B4125 - Determining the association between trauma HPA axis dysregulation and mental health using robust measures - 01/09/2022

B number: 
Principal applicant name: 
Hannah Jones | University of Bristol (UK)
Professor Stan Zammit, Professor Golam Khandaker
Title of project: 
Determining the association between trauma, HPA axis dysregulation and mental health using robust measures
Proposal summary: 

Poor mental health affects more than one billion people worldwide but despite this frequent occurrence and the potential personal burden, treatment options are scarce and not always effective. There is a need, therefore, for a better understanding of the environmental and biological causes of mental health problems, so that new treatments can be developed.
It is known that stressful or traumatic situations can increase an individual’s chance of developing a range of mental health problems. In response to a stressful situation, whether psychological or physical, the human body activates processes that aim to increase the chance of survival. These responses are referred to as “fight-flight-freeze” and can result in giving the body energy, making you feel more, and reducing the sensation of pain. One key hormone involved in this response is cortisol. Although the release of cortisol in response to stress is initially beneficial, evidence has shown that experiencing severe or ongoing stressful events can lead to abnormal cortisol levels, which in turn has been linked to harmful outcomes, including obesity, cancer, heart disease, susceptibility to infection, and poor mental health.
Mental health problems that have been linked to cortisol levels include psychosis, depression, anxiety, and post-traumatic stress disorder (PTSD). For example, studies have shown that individuals diagnosed with depression or schizophrenia have higher levels of cortisol in their blood or saliva when compared to individuals without a psychiatric illness, while individuals with PTSD have lower levels. Some studies also show that high cortisol levels in early life associate with developing a mental health problem later in life, indicating that stress response abnormalities may cause mental health problems. However, findings are not always consistent, and results are hard to compare as the time of day the cortisol measure is taken and the material used for measurement (e.g., saliva, blood, urine) vary across studies.
One way in which cortisol may be causally linked to mental health problems is through inflammation. In normal conditions, cortisol reduces inflammation (e.g., it’s commonly used to treat inflammatory diseases such as arthritis and asthma), however, studies have shown that under abnormal conditions (e.g., during ongoing stress), the relationship changes and high levels of cortisol are associated with increased inflammation. An increase in inflammation can be harmful to neurons in the brain by affecting neuron functioning and decreasing neuron repair. As such, studies have linked stress-related inflammation to poor mental health, however, the size of these studies are small and, again, studies are hampered by inadequate measures of cortisol and inflammation.
As can be seen, there is a need for large studies using improved measures of cortisol to investigate the causal link between stress response and mental health. In this project we therefore aim to generate reliable, robust measures of cortisol and inflammation using serum measures, genetic data and hair samples, to investigate whether cortisol levels lie on the pathway between early life trauma and mental health and whether they influence inflammation.
This work will inform whether interventions targeting the stress response system have the potential to prevent or treat psychiatric disorders.

Impact of research: 
This research will improve our understanding of the role of the body’s stress response in the relationship between trauma and mental health, as well as in priming patterns of inflammation during childhood and adolescence. The hair cortisol measures and longitudinal inflammatory patterns derived by this study will serve as a useful resource for other researchers interested in cortisol and inflammation levels during the life-course. More specifically, findings from this research will inform whether stress response could be a target for treatment, prediction and prevention of mental health problems in young people. Findings could be used to direct future work investigating characteristics of cortisol and inflammation-related mental health and clinical trials of cortisol/immuno-modulating therapies for psychiatric disorders.
Date proposal received: 
Thursday, 11 August, 2022
Date proposal approved: 
Monday, 15 August, 2022
Epidemiology, Mental health, Statistical methods, Genome wide association study