Can a Little Bit of Stress Help?
We close the show by discussing how a mild amount of stress in early life, could actually have a positive effect for some individuals.
Dr. Mathias Schmidt from the Munich Max Plank Institute of Psychiatry studies this, in mice....
Hannah - We close the show by discussing how a mild amount of stress in early life could actually have a positive effect for some Dr. Mathias Schmidt from the Munich Max Plank Institute of Psychiatry studies this, in mice...
Mathias - One of the major risk factors for depression that we know of from the environment is stress exposure. And here especially, stress exposure early in life seems to be very detrimental in determining the risk of later disease.
Hannah - In humans, the type of early childhood stresses that you're talking about that might predispose to depression are things like for example, being affected by violence at home or conflict at home, or even things like moving home or moving schools for example might increase your risk of depression later on in life.
Mathias - Yes, this is true. In mice obviously, we want to have our model system which is very controllable, but we don't want to do anything to the animals which is ethically not supportable. So, what we do is moderate stressors where we basically alter the environment of the mother in a way that the maternal behaviour gets more erratic or less predictable that basically also affects the offspring. Using that sort of model, we can then ask the question of, what is the long term consequence of that.
Hannah - By the stressing the mother, the baby mice actually is still weaning at that time and they're still taking her milk. In that case, could some of these stress factors be passed on through the milk?
Mathias - Yes. There's also a possibility that some of the stress factors of the mother are via the milk, getting into the baby pups. But actually, it was shown that most of the effects are really transmitted via maternal behaviour. So, the mother via her behaviour can actually have a very calming or a very upsetting effect on the offspring. It's really actually a little bit like in humans if you have a very predictable childhood with very clear rules and not erratic situations, then this is usually not very stressful and good. If the situation is very difficult and non-predictable, this is usually what's really stressful for kids and is also very stressful for mice.
Hannah - But it's not the case that every single child that might have to move schools or move house or might experience conflict within their home that they all go on to develop depression or anxiety for example. So, are you seeing that with the mice as well, that some mice are absolutely fine with this early experience in life and some mice just do seem to get depression?
Mathias - Yes. So, this is actually the core of our research approach. So, what we see indeed is that as in humans, not all individuals exposed to stress eventually develop a depression-like symptom.
Hannah - What is that slightly depressed or anxious mice look like?
Mathias - We measure behaviours in terms of anxiety as relatively straightforward. Mice are afraid of open spaces or they are afraid of very bright areas but on the other hand, they want to explore their environment, maybe search for food. So, we generate a little test arena where there's a conflict between exploring and hiding from that part of the arena, we have a very anxious mouse that will not explore those areas. We can measure other things like hormonal regulation and motivation to get reward for instance which is also altered in depressed patients and we can really transpose it quite nicely into the animals.
Hannah - So, you were saying that some mice that experience stress during early childhood still are bold mice, they go and explore their environment. They also seem to have motivation for reward as well. So, why is it that some mice seem okay and others don't?
Mathias - Yes. As in humans, there's a strong genetic component of psychiatric disorders and depression. We see that in humans, we can also confirm that in animals. Here, we have to picture indeed to manipulate the genetic background of these animals and manipulate specific genes. By doing that, we can shift the balance of vulnerability and resilience to stress.
Hannah - So, some of the mice's genetics, they can either be very resilient to early life stresses or they could be very predisposed to depression and anxiety. So, is it the same in humans?
Mathias - Yes, we also find genetic risk factors for depression in humans. On the one hand, stress is a risk factor for disease, but on the other hand, it is adaptive in a way. So, if you're exposed to at least moderate levels of adversity and stress early in life then this can actually shape your physiology in a way, that you're better adapted to similar situations in adulthood.
Hannah - And the stress factor, so the stress hormone in humans is something called cortisol and the cortisol system in the brain is still developing in babies in the first 5 years and even further on into life. So, could it be that stressful experience as very early on childhood could then tweak or change that cortisol system or sensitivity in the brain to then actually help make some children more resilient in the future.
Mathias - Yes. This is indeed what we find. It's not only the cortisol system but the stress system is really an orchestrated system with many factors which are active in the brain and in the periphery. They basically shape the physiology of an individual. Those experiences early in life within a certain range at least, they're really meant to shape your body in a way so that it can deal better with similar situations. We all know that stress is part of everyday life and was, for millions of years before and just our physiology is adapted in a way to deal with that and also, to develop into that. So, if you're growing up in a very adverse circumstances then your body should better adapt to that so that you can actively cope with the situation later on. We are now living where a lot of things change very quickly and I think this is the core of the problem because you're growing up in a very protected home maybe. But then you have to face many stressors in adult life or vice versa. You're growing up on the very adverse situations, but then your adult life is very different.
Hannah - What genes are involved in this resilience to stress? Is it the cortisol system or is it different genes?
Mathias - We do find genes which are involved in the regulation of the stress system such as the main system which is producing cortisol as an end-product in humans, which are also directly modulating the vulnerability of animals to stressful life events.
Hannah - So bottom line then is that stress in early childhood might not actually be a bad thing. it might make you more resilient and more likely to flourish later on in life. Do you think we'll ever get to a stage where we could have biomarkers? So, biological markers which could indicate whether an individual is going to grow up to be a very resilient person later in life or whether they can be more likely to become depressed.
Mathias - Yes. So, this is exactly the way we're going. We hope to get there in the near future. At the moment, as I said, depression is diagnosed just by the symptoms and treated with the same drugs - independent or what genetic background you have, depending on what early life history you have. We are hoping in the animal model, this is really working quite well to identify biomarkers that allow us then to really individualise our treatment and our diagnoses to say, "Patient A has this specific early life history together with the specific set of genes which explains why he or she is suffering from depression and as for her specific treatment, the same treatment would not work in patient B because he or she has a different history, a different set of genes, and just need some different treatment." We just have to step away from this one drug for everyone and just really go on to this personalised medicine and help people.
Hannah - And that's all we have time for this month, I'm afraid. If you have any questions or comments, please do get in touch. It's firstname.lastname@example.org. thanks to all those who took part in the programme, the NSPCC, Amelia Perry, Dr. Anne-Laura van Harmelen, Camilla Batmanghelidjh, Eamon McCurry, Katya Rubia, Hannah Newton and Mathias Schmidt. Signing off, I'm Hannah Critchlow with this special Naked Neuroscience episode supported by the Federation of European Neuroscience Societies. See you next month to open our minds.