Endogenous cortisol in keratinized matrices: Systematic determination of baseline cortisol levels in hair and the influence of sex, age and hair color
Introduction
Cortisol, one of the most important glucocorticoid hormones is synthesized in the adrenal cortex and is a frequently assessed marker in psychoneuroendocrine stress research. Cortisol has been measured mainly in saliva, serum or urine in recent years. Cortisol concentration in these matrices underlies a circadian rhythm which means the concentrations fluctuate during the day. Those matrices allow the analysis of acute dynamic cortisol changes. In contrast, the effects of chronic stress and its implications on health often require the assessment of long-term cortisol levels. The analysis of cortisol in hair has therefore been a major methodological advance as it provides a retrospective measure of cumulative cortisol levels over extended time periods up to several months.
Over the past decade, the validity of hair cortisol as a measure for long term cortisol secretion has been established and the usefulness of hair cortisol as a marker for chronic stress has been demonstrated [1]. It has also been shown that hair cortisol is associated with a range of pathological and/or psychological conditions, such as burnout, Cushing's syndrome, and mood and anxiety disorders [2], [3], [4]. Overall, these studies show that hair cortisol has a great potential in stress research but still further research is needed on fundamental aspects that might influence hair cortisol. The establishment of standardized measurements, the definition of established values (e.g. baseline cortisol levels in untreated hair samples) and knowledge of potential confounding variables such as age, sex and hair color are important prerequisites for the establishment of hair cortisol as a biological marker in the future.
To propose established values, the quality of the analytical method used to measure hair cortisol is of great importance. Mainly immunoassay and LC–MS/MS based protocols have been used so far, revealing highly variable results [5], [6]. Previous research has also repeatedly shown that age has an influence on hair cortisol, albeit with varying results [5], [7]. The main research has been done on specific age groups, like young children or adults and older adults [8]. So far, there is only very limited information on hair cortisol levels in adolescents which is an age group that is very interesting due to changes in the pubertal hormone status. Previous research has also revealed highly heterogeneous findings with respect to sex differences [1]. Several studies have failed to show sex differences but newer studies imply that there are such differences [5]. The effect of natural hair color on cortisol concentration has also been studied but has mostly been found not to be correlated. Some newer literature however does show some association [9] and further investigations are needed to clarify this.
In summary, existing research has identified hair cortisol as a potential biological marker for chronic stress. However, the lack of standardized methods and inconsistent findings demonstrate the need to harmonize measurements and establish value ranges for cortisol in hair. This study was undertaken to address these gaps in research and to try to determine baseline cortisol levels in toddlers, adolescents and adults. Furthermore, the influence of sex and hair color on hair cortisol concentrations has been investigated to further clarify the influence of these variables and an interlaboratory comparison was performed to standardize analytical methods for cortisol measurements in hair.
Section snippets
Subjects
554 subjects from control groups of five independent studies representing the general healthy population of Switzerland and Australia were enrolled in this study. 374 adolescents were included from the “Brisbane Longitudinal Twin Study” [10], [11], 101 adults were included from the “Contact to Nature study” [30], 35 adults were included from the control group investigated within the “Zurich Cocaine Cognition Study” (ZuCo2St) [12], 30 adults from the study “Neurobiological Adaptations and
Age
To investigate the influence of age on hair cortisol the entire study group was first divided into four different age groups: 7 months to 3 years (toddlers), 12–13 years old adolescents (adolescents 1: pre-pubertal), 14–17 years old adolescents (adolescents 2: post-pubertal) and 18–70 years old (adults). Kruskal–Wallis analysis revealed that there was a significant difference between the toddler group and adolescent sub-group 1 (p < 0.0001, d = 0.9) and adolescent sub-group 2 (p < 0.0001, d = 0.56).
Discussion
In recent years, hair cortisol has emerged as a non-invasive measure for long-term hypothalamus-pituitary-adrenal (HPA) axis activity. However, previous research has been limited by the lack of well-established normative values for cortisol in adolescents and adults. Numerous studies have been performed in the past that show large deviations in hair cortisol baseline values [6]. One explanation for this fact might be the use of the analytical method. Previously, immunoassay based methods
Acknowledgment
We thank all the laboratories for participating in the interlaboratory comparison.
Funding for the collection of Australian hair samples was provided by Australian NHMRC (National Health and Medical Research Council (AU); grants APP1049911 and APP1009064). Hair cortisol assays of the Australian hair samples were funded by a grant from the German Federal Ministry of Education and Research (BMBF), through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in
References (30)
- et al.
Evaluation of a method to measure long term cortisol levels
Steroids
(2011) - et al.
Hair cortisol concentrations and cortisol stress reactivity in generalized anxiety disorder, major depression and their comorbidity
J. Psychiatr. Res.
(2017) - et al.
Stress-related and basic determinants of hair cortisol in humans: a meta-analysis
Psychoneuroendocrinology
(2017) - et al.
Hair cortisol, stress exposure, and mental health in humans: a systematic review
Psychoneuroendocrinology
(2013) - et al.
Predictors of hair cortisol concentrations in older adults
Psychoneuroendocrinology
(2014) - et al.
Splitting hair for cortisol? Associations of socio-economic status, ethnicity, hair color, gender and other child characteristics with hair cortisol and cortisone
Psychoneuroendocrinology
(2016) - et al.
Development of an LC–MS/MS method for the determination of endogenous cortisol in hair using (13)C3-labeled cortisol as surrogate analyte
J. Chromatogr. B: Analyt. Technol. Biomed. Life Sci.
(2016) - et al.
Determinants of hair cortisol and hair cortisone concentrations in adults
Psychoneuroendocrinology
(2015) - et al.
HPLC-FLU detection of cortisol distribution in human hair
Clin. Biochem.
(2010) - et al.
Sociodemographic, lifestyle, and psychosocial determinants of hair cortisol in a South London community sample
Psychoneuroendocrinology
(2017)
Hair as a retrospective calendar of cortisol production – increased cortisol incorporation into hair in the third trimester of pregnancy
Psychoneuroendocrinology
Scalp hair cortisol for diagnosis of Cushing's syndrome
Eur. J. Endocrinol.
Hair cortisol as a biological marker for burnout symptomatology
Psychoneuroendocrinology
The assessment of cortisol in human hair: associations with sociodemographic variables and potential confounders
Stress
Hair cortisol in twins: heritability and genetic overlap with psychological variables and stress-system genes
Sci. Rep.
Cited by (48)
Hair cortisol concentration in postpartum dairy cows and its association with parameters of milk production
2023, Domestic Animal EndocrinologyDeterminants of hair cortisol in preschool children and their mothers: A Brazilian birth cohort study
2023, PsychoneuroendocrinologyThe use of biochemical indexes in hair for clinical studies of psychiatric diseases: What can we learn about mental disease from hair?
2023, Journal of Psychiatric ResearchCortisol: Analytical and clinical determinants
2023, Advances in Clinical Chemistry