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This post was written by our guest author, Dr. Jade Tan.
Post-traumatic stress disorder (PTSD) is a psychiatric condition that arises after someone has experienced a traumatic event. Although most commonly associated with veterans, it can happen to anyone regardless of ethnicity, nationality, age, sexuality, or culture. A staggering 3.5% of people in the US are affected every year by PTSD, with women being twice as likely to suffer from this. PTSD is diagnosed when someone is experiencing symptoms that fall into four categories after being exposed to a traumatic event with symptoms occurring for more than a month that interrupt daily functioning.
The four categories of PTSD symptoms are intrusion, avoidance, alterations in cognition and mood, and alterations in arousal and reactivity. These symptoms can be experienced as the presence of intrusive thoughts, memories, dreams, or flashbacks, the 
inability to remember the traumatic event itself, negative thoughts and distorted beliefs about oneself, irritability, and avoiding reminders of the event itself (American Psychiatric Association, 2020).
The symptoms can cause far-reaching effects on a person's relationship with their family and friends due to the problems with trust, communication, and problem solving which are all affected by having PTSD (US Department of Veterans Affairs). In this blog post, we will be investigating the biochemistry of PTSD and the effects it has on the levels of cortisol as well as the circadian rhythm.
The Human Stress System – Going beyond the HPA Axis
Humans have a stress system in place to cope with external and internal stressors to establish homeostasis. It comprises two components, a central component and a peripheral component. Peripherally it contains the hypothalamic-pituitary axis and the autonomic nervous system (comprising the sympathetic nervous system, sympatho-adrenomedullary system, and the parasympathetic nervous system). The molecules that help relay messages are the catecholamines (norepinephrine and epinephrine), acetylcholine, and glucocorticoids. In this blog post, we will be talking about cortisol, which is a glucocorticoid (Agorastos & Olff, 2020).
What is the role of cortisol in the body’s stress response?
Cortisol binds to glucocorticoid receptors, which can be found in virtually every organ system, including the nervous, immune, cardiovascular, respiratory, reproductive, musculoskeletal, and integumentary systems.
Therefore, it is not surprising that cortisol can affect our immune response, glucose, protein homeostasis, and, of course, our stress response. Cortisol participates in a negative feedback loop by feeding back onto the anterior pituitary and the hypothalamus to shut down the release of cortisol when there are sufficient levels of it. This axis follows a 24-hour circadian rhythm which causes cortisol to be high in the morning and low at night (Thau et al., 2019).
The suprachiasmatic nucleus (SCN) of the hypothalamus is in charge of synchronizing the 24-hour rhythms of the body's clock, which is also seen in the gastrointestinal tract, liver, muscle, adipose, and cardiovascular tissue. In an optimal system, cortisol is highest between 7:00am-8:00am and lowest between 2:00am-4:00am. However, this system can be influenced by external factors such as sleep, seasonal changes, and stress (mental, physical, and psychological), which will then impair the HPA axis, affecting circadian rhythm (Mohd Azmi et al., 2021).
What happens to cortisol levels in people with PTSD?
In people with PTSD, their body has been in a state of high pressure or constant fight or flight which causes the passivation of the HPA axis. A systematic review that studied whether the levels of salivary cortisol could be a predictor of PTSD showed that, in the 22 studies that were included, patients with PTSD exhibited lower levels of morning salivary cortisol than the controls (Pan et al., 2018).
In another study that investigated the levels of salivary cortisol in response to reactivation of trauma in 60 survivors of the World Trade Center attacks on September 11, 2001, found that out of the three groups studied (comorbid PTSD and depressive symptoms, PTSD alone, and no pathology), individuals with comorbid PTSD and depressive symptoms have decreased cortisol reactivity while the other two groups did not. The PTSD alone group showed elevated response to the trauma reactivation, which may seem contradictory to the previous study, but at baseline, the group with comorbid PTSD had a blunted cortisol response in comparison to the PTSD alone group.
The hypothalamic-pituitary adrenocortical (HPA) axis, which helps a person adapt and accommodate to threatening situations and/or exposures, triggers a cascade of events when someone is exposed to an event that is stressful and ultimately leads to the release of cortisol. However, people with comorbid PTSD and depressive symptoms did not follow the same pattern of elevation upon reactivation of traumatic events. The authors suggest this might be due to the depressive HPA and cortisol mechanisms predominate over PTSD mechanisms while the difference in cortisol response in the PTSD alone group might be from the patient re-experiencing symptoms (Dekel et al., 2017).
A disrupted circadian rhythm can have lasting effects
The circadian rhythm is a timekeeping system that helps keep everything moving in a select rhythm that corresponds with day-night and light-dark cycles by affecting hormones, temperature, immunity, gene expression, and energy. There is a "master clock" that is located in the central nervous system and peripheral adaptive clocks. The SCN helps maintain a 24-hour oscillation through a feedback loop of a set of clock genes. The peripheral clocks are kept in rhythm by the SCN as well.
