Hair cortisol as a biological marker of chronic stress: current status, future directions and unanswered questions.

Stress responses play a key role in allowing animals to cope with change and challenge in the face of both environmental certainty and uncertainty. Measurement of glucocorticoid levels, key elements in the neuroendocrine stress axis, can give insight into an animal’s well-being and can aid understanding ecological and evolutionary processes as well as conservation and management issues. We give an overview of the four main biological samples that have been utilized [blood, saliva, excreta (feces and urine), and integumentary structures (hair and feathers)], their advantages and disadvantages for use with wildlife, and some of the background and pitfalls that users must consider in interpreting their results. The matrix of choice will depend on the nature of the study and of the species, on whether one is examining the impact of acute versus chronic stressors, and on the degree of invasiveness that is possible or desirable. In some cases, more than one matrix can be measured to achieve the same ends. All require a significant degree of expertise, sometimes in obtaining the sample and always in extracting and analyzing the glucocorticoid or its metabolites. Glucocorticoid measurement is proving to be a powerful integrator of environmental stressors and of an animal’s condition.

https://www.jstor.org/stable/info/41499891

Measuring stress in wildlife: techniques for quantifying glucocorticoids

Changes to long-term secretion of the glucocorticoid cortisol are considered to play a crucial role in mediating the link between chronic stress and the development of numerous immune system related diseases. However, obtaining valid assessments of long-term cortisol levels is difficult due to limitations of previous measurement strategies in blood, saliva or urine. This review discusses evidence on a recent methodological development assumed to provide a considerable advancement in this respect: the analysis of cortisol in hair. Being incorporated into the growing hair, hair cortisol concentrations (HCC) are assumed to provide a retrospective reflection of integrated cortisol secretion over periods of several months. Over the past years, supportive evidence has accumulated regarding several fundamental characteristics of HCC, including its validity as an index of long-term systemic cortisol levels, its reliability across repeated assessments and its relative robustness to a range of potential confounding influences. Based on this groundwork, research has now also commenced to utilise HCC for answering more specific questions regarding the role of long-term cortisol secretion in different stress and health-related conditions. The possibility of extending hair analysis to also capture long-term secretion of other steroid hormones (e.g., androgens or estrogens) provides a further intriguing prospect for future research. Given its unique characteristics, the use of hair analysis holds great promise to significantly enhance current understanding on the role of steroid hormones in psychoimmunological research.

Analysis of cortisol in hair--state of the art and future directions.

Hair cortisol, stress exposure, and mental health in humans: A systematic review

Respiratory depression limits the use of opioid analgesia. Although well described clinically, the specific mechanisms of opioid action on respiratory control centres in the brain have, until recently, been less well understood. This article reviews the mechanisms of opioid-induced respiratory depression, from the cellular to the systems level, to highlight gaps in our current understanding, and to suggest avenues for further research. The ultimate aim of combating opioid-induced respiratory depression would benefit patients in pain and potentially reduce deaths from opioid overdose. By integrating recent findings from animal studies with those from human volunteer and clinical studies, further avenues for investigation are proposed, which may eventually lead to safer opioid analgesia.

Opioids and the control of respiration

Purpose: Stress has been shown to cause a large range of adverse fetal effects. This pilot study is the first attempt to examine cortisol level in the hair of pregnant women and assess its potential as a biomarker of gestational stress.

Patients and Methods: Twenty-five healthy pregnant women, in whom hair cortisol levels and the Perceived Stress Scale (PSS) were measured and correlated.

Results: Maternal hair cortisol levels, ranging between 0.06 and 0.23 nmol/g of hair correlated positively and significantly with measures of perceived stress (ranging between 2-22); (Rs=0.47) (P < 0.05).

Conclusions: Our findings corroborate recent primate studies with induced stress, and suggest that hair cortisol is a potential biomarker of chronic stress in pregnancy. This new long term biological marker may have important implications in research and clinical practice.

https://www.cimonline.ca/index.php/cim/article/download/986/899

The relationship between stress and hair cortisol in healthy pregnant women.

