How cortisol rhythms shape stress resilience and mental health

Objective

BACKGROUND Stress has a major impact on everyday life, yet scientific understanding of resilience to stress remains limited. This is a global problem and leads to increases in stress-related disorders such as depression and anxiety. Cortisol is a key regulator of the stress response. Recent advances in measuring its circadian and ultradian rhythmicity may provide a scientific breakthrough in uncovering why some people are more resilient to stress than others. AIM Based on a novel scientifically rigorous framework, I aim to elucidate the role of cortisol’s circadian and ultradian rhythms as critical mechanisms underlying stress resilience and mental health. APPROACH This comprehensive study combines controlled experimental studies with real-world data, bridging mechanistic insights with practical real-world applications. Recent technological advancements for the first time allow 24h cortisol monitoring at high temporal solution in daily life settings. By combining different research disciplines with technological advancements, I will test three leading hypotheses: (1) daily-life stress prospectively shapes mental health via cortisol rhythmicity in low- and high-resilient individuals; (2) pharmacologically elevated nocturnal cortisol levels influence next-day stress reactivity and brain function in healthy individuals; (3) abnormal cortisol rhythms can be reversed and improve resilience with a glucocorticoid receptor antagonist in a proof-of-concept intervention study in depressed patients with flattened cortisol rhythmicity. IMPACT Capitalizing on rapid advances in sampling technology in naturalistic settings and sophisticated data analytics, RHYTHM will provide unprecedented insight into how cortisol rhythmicity influences stress resilience and mental health. Understanding cortisol rhythmicity as a mechanism for resilience following stress exposure could unlock new ways to cope with stress and lead to innovative interventions.