The Orchard OCD Conversations: The Neurochemical Basis of OCD
Hello and welcome. Um, we are just about to start our webinar at the Orchard OCD conversations. I um I’m going to wait a little bit just to make sure we have as many people as possible watching from the start. So, I’ll give it another minute, see if we get many people joining. And of course, people will join throughout this uh this podcast um this visual podcast. But it’d be quite good to get as many people as we can at the beginning. So, I’ll just give it another minute and then we’ll start uh with our next uh OCD conversations. So, just to say to everybody who’s joined, um we’re going to start in about a minute or so. I’ll give it about 30 seconds and then we’ll start this uh OCD conversations. Okay, I think um I think we should get going. Make sure all the cameras are in the right place. Okay. Hello and welcome to the OCD conversations, a series exploring new and innovative ways to treat obsessivecompulsive disorder. from psychedelics to psychotherapy, deep brain stimulation to ultrasound, ultrasound stimulation, as well as repurposed medications and even computer games. I’ll pick the brains of the groundbreaking people who are pushing the boundaries quite literally when it comes to OCD treatments. We’re really privileged to hear from some of the world’s leading specialists who are transforming the way we view and tackle a condition the World Health Organization classifies among the top 10 most debilitating illnesses globally and which affects about 70 million people worldwide. I’m Sean Fletcher. I’m a mental health campaigner. Um I’m someone who’s um had experience of OCD in my family. It’s affected my family and I have seen firsthand how debilitating and how destructive OCD can be. Now last month um in the OCD conversations I talked to Professor Amy Milton about neurotransmitters glutamate and GABA and the work she’s doing in her rack models with that. It’s well worth a listen. So if you haven’t already done so, please do. Uh today we continue that theme. So I’m joined by a neuroscientist and psychologist using advanced neuroiming methods, behavioral and clinical studies to understand and improve outcomes in people with lived experience of OCD. So I’m going to be joined by Dr. Marjon Ber and let’s see if we can get her on stage now. Maron, great to see you. Really good. I say this every week when we have someone, every month when we have someone on, I press the button and I’m never sure they’re going to appear and you have appeared straight away. So, it’s really good. Thank you very much for joining us. Thanks for having me. I’m excited to be here. Yeah. And we’re really excited to hear about the work you’re doing. I’ve mentioned to quite a few people in the OCD community that I’ll be speaking to you and and quite a few people, many of them have said, “Oh, that’s really exciting. That’s a world first. That’s sort of a gamecher.” So what we’re about to hear for the next 45 minutes hour um it’s is really exciting and I feel really privileged to be able to talk to you to to start with um we’re talking about those neurotransmitters glutamate and GABA. Can you tell us what they are? So neurotransmitters in general they are like they are chemical messengers. They are like text messages between uh the cells in the brain and glutamate and GABA specifically are the main inh excitatory and inhibitory neurotransmitter. So glutamate is excitatory, GABA is inhibitory. What that means is that glutamate um is like uh putting your foot on the gas pedal. It increases the activity of the neurons whereas GABA is like putting your foot on the brake. It reduces the activity. It calms down the neurons if you use a driving car driving analogy. Yeah. No, I mean that’s that really explains it because I on the OCD conversations we’ve got people like you who are who know all about this stuff and who will want to get the sort of meaty detail which we’ll get on to. But we also have people who are like me. We’re lay people and when you explain it like that it just it makes sense. So there’s the you got the you’re in a car, glutamate is the accelerator, GABA is the brake and that’s that’s happen what that’s happening like thousands of times a second in your brain with everything you’re doing. Yeah, exactly. Exactly. So so what have you found in terms of the imbalance between glutamate, GABA and OCD? Um so we have found an imbalance uh between the levels of glutamate and GABA in the brain in regions that are important for habit formation. Uh for example anterior singulate cortex is uh one of the important regions in the network that is relevant for habit formation. So we found an imbalance between glutamate and GABA. But we also found lower GABA and higher glutamate in this region. Um the next important thing that we found was that in uh supplementary motor area or SMA we found a correlation positive correlation between levels of glutamate and how um how much compulsion someone shows and how much habitual tendencies uh someone has. And it’s really interesting because this link between glutamate and habit habitual tendencies and compulsions we didn’t just find it in OCD in patients with OCD. We also found it in our healthy volunteers. So So if you are someone with lived experience of OCD and you are performing compulsions that that’s a higher amount of glutamate in there’s an imbalance with a higher amount of glutamate than GABA. Is that so we didn’t find a difference in the levels of glutamate in the SMA but we found a positive link between glutamate and habitual tendencies or compulsions. So it is true that the more habitual uh someone is or the more uh severe OCD symptoms they have the the more glutamate they have in the SMA. So what’s the what’s SMA mean? Sorry supplementary motor area. Okay. And and that’s a part of the brain is it? So it’s it’s up here. Okay. Fine. It helps me. It’s all it’s all happening up here. So if you’re if you’re experiencing compulsions and you’re struggling with that that it’s it’s sort of in this area that this is all it’s all happening top area of your brain. So it’s not Yeah. I mean it’s not the origin. I don’t think we can claim yet that this is the origin because there is a network um that is you know involved in habit formation. um but SMA and ACC so anterior singulate cortex and supplementary motor area they are playing an important role and these are part of the cortex so the the um they are more evolved in I mean animals don’t have a cortex and they uh they are it’s a lot more expanded in humans and so SMA is here and ACC is a bit lower it’s a bit towards the front I mean ACC is a big region I don’t want to go into details Yeah. Yeah. No. Well, that’s not what we’re here. You’re a science. We are we’re here to talk about your findings. And I suppose this is where the work gets really key. And this is where your findings are are kind of, you know, groundbreaking. I kind of feel like I say that every month we do this podcast. I say groundbreaking, but I am speaking to people like you who are doing groundbreaking things. And this is particularly um you know, it’s sort of you’re you’re at