A novel method using hair for determining hormonal levels in wildlife

QUESTION Recently a newborn died from morphine poisoning when hismother used codeine while breastfeeding. Many patients receive codeine for postlabour pain. Is it safe to prescribe codeine for nursing mothers?

ANSWER When a mother is an ultrarapid metabolizer of cytochrome P450 2D6, she produces much more morphine when taking codeine than most people do. In this situation, newborns might be exposed to toxic levels of morphine when breastfeeding. Options to reduce this risk include discontinuing codeine after 2 to 3 days of use and being aware of symptoms of potential opioid toxicity in both mothers and newborns.

https://www.cfp.ca/content/cfp/53/1/33.full.pdf

Safety of codeine during breastfeeding Fatal morphine poisoning in the breastfed neonate of a mother prescribed codeine

Background: Meconium and hair are two biological markers of in utero exposure to illicit drugs. 

Objective: To compare the sensitivity of the two tests for different drugs. 

Setting: Motherisk laboratory which tests in utero drug exposure in Toronto. 

Methods: Cocaine, benzoylecgonine, opiates, cannabis, benzodiazepines, methadone, and barbiturates were measured in pairs of hair and meconium samples from the same neonates. 

Results: Meconium was marginally more sensitive than neonatal hair for detection of cocaine and cannabis, possibly because it may detect second trimester exposure whereas hair grows only during the third trimester of pregnancy. There was a significant correlation between hair and meconium concentrations of cocaine, cannabis, and opiates. 

Conclusion: In cases of clinical suspicion and a negative neonatal urine test, both meconium and hair are effective biological markers of in utero illicit drug exposure. Meconium may be more sensitive, but neonatal hair is available for three months whereas meconium is available for only one or two days. In contrast, the use of meconium, being a discarded material, is more acceptable to some parents than hair testing, which entails cutting scalp hair from the newborn.

https://fn.bmj.com/content/fetalneonatal/88/2/F98.full.pdf

Comparison of meconium and neonatal hair analysis for detection of gestational exposure to drugs of abuse

The authors report testing the meconium of a newborn for the presence of FAEE. Meconium from a newborn of a woman who acknowledged drinking beer throughout pregnancy was tested. The authors also tested the meconiums of 3 newborns whose mothers did not drink at all while pregnant. The FAEE were extracted from the meconium samples using solid phase extraction (SPE), and were identified and quantitated by gas chromatography with flame ionization detection (FID). For assignment of retention times and determination of individual concentrations, authentic mixtures of FAEE were injected. The total FAEE concentration in the meconium of the alcohol-exposed infant was 13126 ng/g compared to a mean of 410 ng/g in the control meconiums. Also, in this case, palmitic, linoleic, and stearic ethyl esters were found in the alcohol-exposed infant's meconium while they were not found in the unexposed infant's meconium. In a parallel experiment, the authors spiked increasing amounts of ethyl alcohol (0-40mM) into the meconium from a newborn that was not exposed to ethanol in utero. The spiked samples were incubated for 4 hours at 37 degrees C and subsequently assayed for the presence of ethyl linoleate. In these experiments, they document for the first time that FAEE is produced in meconium. If confirmed by large studies, FAEE may become the first neonatal biologic marker for babies at risk for alcohol-related birth defects.

Tatyana Karaskov

Papers

The relationship between stress and hair cortisol in healthy pregnant women.

A novel method using hair for determining hormonal levels in wildlife

Safety of codeine during breastfeeding Fatal morphine poisoning in the breastfed neonate of a mother prescribed codeine

Comparison of meconium and neonatal hair analysis for detection of gestational exposure to drugs of abuse

Fatty acid ethyl esters: a novel biologic marker for heavy in utero ethanol exposure: a case report.