Clare Blake (00:00):
Are you over 16? Maybe you’re in the 43% of those who have experienced a mental disorder of some kind, and those stats are terrifying, but that 43% have provided massive sets of data, opening up a pathway to get better help and sooner. Hi I’m Clare Blake, and you’re listening to Body Lab.
Speaker 2 (00:23):
This is a QIMR Berghofer Medical Research Institute podcast.
Clare Blake (00:28):
Thanks to the many, many people who were suffering but bravely participated, Professor Eske Derks and her team have taken a new step towards precision psychiatry. Professor Eske Derks says, “It is time to translate that into clinics and help those people that are suffering.” Thanks for joining us Eske.
Professor Eske Derks (00:48):
Yeah. Hi Claire.
Clare Blake (00:50):
The field of psychiatric genetics has seen extraordinary advances. What exactly is it?
Professor Eske Derks (00:57):
So it’s studying the genetic risk factors that will increase the chance that someone will have a mental condition. We are studying schizophrenia, depression, anxiety, ADHD, and we as psychiatric geneticists, we are interested in how is it that some people are more vulnerable? Why are they at higher risk to have these disorders, and what do genes… how do they play a role in this?
Clare Blake (01:22):
And I love your insight into the last decade. You really see it as an era of genetic discovery for mental health. What helped this?
Professor Eske Derks (01:29):
About 10 years ago, we had the first large scale, we call them genome-wide association studies, which means that there were technical advances and we can now study the whole genome of individuals, like many millions of genetic variants, and that was not possible before then. What happened is that we all work together in the world, so initially we thought we need genetic studies of maybe 1000 people, 2000 people, 5,000. We discovered that it wasn’t large enough. So rather than each individual research centre doing their own small genetic study, we all started working together. So we had really large studies and we now have studies that include 1 million participants. And that’s how we were able to discover all these genes that are associated with psychiatric disorders and how we learned so much about the genetics of mental health.
Clare Blake (02:24):
That large massive data, why does that make such a difference?
Professor Eske Derks (02:29):
Yeah, you needed the power because we are looking at millions of variants. It’s very complex. There’s not a single gene that causes depression. We’ve learned that a long time ago. It’s hundreds of genes and each of these genes or genetic variants have small effects. So we need really large groups of people to identify these effects.
Clare Blake (02:50):
Last year alone, your team uncovered more than 500 genes shared by depression and anxiety. So what does that mean for those people suffering?
Professor Eske Derks (03:00):
We did a really large study and we were the first to identify hundreds of genes for anxiety. We knew a bit more already about the genetics of depression, but for anxiety we didn’t know so much. So I think there’s a couple of lessons that we have learned from that. First of all, we’ve again shown that genes do contribute to these disorders, to mental health disorders and that they’re in fact, very similar to other diseases like cardiovascular disease and diabetes. They’re not so different. They’re partly heritable and there’s a biological component that contributes to the risk of having these diseases. We shouldn’t look at these disorders differently. Mental health diseases are no different from other conditions, but there’s a lot of stigma in the society around them. Patient with depression often hear like, “You just have to be strong. It’s just in your brain, Come on, you’re just feeling a bit down. Just get over it.”
We show that this is a disorder and that you have genes contributing to the risk. Also that anxiety and depression, we know that they often occur together in the same people. If you have anxiety, you also have a higher chance of having depression, and we show that, that’s partly due because there’s overlap in the genes that play a role in these diseases. These are important lessons, but I also felt a little bit frustrated still because now we have all these genes and you would hope that, that would lead to better treatment, and in this paper, we are not yet able to identify better treatment based on the genes. So there was a little bit of frustration for me as well, because you want to help the people who participated in our studies and the people who suffer from mental health diseases. I mean, we have this list of 500 genes now and that gives us important information on the genes and on the biology. If you stop that, it’s not going to help to make someone’s life better.
Clare Blake (04:51):
And you decided to go away for a weekend away from everything and just try and come up with a plan?
