Hair cortisol as a marker of stress in mild traumatic brain injury: a challenging measure

Cortisol is released through activation of the hypothalamic-pituitary-adrenal axis by physiological and psychological stressors, such as mild traumatic brain injury (mTBI). This hormone is accumulated in hair over longer periods of time, reflecting both acute and chronic forms of stress, allowing for retrospective analyses within certain timeframes. The main objectives of this study were to analyze pre- and post-injury hair cortisol concentrations, and to explore possible associations with personality and recovery after mTBI. Hair samples of 61 mTBI patients were collected at 4-6 weeks post-injury and divided into pre- (1 cm) and post-injury (1 cm) segments. For comparison, hair samples of 24 age, sex and education matched healthy controls (HC) were collected and divided into similar segments. Cortisol was quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). At two weeks post-injury, post-traumatic symptoms (PTS), emotional distress (anxiety/depression), and the personality trait neuroticism were measured. At six months post-injury, PTS and functional recovery (Glasgow Outcome Scale Extended) were determined. A significant increase in hair cortisol concentration from pre- to post-injury was found for both mTBI patients and HC, likely due to washout effects, with similar concentrations in both groups. Neither hair cortisol, nor the interaction with neuroticism, were associated with long-term PTS or functional recovery. Additionally, no differences in hair cortisol were observed between patients with a higher and lower risk of developing persistent PTS based on a modified Post-Concussion Symptoms Rule (PoCS Rule) including demographics, acute symptoms, pre-injury mental health and head CT. Altogether, our findings do not support the current use of hair cortisol as a potential marker of stress in mTBI.