Lectures - Affective Sciences PDF

WEEK 1 - An Introduction to Affective Science and Psychopathology So first, about effective science, what is really effective science and a little bit of history. Effective science has been around for some time, and actually one of the earliest important studies of effective science and the expressi...

WEEK 1 - An Introduction to Affective Science and Psychopathology So first, about effective science, what is really effective science and a little bit of history. Effective science has been around for some time, and actually one of the earliest important studies of effective science and the expression of emotions is this book that you see here on the left. It's by a fellow named Charles Darwin. Many of you will know him for another book that he wrote, where he's a bit more famous for it, On the Origin of Species. But this same Charles Darwin actually was also studying effective responses in different organisms and compared, for example, effective responses in organisms like cats versus organisms like dogs. And that was really one of the important milestones for this field. Now you also see a graph here, and I made this with Google Ngram Viewer, where you can basically see over the course of a period how often specific terms are used. And it's a nice interesting tool that you can use. And I've plotted here the terms cognitive science and effective science, and you can see relative to cognitive science, the term effective science is hardly used throughout the centuries. So whereas cognitive sciences in the 70s really started booming and really took off as a field, effective sciences were much less popular, as you can see. So why is that? Well, for a long time, people thought that studying emotional responses was very, very difficult. They are very subjective, they're very hard to objectify, they're a bit fuzzy, so you could better study things like attention and cognition, which people thought back then were really easier to study. And even when I was a student, when I was a bachelor's student, I had the course Cognitive Neuroscience, and there was one chapter about effective science, and there it said that yeah, effective science is very interesting, but it's very difficult to study. And I hope to show you in this course that that is absolutely not the case. It might be difficult to study, but it's definitely not more difficult to study than topics like attention. And actually, if you zoom in on that effective science line, so this is just a zoomed in line, you can see there's actually a really huge increase recently in the attention for this field. And that's the case for many different reasons, but one of the reasons is that this study might actually be quite important for clinical psychology, as we will see in the course. So what does it mean? What does effective processes mean? What does effect mean? It might be good to start with that, because there are different definitions around there. So the word effect comes from Latin, affectus, which means to have been influenced or attacked. And this kind of grasps that notion that when you have an emotion, sometimes they can overcome us. They can almost seem to appear out of nowhere, almost as if we were attacked by them. So that is where this term comes from. And what effective processes generally involve, and this is a very broad definition, is an evaluation of a situation as salient, salient to us, salient to our survival, salient to our well-being, important to us. And it thereby triggers an evolutionary adaptive response. So very general, but this is the definition that most people agree on. Now, if you think about effective processes and about emotions, I would bet that many of you would think about mainly about the subjective component. Is that right? So you're thinking about feelings, how you feel when you talk about emotions. Is that right? That is, for most people, the first connotation of these terms. However, when we study effective processes scientifically, we define them more broadly, because actually there are also other aspects. So you do have these negative and these positive feeling components, and they're very important, and we are very aware always of these processes, of course, because they're the things that we subjectively experience when we have an emotion. But we should not forget their important behavioral and physiological aspects. And for behavioral aspects, for example, you can think about motor expression, think about facial postures, for example. Think about inclinations to show a specific type of behavior, running away, aggression. And there's a whole physiology behind it, of course. So there are brain and body components that support both behavioral and subjective aspects. So this is something you were probably taught also in the course emotion, but it's good to repeat that we think of emotions and effective processes as consisting of these different elements. Does that make sense for people? Now, one of the papers you're going to read this week, maybe some of you have read them already, probably most of you haven't, and that's completely fine, it's Monday morning at 8.30. But one of the first papers actually for this week is by James Gross, and he's very famous for his work on emotion and emotion regulation. And he came up with this model that he's describing in this paper, and it's called the modal model. And I'm going to briefly go over it with you, but you can read more about it in the paper. So for every emotional response, there are these different elements that you can see here. Situation, attention, appraisal, response. So as you can see already in the definition, evaluation of a situation is salient. There needs to be a situation, something that triggers this effective response. Let's say, for example, me giving this lecture, and perhaps that is something that's very important for me. I want to make a good impression on you guys. It's the first lecture of the course, of course. So that could be a situation that triggers something in me that would