Professor Eske Derks (04:57):
Yeah, we went with the three of us. Zack (Dr Zachary Gerring) is a post-doc in my group, and Jackson (Jackson Thorp) was a PhD student. He recently finished his thesis. There’s definitely something missing still because we can’t translate that information to the clinic yet, and I think it’s time to focus on that. Think about which challenges are we still facing and what do we need to do to make that happen? And it won’t happen tomorrow. We went to Tamborine Mountain with this beautiful quiet place with a beautiful garden and flowers. We played some board games and we wrote this paper basically in three days. Before we went, we had some idea. We identified which 10 challenges we felt were important, and then we did our work and our reading and we basically wrote a paper in three days. You’re always so busy with your daily tasks and there’s sometimes not even as a researcher, sometimes it’s difficult to find time to think, but that really gave us that opportunity to think and discuss.
Clare Blake (06:01):
And it worked.
Professor Eske Derks (06:02):
And it worked. Yes.
Clare Blake (06:03):
So tell us about this paper, which is now just freshly minted. Congratulations, by the way.
Professor Eske Derks (06:08):
Yeah, thank you. I was feeling also so grateful towards these people because we have a million people who share their DNA, not necessarily directly with us. We didn’t have access to the genetic code, but indirectly though. We identified 10 challenges that we need to overcome to be able to translate this information to the clinic. Of course, we want more effective treatment, like more effective drugs.
I’m in training to become a psychologist, so I’m seeing clients and I’m working as a therapist at the moment. I can see that the patients who have depression or anxiety, not all of them, but some will start on medication if it’s really severe and they’ve tried therapy and it’s not working for them, but, then it’s a lot of trial and error. We are not able to predict which medication will work for which patient. You have to increase the dose very slowly, so it can take a couple of months before you know if it’s working or not, and then if you’re lucky, it’s working. Then if it’s not working, you have to try another drug. So there’s a lot of trial and error, and a lot of patients respond to treatment eventually, but some do not.
Clare Blake (07:20):
For some patients, just getting themselves to a practitioner is so exhausting. If you could go and have one session and get some results straight away, that it’d have a massive impact, wouldn’t it?
Professor Eske Derks (07:32):
It would, yes, it would.
Clare Blake (07:33):
What are the other challenges?
Professor Eske Derks (07:35):
A really important one is that, we know a lot about which genes are associated with mental health disorders, but we don’t know the biological function of all these genes. How do they lead to increased risk for mental disorders? That’s something we need to study a lot more. Another challenge is that, we know as a concept, anxiety and depression, they have been developed by a psychiatrist many years ago. In some way, they are different from each other, anxiety and depression, but we also know that they often co-occur together in the same patients, and does the diagnosis that we are using at the moment, like anxiety, depression, do they really make sense at the biological level or is there more… Because there’s so much sharing of the genes for these disorders, maybe there would be a better way of conceptualizing mental disorders.
And also we know that sometimes you can have two patients and they’re both diagnosed with depression, but they can have very different symptoms. Some patients with depression will sleep more than usual and some will sleep less and some will have increased appetite and some will have decreased appetite, and so you can have two different patients. They both have depression, but their symptoms and the way they feel and experience their disease are actually very different.
Clare Blake (09:00):
And there’s other challenges that you’ve outlined in this paper too. It’s really a rallying cry to the research and funding community that now is the time to act.
Professor Eske Derks (09:08):
Clare Blake (09:10):
And no wonder, mental health disorders are rising and they can really impact a person’s quality of life.
Professor Eske Derks (09:16):
They do. For those suffering from mental disorders and for the relatives as well, it can have such a huge impact on their life. We have put in so much investment in collecting all these genetic data. We spend a lot of funding collecting these data. So I feel that we have such good resources now. We’ve never been in this position where we are now, where we have a lot of resources to do this work and we actually don’t need that much money probably to do the next steps. We need smart people who do the work, so we need the salaries, but the genetic data, we have that in place, so we have to use it in better ways.
Clare Blake (09:58):
Your dream scenario, how would it work?
