Cortisol Awakening Response (CAR) and Morning Anxiety

Ever wake up feeling anxious? That’s thanks to the good old diurnal secretion of cortisol, also known as the body’s primary stress hormone. Through exploring the topic of how the endocrine system and nervous system interact with one another, my project examines the cortisol awakening response (CAR) and its effects on morning anxiety. Cortisol is secreted in response to circadian rhythms, following the perception of the biggest zeitgeber (night and day), and commonly after a period of rest or sleeping (Contreras and Gutiérrez-Garcia, 2018). The intriguing aspect of the CAR response is the secretion of stress hormones in the absence of threats or danger. Research suggests that this occurrence is an adaptive-allostatic feature that helps to prepare us for the forthcoming events of the day (Contreras and Gutiérrez-Garcia, 2018). 

Allostasis provides insight into how individuals adapt to their environment. It refers to the changes in hormones and mediators that occur in response to stressors in the internal and external environment, used by the body to regain homeostasis. The implication here is that CAR prepares individuals to respond to the perturbations and demands the day will present. Things such as deadlines, duties and activities, social interactions, etc. Cortisol levels rise by 50-60% within the first 30-40 minutes of awakening and remain elevated for at least 60 minutes, declining to their lowest rate around bedtime (Contreras and Gutiérrez-Garcia, 2018). Highest blood concentrations of cortisol occur between 8 and 10 a.m. (Dziurkowska and Wesolowski, 2021).

Circadian rhythms are driven primarily by the suprachiasmatic nucleus (SCN), our master biological clock. This collection of neurons situated within the hypothalamus drives nearly all physiological processes. In mammals, the SCN converts external light information from the perception of photons into efferent signals, which are then sent to the paraventricular nucleus (PVN) (Starnes and Jones, 2023). The paraventricular nucleus, also within the hypothalamus, is responsible for the production and secretion of corticotropin-releasing hormone (CRH). 

 The emotional memory circuit is believed to play an important role in evoking a response in the PVN of the hypothalamus through its connection to the SCN, though the interaction is not yet well understood. This circuit involves the hippocampus and deep temporal lobe structures, such as the amygdala, mesolimbic system, and interactions between such structures, the prefrontal cortex, and other connections. Neural circuits regulating emotional memory project into the HPA axis, which regulates the secretion of hormones such as cortisol and the activation of the adrenal glands (Contreras and Gutiérrez-Garcia, 2018). Researchers believe the emotional memory circuit allows individuals to pick up on environmental cues and determine the best course of action (coping) through the use of recent and remote memories. The PVN, in response, secretes CRH into portal circulation (a system of capillaries that allows for chemical communication between HPA axis structures) from the hypothalamus. CRH travels to the pituitary gland, triggering the release of adrenocorticotropic hormone (ACTH). ACTH, in turn, travels to the adrenal glands, which are situated atop the kidneys, respectively, prompting the release of cortisol from the adrenal cortex into plasma for circulation throughout the body. 

This process promotes allostasis. Here are some of the methods cortisol uses to try to maintain homeostasis in response to stress. The first is by providing an increase in energy sources through an increase in blood glucose and a decrease in glucose reuptake, as well as the breakdown of lipids (lipolysis) stored in the body, which provide energy. Another is to increase heart rate, causing pulse rate and blood pressure to spike in hopes of getting nutrients to body cells faster. The third is increased water levels. This is done through the use of mineralocorticoid receptors, which have a high affinity for cortisol, saturating to around 90% (Dziurkowska and Wesolowski, 2021). These receptors are important for electrolyte balance and sodium and water reuptake. The third is the anti-inflammatory actions of cortisol, which decrease inflammation, allowing the body to focus on immediate stress/threats. 