have an effect on my attention. It needs to grab my attention somehow, otherwise, of course, there is no influence on me. And of course, if the situation is indeed very important for me, then indeed my attention is more easily focused on that. Then there is an appraisal of the situation. And appraisal is another word for evaluation, basically. So I have to evaluate it as being important to me somehow. So that is the appraisal part. And then I think, yes, this is something that is important for me. It is a situation where I want to do really well, otherwise, people might laugh at me. People might think the course is not interesting, et cetera, et cetera. And then there will be a response. And that response will be there on these three different levels, potentially. On the subjective level, I might feel very nervous, for example. I might feel anxious. On the behavioral level, maybe I start trembling or freezing a little bit. And of course, that is supported by these physiological brain-body components as well. I might feel my heart racing, for example, dry mouth. All the phenomena that you know are associated with anxiety. OK, so this is a very general, basic model of emotions and affective processes. Now, what he describes is that you can also regulate emotions at these different moments. So again, emotions are triggering an adaptive response. But it doesn't mean that, especially in us humans, we can't regulate those responses anymore. There are different opportunities for us to regulate these emotions as well. And the first opportunity for regulating actually comes before the situation is encountered, in terms of situation selection. So let's say I was so nervous for coming to this lecture that maybe I called in sick. Or maybe I let someone else do the lecture instead. So I wouldn't even show up for the lecture. That is a form of emotion regulation. It feels a bit weird, perhaps, because the emotion is not even there. But you are regulating your emotion before it is there by selecting a situation. A second opportunity is when you're in the situation already, you might modify it a little bit. So for example, I could maybe do the lecture partially online. Or maybe I do it in a way that I don't have to look at your faces as much. Because one of the things that we know when people are a bit socially anxious that triggers a lot of emotions is looking at faces. So you're in the situation, but you try to modify the situation a little bit. Attentional deployment is a third option where you steer your attention in a certain way to reduce your emotions. For example, you can distract yourself during the lecture of these negative thoughts and of emotional aspects. So that is another way of regulating. And these things are all explained in the paper quite well and quite clearly. So if you don't immediately fall in love, then just please take the time to read it in the paper. A fourth option is during the appraisal moment where you can apply cognitive change strategies or reappraisal as it's sometimes always called. So that means interpreting the situation in a different way. So whereas my original appraisal was, well, I need to do really well, otherwise people will laugh at me, et cetera, et cetera. I might try to reappraise and think, well, actually, this is a very interesting learning experience for me. I want to see if I can improve from last time. So reappraising in this way can help regulate our emotions. And finally, there's response modulation. And that involves directly modulating the ongoing emotional responses there. So for example, if I feel my heart racing, I have a very dry mouth, I might start applying breathing techniques, for example, to try to modulate, to try to reduce my arousal in the moment. And that is an example of response modulation. OK. Does that make sense? Yep. Now, I want to say a few things about terminology. Because you hear me talking about emotions. You heard me talking about affect. How do these things relate to each other? Are they the same? Are they slightly different? Does someone have an idea about that? And there are no wrong answers here. We're just trying to get on the same page that we understand each other. Yes? I think emotions are more specific. So you have specific types of emotions. Well, affect is more a general description. So you are feeling something. So affect is a more broader term. Thank you. Thank you. Other thoughts as well on this? People agree on this? Maybe you have another idea about this? Yes? Can you describe it right now to appear as an example? But in general, it sounds like affect is more driven than you feel. OK. Interesting. Thank you. Yeah, it's not that easy. I actually, I wasn't sure myself before I started this course. And that's why I started diving into this. Because you can see there's different opinions about this. And that's why it's interesting to look into this. So I've made this little schedule here, where I've put different terms, different affect-related terms, and how they are related. And what helps is to put them on this two-dimensional scale, where on the one hand, we have event focus. And the other hand, we have embodiment. So let's start with event focus. Event focus means how much an affective response is triggered, is directly linked to an experience that we've had, an event that has occurred. And on the other hand, we have embodiment. And that is more linked to how strong of a physiological response we have. So similar to what you've said, actually. And now you can see where these terms are a little bit. So let's start, for example, with the term stress. You all know the term stress. Stress is quite high on both of these lines. So it has a relatively strong event focus, meaning that typically when we're stressed, it's quite clear that there was a specific occasion, a specific situation, something that we're stressed about, that triggered this. So it's quite high on event focus. And it's also very, very strong on embodiment. Because we know that stress not only influences things like our