At the Interface of Life

It has long been a topic of debate among scientists: Are our personalities determined by our genes or by our environment? Until now, scientists have assumed that the risk of mental illnesses such as anxiety disorders or depressions stems from the interaction of genetic and environmental factors. About 30 to 60 percent of anxiety disorders and affective disorders are attributable to genetic causes. The environmental factors include acute and chronic stress, the loss of a loved one, and traumatic events such as abuse. The psychiatrist Prof. Dr. Dr. Katharina Domschke conducts research at the interface between genetic and environmental factors: Her area of specialty is epigenetics, which deals among other things with the question of how environmental influences activate a biological predisposition to mental illnesses.

Searching for the causes of a depression: Are our personalities determined by our genes or our environment? Photo: dodoardo/stock.adobe.com

Epigenetic mechanisms function like translators between the environment and our genes, determining which genes are read from the DNA and how active they are. “Our genetic code is like a book whose content is composed of four letters in different combinations. We might compare epigenetic mechanisms with markings like turned-down corners, underlining, bold-faced print, or italics: They help us to highlight particular passages,” explains Domschke, director of the Department of Psychiatry and Psychotherapy at the Medical Center – University of Freiburg. These processes take place in the human genome, also in genes that are relevant for mental processes. For instance, epigenetic processes influence genes that regulate the distribution of serotonin and noradrenaline, neurotransmitters that are responsible for mood and initiative. Most epigenetic mechanisms are relatively stable, meaning that they do not respond constantly to environmental influences. In this way, they ensure that the processes in the human organism remain relatively constant.

Biomarkers for Illnesses

“Even minor epigenetic changes that are not pathological on their own can lead to changes in the neurotransmitter systems, thus increasing the risk of mental illnesses,” explains the scientist. Domschke uses epigenetic biomarkers to study processes which could lead to mental illnesses. They also indicate whether a patient is responding well or poorly to a therapy. Other possible biomarkers for mental illnesses besides epigenetic mechanisms include genes, hormones, or parts of the immune system or the blood circulation. In the future, the study of biomarkers could facilitate the diagnosis and treatment of mental illnesses, explains the Freiburg researcher.

Genetic and epigenetic processes are the basis of many biological processes. In the DFG-funded Collaborative Research Center “Fear, Anxiety, Anxiety Disorders,” Domschke is collaborating with researchers who are using imaging diagnostic methods to determine whether anxiety disorders might possibly be explained by the fact that the amygdala, a core region of the brain, is particularly sensitive to stress. With methods from endocrinology, the study of hormonal and metabolic processes, the researchers are looking into the question of how stress affects the release of cortisol in the brain. Other researchers at the University of Freiburg’s psychological institutes are studying the development of mental illnesses, while physiologists are using animal models to investigate genetic mutations or epigenetic mechanisms discovered in humans. This allows them to model corresponding factors and to analyze just how the epigenetic mechanisms function in a nerve cell.

Researchers are studying how the acute and long-term effects of the pandemic are influencing people’s psychological well-being. Photo: Maria Sbytova/stock.adobe.com

New Methods for Therapy

By identifying genetic and epigenetic biomarkers and drawing on additional information on environmental and life history risk factors, scientists might in the future be able to better predict whether healthy people are at greater risk of developing a mental illness in their lifetime. Researchers could offer risk groups specific preventive treatments to prevent them from developing illnesses from the outset. These patients would then not have to undergo therapy. For example, there are preventive programs that strengthen people’s resilience or psychological resistance, making it easier for them to deal with anxiety-laden situations.

The Freiburg researcher wants to use biomarkers to determine at an early stage what drugs a patient needs and what effect may be expected. This would allow the therapy to be tailored to the patient’s individual needs, enhancing the effect of the drugs and minimizing their side effects. Finally, Domschke’s research on genome-wide associations of genes or epigenetic mechanisms with mental illnesses could also serve as a basis for developing innovative therapies: “What we are studying with our approach is not genes we already suspect are connected to the illness but the entire genome. The idea is to find new genes that are risk factors for mental illnesses. Newly discovered mechanisms could then be treated specifically with drugs.”

According to Domschke, however, epigenetic processes should not be seen as the only translator between genes and the environment, because humans are more complex: “We are currently asking ourselves how the environment speaks with the genes via the epigenetic processes. But how does the environment speak with epigenetic processes? This ‘domino’ in the development of mental illnesses is just one of many that we have to identify individually and in interaction with one another.” Hence, epigenetic changes can in principle increase the risk of mental illnesses. But patients can also change their own epigenetic predisposition by doing things like maintaining a healthy diet, refraining from smoking, or undergoing psychotherapy if necessary, emphasizes the researcher. “With a healthy lifestyle, there is a good chance that we can normalize epigenetic risk patterns to an extent. The good news is therefore that we are not entirely at the mercy of our own nature.”

With the virus SARS-CoV-2, however, nature has changed the lives of many people worldwide. That is why Domschke and around 200 researchers from more than 40 countries are now studying how the acute and long-term effects of the pandemic are influencing psychological well-being. The first of three phases of the study “COH-FIT: Collaborative Outcomes Study on Health and Functioning during Infection Times” involves surveying people during the coronavirus pandemic. In phases two and three, the researchers will conduct follow-up surveys six and twelve months after the pandemic, respectively. More than 25,000 people have taken part in the study so far.

“We can use this exceptional situation to obtain valuable information from the public and learn about how they are dealing with the pandemic. Our goal is to provide people with better therapeutic support in times of crisis,” explains Domschke. In addition, the researchers will use the data to help identify people who exhibit an increased risk of physical and mental health problems during a pandemic. People at particular risk can be offered appropriate therapies: “This will allow us to better predict, reduce, and in the future perhaps also prevent short- and long-term psychological burdens.”

Patrick Siegert