Persistent or chronic low stress can keep the HPA axis activated. The cumulative burden of chronic stress and the body’s effort to maintain homeostasis in spite of it is referred to as allostatic load. Allostatic load can turn to allostatic overload, which is the inability to cope with an immense amount of stress, resulting in inefficient processing of cortisol and high cortisol levels. These disruptions in psychological systems can lead to mental disorders such as chronic anxiety, depression, and insomnia, as well as other mental disorders. Elevated cortisol levels can lead to things such as weight gain due to increased appetite, increased water retention, irritability, fatigue, high blood pressure, and brain fog, to name a few.

If you’re someone like me, allostatic overload is hard to overcome. In the morning, when those cortisol levels rise on a particularly unpleasant day, it’s easy to try to escape your thoughts. Thinking about the duties and adversities of the oncoming day is stressful! During this time, it’s important to engage in activities that can lower stress levels and benefit both your mind and body. By doing things such as meditating, reading something you enjoy, getting ready for the day,  and moving around, you can overcome that morning anxiety and prepare for what the day brings, rather than stressing over it (then stressing over the amount of time wasted stressing over things). I’m still working on overcoming my morning anxiety myself, and the progression is by no means linear. But next time you wake up feeling anxious, give yourself some grace and go and do something that calms you and your body down. If not, the aspects of your health that are negatively impacted by chronic stress will be added to your list of morning anxieties.

          References

Contreras, C. M. (2018). Cortisol Awakening Response: An Ancient Adaptive Feature. Journal of Psychiatry and Psychiatric Disorders, 2(1), 29–40. https://fortunepublish.com/articles/cortisol-awakening-response-an-ancient-adaptive-feature.html

Dziurkowska, E., & Wesolowski, M. (2021). Cortisol as a Biomarker of Mental Disorder Severity. Journal of Clinical Medicine, 10(21), 5204. https://doi.org/10.3390/jcm10215204

Dudas, B. (2021). Morphology of the human hypothalamus. Atlas of the Human Hypothalamus. https://doi.org/10.1016/b978-0-12-822051-1.00001-8 

Fogwe, L. A., & Mesfin, F. B. (2019, February 28). Neuroanatomy, Hippocampus. National Library of Medicine; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK482171/ 

Gerstner, J. R., & Yin, J. C. P. (2010). Circadian rhythms and memory formation. Nature Reviews Neuroscience, 11(8), 577–588. https://doi.org/10.1038/nrn2881 

Jones, J. R., Chaturvedi, S., Granados-Fuentes, D., & Herzog, E. D. (2021). Circadian neurons in the paraventricular nucleus entrain and sustain daily rhythms in glucocorticoids. Nature Communications, 12(1), 5763. https://doi.org/10.1038/s41467-021-25959-9 

LeWine, H. E. (2024, April 3). Understanding the stress response. Harvard Health. https://www.health.harvard.edu/staying-healthy/understanding-the-stress-response 

Logan, J. G., & Barksdale, D. J. (2008). Allostasis and allostatic load: expanding the discourse on stress and cardiovascular disease. Journal of Clinical Nursing, 17(7b), 201–208. https://doi.org/10.1111/j.1365-2702.2008.02347.x 

McFarland, N. R., & Haber, S. N. (2002). Thalamic Relay Nuclei of the Basal Ganglia Form Both Reciprocal and Nonreciprocal Cortical Connections, Linking Multiple Frontal Cortical Areas. The Journal of Neuroscience, 22(18), 8117–8132. https://doi.org/10.1523/jneurosci.22-18-08117.2002 

Olejniczak, I., Campbell, B., Tsai, Y.-C., Tyagarajan, S. K., Albrecht, U., & Ripperger, J. A. (2022). Suprachiasmatic to paraventricular nuclei interaction generates normal food searching rhythms in mice. Frontiers in Physiology, 13. https://doi.org/10.3389/fphys.2022.909795 

Starnes, A. N., & Jones, J. (2023). Inputs and Outputs of the Mammalian Circadian Clock. Biology, 12(4), 508–508. https://doi.org/10.3390/biology12040508