Usually, the circadian rhythm helps create a dynamic internal 24-hour rhythm that prepares people for expected cyclical challenges. It interacts with the stress response system which also has circadian activity. This is shown through cortisol levels rising in the middle of the night and peaking in the morning (active), with a dip before the inactive phase (rest and restore). This corresponds with a peak in sympathetic nervous system activity and a decrease in parasympathetic nervous system activity in the morning which is our active phase.
However, this system is influenced by a lot of factors, such as genetics, early environment, and cacostatic load. Usually, when stressors exceed a certain threshold there are compensatory mechanisms that help redirect processes to fill the current need. Chronodisturbances that exceed a certain homeostatic threshold cause a loss in the balance, which causes an acute chronodisruption (a breakdown and dissociation of the temporal relationship between the different clocks). If sustained, this can change the brain's ability to regulate neuroendocrine, immune, metabolic, and autonomic systems. This can also have an impact on how someone adapts to stressors due to increased stress vulnerability and sensitivity, and lead to a sustained chronodisruption, which affects peripheral and central clocks, the SCN, memory consolidation, and sleep centers. Ultimately, this can predispose someone to developing PTSD from the sustained chronodisruption. Some animal studies showed that prolonged chronic stress disrupts circadian gene expression in peripheral tissues as well as the hippocampus, amygdala, and the SCN (Agorastos & Olff, 2020).
Circadian rhythm in patients with PTSD
Now, let us look into what happens to the circadian rhythm when someone has PTSD. Another small study that investigated the association between our circadian rhythms and PTSD found a time-dependent correlation between intrusive memories. Besides a circadian rhythm for cortisol, there is a diurnal rhythm for alertness as well with peak alertness occurring between 10:00am-2:00pm and between 4:00pm-10:00pm. This pattern of alertness is seen in attention, working memory, and executive function. The study recruited 50 survivors of assault or road traffic accidents to capture the effects of intrusive re-experiencing using an ecological momentary assessment. This assessment involved repeated real-time sampling of intrusive memories in survivors over seven days and intrusive memories experienced were assessed using the adapted version of the Intrusion Questionnaire.
They found a curvilinear pattern to intrusive memories that peaked at 2:00pm. Participants with PTSD experienced a heightened constant level of intrusive episodes in the afternoon and evening with a descending slope in non-PTSD participants. In addition, the highest frequency of intrusive memories was in the morning for participants with PTSD, which might be due to the chronodisruption experienced by these individuals (Rosi-Andersen et al., 2022).
In conclusion, post-traumatic stress disorder is a psychiatric disorder that arises from chronic chronodisruption to the neuroendocrine, autonomic nervous system, and immune system, which subsequently affects cortisol levels and circadian rhythms. The information and data presented in this blog post can both inform clinicians of the far-reaching effects of PTSD on patients and the ways to better support patients through more targeted treatments.
References:
- Agorastos, A., & Olff, M. (2020). Traumatic stress and the circadian system: neurobiology, timing and treatment of posttraumatic chronodisruption. European Journal of Psychotraumatology, 11(1), 1833644. https://doi.org/10.1080/20008198.2020.1833644
- American Psychiatric Association. (2020). What is posttraumatic stress disorder (PTSD)? Psychiatry.org; American Psychiatric Association. https://www.psychiatry.org/patients-families/ptsd/what-is-ptsd
- Dekel, Sharon, Ein-Dor, Tsachi, Rosen, Jeffrey B., & Bonanno, George A. (2017). Differences in Cortisol Response to Trauma Activation in Individuals with and without Comorbid PTSD and Depression. Front. Psychol.,8. https://doi.org/10.3389/fpsyg.2017.00797
- Mohd Azmi, N. A. S., Juliana, N., Azmani, S., Mohd Effendy, N., Abu, I. F., Mohd Fahmi Teng, N. I., & Das, S. (2021). Cortisol on Circadian Rhythm and Its Effect on Cardiovascular System. International Journal of Environmental Research and Public Health, 18(2), 676. https://doi.org/10.3390/ijerph18020676
- Pan, X., Wang, Z., Wu, X., Wen, S. W., & Liu, A. (2018). Salivary cortisol in post-traumatic stress disorder: a systematic review and meta-analysis. BMC Psychiatry, 18(1). https://doi.org/10.1186/s12888-018-1910-9
- Rosi-Andersen, A., Meister, L., Graham, B., Brown, S., Bryant, R., Ehlers, A., & Kleim, B. (2022). Circadian influence on intrusive re-experiencing in trauma survivors’ daily lives. European Journal of Psychotraumatology, 13(1). https://doi.org/10.1080/20008198.2021.1899617
- Thau, L., Gandhi, J., & Sharma, S. (2019, February 15). Physiology, Cortisol. National Library of Medicine; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK538239/
- S. Department of Veterans Affairs. (2014). Effects of PTSD - PTSD: National Center for PTSD. Va.gov. https://www.ptsd.va.gov/family/effects_ptsd.asp