the boundaries of where we’re finding things. So, how do you measure glutamate and GABA in the brain? And because that’s the the key thing, isn’t it? Yeah. So um we use a specific uh technique called magnetic resonance spectroscopy. So we use a scanner which looks which is an MRI scanner. It looks like an MRI scanner and you can measure the neurochemical levels in an noninvasive way. Um I don’t know if you could show like some of the images that I have sent. We can this is sort of the first time I’ve used this technology on on this this platform. So I’m quite excited about this as well to to tell us what we’re seeing here. Um so I don’t know if you can see my mouse but if uh I mean I can explain. So in the blue uh square that you can see that’s anterior singulate cortex and um in gray you can see an MRI scan of the brain. So that we have a picture of the brain and on the right side we have uh the neurochemicals. That’s how we can see the signal. That’s how we visualize the signal. So the red line is the signal we are measuring. Uh actually the red line is the noise. The black line is the signal and you can see like how good our signal is because uh the the the sorry it’s not the noise. The this you can see how close they are. It shows that our signal to noise ratio is very high and accurate. Okay. So uh if you go to the next slide and I can show you uh how glutamate and GABA signal looks like. C can I just ask you a few questions on that? So the blue box is on in that the left hand photo. So that’s an MRI scan of someone side on and the blue box is the particular area that you’re looking at. Yeah, exactly. And when we do um MRS, magnetic resonance spectroscopy, we need to first take a picture of of the brain and then we will place boxes in the regions that we want to measure the neurochemicals. And because um the reason we do that is because every brain is different the same way that every person looks different from from another. So we take uh to be accurate we take a picture of the brain we place a box. This is the box for anterior singulate cortex and then we will measure durochemicals in that area and that’s the area that’s being scanned. Sorry just to go on the table. So the the red line and the when you said the black line is the the measuring of the GABA or glutamate imbalance is that the top the top line you’re saying no sorry the where we have the red line uh there is a black line underneath so that’s how we are modeling actually how we are modeling the signal and um yeah and so and so the scan which we’ll get on to MRI MRS you mentioned we’ll get on to that in just a moment that that’s what’s That’s the MRS is basically measuring that and you’re measuring the imbalance between glutamate and GABA which is what we’re establishing is key. Exactly. Yes. So on the right side we Sorry. Yeah. You want me to go on to the next slide, don’t you? But carry on. Yeah. Yeah. So on the right side we have MRS. On the left side we have MRI scan. I see. I see. Okay. So sorry the Oh, I see. On the left side is MRI. MRS is the right hand side. Yeah. Okay. And we for people listening who are thinking what is MRS? We will explain that in just a moment. This is the next table that you wanted me to show. Yeah. So um so the black line is showing a signal for all the neurochemicals we have in the brain. We have a lot of different types like uh creatine, na uh we have many different types of neurochemicals. Each of them they have a role in the brain. Um and the reason um it has been difficult to measure glutamate and GABA um in the past is because um glutamate and GABA. So on the left side we have GABA and that’s the red line and on the right side we have glutamate in in the red line and the peaks that you can see the three peaks that you can see they are the peaks for GABA and glutamate and the black line that you see above that that is all the other neurochemicals accumulated. And the problem is when you have neurochemicals that are bigger than glutamate and GABA they would cover glutamate and GABA. And if you don’t have scanners that are powerful enough, they cannot be detected accurately. So people may have tried this in the past, but they didn’t do it strong enough so that that the the other neurotransmitters just clouded everything. Yeah. So people have tried to model them, tried to estimate, but because these neurochemicals were covering them and the scanners were not not were not powerful enough to measure them accurately um we didn’t have very accurate measures before our study. And I also have to say um in the past or like in in the scanners that were less powerful than seven Tesla, our scanner was seven Tesla. I can tell you a bit about it later. Um in the past people used to combine uh to estimate these generic chemical levels together. So they would say glutamate and glutamine uh are at this level. They couldn’t separate them. Glutamate, glutamine and GABA are at this level. They couldn’t separate them. But it’s really crucial to be able to separate them because they have different roles. And um can I just ask what’s what’s on the bottom there? My eyesight’s not very good there. I probably need my glasses. What what’s the what from left to right? What is that? What is that? Time over time. No, that’s the chemical shift. That’s parts per million. Would you like me to explain how we measure them? I I think it would be helpful, but I mean there’ll be people who know all about this, but there’ll be others who will be thinking like a chart. I think I get it, but I’m not quite sure what that means. What What’s the bottom? So um I’m going to explain how we measure this how M um MRS works how the scanner measures the signal so you can understand what is this Should I show I show the next picture would that be helpful sure um can you show the next one but then go back to this one yeah we’ll come back to that so so this is this is because the top left look that looks familiar that looks like an MRI scan that’s exactly an MRI scan it’s not the one that we use we use the seammen’s brand but this is the picture I found online um so on the left side we have an MRI scanner which you can use also to measure the neurochemicals. On the right side this is me and and a colleague and you can see that we have taken a picture of the brain and we were trying to place the box in the region that we wanted to measure the neurochemicals in. So when people are inside the scanner because of the magnetic field of the scanner uh the hydrogen nuclei inside each uh molecule in in the ACC um they will um they will become um aligned. So imagine them like needles and each of them will have uh um each of them will have I don’t know how to explain it. They will be for example imagine these are needles and they will be all aligned because of the magnetic field. Yeah. And then once that happens we will on the computer we will send a radio frequency pulse and that would make them unaligned. I see. And then we will wait for them because of the magnetic field they would need to become aligned again and then we would need we would wait for this to happen. Um and that is the uh shift the chemical shift that we