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University of Bristol researchers uncover new insights into the body’s stress hormone dynamics.

A groundbreaking study from the University of Bristol has overturned the long-standing belief that waking up triggers a surge in the release of cortisol, the body’s primary stress hormone. Published on January 15 in Proceedings of the Royal Society B, the research reveals that cortisol levels rise naturally in the hours leading up to waking, as part of the body’s circadian rhythm, rather than spiking in response to waking itself.

For decades, the so-called “cortisol awakening response” (CAR) has been considered a key marker in the study of clinical conditions such as PTSD, depression, obesity, and chronic fatigue syndrome. However, the new findings suggest that this interpretation may have been flawed, as earlier studies relied solely on post-wake saliva samples and overlooked changes occurring prior to waking.

Methodology and Key Findings

To address this gap, the research team employed automated sampling systems to measure tissue cortisol levels in 201 participants, aged 18 to 68, both before and after waking. Their analysis revealed no significant increase in cortisol secretion rates after waking compared to the pre-waking period. Instead, any post-wake changes in cortisol appear to reflect the tail end of a natural circadian rhythm that starts hours before habitual wake time.

The study also noted substantial individual differences in cortisol concentrations and dynamics, which may be influenced by variations in sleep duration and timing. These findings emphasize the need for caution when interpreting cortisol data based solely on post-wake measurements.

Implications for Health and Research

The results challenge previous assumptions about the role of cortisol in the sleep-wake cycle. Rather than responding to the act of waking, cortisol fluctuations seem more closely tied to factors that initiate waking and the body’s natural circadian rhythm. This insight is particularly important for understanding conditions linked to circadian disruptions, such as depression, metabolic disorders, and immune dysfunctions.

Professor Stafford Lightman, a lead author of the study, highlighted its broader significance: “Our study opens up a whole new framework for understanding the relationship of overnight increases in cortisol with sleep, and how this may be disrupted in sleep disorders, depression, and many other conditions.”

Co-lead author Dr. Thomas Upton underscored the importance of capturing both pre- and post-wake data for accurate insights. “This study provides crucial insight into the dynamics of cortisol with respect to sleep and endogenous rhythms,” he said. “Caution is needed when interpreting post-wake cortisol values without understanding the pre-wake state.”

Revisiting “Received Wisdom”

The research also serves as a reminder to question established scientific assumptions. Professor Marcus Munafò, who contributed to the study, remarked, “This work illustrates how findings that have become received wisdom within the research community may be wrong. Ensuring that our work is robust and reproducible is a central part of the research culture we foster.”

Looking Ahead

The researchers call for future studies to examine the mechanisms of arousal from sleep and their relationship with cortisol dynamics. Special attention should be given to the hypothalamic-pituitary axis, the system responsible for regulating stress responses, in addition to the interplay between sleep patterns and behavior.

The findings mark a significant step forward in understanding the biological intricacies of sleep and stress, offering new avenues for exploring treatments for sleep disorders and stress-related conditions.

Reference:
Samantha Klaas et al., Awakening not associated with an increased rate of cortisol secretion, Proceedings of the Royal Society B: Biological Sciences (2025). DOI: 10.1098/rspb.2024.1844

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