1 00:00:01,020 --> 00:00:08,250 Welcome to the Oxford Psychiatry Podcast series. I'm Charlotte Allen, and today I'm here with Professor Catherine Hamah, 2 00:00:08,250 --> 00:00:13,860 who's a professor of cognitive neuroscience and research fellow at Corpus Christi College. 3 00:00:13,860 --> 00:00:20,880 She's also director of the Psychopharmacology and Emotional Research Lab here at the Department of Psychiatry. 4 00:00:20,880 --> 00:00:25,170 And her research focuses on the psychological mechanisms of antidepressant 5 00:00:25,170 --> 00:00:30,780 drug action by exploring drug effects on human models of emotional processing. 6 00:00:30,780 --> 00:00:37,710 And I'm sure she'll tell us today a little bit more about what that means, a bit more about her current research. 7 00:00:37,710 --> 00:00:43,350 Welcome, Governor. Thank you for coming today to talk to us. Before we talk about your research. 8 00:00:43,350 --> 00:00:51,150 Could you tell me a bit about your career so far and how you ended up working in psychology and the boundary between psychology and psychiatry? 9 00:00:51,150 --> 00:01:01,260 Sure. Yes. Well, thank you very much for having me on your podcast. And I started off studying experimental psychology at the University of York, 10 00:01:01,260 --> 00:01:06,660 and I became particularly interested in how the brain works and how it could go 11 00:01:06,660 --> 00:01:12,180 wrong and how we might be able to treat things that go wrong with the brain. 12 00:01:12,180 --> 00:01:22,770 And then I decided to do a study looking at the role of dopamine and the effects of drugs that would be on dopamine and how 13 00:01:22,770 --> 00:01:33,600 we process reward and pleasure and how we learn about these kinds of things to do with drugs like amphetamine or cocaine. 14 00:01:33,600 --> 00:01:44,010 But then I was really interested in applying this same kind of background to human psychopharmacology and psychiatry and disorders like depression, 15 00:01:44,010 --> 00:01:48,180 anxiety disorders and bipolar disorder. 16 00:01:48,180 --> 00:01:59,940 And I was able to come here to Oxford as my first postdoctoral research position was working with Professor Clive Goodwin and Professor Philip. 17 00:01:59,940 --> 00:02:09,180 I'm looking at the effects of an amino acid depletion in acutely unwell manic patients. 18 00:02:09,180 --> 00:02:19,020 So that was a really interesting experience because I got the opportunity to be in psychiatry department for the first time in a psychiatric ward. 19 00:02:19,020 --> 00:02:31,410 I got to learn about how to assess patients who were undergoing those kinds of experiences and looking for changes with this amino acid milkshake. 20 00:02:31,410 --> 00:02:38,730 So that was a steep learning curve. And then I became particularly interested in how antidepressant drug treatments may work, 21 00:02:38,730 --> 00:02:44,370 particularly this interface between psychology and psychiatry and pharmacology, 22 00:02:44,370 --> 00:02:52,020 and really trying to understand how the drug treatments which are using these kinds of conditions, 23 00:02:52,020 --> 00:02:59,190 affect how we deal with emotional information, how our brain responds to different types of emotional and social situations 24 00:02:59,190 --> 00:03:04,260 in a way that can help us understand how these drug treatments are working. 25 00:03:04,260 --> 00:03:10,800 And so since that time, I've seen that kind of line of research through a series of different types of roles. 26 00:03:10,800 --> 00:03:19,320 I got a training fellowship from the Medical Research Council to set me off on that path and then a subsequent fellowship. 27 00:03:19,320 --> 00:03:25,870 And I'm now here as a professor of cognitive neuroscience department parliament. 28 00:03:25,870 --> 00:03:32,940 That's really interesting. Thank you. This what inspired you to embark on this research career? 29 00:03:32,940 --> 00:03:38,940 I think it started from a very basic interest in the brain being this complete mystery and 30 00:03:38,940 --> 00:03:43,590 knowing very little about the brain and what happens when different things go wrong in the brain. 31 00:03:43,590 --> 00:03:50,430 And it seems to me really uncharted territory and also in a way that might be particularly useful to 32 00:03:50,430 --> 00:03:57,120 human health when things go wrong in the brain or when people suffer from mental health disorders, 33 00:03:57,120 --> 00:04:01,050 there are treatments available, but they're not perfect and treatments. 