are measuring. I see. So you’re so in a way you you’re trying to mess everything up and then waiting for it all to come back. Exactly. That’s the bit you’re measuring. When you say the needles and I’m sorry I’m sounding like a complete lay person here. What is that? What is that? The the that they are the neurotransmitters or sorry no that was that might not have been a good example. So that’s the hydrogen hydrogen nuclei. Okay fine. And the protons protons. Yeah the protons uh become aligned or unaligned. I see. You’re unaligning them and when they when they then naturally go back form back in the same direction that’s what you’re measuring. Exactly. Yeah. And we have them in every neuron. I see. I see. So So tell and that and that gives you the level of imbalance between glutamate and GABA which is where we Exactly. Yes. If you go back to the previous slide. Yeah. That’s the one. So the numbers that you see on the x-axis that is the chemical shift that we are measuring waiting for them to become aligned. Um yeah and what and so what I noticed from that so you’re saying on the left is GABA as we can see the red line is GABA on the right the red line is glutamate. I mean glutamate occasionally seems to follow what all the other transmitters are doing but doesn’t much gaba doesn’t at all. So if you are measuring if you’re getting them all mixed up, you are not getting a clear picture at all. I can quite I can see that you need to separate the different neurotransmitters. Yes, exactly. And sorry, I have to correct myself. So it’s not the red lines, but the peaks in the red line. You see the three little peaks. Yes, I see that. Yeah. But but when the other neurotransmitters are peaking, GABA isn’t always peaking. It’s not always following the the No, they have different peaks. Yeah. Yeah. And the same with glutamate. So actually by not being able to separate them, it’s sort of worthless. Yeah. But what you were doing was separating the neurotransmitters which is that’s the breakthrough. That’s the that’s the new thing that you were doing. So So can can you tell you may have already explained it. What’s the difference between MRI and MRS? You’ve mentioned MRS and MRS is the key thing that you’re doing, isn’t it? Yes, it is. Sorry. Can I just can I just mention something before answering this question? I mean I know that there have been studies that have done this so I cannot say they were worthless but it’s just difficult to estimate them. They are more inaccurate that the findings have been mixed. Some people had similar results to us. Some people had opposites. Some people didn’t find anything. Um it’s just more inaccurate. Yeah. Yeah. So when they’re accurate, isn’t that just luck or it what? It’s hard to Exactly. It’s hard to claim because the signal to noise ratio is lower and we know that it’s hard to measure these neurochemicals more accurately. Yeah. Yeah. I mean, it’s absolutely fascinating. I It’s kind of it’s obviously this is you’re leading in your field and it’s very complicated and I’m sure you’re simplifying with someone like me, but I kind of feel like my brain’s going to blow up just just hearing all this, but I I kind of get it. I kind of get what you’re saying. So, can you explain what the difference is because many people are watching this will know what an MRI scan is. They may have had one on an injury or something like that. What what’s the difference between that and an MRS? And then you mentioned the power. I can’t remember the um the unit you said a Tesla or something like that. Can you explain what that is? Yes. Um so, MRI is I don’t know if you want to go back to the first picture you showed. Um um so this one. Uh no, the other one. This one. Yeah. Yeah. So on the left side we have an MRI. So MRI basically is a picture of the brain. Uh it will show us the structure. It will show us if there are any problems with the structure. If there is loss of gray matter for example um um an MRS so you can imagine you can imagine an MRI scan like a snapshot picture of your brain. Yeah. And MRS maybe you can think of it like a blood test. It will a blood test that is noninvasive. You know it can tell you which neurochemicals and how much of them are available. But what’s what’s actually happening? Are they are they completely different processes or when we go back to this slide does it look does an MRI scan look exactly like that? It’s exactly like that. And actually we have used uh the same scanner to take an MRI picture. So you can see on the right side we have used exactly the same scanner. Uh so you can see four different um don’t know why we have four of them there but um the picture that you you can see on the screen is exactly an MRI picture and we needed to have a snapshot of the brain to be able to find where anterior singlet is for this specific person or where supplementary motor area is. And in the same scanner after we’ve done the MRI, which takes about maybe 10 minutes, we will use um the same software but a different option to run the MRS and it takes about 20 minutes. It will uh we are still having the MRI scan in front of us and then we will also see the neurochemicals um the graph that I showed you, we see a similar graph in front of us as well. Yeah. And and going back to this one, the so the MRI establishes where you’re going to focus your MRS. That’s the blue box there. And then you use the MRS on that area of the blue blocks, which then gives you the data that we just saw in one of the other. Exactly. Exactly. Yeah. It’s all It’s all making sense. Yeah, I get that. So something like this feels like um given that you’re saying this is kind of groundbreaking, it’s the first time it was done. Um, it’s new. It It sounds like that takes a long time. It needs a lot of funding. Can you talk us through that side of things? Yeah. Um, well, first of all, I would like to thank our funders, Welcome Trust, who funded our study. Uh, it was a grant um uh for uh given to Professor Trevor Robbins for the MRS’s study. And I also would like to thank um the funders who funded my PhD, mental health research UK. uh without their supports this study would not have been possible. Um so this study took quite a long time actually. Uh it took about um so the data collection the ethics data collection everything took about four years but it was because we also had the pandemic so there was a pause in between we could not do any testing. And another reason that it took a bit longer was because we wanted to make sure that the data quality is is as best as it can be. So we spent actually one whole year just trying to optimize the signal. We did a lot of pilot scans and the software that I mentioned we run the radio frequency post like they all use a sequence. I don’t want to go into a lot of technical details but we made sure that the signal to noise ratio so the amount of signal that we get from the neurochemicals is much higher than the noise uh because when you have a strong magnet you don’t just measure signal accurately you also magnify the noise so we had to be very careful to u eliminate the noise so we we spent one year on that um so yeah I guess the