Stress in the Female Brain

Sex hormones influence stress responses in the brain affecting mental illnesses and treatment. Medicine has some catching  up to do: Many medications and therapies are based on the male standard model.

2106.” Lydia Kogler gives me a four-digit number. “And now count backwards in steps of 17.” Oh dear! I’m not good at mental  arithmetic at all. Anyway, what are calculators  for? We don’t get off to a good start. “Wrong!”  says Kogler sternly. “Start over! 2106.”

Psychologist Dr. Lydia Kogler certainly creates stressful conditions for her participants. Especially when you consider that they have to complete the mental arithmetic exercise not sitting at a table like me, but lying in an MRI scanner: While they calculate, their brain activity is recorded using magnetic resonance imaging (MRI). Movement is strictly forbidden.

Another test that can be done in the scanner sounds like more fun: Cyberball. It involves playing a ball game with imaginary  partners on the screen. But  the catch is that imaginary partners can exclude them  from the game, causing social stress.  Lydia Kogler  knows from series of experiments that she conducted – in Vienna, Aachen, Philadelphia (USA) and Tübingen – that women react more strongly to social stress compared to men, which can be measured in brain networks. “Women suffer more from social exclusion than men,” she explains.

Sex hormones and stress

Why is it important to know something like this? Kogler and her colleague Dr. Ann-Christin Kimmig explain it to me: Stress is an umbrella term for a phenomenon that touches many levels. It is perceived subjectively (or not), it manifests physiologically, for  example through sweating or an accelerated pulse. The brain can help to regulate stress. And hormones have an effect, not just the “stress hormone” cortisol, but also male and female sex hormones.  Emotions play a role, such as the fear of failure. Or social interactions – a strict judgment or a gentle touch that can have a  calming effect.

“A healthy stress response can be very positive,” emphasizes Kimmig. “It is relevant for achieving success, motivation and drive.” On the other hand, chronic stress is bad, for example when there are no breaks for recovery. Chronic stress can lead to mental disorders such as depression, which are more prevalent in  women than in men. “At all ages from puberty onwards,  the prevalence of depression in women is higher than in men,” Kogler knows.

Kimmig explains that sex hormones can play a role in this, using the side effects of the birth control pill as an example: The artificial hormones can cause mood swings and even depressive symptoms in some women. In others, however, the pill dampens mood swings that occur during the menstrual cycle known  as “premenstrual syndrome”. The effects are therefore very individual.

Other vulnerable phases for a woman’s mental health are the birth of a child or the menopause. Changes in mental health can be triggered by the rapid decline of a previously high hormone level. However, in addition to biological factors, there are also socially induced stressors and expectations that women are often more exposed to in everyday life than men, such as a greater double burden of career and children. Lydia Kogler, mother of three young children, can confirm this.

Elaborate experiments

Since the 1990s, psychology and brain research have known that there are gender differences in stress and coping with  stress. Meanwhile, especially from animal experiments, details about the interaction of stress hormones, sex hormones, their receptors, and their effects on the nervous system are known. Thanks to imaging techniques such as functional magnetic resonance imaging, it is even possible to decipher quite precisely which networks in the brain are involved in the stress response.

Lydia Kogler has designed experiments using brain scanners to investigate this. Recently, Tübingen doctoral candidate Zoé Bürger evaluated data from an experiment with 77 healthy subjects, including 40 women, and analyzed networks in the brain. The work “Stressor-Specific Sex Differences in Amygdala-Frontal Cortex Networks” was an international collaboration published  in 2023.

Analyzing brain activity is elaborate research that consumes a lot of time and money. To get reliable data, many subjects of both sexes must be recruited. Experiments can take the entire day,  involving brain scans, questionnaires, physiological measurements, and blood tests. Large amounts of data are generated and must be evaluated gradually.

We know more about space

Fortunately for researchers like Kogler, Kimmig, and Bürger, who are interested in sex and gender differences in the brain, there is a professor in Tübingen who repeatedly manages to attract large research projects and the necessary funding to the university: Austrian Birgit Derntl, in Tübingen since 2015, heads the group “Women’s Mental Health and Brain Function” at the  Faculty of Medicine, and since January 2023 also the DFG international research training group 2804 on “Women’s Mental Health Across the Reproductive Years”. Kogler, who moved to Tübingen with Derntl in 2015, is her deputy.

Her personal goal is not only to conduct research. She also wants to intervene as a psychologist and help patients manage stress better to protect the brain. However, her research is currently taking up all her time. A new brain scanner has just been installed at the Department of Psychiatry and Psychotherapy,  which will mainly be used for research. This is important to her,  as there is much to catch up on.

A pioneer for Derntl’s work is the American psychologist Emily G. Jacobs from the University of Santa Barbara, California. Jacobs calculated that among the approximately 50,000 scientific papers on brain research that have been published since 1995,  just 0.5 percent deal with the mental health of women. In a stirring video promoting the Ann S. Bowers Women´s Brain Health Initiative that she leads, Jacobs lists the areas humanity knows more about than the female brain: the ocean floor, dinosaurs, male baldness, erectile dysfunction, space …

Medical research is often focused on males

Medicine has focused on the male for far too long, believes Ann-Christin Kimmig. “Until the 1990s, medications were almost  exclusively tested on men and male experimental animals, and even today there is an imbalance with many medications.” This is partly explainable, women are more complicated than men, due to the hormonal fluctuations their bodies are subjected to. But the neglect of the female sex in research has consequences. “Medications do not work the same in men and women. Women more  often have unwanted side effects, and the effectiveness of medications  tends to be lower.”

Even the newly approved Alzheimer’s medications in the USA are less effective for women than in men, as is already known. Yet, statistically speaking, women are more at risk of Alzheimer’s disease and depression. This is not only because women on average live longer than men, but probably also due to their hormones – among other things, the menopause seems to be a risk factor. Evidently there is still a long way to go before we reach gender equality in healthcare.

Text: Judith Rauch