34 00:04:01,050 --> 00:04:07,590 And so I think it's it's a much needed area to try and develop and understand how treatments are working so 35 00:04:07,590 --> 00:04:14,590 we can develop new ones and improve the overall treatment of all of these different kinds of disorders. 36 00:04:14,590 --> 00:04:15,360 And so I think for me, 37 00:04:15,360 --> 00:04:24,630 it's a combination of being a very exciting and research trajectory with lots of unanswered questions and lots of things to find out about. 38 00:04:24,630 --> 00:04:35,070 Every day is different, but also it's research within a very applied setting with the real aim is to try and improve and treatment for people, 39 00:04:35,070 --> 00:04:39,840 particularly with depression and mood disorders and anxiety disorders. 40 00:04:39,840 --> 00:04:48,570 And so I think that that is a it's a really exciting and much needed area that kind of keeps me going and getting out of bed in the morning. 41 00:04:48,570 --> 00:04:57,570 Yes, it is a valuable thing to do. Yes. And could you say a bit more about what you've done so far with your research about what your findings were, 42 00:04:57,570 --> 00:05:01,290 how the antidepressants do work, actually? Yes. 43 00:05:01,290 --> 00:05:14,220 So when we started taking antidepressant drug action, the most often viewed with antidepressants work by reversing chemical imbalances in the brain. 44 00:05:14,220 --> 00:05:21,660 So things like serotonin were thought to be important in depression and how drug treatments work. 45 00:05:21,660 --> 00:05:29,640 And so if you went along to the doctor or your friends, how how my treatment has my treatment working, most people would answer that kind of level. 46 00:05:29,640 --> 00:05:37,320 It works by increasing level of serotonin in your brain, but it became clear that that's only really part of the answer. 47 00:05:37,320 --> 00:05:44,620 It doesn't really tell you why increasing serotonin in your brain can help to treat them any different, often psychological symptoms of depression. 48 00:05:44,620 --> 00:05:52,230 So feeling low, not having the same kind of pleasure in things that you normally enjoy, problems and concentration, anxiety. 49 00:05:52,230 --> 00:05:59,250 It's not really clear how changing serotonin is leading to changes in those kinds of symptoms at the same time. 50 00:05:59,250 --> 00:06:07,470 Psychologists often focus on negative biases in how we process information so that when we're depressed, 51 00:06:07,470 --> 00:06:15,480 we know that we're more likely to focus on negative things that have happened or negative cues in the environment, 52 00:06:15,480 --> 00:06:22,530 much more than we focus on positive keys. And we do this even when we're not noticing that we're picking up any information at all. 53 00:06:22,530 --> 00:06:28,170 So very implicit ways of dealing with emotional information become much more negative when you're depressed. 54 00:06:28,170 --> 00:06:35,640 So effectively, you're just receiving a lot more negative information without being aware of where it's coming from. 55 00:06:35,640 --> 00:06:41,430 And we were able to put these two things together because we found that when we gave people an antidepressant, 56 00:06:41,430 --> 00:06:48,060 the processing became a lot more positive. They were more likely to pick up on positive facial expressions of emotion. 57 00:06:48,060 --> 00:06:52,860 They were more likely to remember positive words in a memory test. 58 00:06:52,860 --> 00:07:00,300 And the interesting thing was that that happened without them noticing not they didn't feel any happier or any more positive at that stage. 59 00:07:00,300 --> 00:07:07,560 And it also occurred very, very quickly. And we know that with antidepressants traditionally need to take the drugs for 60 00:07:07,560 --> 00:07:12,330 a good few weeks before he noticed any change in your symptoms of depression. 61 00:07:12,330 --> 00:07:19,440 But actually, this research showed that as soon as you take in the very first advanced depressant and it's been absorbed, 62 00:07:19,440 --> 00:07:23,520 you can start to see the psychological changes. You feel any better. 63 00:07:23,520 --> 00:07:30,360 But your your brain and your psychology is becoming shifted towards the more positive perspective. 