data collection took us around 3 years Um, wow. I mean that that’s a that’s a huge project. I’m just thinking about my world. We you do a live program, you go in in the morning and it’s done and then you’re out by the afternoon. So the sort of the really long project. I just wanted to add um about the welcome trust because they they’ve obviously played a key role in that. I think they they do really play a key role in um for the the OCD community. There’ll be people watching who pro you know probably won’t know too much about the welcome trust but they obviously funded this absolutely groundbreaking research which is is very important. They’re also just just addition to that um funding um a conference that Orchard the the Orchard charity are going to be um hosting next year. So this is the end of spring next year where we’re bringing together all the sort of great minds around the world um in terms of OCD. You’ll I’m sure be getting an invite I’m sure um Maron but people from around the world who are doing the sort of work you’re doing and other work in the O for the OCD community. We’re going to be bringing them together. I suppose just thinking about this, I’m into sport. I’m I’m not so much of a scientist, but it’s a bit like you think about all the best football teams around the world. We’re bringing the best players together, a bit like the World Cup. We’re bringing them together so that they will be talking and sharing ideas. Also, people who with lived experience will be at that conference too. So, um there’ll be a chance for you know everybody to be other people to be invited. It these sorts of things are important. I mean maybe you could explain mod bringing bringing academics together who are doing similar sort of work how important is that to share stuff because I can imagine you could all be quite siloed in your own areas and not sharing is is that sort of thing really important? Absolutely. I think it is really really crucial. Um and you know going to conferences like this creates an opportunity for us to talk to each other find out more about our research because when you have more casual chats with people I mean obviously listening to each other’s talk having the opportunity to ask questions but then during the coffee breaks you know having the opportunity to have a casual um talk you know these are the moments that you might come up with groundbreaking ideas for new types of research and I think for this conference it’s not just research researchers, but you know, people with lived experience. And this is really um we really need people with lived experience to give us feedback and ask us questions because otherwise we will come up with ideas that might not even make any sense or might not even be relevant. So we really need to work with researchers but also people with lived experience. And I think yeah, I think this opportunity is really really uh amazing. Yeah, I I just so just to add to that to round that off, thank you very much for the welcome trust because those are the sorts of things that really make difference and that’s actually really interesting to hear that it’s not necessarily the talks that do it that’s really important but it’s those breakout sessions when people are just chatting casually when some of these great ideas are founded. So um amazing work that the welcome trust are doing for the OCD community. But let’s get it back onto your work. Um you’ve already I think you’ve touched on this. No one no one else was doing this kind of work in the world when you and you mentioned Trevor Robbins were doing this. This is this is a this is a first. Um it is the first uh seven Tesla study in OCD. There have been many studies before. Maybe now is a good time to talk about what seven Tesla means. Yes. So seven Tesla is the strength of the magnets. I did explain to you like the magnets creating a magnetic field and the hydrogen atoms becoming aligned and unaligned and that’s the key for measuring uh the neurochemicals accurately. So the scanners that um we use in hospitals their strength is three Tesla just to give you an idea and the scanner that we use is um almost double as much so 7 Tesla and uh the studies be uh previous to our study they had used magnets that were 1.5 Tesla or three Tesla so the findings have been quite mixed and we were the first study using a 7 Tesla uh scanner and we were the first study to show both an imbalance between glutamate and GABA and higher levels of glutamate, lower levels of GABA and the link between um these neurochemicals and habitual tendencies, compulsivity and um also showing the link between compulsivity not only in OCD but also as a transdiagnostic um problem and and that we’ve had some questions coming in. Please do send your questions in. I’m sure many people watching thinking I you know I’ve got a burning question and I haven’t answered it. So please send them in. Margarita has messaged in on I think that sort of ties in with that. So is the glutamate increase particularly relevant for specific OCD subtypes rather than others or not really. Do we have any evidence about this? I think what Margaret is saying you may be able to correct me that you know if you have a certain type of OCD maybe it’s contamination OCD is that different does that display differently with glutamate and GABA imbalances to say puro or something like that? Yeah. Uh we haven’t found any evidence of that. So people that we have studied uh we found this um increased glutamate reduced GABA and the imbalance um amongst all people with OCD. So we haven’t found any evidence that uh the glutamate increase is specific to uh subtypes or the relationship between uh glutamate and and habit formation for example in SMA is specific to a certain subtype. Yeah, it seems to be a more general. Okay. How how did you know in the first place to search for glutamate and GABA levels in people displaying compulsive behavior? Would would you have a tip off you know do other people doing research and they sort of establish this or did you you know what was the sort of the spark that made you look for that? So as I mentioned in the beginning glutamate is the main excitatory neurotransmitter in the brain. It means that it sends messages to other neurons to increase their activity. So there have been studies um showing increased activation in OCD in regions that are important for OCD symptoms. So that was one uh you know one type of of hints that we should be studying glutamate and you know if you have increased activation it mean um we could um you know we could suspect that there is increased glutamate but reduce GABA because if you have increased GABA and increased glutamate GABA would probably control glutamate and not allow it to increase the activity. So um that’s why you hypothesize that we would find increased glutamate reduced GABA in regions that are important for OCD symptoms. But there have been also other types of studies like animal studies um genetic studies um about the glutamatergic abnormality in our city. So was there a moment where um you you weren’t sure and you got the results? I’m just sort of have visions of the the day that