Professor Eske Derks (10:00):
So in my dream scenario, I would be able to at least keep all these really smart people who I currently have working on my team and to have them work on this in the next 10 years. And there’s a lot of challenges for a lot of people, but in research we have our own challenges. Funding rates have gone down from maybe 30% to 7% at the moment. In the past, if you would publish in Nature Genetics, that would make your career. It’s one of the most prestigious journals, and even though I’ve published in Nature Genetics multiple times now, it’s still really difficult to access funding. So, especially for the young people like Zach and Jackson in my team. They are so smart, they’re so dedicated. They don’t have crazy high salaries compared to how smart they are. They could probably make a lot of money in corporate, but they chose to work in science because they have this ambition to do something useful, but there’s a lot of job insecurity for them, even for those who are extremely successful.
Clare Blake (11:03):
What would funding allow them to do?
Professor Eske Derks (11:06):
Continue the next 10 years to use this data to find more effective treatments and better prediction tools, and to do all this work that we’ve outlined now in this paper and to really translate these genetic results to the clinic, so that we can help the people who are suffering.
Clare Blake (11:25):
How would it be different for a patient diagnosed now as to somebody when you get the results of these challenges?
Professor Eske Derks (11:32):
So when we’ve been able to do our work, and it will not be tomorrow, let’s say it will be five years from now or 10 years from now, but my hope is that someone will experience depression, they are aware that they have something going on. Then the GP and a psychologist or psychiatrist together, they’ll be able to look at these patients, to look at their DNA, to look at their genetic profile and to look at the symptoms that they experienced, to look at their history, the family history, to look at any stresses that they’ve had, life stresses, trauma, and that they can use all this information and say, “Oh, we can predict that this treatment, treatment A will work for you and treatment B and C probably won’t work for you as well.” And for another patient it will be treatment B that works best because they’re different. The treatment will be individualised and someone comes and seeks help, that we can help these patients better, more effectively, and also sooner. That they don’t have to go through this whole trial and error process.
Clare Blake (12:35):
Knowing more about their DNA, we might know more about who is likely to get depressed. So we might be able to intervene earlier.
Professor Eske Derks (12:44):
At this time, it will be difficult to do prediction at an individual level. It will never be in isolation probably. It will never be it… We just look at someone’s DNA and that we can then predict the risk. Disorders are partly heritable, but there’s also other factors, but it could be that, if we combine everything that we know about mental health disorders and look at the genetic risk, but also at other factors that are important, childhood trauma, life stresses, have they gone for a divorce recently – we can then do a prediction using all this information.
Clare Blake (13:17):
These are genes that affect people just like diabetes or cardiovascular disease. Can you imagine somebody saying to someone with cardiovascular disease, “Just toughen up.”
Professor Eske Derks (13:26):
Clare Blake (13:27):
You’re looking for a complete change in the stigma, aren’t you?
Professor Eske Derks (13:31):
Yes. Yeah. I think that’s really important to me personally. Yes. I mean cardiovascular disease, we know that there’s environmental factors as well like diet, like healthy lifestyle. Skin cancer for example, like sun exposure. There’s always risk that we can control to some extent, and then there’s a biological component, but for some reason we’ve decided as a society that we look differently at mental health diseases.
Clare Blake (13:58):
Do you think that’s changing?
Professor Eske Derks (14:00):
I do think it’s changing. When you look at the media and the way they talk about mental health disease, I think there’s a lot more attention for it, which is a good thing. “R U Ok Day?” for example, there’s the mental health week in October. So I do think there’s more awareness. I also think that, the way we talk about mental health diseases in the media is much more nuanced. There’s much more awareness of the factors that lead to mental health disease, but still, I see a lot of patients and a lot of people who are suffering, who feel they are a burden to other people when they suffer from depression or anxiety.
Clare Blake (14:39):
It’s another burden that they don’t need trying to recover. If you get your way and people understand that the treatments are better, then they’re more likely to go and try it.
Professor Eske Derks (14:48):
Yes, and that’s a problem with depression as well, that you have lower motivation that’s part of your symptoms. So it can be really difficult for people to take that first step, and I really hope to contribute to that change.
Clare Blake (15:00):
And if you’d like to donate to something so important like this to Professor Eske Derks and her team, go to qimrberghofer.edu.au Thanks Eske.
Professor Eske Derks (15:13):
Thank you Clare.