Glucocorticoid-endocannabinoid interaction in cardiac surgical patients: relationship to early cognitive dysfunction and late depression
Open accessAbstract
BACKGROUND: Endocannabinoids (ECs) are rapidly acting immune-modulatory lipid-signaling molecules that are important for adaptation to stressful and aversive situations.They are known to interact with glucocorticoids and other stress-responsive systems. Maladaptation to acute or chronic stress represents a major risk factor for the development of psychiatric disorders. In the present study, we administered stress doses of hydrocortisone ina prospective, randomized, placebo-controlled double blind study in patients undergoing cardiac surgery (CS) to examine the relationship between the use of glucocorticoids, plasma EC levels, and the occurrence of early postoperative cognitive dysfunction (delirium) and of later development of depression. METHODS: We determined plasma levels of the ECs anandamide and 2-arachidonoylglycerol (2-AG) in CS patients of the hydrocortisone (n=56) and the placebo group(n=55) preoperatively, at postoperative day (POD) 1, at intensive care unit discharge, and at 6 months after CS(n=68). Postoperative delirium was diagnosed according to Diagnostic and Statistical Manual of the American Psychiatric Association IVth Edition (DSM-IV) criteria, and depression was determined by validated questionnaires and a standardized psychological interview (Structured Clinical Interview for DSM-IV). RESULTS: Stress doses of hydrocortisone did not affect plasma EC levels and the occurrence of delirium or depression. However, patients who developed deliriumon POD 1 had significantly lower preoperative 2-AG levels of the neuroprotective EC 2-AG (median values, 3.8 vs. 11.3ng/ml; p=0.03). Preoperative 2-AG concentrations were predictive of postoperative delirium (sensitivity=0.70;specificity=0.69; cutoff value=4.9 ng/ml; receiver operating characteristic curve area=0.70; 95 o/o confidence interval=0.54-0.85). Patients with depression at 6 months after CS (n=16) had significantly lower anandamide and 2-AG levels during the perioperative period. CONCLUSIONS: A low perioperative EC response may indicate an increased risk for early cognitive dysfunction and long-term depression in patients after CS. Glucocorticoids do not seem to influence this relationship.
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Low circulating 2-AG levels predict rates of depression after cardiac surgery.
“another study found that low circulating 2-AG levels predict rates of depression after cardiac surgery (Hauer et al., 2012).”
From The endocannabinoid system as a target for novel anxiolytic drugs (2017) · cites this paper as Hauer et al., 2012
Patients undergoing cardiac surgery who showed an impaired EC response during the stressful postoperative period were at an increased risk for depression at 6 months after surgery.
“Likewise, patients undergoing cardiac surgery who showed an impaired EC response during the stressful postoperative period were at an increased risk for depression at 6 months after surgery [39].”
From Plasma concentrations of endocannabinoids and related primary fatty acid amides in patients with post-traumatic stress disorder (2013) · cites this paper as [39]
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“This assumption results from a pilot trial that demonstrated increased circulating concentrations of ECs in CS patients with traumatic memories and PTSD symptoms [37], a larger study in individuals with PTSD from war and torture experiences [38] and decreased perioperative plasma levels of ECs in CS patients who devel…”
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“07, I2 = 61%] (Figure 9), duration of mechanical ventilation [two trials (Hauer et al., 2012; Glumac et al., 2017); RR: −2.”
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“Three found that stress doses (glucocorticoid administration equivalent to the endocrine secretion rate of the adrenal gland under maximal stimulation) of hydrocortisone reduced PTSD and stress symptoms (20–22), but one found no effect (23).”
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“Hauer 2012 [25] Germany Cardiac surgery NM General anaesthesia Hydrocortisone 100 mg followed by tapering infusion for 4 days (56) Placebo (55)”
Delirium and Its Prevention with Melatonergic Drugs
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“Most of the included studies chose to evaluate 1–3 days after surgery [19, 20, 25], one study evaluated on the third day [22], two evaluated 1-5 days after surgery [21, 26], one study [23] chose to evaluate 1–4 days after surgery, and one study [24] evaluated only on the first day.”
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Modulation of the Core Neural Network in Stress: The Role of Endocannabinoids and LTD
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Ramelteon and the Prevention of Delirium
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Blood Cortisol as a Biomarker in Intensive Care Unit
Pektezel, M. Y., & Pektezel, L. D. (2022) · Biomarkers in disease · doi:10.1007/978-3-030-87302-8_66-1
Blood Cortisol as a Biomarker in Intensive Care Unit
Pektezel, M. Y., & Pektezel, L. D. (2023) · Biomarkers in disease · doi:10.1007/978-3-031-07395-3_66
- Authors
- Hauer, D., Weis, F., Campolongo, P., Schopp, M., Beiras-Fernandez, A., Strewe, C., Giehl, M., Toth, R., Kilger, E., & Schelling, G.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- Sapienza University of Rome (IT)
- Corresponding author
- Hauer, Daniela
- Venue
- Reviews in the Neurosciences
- Publisher
- Walter de Gruyter GmbH
- Published
- 2012-01-01
- Volume
- 23
- Issue
- 5-6
- Pages
- 681-90
- ISSN
- 0334-1763 (ISSN-L)
- 2191-0200
- OpenAlex
- W2156103366
- Cited by
- 33
- References
- 54
- Citations by year
- 2024: 4 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 5 · 2013: 6
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- Locations
- Reviews in the Neurosciences (publishedVersion)
- PubMed (publishedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- glucocorticoids, endocannabinoids, cardiac surgery, postoperative delirium, postoperative depression, cortisol, 2-arachidonoylglycerol, anandamide, stress response, preoperative biomarkers, neuroprotection
- MeSH terms
- Aged, Arachidonic Acids, Cognition Disorders, Depression, Double-Blind Method, Female, Follow-Up Studies, Glucocorticoids, Glycerides, Heart Diseases, Humans, Hydrocortisone, Luria-Nebraska Neuropsychological Battery, Male, Middle Aged, Postoperative Complications, Prospective Studies, Psychiatric Status Rating Scales, Psychometrics, Outcome Assessment, Health Care, Statistics, Nonparametric, Polyunsaturated Alkamides, Endocannabinoids
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