When stress makes you sick

It’s no secret that stress can make you sick. And yet, people are less aware that ongoing negative stress not only impairs your mental health, but can also affect your body. “Chronic stress, especially when experienced during childhood, is a risk factor for the development of common neuropsychiatric disorders later in life,” says Isabelle Mansuy. The professor of neuroepigenetics at ETH Zurich and the University of Zurich heads the new “Hochschulmedizin Zürich” (HMZ) flagship project together with Birgit Kleim, professor of psychology at the University of Zurich.

The project, with a name that is simple and to the point, STRESS, will start on 1 January 2022 and is funded with 1 million Swiss francs, with ETH Zurich and University of Zurich sharing the costs. A five-member Steering Committee includes ETH Zurich Professors Johannes Bohacek and Nicole Wenderoth. HMZ presented the new project yesterday at its annual event.

The new flagship project aims to understand, diagnose and treat the effects of stress on people’s mental and physical health. Researchers from ETH, University, University Hospital of Psychiatry and University Hospital Zurich are involved in the research collaboration. They are exploring a public health problem that has serious consequences for our society. Over the past decades, the effects of stress on health have become of major concern and perhaps reached a peak during the Covid pandemic.

One in four children affected

Generally speaking, stress can be divided into two types: healthy eustress and unhealthy distress. While eustress has a positive effect and can even increase short-term performance, distress reduces cognitive performance, affects the immune system, and will eventually make you sick. When we experience stress, our body gets ready to face and react to the danger. Adrenaline, noradrenaline and corticoids are released, heart rate and blood flow increase, glucose level rises and gastrointestinal activity is reduced. Our body prepares for fight or flight, much like our ancestors did when faced with a threat. But if stress is strong and becomes chronic, an excess of cortisol can damage important cells in our brain. In the long-term, stress hormones can even alter the physiology and anatomy of the brain.

Stress is thus a major risk factor for chronic diseases such as psychiatric and neurodegenerative disorders like bipolar depression or dementia, but also cardiovascular diseases and type 2 diabetes. The coexistence of several diseases, a phenomenon called comorbidity, is characteristic of people exposed to severe stress. Further, since stress is extremely common during childhood – with one in four children worldwide being exposed to physical or sexual abuse according to WHO estimates – the negative consequences can be felt throughout a person’s entire life.

Across disciplinary borders

Despite these facts, psychiatric and cardiovascular diseases are still only rarely looked at together, and diagnosis and treatment are usually conducted separately. One of the reasons is the traditionally strict separation between psychiatry and cardiology.

This is precisely what the new HMZ flagship project wants to address. The STRESS consortium brings together experts from the field of psychiatry/psychology, neurosciences, cellular and molecular biology, cardiology, engineering and translational bioinformatics to investigate the risk and resilience to stress across life. “We’ll be working with animal models. But we’re also going to conduct long-term studies with people suffering from stress,” explains Isabelle Mansuy.

For example, one of the planned projects is a cohort study with over 100 medical students completing their internship in a stressful environment such as the emergency room, intensive care or oncology units. Six months after the start of their internship, the students’ anxiety level, symptoms of depression, psychosocial functioning and perceived stress will be recorded as stress-related psychopathological manifestation. Further analyses conducted over a longer period will enable the researchers to draw individual health trajectories within the cohort.

Recognizing and treating alarm signals

STRESS is articulated around five sub-projects that focus on different topics in humans and animal models. They include behavioral and cardiometabolic phenotyping, identification of RNA signatures, neurofunctional profiling and data processing using machine learning, as well as translational treatment strategies based on neurofeedback.

The scientists involved in STRESS want to fill the knowledge gap about the biological consequences of chronic stress on the brain and body. A better understanding of the biological pathways activated by stress will make it possible to improve diagnoses and develop preventive and therapeutic measures.