autonomic nervous system, like heart rate and sweating and these type of things. It also has a longer term effect on our physiology in terms of, for example, hormonal changes. So it's a longer lasting process in that sense. So it has a very strong embodiment. So a very strong effect on our physiology. Now, let's look at effective dispositions, for example. You guys have an idea what I mean by that, effective dispositions? So you can think about something like, for example, trait anxiety. So something that you have a general inclination to act in a certain way, to be anxious, generally. Now, that is there completely in the top corner because it's not linked specifically to any event because it's more like a trait. It's really a disposition that you carry with you in whatever situation you are. And it also has a relatively low embodiment because you have that also when you're sleeping. It's always there. It's not necessarily directly linked to a strong physiological response in the moment. Moods are a bit more concretely linked to events. Sometimes you know that you're in a certain mood because something happened. Sometimes also not. They're not completely event focused moods. And they have a little bit stronger embodiments than dispositions, but not as strong as stress, for example, and emotions. And emotions are then quite strongly embodied, similar to stress, a bit lower because emotions typically are a bit shorter lived. So when we talk about emotions, what we mean is these effective responses that typically last in the order of seconds to minutes, whereas stress can really last a lot longer. And sometimes when the emotion is very, very intense, that can, of course, last also for an hour. But it's really exceptional that we're really that emotional for that long. But it can happen. But stress, for example, can easily last for days. Yeah. Does that help? Does that clarify things? Are there any questions on this? Yeah? I'm not sure if I just missed it, but I guess emotion is also strong on event-focused, right? Yes, yes. Especially strong on event-focused. So it's really triggered by specific events, very discrete events. So you really have this event, and then you get the emotion. So even stronger than stress. Yeah? Do mental events count into the events as well? So for example, somebody thinks about memory, or something like that, would that be an event? So do you, so memory events, is that the term you'd use? I didn't hear it at first. Yeah, if somebody, for example, has a bad time, or maybe something less dramatic, like just thinking about that situation. Yeah. And then concluding with that. Yeah, absolutely. So the question is, for those of you that didn't get it in the back, whether if you recall an event, whether that also counts as an event. And I would say yes, absolutely, because usually that is less strong than the initial emotion, but sometimes not, sometimes even stronger. So yes, definitely, that would be an event as well. More thoughts, questions on this? No? OK. So then let's start talking about the link to psychopathology. And why is effective science, why should you care about effective science if you're interested in psychopathology? Well, the first thing that maybe comes to mind for many of you is effective disorders, where it is very clear that disturbances in emotions, effective processes, are super central to the psychopathology, right? And you can think about depression, you can think about anxiety, all the different anxiety disorders, PTSD, phobia, generalized anxiety, panic, everything, and bipolar disorder as well. And actually, these are the most common forms of psychopathology in our society. So for that reason alone, quite important to study. With depression leading, being among the top-ranked disturbances in terms of disability that it causes. So these effective disorders, as they are called, have a huge impact on our society. And you know all about that, of course. But it's not only effective disorders where effective science potentially can weigh in, because there are many other instances of psychological disorders where effective disturbance really plays a very important role. Can someone name another disorder where effect and the disturbances in effect play an important role, other than anxiety, depression, and bipolar disorder? Who has an idea? Yeah? Would it be something like antisocial personality disorder? Absolutely, antisocial personality disorder, absolutely, where you get a lot of unregulated aggression. More? Yeah? Schizophrenia. Yeah, can you say why schizophrenia? What symptoms are you thinking of? Can be, for example, hallucinogenic effects, which can involve a bunch of anxiety and can also be related to aggression. Absolutely, hallucinations, paranoia, aggression. Yeah? You? ADHD, yeah, can you say what symptoms are you thinking of? Emotion regulation, yeah. Yeah, thank you. There was a hand also somewhere else I saw. Yeah? Borderline personality disorder, because? Mood swings, yeah, difficulty regulating, absolutely. More? There is more, yeah, in the back. Perhaps ASS. ASS, can you say why? For emotional regulation. For emotional regulation, yes, absolutely. PTSD. Yes, absolutely, PTSD is very clear. But PTSD officially is no longer part of the anxiety disorders, indeed. So it's good that you mentioned it. It's called the trauma disorder, although in my mind it's still an anxiety disorder. But absolutely, yeah, very strong. Yeah? Maybe agoraphobia, when you're scared of something. Absolutely, agoraphobia, very often combined with panic. Part of anxiety, very central, absolutely, yes. So you can go on, and we can fill probably the whole hour with this. Here are a couple of others. We already discussed schizophrenia, psychopathy would be there. You can think of addiction. Many people don't initially think of addiction. But think about this very strong craving responses, very motivational responses to reward cues. Autism, it's also important. And then borderline cognitive disorder were discussed. So you can see how these