you discovered that ah yeah there is an imbalance or was it a slow process? Was there sort of a just a sort of a eureka moment? Um so we started seeing a trend even with a smaller sample size and when we increased the sample the the trends be became very significant. But I do remember the moment that I I I was analyzing the data and exactly like I was looking outside and I was thinking did I make a mistake? Is that real? And I needed to talk to my PhD supervisor Trevor Robbins and I had to repeat the analysis because I thought is this just a you know a fluke? Is that a mistake? Mhm. And Trevor reassured me, “No, this this is correct.” And yeah, I mean, what your the way you’re explaining it, you’re you’re smiling because obviously that’s a really key moment and we should all be smiling because it’s a key moment for anyone who has any sort of experience of OCD. Do did what do you do as a scientist? Do you sort of go around, you know, drinking champagne or do you do you sort of that then are there lots of other tests you have to do to verify that? Um I did repeat a test and um I think we might have gone on gone out with my husband for dinner or drink but cannot remember. I was also exhausted both because I had I had worked hard and analyzed the data but also because of how much excitement I had. But we did celebrate. It’s three or four years work. I mean you deserve to celebrate. So So tell me what parts of the brain I think you might have actually alluded to this. what parts of the brain um are the imbalances most prevalent when someone with lived experience of OCD when OCD is really you know taking hold. Yeah. Um so as I mentioned um the OCD symptoms like we think that the OCD symptoms might arise from an imbalance between the habit system and the goal directed system and there is a whole network uh running these systems but um we um we studied anterior singulate cortex and supplementary motor area because we thought these are two very key regions in the network. These are at the top there and a bit. Yeah. Okay. Then these are the parts of the brain that animals don’t have or have very small versions of and we as human beings that sort of separates us from and that’s where this is this is happening. Um what does it give us of more of an understanding of OCD? You know what does it mean for our understanding of OCD? Yeah. Um, I guess you know I’ve I’ve spoken to um to some people with OCD and they have told me that they are relieved to hear that OCD is not their fault having too many thoughts or not being able to control their behaviors. OCD seems to be a neurochemical problem and yeah that’s and that’s so that’s sort of saying it’s not it’s not you it’s the it’s the thing it’s the neurotransmitters. Yeah. Because you know OCD can be really debilitating impacting not just the person the whole family and a lot of times people feel guilty because they can see the negative impact it has but it’s hard for them to make a change on their own and you know hearing that there is a chemical imbalance in the brain it it provides some relief for for many people. Yeah. And I guess um the second thing is it highlights again the importance of the habit system in OCD. Um and you know it really um there have been many studies about the habitual and goal directed system but seeing a link between you know having kind of a neural um um mediator for for the habit habitual tendency. Um that is the first time you’re showing it and I mean in terms of the neurochemicals that what does it mean for high for for high habitual tendencies? What what does this these findings mean? Um so habitual tend should I explain how we’ve done it in the study or should I define what habitual can you do both? Can you do both? What are high habitual tendencies? Yeah. So maybe I define what they are and then I’ll explain how we did it in the study. Um so habitual tendency means we do things in a in an automatic way and this is really crucial you know we cannot imagine um learning everything for the first time. Imagine um you’re going to work for the first time. You have to remember where you’re going. You need to look at all the streets and you need to be really vigilant and present. Um can you imagine doing that every time you go to work even after one year two years. Um so when you when you do something many times repeatedly it it becomes a habit like maybe like after 3 months you can be on your phone you can be doing other stuff you can be thinking about other stuff and you still manage to get to work. Um sometimes um there is something called a sleep of action. you might be um you might want to stop the habit. For example, you have a dentist appointment um and you the route to your dentist is halfway through the the route that you take to your work and you want to go to the dentist and then you end up finding yourself in in front of your office building and that is a sleep of action because it is so habitual that even one time that you don’t want to go to work you want to go to the dentist you end up taking the same route. Yeah. Um so habies are extremely helpful but they become a problem when uh there is perveration when they are rigid. Um and that is what happens in OCD. Um so habitual tendency means that you know something else is better for you and that is the goal directed behavior. If you see something is better you change your behavior. But habitual tendency means um you still um do what you’re used to what is automatic and there is a def there is a deficit in the habit system um if you still stick to what is automatic and habitual instead of what is better for you what is goal directed I have to say I did say there is a deficit in the habit system but it might be that there is a deficit in the goal directed system and because the goal directed system is not working properly, the habit system takes over. Or it could be one level higher, the arbitration system, the system that decides whether for this action we need to take um we need to use the habit system versus the goal directed system. So if the arbit arbitration system uh doesn’t work properly and it keeps favoring the habit system, then we might see the same thing. Now coming back to our study, the way we tried to study the habitual tendency was using a computer task um that um it’s called contingency degradation task actually it’s a very elaborative task but for the purpose of of our neuro imaging study we really simplified it. Um basically people will see um a picture of a vase and they have to press on the space bar to put flowers in the vase and then there are different blocks. So uh some you will sometimes you will receive a reward. It would be um you will see coins like it is monetary reward. Um so when you uh there are some blocks that you get the reward by pressing the space bar. So if you are uh goal directed and if you want the reward you need to press the space bar often. Um and when you manage to put the flower in the vase you get the money you get you get the reward. Um and over time you know after many trials uh this tends to become habitual because towards the end there is a block where you will get the money regardless of