Cortisol in functional neurological disorders: State, trait and prognostic biomarkers

Objective: Biological stress dysregulation, such as a flattened cortisol awakening response (CAR), has been identified in functional neurological disorder (FND). This longitudinal study aimed to explore whether CAR alterations in FND serve as state or trait biomarkers, assessing temporal changes in cortisol and clinical outcomes to test its prognostic value. Methods: Salivary cortisol was measured in 53 patients with mixed FND at two visits separated by eight months (M0 and M8). CAR was calculated based on five consecutive samples, each taken with 15-min time intervals, collected upon awakening, whereas cortisol amplitude (CAmp) was calculated as the difference between the morning peak and the afternoon trough. Clinical outcome was assessed with the Functional Movement Disorder Rating Scale (S-FMDRS), Clinical global impression (CGI) scores for severity (CGI-S) and improvement (CGI-I) and the short-form health survey (SF-36). Results: No differences in CAR levels were found between M0 and M8 regardless of clinical outcome (remained flattened). However, a good clinical outcome was associated with an earlier peak in the CAR (p = .013, odds ratio: 1.78; 95%-confidence interval: 0.095-1.13). A higher CAmp at M0 predicted a better outcome at M8 (beta = 1.14, 95%-confidence interval:0.15-2.13, p = .03). Conclusion: A flattened CAR might represent a trait marker for FND, when an earlier peak in the CAR may serve as a state biomarker. The CAmp demonstrates predictive power for clinical outcome, potentially representing a prognostic biomarker for FND. Further replication and follow-up studies are essential to confirm this suggested role of cortisol as a multifaceted biomarker of FND.