emotions are really quite central to many different types and forms of psychopathology. And the question is then, what types of disturbances might there be? And I always like to use this quote from a book. Some of you will probably know. Do people know this book by Jonathan Safran Foer? No? Someone? No? Yeah, you do? Yeah. Did you like it? Well, I haven't read it yet. Ah, but you can just know it by name. It's an interesting book. It's a very original book about autism, written from a first-person perspective. It's very interesting. Highly recommend it. And the main character says, I feel too much. That's what's going on. And the question is, do you think one can feel too much, or just feel in the wrong ways? I thought it was a beautiful way of thinking about how can you have different disturbances in your feeling? And it relates really well, actually, to what you will read when you read in the paper by Gross again, about categories of different affective disturbances that can occur. Because you can have disturbances in different areas. You can have it in the reactivity, emotional reactivity problems. So how the emotions unvolve. But you can also have problems more specifically in the regulation area. And in the paper, this is very nicely explained. So I'm not going to go over this very extensively. But you can think about, when you talk about the emotional reactivity problems, you can think about the intensity, indeed, with over- or under-reactions. Where we saw some examples already previously, where in anxiety, for example, you can have over-reactions in situations. And you get emotional flattening sometimes in schizophrenia, which would be an under- reaction. You can have disturbances in the duration, where responses are too short, too long. The frequency, how often something occurs. So when you think about antisocial personality disorder, for example, there's a bit too much of aggression sometimes, perhaps, too frequent. So it's not only the intensity, but also how often. And you can also think about the emotion type, where you can have, in some cases, maybe a response that could be potentially quite normal, but that, given the situation, is really inappropriate in that moment. Can you think of examples for that? Someone? Yeah? Being happy during a funeral. Could you make it a bit louder? Being happy during a funeral. Being happy during a funeral, yes. That would be very inappropriate, indeed. And in what type of disorder could you see something like that? Three questions. Yeah? Well, it could be schizophrenia, for example. Someone who has really lost contact with reality. OK. So emotional reactivity problems on the one hand. On the other hand, emotion regulation problems. So problems with controlling the emotions. And these are categorized into three parts. Awareness, which has to do, of course, being aware of your emotions is very important if you want to regulate them, because that really helps us as humans that we become aware of our emotions sometimes. And then we can say, OK, I probably need to regulate right now. I've become aware of being very anxious during this lecture. I would be able to do breathing exercises. So awareness typically helps. But you can also have over-awareness or under-awareness. And over-awareness, for example, would be in perhaps panic disorder, where people are really, really aware of their physiological sensations that are going on. You can also have problems with goals in emotion regulation. And that is why I have this picture here of the lady over there. I'm not sure if people are familiar with Homeland, the series. Is anyone still familiar with that? Raise your hand if you know the series. You again. Yeah? A few people. A few people, not many. It's a series about this woman. She's a brilliant CIA agent who is also diagnosed with bipolar disorder. And she really uses sometimes the manic phases in her disorder to do really amazing work, which means that she really profits sometimes from being manic, like many people with bipolar disorder sometimes can be extremely productive in these periods. So she's really searching for that peak sometimes, which would be an example of a wrong emotion regulation goal. She's regulating her emotions, but not in a way that leads her to cope better with her disorder. Strategies is the final one, where you can have emotion regulation strategies that can be really effective, but you can overuse them or implement them in the wrong way. And there, I typically think of, for example, avoidance as a strategy, which is a really effective strategy for regulating your emotions. Again, not showing up to this lecture would be awesome if I would want to regulate my anxiety and make sure that I wouldn't experience any anxiety. That would be perfect. But overusing avoidance, of course, is very detrimental because it doesn't resolve anything. There's no extinction of your anxiety. You keep avoiding all the time. And it's very bad, of course, for your personal and professional life. So this is kind of the bird's eye view of these different types of disturbances. There are all kinds of examples also in the paper that you can read about. But it helps if you think about, during the course, we're going to talk about many different types of effective processes related to different types of psychopathology. And then you can think about, OK, what type of disturbance is actually going on there? And you can think about these categories. So I hope that helps. So almost time to go to the break. And we've covered, actually, we're coming back to the learning objectives for this week. And we've covered the first part, talking about what effect is and how it might be disrupted in psychopathological processes. What shall we do? Shall we move a little bit on? Or do you feel like a break? Anyone? No? OK, I'll keep going then for 10 more minutes before we go to the break. So how can we use effective science to improve understanding and treatment of psychopathology? Now, I want to show you the traditional approach for studying