what you do regardless of your action whether or not you press the space bar or not. And we know that people with OCD will learn they it’s not a problem of learning because they will learn um the consequence of of this action but still they’re not able to stop pressing they are they they keep pressing on on on the space bar. So they’re going to get the coins anyway but they but they keep pressing on the space bar. Yeah. So in our study we didn’t find um an increased pressing in in um in the OCD group but there as I mentioned because they didn’t use a very elaborative task. There have been other studies in drug addiction and in OCD and then they use that very elaborative task which is a lot more difficult. They have shown significant differences between people with OCD and healthy volunteers. In our uh study we wanted to so we have measured the habitual tendency. The habitual tendency is pressing the space bar uh when you don’t even get any rewards for it. It’s not goal directed. It’s just because you’ve used to pressing it in the previous trials. So we have found a correlation between the neurochemicals in the brain in both anterior singulate cortex and supplementary motor area and this habitual tendency. I see I there’s a question from Nickuro. Um uh hi Margin um you also published a paper showing a link between excessive checking and the glutamate gab balance that’s what you’re talking about now is it or is that no this is this is the habitual tendency but that is something else yeah thanks Nick for the question yeah can you explain a bit more about that that work you do yes so um we wanted to have a measure of of checking an exper in an experimental setting because having questionnaires um it’s it’s very subjective. So first before doing the study I had to design and develop a checking task uh to be able to measure checking um compulsive checking in in a laboratory setting. And we did find that um people with OCD they checked a lot more in the task. Um and that was when they were not they were less confident when they were more anxious. Um and we also found that this type of checking was correlated with this imbal this glutamate and GABA imbalance in anterior singulate cortex and it is probably because because they were anxious and they they had less confident. They felt the need to check more and um they were feeling conflict. you know they were checking more but they still were not confident and they were they were feeling the conflict and there is something called error monitoring and that is actually one of the functions of anterior singlate you know this constant feeling that something is wrong and um so we think that’s why anterior singlaid um was engaged and we know that anterior singleate activity is related to error monitoring in OCD and um yeah we think that’s why we found this relationship. So So going back to your your MRS um study. I I’m just I’m just thinking I’m putting this together and thinking then doctors in the future could just measure brain chemicals to measure OCD. Is that is that a thing or am I jumping a bit too far ahead? I wish I wish we could. Um but it’s really important to say that uh the levels of glutamate and GABA can change in the same person for various reasons depending on time of the day um time of the month for women and also if they’ve had coffee, if they’ve had if they had smoked but also there is individual variability. So for our study to make sure that we get rid of these issues we had to use many many people and average the signal. When we average the signal we average out these type types of noises if that makes sense. Um, so I have received so many emails from people with OCD from their families asking whether it’s possible to take an MRS scan of their brains to confirm the OCD, but also for treatment purposes. But unfortunately, that’s not how we can use MRS. What about if if I know this would be too expensive to do, but if you say measured my brain every day for a month, then you get a pattern of, you know, if I’m smoking, if I’m not sleeping well, could you do it then? Obviously that’s not probably because it would cost too much money but that that’s how you would be able to do it. Yeah. Exactly. Yeah. Basically building up a pattern of what when my gluten mate and GABA is high and low or the balance is right or imbalance. Yeah. I think then from there you could work Yeah. I think maybe if we had thousands and thousands of or maybe more, maybe millions, I don’t know, like of of brain scans from people and we had literally every other information from them. Um maybe then we could predict, okay, when we take this scan, we have the information of this person and we have modeled based on thousands or millions of brain scans that probably this person has OCD. But at the moment we we don’t have that and it’s very unlikely that we can do that because it’s hard to control for every variable. So, so, so if we had a lot of brain scans, I mean, I’m just thinking about AI. Can’t AI replicate kind of just replicate what brain scans, you know, as in it could look at 20 and then say, well, actually 20 means that a thousand would look like this. And then you from that you could go on and then start to build a pattern of what people’s brains are. Is that am I just jumping um to conclusions that I shouldn’t be? Yeah, I’m just I’m trying to remember the phrase that we use in in machine learning and AI. When you have a small sample size, I cannot remember. It will be biased towards that sample. It will have a perfect fit to your sample, but it doesn’t mean that it’s accurate. Yeah. Yeah. Yeah. I see. Yeah. You’re all you’re always tied to that original sample and the size. If you only got 20, then ultimately you’ve only got 20. Yeah, I get that. Um, so what are you doing in terms of the next stage of the research? are you taking this on or are you doing something else? Um so when I you know published these studies when we published these studies and I was thinking what would be the best next thing and you know I was thinking about impact and I think the best impact with the results that we got would have been building treatment and um I know you know there are great people working on treatments um probably people have heard from um professor Amy Milton in last month. If you haven’t watched her talk, I think it’s amazing. You should. Um, and we have Nick Siro, his his biotech company working on a new medication. So, I thought what would be the best next thing for me and I still want to create impact. So um I’m still thinking about treatments because medication we know it takes some time and we know that maybe medication might not be for everyone but also we know that the best treatment outcome is according to nice guideline when you combine both medication and psychological therapy. So my current research is about how we can use AI um to make treatments more effective but it’s not just yeah so what as in literally just asking AI how you can make can you go into more detail not I’ve been I’ve been very vague um probably on purpose because you don’t want to give anything away is that is that am I delving too far into this or is it No