospinal fluid but not in plasma of humans. J Clin Endocrinol Metab 57:947–951
Andersson K-E (2001) Pharmacology of penile erection. Pharmacol Rev 53:417–450
Backhaus J, Junghanns K, Hohagen F (2004) Sleep disturbances are correlated with decreased morning awakening salivary cortisol. Psychoneuroendocrinology 29:1184–1191. doi:10.1016/j.psyneuen.2004.01.010
Bartz JA, Hollander E (2006) The neuroscience of affiliation: forging links between basic and clinical research on neuropeptides and social behaviour. Horm Behav 50:518–528. doi:10.1016/j.yhbeh.2006.06.018
Bierwolf C, Struve K, Marshall L, Born J, Fehm HL (1997) Slow wave sleep drives inhibition of Pituitary–Adrenal secretion in humans. J Neuroendocrin 9:479–484
Bonnet MH, Arand DL (2010) Hyperarousal and insomnia: state of the science. Sleep Med Rev 14:9–15. doi:10.1016/j.smrv.2009.05.002
Born J, Wagner U (2004) Memory consolidation during sleep: role of cortisol feedback. Ann NY Acad Sci 1032:198–201. doi:10.1196/annals.1314.020
Born J, Wagner U (2007) Sleep, hormones, and memory. Sleep Med Clin 2:209–227. doi:10.1016/j.jsmc.2007.03.005
Born J, Kern W, Bieber K, Fehm-Wolfsdorf G, Schiebe M, Fehm HL (1986) Night time plasma cortisol secretion is associated with specific sleep stages. Biol Psychiat 21:1415–1424. doi:10.1016/0006-3223(86)90333-1
Campbell A (2010) Oxytocin and human social behavior. Pers Soc Psychol Rev 14:281–295. doi:10.1177/1088868310363594
Carter CS, Pournajafi-Nazarloo H, Kramer KM, Ziegler TE, White-Traut R, Bello D, Schwertz D (2007) Oxytocin behavioral associations and potential as a salivary biomarker. Ann NY Acad Sci 1098:312–322. doi:10.1196/annals.1384.006
Davidson JR, Moldofsky H, Lue FA (1991) Growth hormone and cortisol secretion in relation to sleep and wakefulness. J Psychiat Neurosci 16:96–102
de Quervain DJ, Aerni A, Schelling G, Roozendaal B (2009) Glucocorticoids and the regulation of memory in health and disease. Front Neuroendocrin 30:358–370. doi:10.1016/j.yfrne.2009.03.002
Diekelmann S, Born J (2010) The memory function of sleep. Nat Rev Neurosci 11:114–126. doi:10.1038/nrn2762
Diekelmann S, Wilhelm I, Born J (2009) The whats and whens of sleep-dependent memory consolidation. Sleep Med Rev 13:309–321. doi:10.1016/j.smrv.2008.08.002
Elder GJ, Ellis JG, Wetherell MA (2012) Associations between stages of sleep and the cortisol awakening response. Sleep 35(Abstract supplement):A56
Fogel SM, Smith CT (2010) The function of the sleep spindle: a physiological index of intelligence and a mechanism for sleep-dependent memory consolidation. Neurosci Biobehav Rev 35:1154–1165. doi:10.1016/j.neubiorev.2010.12.003
Follenius M, Brandenberger G, Simon C, Schlienger JL (1988) REM sleep in humans begins during decreased secretory activity of the anterior pituitary. Sleep 11:546–555
Follenius M, Brandenberger G, Bandesapt JJ, Libert JP, Ehrhart J (1992) Nocturnal cortisol release in relation to sleep structure. Sleep 15:21–27
Forsling ML (1993) Neurohypophysial hormones and circadian rhythm. Ann NY Acad Sci 689:382–395
Forsling ML, Montgomery H, Halpin D, Windle RJ, Treacher DF (1998) Daily patterns of secretion of neurohypophysial hormones in man: effect of age. Exp Physiol 83:409–418
Gais S, Born J (2004) Declarative memory consolidation: mechanisms acting during human sleep. Learn Mem 11:679–685. doi:10.1101/lm.80504
Gimpl G, Fahrenholz F (2001) The oxytocin receptor system: structure, function, and regulation. Physiol Rev 81:629–683
Goldberg DP, Williams P (1991) A user’s guide to the General Health Questionnaire. NFER-Nelson Publishing Company Ltd., Windsor
Gordis EB, Granger DA, Susman EJ, Trickett PK (2006) Asymmetry between salivary cortisol and alpha-amylase reactivity to stress: relation to aggressive behavior in adolescents. Psychoneuroendocrinology 31:976–987. doi:10.1016/j.psyneuen.2006.05.010
Gordis EB, Granger DA, Susman EJ, Trickett PK (2008) Salivary alpha amylase-cortisol asymmetry in maltreated youth. Horm Behav 53:96–103. doi:10.1016/j.yhbeh.2007.09.002