64 00:07:30,360 --> 00:07:37,170 And our hypothesis is that these changes in processing of what allows patients to feel better at the time, 65 00:07:37,170 --> 00:07:44,100 as he starts taking more positive information, it starts to reinforce more positive views of yourself and your place in the world. 66 00:07:44,100 --> 00:07:49,680 And this allows you to recover in interactions with things that are going on in your environment. 67 00:07:49,680 --> 00:07:56,490 And so this really puts a very psychological view on how antidepressant drug treatments are working. 68 00:07:56,490 --> 00:08:04,200 And it gives you all kinds of ideas about how you might facilitate the effects of antidepressants or how you might be able to test new ones, 69 00:08:04,200 --> 00:08:09,930 or how you might be able to think about combining psychological treatments with drug treatments. 70 00:08:09,930 --> 00:08:16,170 And so I think it's it's an interface of lots of different areas that hopefully by having this broader perspective, 71 00:08:16,170 --> 00:08:22,710 we can give a better answer for how these drug treatments are working in a way that might help treatments in the future. 72 00:08:22,710 --> 00:08:27,270 Certainly seems very helpful for patients to know about that and also for clinicians 73 00:08:27,270 --> 00:08:31,650 who are prescribing drugs to know how their treatments might be being affected. 74 00:08:31,650 --> 00:08:36,270 Yes, as you say, he can boost that with the psychological treatment than the latter. 75 00:08:36,270 --> 00:08:42,880 Absolutely. And a lot of patients and clinicians have got to move up in presenting this work at conferences, 76 00:08:42,880 --> 00:08:51,510 meetings and said it seems to ring true that actually you can start to see differences in patients, perhaps how they're interacting, 77 00:08:51,510 --> 00:08:59,280 perhaps how they're smiling in response to things that the other people are doing that seem to suggest that the anti depressants, 78 00:08:59,280 --> 00:09:06,420 it's not like a switch that's directly targeting your mood, per say, but it's affecting how you're taking in information. 79 00:09:06,420 --> 00:09:11,970 And if you're taking in more positive information, you can respond to it even before you necessarily conscious of it. 80 00:09:11,970 --> 00:09:19,860 So it certainly seems to me to be something that is that lines up with with what patients themselves have experienced, 81 00:09:19,860 --> 00:09:24,720 as well as the clinicians treating them. Well, that's great. 82 00:09:24,720 --> 00:09:27,900 What's your current research focussing on? 83 00:09:27,900 --> 00:09:35,850 Well, we're we're continuing with this research, looking at the effects of antidepressants on emotional processing. 84 00:09:35,850 --> 00:09:43,050 But we're particularly interested in if we can use this approach to predict who's likely to respond to antidepressant drug treatment. 85 00:09:43,050 --> 00:09:48,780 So we know that there's a lot of variability in the response to different types of treatment. 86 00:09:48,780 --> 00:09:57,990 Around 40 to 60 percent of patients will respond to any first given antidepressant treatment. 87 00:09:57,990 --> 00:09:59,840 But the moment there's no real way. 88 00:09:59,840 --> 00:10:07,780 Knowing who is likely to benefit from a particular treatment and because of the delay in seeing antidepressant effects, 89 00:10:07,780 --> 00:10:13,990 this can often be a very long and frustrating experience for patients because they may try one antidepressant. 90 00:10:13,990 --> 00:10:22,190 It doesn't work and they might have to try a different dose or a different type of antidepressant effectively through a process of trial and error. 91 00:10:22,190 --> 00:10:29,680 So what we are interested in is that if these early changes in emotional processing are a mechanism by which the treatments are working, 92 00:10:29,680 --> 00:10:32,800 then those patients that show really good changes, 93 00:10:32,800 --> 00:10:38,800 early changes in emotional processing should be the ones who then go on and respond to the treatment in question. 94 00:10:38,800 --> 00:10:41,690 And if you can tell that after just one dose, after a few days, 95 00:10:41,690 --> 00:10:52,210 is that really dramatically reduces the waiting time for quite a dramatic effect on patients and their ability to get effective treatment. 96 00:10:52,210 --> 00:10:58,870 So the aim is that it would result in speedier and more timely management of patients with depression. 