Conditioning cortisol in healthy young women – A randomized controlled trial

Tekampe, J.; Middendorp, Henriët van; Biermasz, Nienke R.; Sweep, Fred C.G.J.; Meijer, Onno C.; Pelsma, Iris C. M.; Pereira, Alberto M.; Hermus, A.R.M.M.; Evers, Andrea W M

doi:10.1016/j.psyneuen.2020.105081

Cited by 6 publications

(7 citation statements)

References 52 publications

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“…Apart from factors specific to this study’s design, a null result may indicate that pharmacological conditioning of cortisol levels in humans may not be feasible in general. The mixed results in existing studies might be the result of underlying confounds or sample fluctuations; several early studies rely on relatively small samples or groups [ 21 , 23 ] or suffer from unexpected baseline differences [ 19 ]. We hope that this study will avoid these issues and offer more clarity.…”

Section: Discussionmentioning

confidence: 99%

“…To measure positive and negative affect, the Positive and Negative Affect Schedule (PANAS [ 50 , 51 ]) is used. Stress is measured using a custom-made Numerical Rating Scale (NRS) asking participants to score themselves between 0 (“not at all”) and 100 (“very much”) on 7 stress-related words [ 19 , 52 ]. Vitality is measured using the Subjective Vitality Scale (SVS [ 53 ]), and fatigue using the fatigue subscale of the Checklist Individual Strength (CIS [ 54 ]) adjusted to measure the current state of fatigue.…”

Section: Methodsmentioning

confidence: 99%

“…These principles can be applied to cortisol-affecting medication. After repeated pairings, the CS will “remind” the body of the UCS and evoke either the cortisol change produced by the medication or a compensatory feedback mechanism [ 18 , 19 ]. A review of human and animal studies [ 20 ] found that this type of pharmacological conditioning was effective in animals, with 13 out of 15 studies finding the expected effect but less often tested and not as effective in humans.…”

Section: Introductionmentioning

confidence: 99%

“…Two other studies relied on a direct increase in cortisol. Sabbioni et al [ 23 ] used dexamethasone, a glucocorticoid, while Tekampe et al [ 19 ] used hydrocortisone. In both cases, the CS was a strongly flavored drink combined with oral intake of the UCS on 3 occasions during the conditioning period.…”

Section: Introductionmentioning

confidence: 99%

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Conditioning of the Cortisol Awakening Response in Healthy Men: Study Protocol for a Randomized Controlled Trial

Wolters¹,

Middendorp²,

Bergh³

et al. 2023

JMIR Res Protoc

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Background The hormone cortisol plays important roles in human circadian and stress physiology and is an interesting target for interventions. Cortisol varies not only in response to stress but also as part of a diurnal rhythm. It shows a particularly sharp increase immediately after awakening, the cortisol awakening response (CAR). Cortisol can be affected by medication, but it is less clear whether it can also be affected by learning. Animal studies have consistently shown that cortisol can be affected by pharmacological conditioning, but the results in humans have been mixed. Other studies have suggested that conditioning is also possible during sleep and that the diurnal rhythm can be conditioned, but these findings have not yet been applied to cortisol conditioning. Objective The objective of our study was to introduce a novel avenue for conditioning cortisol: by using the CAR as an unconditioned response and using scent conditioning while the participant is asleep. This study investigates an innovative way to study the effects of conditioning on cortisol and the diurnal rhythm, using a variety of devices and measures to make measurement possible at a distance and at unusual moments. Methods The study protocol takes 2 weeks and is performed from the participant’s home. Measures in week 1 are taken to reflect the CAR and waking under baseline conditions. For the first 3 nights of week 2, participants are exposed to a scent from 30 minutes before awakening until their normal time of awakening to allow the scent to become associated with the CAR. On the final night, participants are forced to wake 4 hours earlier, when cortisol levels are normally low, and either the same (conditioned group) or a different (control group) scent is presented half an hour before this new time. This allows us to test whether cortisol levels are higher after the same scent is presented. The primary outcome is the CAR, assessed by saliva cortisol levels, 0, 15, 30, and 45 minutes after awakening. The secondary outcomes are heart rate variability, actigraphy measures taken during sleep, and self-reported mood after awakening. To perform manipulations and measurements, this study uses wearable devices, 2 smartphone apps, web-based questionnaires, and a programmed scent device. Results We completed data collection as of December 24, 2021. Conclusions This study can provide new insights into learning effects on cortisol and the diurnal rhythm. If the procedure does affect the CAR and associated measures, it also has potential clinical implications in the treatment of sleep and stress disorders. Trial Registration Netherlands Trial Register NL58792.058.16; https://trialsearch.who.int/Trial2.aspx?TrialID=NL7791 International Registered Report Identifier (IRRID) DERR1-10.2196/38087

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Conditioning of the Cortisol Awakening Response in Healthy Men: Study Protocol for a Randomized Controlled Trial

Wolters¹,

Middendorp²,

Bergh³

et al. 2023

JMIR Res Protoc

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“…Intranasal insulin administration affected two of the three physiological outcomes of the study: it decreased C-peptide levels in healthy participants and stabilized (prevented from dropping) the glucose levels in patients of both sexes and healthy men. Pharmacologically conditioned effects should normally mimic the effects of the drug, even though in some cases, opposite effects can be found because of negative feedback loops ( 34 ). Indeed, we found that the direction of the effects of intranasal insulin administration on blood glucose levels on day 1 corresponded to the direction of the conditioned effects on day 2.…”

Section: Discussionmentioning

confidence: 99%

Influencing the Insulin System by Placebo Effects in Patients With Diabetes Type 2 and Healthy Controls: A Randomized Controlled Trial

et al. 2023

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Objective The objective of this study was to investigate whether placebo effect induced by pharmacological conditioning with intranasal insulin can affect glucose, insulin, C-peptide, hunger, and memory in patients with diabetes type 2 and healthy controls. Methods Placebo effect was induced by pharmacological conditioning. Thirty-two older patients (mean age = 68.3 years) with diabetes type 2 and age- and sex-matched thirty-two healthy older adults (mean age = 67.8 years) were randomly assigned to a conditioned or a control group. On day 1, conditioned group received six administrations of intranasal insulin with a conditioned stimulus (CS; smell of rosewood oil), whereas the control group received a placebo with the CS. On day 2, both groups received a placebo spray with the CS. Glucose, insulin, and C-peptide were repeatedly measured in blood. Hunger and memory were assessed with validated measures. Results Intranasal insulin stabilized dropping glucose levels in patients (B = 0.03, SE = 0.02, p = .027) and healthy men (B = 0.046, SE = 0.02, p = .021), and decreased C-peptide levels in healthy controls (B = 0.01, SE = 0.001, p = .008). Conditioning also prevented the drop of glucose levels but only in men (both healthy and patients; B = 0.001, SE = 0.0003, p = .024). Conditioning significantly decreased hunger in healthy participants (B = 0.31, SE = 0.09, p < .001). No effects were found on other measures. Conclusions Placebo effect induced by conditioning with intranasal insulin modifies blood glucose levels and decreases hunger in older adults, but its effects depend on health status and sex. Insulin conditioning might be beneficial for groups suffering from intensive hunger but seems not be particularly suitable for blood glucose reduction. Trial Registration Netherlands Trial Register, NL7783 (https://www.trialregister.nl/trial/7783).

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