In response to a stressful situation, whether psychological or physical, the human body activates processes that aim to increase chance of survival. This “fight-flight-freeze” response could include making you feel more alert, giving the body energy and making you feel less pain. One key hormone involved in this response is cortisol.
Although the release of cortisol in response to stress is initially beneficial, it is thought that experiencing severe or ongoing stressful events can lead to a maladaptive stress response which can result in harmful effects on the body[1]. As such, the stress response system has been implicated in a range of adverse outcomes including obesity, cancer, heart disease, susceptibility to infection, and psychiatric disorder[2].
Commonly, cortisol is measured from saliva samples two or three times daily. However, as cortisol is secreted in a pulsatile fashion throughout the day, these measures are difficult to interpret and compare as it is uncertain whether samples are taken at the same time point along a pulse. Furthermore, saliva measures provide limited information about long-term cortisol secretion.
In contrast, hair cortisol concentration can provide a non-invasive, alternative assessment method capturing information about cortisol levels over the course of several months, thus overcoming the difficulties of single timepoint measures. Validation studies strongly support the assumption that hair cortisol concentration provides a valid index of long-term cortisol concentrations[3]. As such, given its advantage of providing information on the mean stress levels during a chosen extended period, hair cortisol analysis is increasingly being applied in many studies of physical and mental health[4-6].
We propose to conduct a pilot study in ALSPAC (n= 10-20 hair samples, collected at age 15years) to determine the feasibility of measuring steroid hormone concentrations from adolescent hair samples using liquid chromatography tandem mass spectrometry (LC-MS/MS)[7]. If successful, these results will be used in a funding proposal to extend measurement to a larger number of ALSPAC hair samples.
Within the funding proposal, we aim to use measures to investigate the associations between hair cortisol concentrations and subsequent mental health, and to perform a genome-wide association study (GWAS) of hair cortisol concentrations. GWAS results will be meta-analysed with 9 other cohorts within the CORtisol NETwork (CORNET) to provide the first GWAS to date of hair cortisol concentrations.

References
1. Charmandari, E., et al., Endocrinology of the stress response. Annual Review of Physiology, 2005. 67: p. 259-84.
2. Adam, E.K., et al., Diurnal cortisol slopes and mental and physical health outcomes: a systematic review and meta-analysis. Psychoneuroendocrinology, 2017. 83: p. 25-41.
3. Stalder, T., et al., Analysis of cortisol in hair--state of the art and future directions. Brain, Behavior, and Immunity, 2012. 26(7): p. 1019-29.
4. Iob, E., et al., Cardiovascular Disease and Hair Cortisol: a Novel Biomarker of Chronic Stress. Current Cardiology Reports, 2019. 21(10): p. 116.
5. Ling, J., et al., Body mass index, waist circumference and body fat are positively correlated with hair cortisol in children: A systematic review and meta-analysis. Obesity Reviews, 2020. 21(10): p. e13050.
6. Koumantarou Malisiova, E., et al., Hair cortisol concentrations in mental disorders: a systematic review. Physiology & Behavior, 2021. 229: p. 113244.
7. Gao, W., et al., Quantitative analysis of steroid hormones in human hair using a column-switching LC–APCI–MS/MS assay. Journal of Chromatography B, 2013. 928: p. 1-8.