it’s just it’s just because I’m also quite early on so we still need to define and the details of it. Um, so I am doing another doctorate in clinical psychology. So I’m training to become a clinical psychologist and there are competencies that we need to learn. We will be assessed based on these competencies. So with um so the research I I’m doing now with my current supervisor um at King’s College London um we are trying to see how we can train an AI agent for example the same competencies that I am learning um and then we are thinking about the things that people can do while they’re wait they’re waiting to receive treatment. I see. So, so the the you’re learning um therapeutic um you know as in psychology you’re you’re learning how to give someone do CBT with someone. Um there’s a there’s a huge waiting list. There’s lots of people will know um I mean some people are waiting for over a year before they get any treatment when they present with OCD. And you’re saying that an an AI or an app or something could help bridge that gap. And you know obviously the better that it gets the the I mean the problem is it might put you out of a job. That’s the the problem John. But um but that’s the plan that it would be it would fill that gap. Yeah. I have to say that what I’m working on is not specific for OCD. It’s for all kinds of presentations. Um and um sorry I I forgot what else what else you um you asked me but ju just that it would fill the gap for waiting list. I mean all mental health conditions in the UK there is a long waiting list and I’m sure that that’s the same in lots of countries. Yeah. Yeah. Yeah. And we are just um because in the context of of the doctorate I’m doing now I wanted to build something that is very comprehensive but I received the feedback that it’s too ambitious for the context of the doctorate. So I’m focusing on a few things that we think can be effective and people can use in the meantime. Um, can I take you back to what you were saying about the work you’ve done with the the scanning of and the MRS scan to work out the the imbalance between glutamate and GABA? So, you’re saying that people Oh, were you going to Can I just Can I just make a comment? I remember, but I wanted to say something and I forgot. You made a comment about um me, you know, um becoming jobless because of this AI thing. I don’t think so. I think we will always need human therapists that are specialized for various reasons. Some people need to talk to a real human and there are certain things that AI just cannot do because AI has not really lived and felt the way we do. Um, so when we’re thinking about jobs in the future that are safe, probably a therapist is is a good one to to go into because lots of other jobs AI is um getting threatening. I think that would be probably the latest one and like if you are more specialized it will be you know you cannot replace those and the jobs that we already people are using activity for to write codes and those type of jobs. I think they would be the first but I think we will be we will be saving. Fingers crossed because I know well I know with presenters we’re gone when AI takes over they don’t need me so I’m hoping I’ve retired by that but you’re going to be fine. So um when we um you didn’t mention the work that Amy Milton’s doing and we we talked to Amy Milton um last month. So in a way we probably could have got the podcast the other way around. Your work is discovering that glutamate the glutamate and GABA imbalance in people who present with OCD and that’s about finding out that imbalance. Her work is building on that to see what what we how we can control um the glutamate gabber and you mentioned Nick Zero. He’s trying to raise funds to to find a a a drug that can redress that balance. So, correct me if I’m wrong here. Someone who’s presenting with OCD, say in the future, we will know that they have a glutamate and GABA imbalance because of what you’ve discovered and then we will have some medication that will be able to say we’re going to reset that balance so that it’s it’s it’s imbalance and so the OCD, the compulsions aren’t as strong. That that’s effectively and you’re part of that building block to get to that place. I think so. Yeah. In the in the earlier earlier building blocks. Yeah. Yeah. Do I mean that that’s sort of quite key and we’ll see in the years to come how crucial what you’ve done has has been. I mean it feels very key at the moment but maybe in the future we will look back on the work you and Trevor Robbins did in your lab and say that that was absolutely fundamental for a very important treatment for for OCD. Does that ever sink in that actually you’ve played a really important role and that’s it’s going to look even bigger as time goes on and more treatments come out because of the work you’ve done? Um I mean I have to say because I think we were a big team. Um, so I and like everyone I work with is so talented and extremely intelligent and so I I did believe that working with a great team, you know, also hopefully leads to great research and that was when I was doing research um and I would see people with OCD and their families um being really helpless and that was that was the only thing I could hope for that this would be the outcome of it. I’m not sure if it has sunk in yet, though. Is I kind of ask a lot of people like you. Yeah. Do you feel like you’re doing really important work? And you’re always so modest. If you worked in the television world in media, you’d be saying, “Yeah, it’s me. I’m great. We’re all We’re all big heads and big egos, but actually you in the academic world always play it down.” But actually, you’re doing really important work and it does it does make a really big difference. Did did you find meeting people with lived experiences with OCD that sort of drove you on? Um and if not, what is the driving factor? What has brought you to this to do this work? Um so yeah, I have definitely seen many people with OCD, their families. I received so many emails still to this day uh from families uh feeling really helpless. they don’t know what else they can do to help their child from people with OCD themselves. Um so it has definitely given me the motivation to keep going and to create more impact. Uh but I think what it’s what started all of this was having the firsthand experience of of different types of mental health problems in my own family. M so as a child I could see the impact the negative impact that uh the mental health problem can have on on the whole family system. Um so I was always curious about how do these negative outcomes happen? Uh why do some people develop mental health problems? What’s happening uh in your brain and how can that change? Um can we change something about the brain to change that? Can we change something about the behavior to change the brain? So I was always curious about that. So that led me to study psychology and neuroscience, PhD in cognitive neuroscience and now a clinical psychology. But the reason I’m studying OCD spec I started studying OCD specifically was because uh you know the moment I found out uh what the role of the frontal