Gordon I, Martin C, Feldman R, Leckman JF (2011) Oxytocin and social motivation. Dev Cogn Neurosci 1:471–493. doi:10.1016/j.dcn.2011.07.007
Grewen KM, Davenport RE, Light KC (2010) An investigation of plasma and salivary oxytocin responses in breast- and formula-feeding mothers of infants. Psychophysiology 47:625–632. doi:10.1111/j.1469-8986.2009.00968.x
Gronfier C, Brandenberger G (1998) Ultradian rhythms in pituitary and adrenal hormones: their relations to sleep. Sleep Med Rev 2:17–29
Gronfier C, Luthringer R, Follenius M, Schaltenbrand N, Macher JP, Muzet A, Brandenberger G (1997) Temporal relationships between pulsatile cortisol secretion and electroencephalographic activity during sleep in man. Electroenceph Clin Neurophysiol 103:405–408
Gronfier C, Simon C, Piquard F, Ehrhart J, Brandenberger G (1999) Neuroendocrine processes underlying ultradian sleep regulation in man. J Clin Endocrinol Metab 84:2686–2690. doi:10.1210/jc.84.8.2686
Heinrichs M, Von Dawans B, Domes G (2009) Oxytocin, vasopressin, and human social behavior. Front Neuroendocrin 30:548–557. doi:10.1016/j.yfrne.2009.05.005
Hirshkowitz M, Schmidt MH (2005) Sleep-related erections: clinical perspectives and neural mechanisms. Sleep Med Rev 9:311–329. doi:10.1016/j.smrv.2005.03.001
Hollander E, Novotny S, Hanratty M, Yaffe R, DeCaria CM, Aronowitz BR, Mosovich S (2003) Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger’s disorders. Neuropsychopharmacology 28:193–198. doi:10.1038/sj.npp.1300021
Horne JA (2000) REM sleep: by default? Neurosci Biobehav Rev 24:777–797. doi:10.1016/S0149-7634(00)00037-3
Hucklebridge F, Clow A, Rahman H, Evans P (2000) The cortisol response to normal and nocturnal awakening. J Psychophysiol 14:24–28. doi:10.1027//0269-8803.14.1.24
Iber C, Ancoli-Israel S, Chesson A, Quan SF, For the American Academy of Sleep Medicine (2007) The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications, 1st edn. American Academy of Sleep Medicine, Winchester
Kalsbeek A, van der Spek R, Lei J, Endert E, Buijs RM, Fliers E (2012) Circadian rhythms in the hypothalamo-pituitary-adrenal (HPA) axis. Mol Cell Endocrinol 349:20–29. doi:10.1016/j.mce.2011.06.042
Lancel M, Krömer S, Neumann ID (2003) Intracerebral oxytocin modulates sleep-wake behaviour in male rats. Regul Peptides 114:145–152
Landgraf R, Neumann ID (2004) Vasopressin and oxytocin release within the brain: a dynamic concept of multiple and variable modes of neuropeptide communication. Frontiers Neuroendocrin 25:150–176. doi:10.1016/j.yfrne.2004.05.001
Lorr M (1984) Profile of Mood States: bi-polar form (POMS-BI): manual. Educational and Industrial Testing Service, San Diego
Ludwig M, Leng G (2006) Dendritic peptide release and peptide-dependent behaviours. Nat Rev Neurosci 7:126–136. doi:10.1038/nrn1845
McNamara P, Andresen J, Clark J, Zborowski M, Duffy C (2001) Impact of attachment styles on dream recall and dream content: a test of the attachment hypothesis of REM sleep. J Sleep Res 10:117–127. doi:10.1046/j.1365-2869.2001.00244.x
Meyer-Lindenberg A, Domes G, Kirsch P, Heinrichs M (2011) Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine. Nat Rev Neurosci 12:524–538. doi:10.1038/nrn3044
Nielsen T, Lara-Carrasco J (2007) Nightmares, dreaming, and emotion regulation: a review. In: Barrett D, McNamara P (eds) The new science of dreaming, vol 2. Praeger, London, pp 253–284
Pace-Scott EF, Vijayakumar S, Milad MR, Orr SP, Pitman RK, Spencer R (2012) Endogenous cortisol levels predict poorer extinction learning in the morning but not the evening. Sleep 35(Abstract supplement):A99
Panksepp J (2006) Emotional endophenotypes in evolutionary psychiatry. Prog Neuropsychopharmacol Biol Psychiatry 30:774–784. doi:10.1016/j.pnpbp.2006.01.004
Pannain S, Van Cauter E (2007) Modulation of endocrine function by sleep–wake homeostasis and circadian rhythmicity. Sleep Med Clin 2:147–159. doi:10.1016/j.jsmc.2007.03.001
