23. Nov. 2023

Prenatal programming and its association with mental health problems in adulthood opens up new avenues of research. An interview with Klára Marečková from CEITEC reveals what factors during pregnancy influence fetal brain development and what long-term impact they have on mental health of the individual. Research shows that maternal depression during pregnancy can leave its mark on the biological age of the offspring and influence its predisposition to psychological disorders in later life. Klára describes her journey through the research topic to winning the prestigious Czech Grant Agency JUNIOR STAR 2024 grant, which will enable her to expand her knowledge in the field of prenatal development and its impact on the human brain. Her work not only reveals the connections between the prenatal environment and mental health but also brings hope for more targeted interventions and personalized medicine for future generations.

Klára, is prenatal programming related to an individual's health predispositions that are "set" in the fetus during pregnancy?

Yes, in addition to genetics and the external environment in which one lives, there is one more important factor that influences brain development - the prenatal environment. For example, changes in the hormonal environment induced in the pregnant mother by stressful situations. When a mother experiences stress during pregnancy – for example, she has financial difficulties, her pregnancy is unplanned or she has lost someone close to her – on a biological level, this stress manifests itself in changes in the level of cortisol in the blood, which is a hormone that mobilises the body in case of stress. There are also changes at the level of inflammatory markers and all these circumstances contribute to the turbulent development of the fetal brain and contribute to what is known as accelerated aging and the development of psychological disorders in adolescence and adulthood.

How does this 'accelerated aging' actually manifest itself?

Accelerated aging can start already in the mother's womb due to psychological discomfort. If the baby receives signals through the placenta that the environment it is about to enter is stressful and unpleasant, its body reacts protectively by accelerating the process of maturation, which can manifest itself, for example, in girls by an earlier onset of puberty.

 Our research, which was the subject of a previous grant and the results of which were published this year in JAMA Network Open, disproved the hypothesis that brain aging is influenced by a combination of the mother's mental health during pregnancy and the level of stress experienced by the person herself during adulthood. We have shown that the influence of maternal mental health in fetal development has a long-lasting and stable effect on human brain aging independent of recent stressful events.

How will you build on this research with the grant you have now received from the Grant Agency of the Czech Republic (GA ČR) as part of the JUNIOR STAR 2024 project, which you will implement at CEITEC, Masaryk University?

The main goal of the JUNIOR STAR grant is to collect neuroimaging, epigenetic and psychological data to look at exactly how prenatal development and biomarkers influence brain development and child behaviour.
The CELSPAC: The Next Generation (TNG) study has been running at Masaryk University for several years now It recruited mothers who gave birth at the Brno Maternity Hospital in Bohunice or Obilní trh and asked them to fill in questionnaires during pregnancy and the following 5 years of the child's development, but also to give extra blood during standard examinations during pregnancy, cord blood at birth, buccal swabs from the mother's and child's mouth after birth, and other samples. Thus, there is already a huge source of data, which is managed by the RECETOX MU research centre. Our neuroimaging, epigenetic, and psychological data will augment these existing data to answer new questions about prenatal programming of brain development and child behaviour.

The GA ČR grant is a multidisciplinary grant, we have neuroimaging experts, psychologist, or bioinformatician in our team, and the funding will be spent primarily on scanning, and analysis of blood and other biological samples.

You were involved in a similar type of study during your time at Harvard. How will your current research be different?

When I was a postdoc at Harvard, they had a large unique study that started in the 1960s where they froze blood samples from pregnant women and we could look at their levels of prenatal cytokines. Therefore, we knew that there was some connection between the prenatal environment and the brain function in adulthood. These results were published in the prestigious journal PNAS. However, at that time in the US we only had four basic and well-known markers, whereas thanks to the current grant we will be able to look at 32 inflammatory markers, including the less well-known ones, and their ratios, so the resulting analysis will be much more comprehensive.

What was at the very beginning of your scientific curiosity? Were you looking for the cause of mental disorders and going backwards to prenatal development, or was your first question mark in pregnant mothers who were experiencing some type of stress?

When I was doing my PhD in Toronto, I was interested in the effect of prenatal androgens on brain development. The size and connectivity of different brain regions differ between men and women, and prenatal androgens contribute to the degree of masculinity or femininity of the brain and behaviour. Over time, however, I became more interested in mental health and its relationships with prenatal factors.

How does a researcher who studies the relationship between pregnant women's stress and adult mental well-being actually experience her own pregnancy? Were you more of a mom or a researcher at the time?

When I give talks about my research, I always try to convey the message, and it was true for myself during pregnancy too, that expectant mothers should be as relaxed and happy as possible because that is important for the health of their offspring. So, scheduling enjoyable activities and get-togethers is not a luxury, but an investment in your baby. :-)

If you looked into a crystal ball, can you guess where you see your research with the help of the GA ČR JUNIOR STAR grant in five years?

The research should provide a better understanding of the mechanisms that explain the relationship between maternal mental health during pregnancy and the brain and behaviour of the baby. It should also show what environmental factors can mitigate or intensify its biological processes, which could lead to more targeted treatment interventions and personalised medicine. The longitudinal multidisciplinary data from our research will also be a unique resource to answer further scientific questions brought by the new horizon of our knowledge, and enable collaboration with leading research centres abroad.

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