regions of the brain is so like all these areas and for example the SMA supplementary motor area that they are the control seat of the of the brain. So I was curious to study these regions and I decided to study um obsessivecompulsive disorder because we knew that these regions um have deficit in OCD. That was the start of it but I have become very much I don’t know it’s also an emotional um problem now because I’ve been heartbroken so often that I really feel I need to do something. it gives meaning to the work that I’m doing if I’m you know finding impactful um I don’t know if if my research leads to impact uh on the treatment for a city um yeah and I mean it it I I guess in some ways academia and academic work is is far in some ways far removed because the work that you do might get the the treatment in 10 years time that people who are with lived experience of OCD will will experience so it’s quite a there’s a long gap it took you three and four years to do what you But it’s absolutely crucial in in laying the foundations for perhaps something that will change people’s lives in the future. And um there’ll be people listening to this who will, you know, who will be desparing. And I know it, you know, it can be really debilitating. It can ruin families. It can be so hard. So it’s it’s really important that you do the the work you do. um uh in 10 years time, maybe 50 years time, can you sort of tell us where you would like to see uh OCD treatment? Where perhaps building on the work that you’ve done, where we’ll be in 10 years time, where will we be in 50 years time? I mean, I don’t think I’ll be here in 50 years time, but what what do you think the state of OC treatment will be? Um well, I’m I’m really bad at planning and and these type of things, but I tend to think about the ideal scenario and what my dream would be. This this is the dream. So you can you can say whatever you like and then in 10 years time we’ll get you back on and we’ll say you said this. No, we won’t. Don’t worry. And I hope it happens less than 10 years. I hope it happens maybe in five years. Um so I’m really hoping um that everyone will get the individual like an individualized treatment according to their need whatever their need would be whether it’s medication whether it’s neurom modulation you know when like about TMS for example which is non-invasive treatment whether it’s psychological treatment or new types of treatments that we cannot even imagine right now um and for treatment to be accessible to everyone. Um and for for people to find out they have OCD as soon as they start showing symptoms because I know so many people suffer for many years. I think the average uh time for diagnosis is about 12 years and the average time until people start receiving their first treatment is 17 years. So if you can imagine you know an OCD starts you know for many people during childhood it really impacts um someone’s future if they cannot study if they cannot go to university if they cannot find um you know someone to get married to like it impacts the whole family and waiting so long. So I think the dream would be getting the help they need as fast as possible and individualized to them. Yeah. And and that’s what we’re doing. That ties in really well your message there with what we’re doing or aiming to do on or with Orchard. Give clinicians an armory of medications and treatments and other treatments. Doesn’t have to be medication. Um so that at the moment and and has as has been the case for so many years, the go-to is SSRIs and CBT coupled with it, which works for some people. Well, it works for many people, but it doesn’t work for everyone. And that’s what we’re trying to do with Orchard to so someone presents and and you will be able to have an individualized treatment that oh that works for you, but this one works for you and that’s other one works for this person. In the same way that cancer treatment has become a lot more individualized and you know a lot more technical than it was say 30 years ago and it doesn’t feel like that that has happened in OCD and you are playing a key key role in that maron. So, thank you very much and we we’ve come to the end of our hour. So, thank you very much for speaking to us and giving us an amazing insight into the work you’ve done and this this fantastic work that as I say it looks like it’s going to be the building block for something really special for people who have lived experience of OCD. Maron, thank you very much. Thank you very much for everybody for watching and and sending your questions. Maron, thank you. And we’ll see everybody again. I say in a month’s time. A month’s time. Well, next month, but next month is tomorrow, isn’t it? So in August we will have another OCD conversations. We’ll be speaking to another person just as interesting as Marjon. Uh so we’ll see you then. And thanks once again Mar. Thank you. Bye.
We’ve teamed up again with our friends at Orchard OCD for a conversation with Dr Marjan Biria and Sean Fletcher about The Neurochemical Basis of OCD.
Keep up with Orchard’s work at https://www.orchardocd.org
ABOUT DR MARJAN BIRIA
A scientist in cognitive neuroscience and psychology, Dr Marjan Biria applies advanced neuroimaging, behavioural, and clinical research methods to understand and improve mental health, with a particular focus on obsessive-compulsive disorder (OCD). Her multidisciplinary training spans neuroscience, cognitive psychology, computer science, and clinical psychology, with a BSc in Clinical Psychology and an MSc in Neuroscience.
She is completing a doctorate in Clinical Psychology at King’s College London. She remains driven to translating scientific discovery into innovative clinical interventions, aiming to bridge research and practice to improve outcomes in OCD and broader mental health.
ABOUT SEAN FLETCHER
Sean Fletcher has been broadcasting on the BBC, ITV and Sky for more than 15 years. His journalism includes the Panorama investigation, Kids in Crisis, which asked whether the Child and Adolescent Mental Health Services are fit for purpose. He also presents on Countryfile, Inside Out and Good Morning Britain.
ABOUT MADE OF MILLIONS
The Made of Millions foundation is a global advocacy nonprofit on a mission to change how the world perceives mental health.
Each year, millions of people around the world are diagnosed with a mental health condition. People of every age, country, gender and ethnicity. Millions more go undiagnosed, and are forced to battle their symptoms without the care and support they deserve.
As sufferers, we know their pain. We know the isolation they experience at the hands of cultural stigma. We know the anger they feel at media outlets who misrepresent their conditions. And we know the frustration they have with healthcare systems that make it impossible to find help. The Made of Millions Foundation wants to heal this pain.
Using the power of art, media and digital technology, we’re on a mission to transform how the world perceives mental health. And in doing so, create a safer and more inclusive future for sufferers everywhere.
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