Papanicolaou DA, Mullen N, Kyrou I, Nieman LK (2002) Nighttime salivary cortisol: a useful test for the diagnosis of Cushing’s Syndrome. J Clin Endocrinol Metab 87:4515–4521. doi:10.1210/jc.2002-020534
Parker KJ, Kenna HA, Zeitzer JM, Keller J, Blasey CM, Amico JA, Schatzberg AF (2010) Preliminary evidence that plasma oxytocin levels are elevated in major depression. Psychiat Res 178:359–362. doi:10.1016/j.psychres.2009.09.017
Payne JD (2010) Memory consolidation, the diurnal rhythm of cortisol, and the nature of dreams: a new hypothesis. Int Rev Neurobiol 92:101–134. doi:10.1016/S0074-7742(10)92006-0
Payne JD, Nadel L (2004) Sleep, dreams, and memory consolidation: the role of the stress hormone cortisol. Learn Mem 11:671–678. doi:10.1101/lm.77104
Payne JD, Schacter DL, Propper R, Huang L-W, Wamsley E, Tucker MA, Walker MP, Stickgold R (2009) The role of sleep in false memory formation. Neurobiol Learn Mem 92:327–334. doi:10.1016/j.nlm.2009.03.007
Peters KR, Ray LB, Smith V, Smith CT (2008) Changes in the density of stage 2 sleep spindles following motor learning in young and older adults. J Sleep Res 17:23–33. doi:10.1111/j.1365-2869.2008.00634.x
Ross HE, Young LJ (2009) Oxytocin and the neural mechanisms regulating social cognition and affiliative behavior. Front Neuroendocrinol 30:534–547. doi:10.1016/j.yfrne.2009.05.004
Smith C (2010) Sleep states and memory processes in humans: procedural versus declarative memory systems. Sleep Med Rev 5:491–506. doi:10.1053/smrv.2001.0164
Spath-Schwalbe E, Gofferje M, Kern W, Born J, Fehm HL (1991) Sleep disruption alters nocturnal ACTH and cortisol secretory patterns. Biol Psychiatry 29:575–584
Tomfohr LM, Edwards KM, Dimsdale JE (2012) Is obstructive sleep apnea associated with cortisol levels? A systematic review of the research evidence. Sleep Med Rev 16:243–249. doi:10.1016/j.smrv.2011.05.003
Troxel WM (2010) It’s more than sex: exploring the dyadic nature of sleep and implications for health. Psychosom Med 72:578–586. doi:10.1097/PSY.0b013e3181de7ff8
Ulrich-Lai YM, Herman JP (2009) Neural regulation of endocrine and autonomic stress responses. Nat Rev Neurosci 10:397–409. doi:10.1038/nrn2647
Van Cauter E, Tasali E (2011) Endocrine physiology in relation to sleep and sleep disturbances. In: Kryger MH, Roth T, Dement WC (eds) Principles and practice of sleep medicine, 5th edn. Elsevier, Philadelphia, pp 291–311
Vitiello MV, Larsen LH, Moe KE, Borson S, Schwartz RS, Prinz PN (1996) Objective sleep quality of healthy older men and women is differentially disrupted by nighttime periodic blood sampling via indwelling catheter. Sleep 19:304–311
Wagner U, Born J (2008) Memory consolidation during sleep: interactive effects of sleep stages and HPA regulation. Stress 11:28–41. doi:10.1080/10253890701408822
Wagner U, Gais S, Born J (2001) Emotional memory formation is enhanced across sleep intervals with high amounts of rapid eye movement sleep. Learn Mem 8:112–119. doi:10.1101/lm.36801
Walker MP, Stickgold R (2006) Sleep, memory, and plasticity. Annu Rev Psychol 57:139–166. doi:10.1146/annurev.psych.56.091103.070307
White-Traut R, Watanabe K, Pournajafi-Nazarloo H, Schwertz D, Bell A, Carter CS (2009) Detection of salivary oxytocin levels in lactating women. Dev Psychobiol 51:367–373. doi:10.1002/dev.20376
Zetzsche T, Frasch A, Jirikowski G, Murek H, Steiger A (1996) Nocturnal oxytocin secretion is reduced in major depression. Biol Psychiatry 39:584. doi:10.1016/0006-3223(96)84235-1
Acknowledgments
Study was funded by the Wales Institute for Cognitive Neuroscience.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Blagrove, M., Fouquet, N.C., Baird, A.L. et al. Association of salivary-assessed oxytocin and cortisol levels with time of night and sleep stage. J Neural Transm 119, 1223–1232 (2012). https://doi.org/10.1007/s00702-012-0880-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00702-012-0880-1