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Keep calm and carry to term

by Guest Author on 28 Nov 2018

Fraser Shearer, MRC PhD student at the Centre for Cardiovascular Science, The University of Edinburgh was commended in this year’s Max Perutz Science Writing Award. He describes how understanding the impact of stress hormones during pregnancy on a child’s lifelong mental health, could help us treat poor mental health more effectively in future.Fraser Shearer & Fiona Watt

In just a few weeks my first child is due. I have unbuilt furniture sitting in a wholly unprepared ‘nursery’ which is also my partner’s office, a pram that I am still unsure about, sleep sacks that are apparently a thing babies use and, for someone who does not have breasts, I have a wealth of knowledge about breast pumps. This, however, pales in comparison to the list of things I do not have and the window for fulfilling that list is rapidly shrinking. Suffice it to say, my stress hormone levels are elevated.

As the man in this story, though, my stress hormone levels are nothing compared to my partner’s. A woman’s stress hormone levels rise throughout pregnancy and in the third trimester can be three times higher than pre-pregnancy.

This increase is normal, reflecting the fact that the baby needs stress hormones at the end of pregnancy to properly develop. But in pregnancy, as in comedy, timing is everything. In early pregnancy, stress hormones are so unwanted by the baby that it has a defence mechanism – a chemical that inactivates stress hormones. This ensures that even as Mum’s stress hormone levels increase, baby stays in a zen-like state with stress hormone levels up to 10 times lower than Mum.

Unfortunately, the defence mechanism isn’t completely impenetrable. If Mum’s stress levels are increased early, maybe by something traumatic like a car crash, this can overcome the protection, exposing the baby to stress hormones.

Exposure to stress hormones at the wrong time can have a profound and long-lasting effect on the child. Starting with a lower birth weight and then an increased chance of lower IQ, depression and anxiety disorders continuing throughout their life. Mental health issues are thought to be the second leading cause of disability worldwide, so understanding how stress hormones might predispose us to poor mental health could help us treat it more effectively. To do this we need a way to look at how the developing brain is affected by stress hormones in pregnancy and for that we turn to mice.

The mice in our lab are almost completely normal but we have removed the defence mechanism from their brains. So, in the womb, any stress hormones that reach the brains of the mice are not inactivated, they affect the brain all the way through pregnancy not just at the end. As adults, these mice have some memory problems and depression-like symptoms similar to those we see in humans.

It’s amazing that in the vastly complicated process of brain development, a change as small as raising stress hormone exposure early can have such a big effect throughout the entire life of an animal.

The aim of my PhD project is to examine how this happens. What is different in the brains of these mice compared to normal mice? How could early exposure to stress hormones cause the symptoms we see in adults?

To try and answer these questions, I am taking brain tissue from our mice at different times during development. I look at how ‘turned on’ certain genes are in their brains compared to normal mouse brains. A big question for me, though, is which genes should I look at?

Some clues might lie in what we already know about mental health. In people with depression, a chemical called serotonin is often found to be decreased in the brain. In fact, this finding forms the basis of many of the treatments for depression. In the growing brain, serotonin is also very important, so it gives us a link between development and depression. Interestingly, in our mice I have found that a serotonin-related gene is reduced, suggesting that the early stress hormone exposure might be affecting how serotonin functions. If serotonin isn’t doing its job properly, that could change how the brain grows, another small change having a big effect.

This is far from the whole picture – brain development is a series of small things having big effects and stress hormones have wide-ranging and varied effects – but certainly it suggests that serotonin may be altered long before symptoms of depression arise. Perhaps the problem in depression isn’t low serotonin in the adult brain, but changes to how the brain grows after early exposure to stress hormones and serotonin is just the middleman.

It’s impossible to predict stressful events and to protect pregnant women completely from exposure to stress, but by finding out exactly how it affects the baby we might be able to prevent the later life effects in the future. For now, if you know any pregnant women, make sure they are happy and safe; it’s a small thing but it could have a big effect. And frankly, I can’t stress that enough.


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