97 00:10:58,870 --> 00:11:03,490 And so if if you're a patient and you're experiencing these kinds of symptoms instead 98 00:11:03,490 --> 00:11:07,720 of waiting effectively months before you find the right combination of treatments, 99 00:11:07,720 --> 00:11:16,810 you could cycle through these different options much more quickly and effectively come up with the right balance of treatments and much more quickly. 100 00:11:16,810 --> 00:11:20,770 And we know that the experience of depression is a very individual experience. 101 00:11:20,770 --> 00:11:27,310 Not all treatments will work for everybody, and often it is about trying different things and different combinations, 102 00:11:27,310 --> 00:11:33,400 different doses and and getting the best possible combination for each and every patient. 103 00:11:33,400 --> 00:11:43,230 So one of the aims that we're currently working on is looking at these these early shifts in emotional processing as predictors of clinical response. 104 00:11:43,230 --> 00:11:50,710 That sounds really useful and nice that the research is applicable in clinical practise and we'll have quite a major impact. 105 00:11:50,710 --> 00:11:57,820 Yes. And I think the second potential application of that is that we're working together with pharmaceutical drug 106 00:11:57,820 --> 00:12:05,740 companies to use these kinds of measures as screening tools for completely new types of treatment for depression. 107 00:12:05,740 --> 00:12:14,860 So at the moment, most treatments target the same kinds of chemicals in the brain, particularly ones like serotonin and noradrenaline. 108 00:12:14,860 --> 00:12:22,360 But there's lots of interest and lots of research on completely different types of target in the brain for depression. 109 00:12:22,360 --> 00:12:32,020 And the key problem that pharmaceutical companies have is how to prioritise testing different treatments over one another. 110 00:12:32,020 --> 00:12:36,850 There have been huge advances in the chemistry and biology of making new drug treatments, 111 00:12:36,850 --> 00:12:44,330 but to actually effectively test it in a sample of depressed patients takes many years and many billions of pounds. 112 00:12:44,330 --> 00:12:50,560 And what we hope to do is use these kinds of early markers as a way of screening new treatments that look 113 00:12:50,560 --> 00:12:56,170 particularly promising and may therefore be fast tracked through to the full randomised clinical trial. 114 00:12:56,170 --> 00:13:03,580 And I think this potentially this kind of approach may have a huge impact on how drug treatments are developed and particularly, 115 00:13:03,580 --> 00:13:08,320 again, making these drug treatments available in a more timely manner. 116 00:13:08,320 --> 00:13:16,100 And I think this could be a particularly exciting way forward because there is such a lot of new knowledge about new targets for depression. 117 00:13:16,100 --> 00:13:23,080 And yet there's this real bottleneck in getting them tested out into the in the clinic and so we can prioritise which ones are the most important. 118 00:13:23,080 --> 00:13:27,670 I think that this is another potential application of this kind of work. 119 00:13:27,670 --> 00:13:31,840 Oh, I agree. It's a really exciting as a way forward thinking. 120 00:13:31,840 --> 00:13:37,990 If people want to learn more about your research, particularly psychiatrist or psychologist interested in doing research, 121 00:13:37,990 --> 00:13:42,160 how should they contact you or where can they find more information? 122 00:13:42,160 --> 00:13:48,970 You can find more information on our in the Department of Psychiatry university page. 123 00:13:48,970 --> 00:13:58,750 There's also a short video about some of this work with some pictures of the kinds of emotional stimulus stimuli that we use 124 00:13:58,750 --> 00:14:08,860 in these kinds of studies on YouTube that you can have access to by typing something like Catherine Harmer and Depression. 125 00:14:08,860 --> 00:14:13,810 And of course, everyone's very welcome to email me directly for more information. 126 00:14:13,810 --> 00:14:21,400 And I can be very happy to send papers to meet people who are interested in doing this kind of research. 127 00:14:21,400 --> 00:14:24,810 Great. Well, thank you very much for talking to me today. Thank you very much. 128 00:14:24,810 --> 00:14:25,698 Thanks.