effective processes in psychopathology first. And then I'm going to contrast it with a newer approach. Now, a typical approach that has been very, very popular for studying problems in different disorders is you get a group of patients with a certain disorder, defined by the DSM very often. Let's say schizophrenia. You get a healthy control group, a group that is absolutely not diagnosed with any disorder. You match those groups as carefully as you can. You look carefully at their age distribution, their sex distribution, maybe other aspects as well. Anything that can confound the comparison between these groups, you try to rule out. And then you compare these groups on some effective process. Let's say you're looking at anxiety responses, for example, in the laboratory, or you're doing a task in the fMRI scanner and you try to probe biological aspects, or perhaps you're looking at a specific type of behavior, or you're looking at psychological responses, subjective experiences that these people have, and you compare them between the groups. Doesn't matter. It can be in all these levels. And then you look for a significant difference, and then you say, well, this group has more amygdala reactivity, stronger subjective responses, some behavioral response that is stronger than the healthy control group, and that potentially indicates that there is a problem with this specific effective process in this disorder. Makes sense? Does that sound like a solid approach, something that you've probably seen already? Another approach, kind of a variant of that, is that maybe you have another type of disorder, let's say panic disorder, again defined by the DSM, and you're going to test the efficacy of a certain treatment. And that can be maybe a psychological treatment, a therapy, or it could be maybe an innovative biological treatment, psychopharmacological treatment, and you're going to compare that to a control treatment. Why? And again, you compare the different treatments and see whether there is any difference in treatment efficacy. Again, a very logical approach, right? People have done this. Researchers have done this for decades, and for good reasons, because this makes sense. This sounds like a very solid approach. But there is a problem. And the problem is that despite all the research that has been done over decades, the efficacy of current psychological and pharmacological treatments for different types of mental disorders is somewhere around 50% on average. It's very hard to calculate these numbers, but it's around that number. And that is not incredibly bad, of course, and that is great for the 50% of the people that do profit from these treatments. But there is, of course, room for a lot of improvement as well. And the question is, what might be the reason for this? Why is it that despite all this research that has been done, we're still not able to come up with treatments that cure a large majority of the people? I'm going to, yeah, you have a thought about it already? Oh, yeah, maybe. Hold that thought, because I want you guys to briefly discuss amongst each other with your neighbor. So just grab the person that's next to you or close to you. What do you think the reasons are? And then I want to hear your thoughts, OK? So I'm going to give you two minutes to discuss this with your neighbor, think about this, and then I'm going to see what your answers are, and I'm going to start with you. All right? So two minutes. All right, two minutes are up. Let's hear it. What do you think? Yeah, so what you talked about was, first of all, that you cannot have a one approach for all kind of patients, so it's pretty individual. Second thing would be that maybe the medication is not working for some of the patients. And the third thing I thought of before would be that maybe for some people, it's more difficult to apply the strategies learned in therapy, for example, than for others. So that might be one of the reasons that it's not as efficient. Yes, thank you. So just to summarize, you said, well, there's no one-size-fits-all approach, so different things might work for different people. That was your first point, but I think it's also kind of summarizing a bit your other two points that also fall under that category, because you said, for example, psychopharmacology doesn't work for everyone. Certain types of drugs don't work for everyone. And applying certain strategies that you were maybe taught in therapy might be different for specific groups as well. So indeed, different people have different needs in terms of how they can maybe get the best treatment. Does that summarize? Yeah? Great. Maybe also that it should be more holistic for treatment in general and not only focused on psychotherapy and pharmacology. OK. A more holistic approach. Which would mean that the current treatments just need to be developed more to be more effective in a way. Yeah, OK. I'm curious about more thoughts and things that you came up with. Maybe someone from that corner. I haven't seen many people from that corner yet. Anyone from that area? Yeah? Yeah, we thought it was a bit funny. Emotions and feelings and how they are harder to grasp and work on, maybe. Harder compared to? Harder compared to talking about the behavior and your thoughts, the thought processes. So I think therapy can mostly talk about the problems instead of trying to grasp the feelings that are underneath it. OK. Interesting. So that is why you think, especially emotion-related disorders might be harder to treat because they're harder to grasp. Thank you. Thank you. OK. There will also be something about the classification in that there could be potentially different phenotypes in these disorders. You just didn't know yet. And that health care therapy would just focus on volunteers and not the others. So that is very interesting. So you're saying there are different groups of patients that fall under one diagnosis, potentially. So it's a bit related to what she was saying. There's heterogeneity, you could also call it, in terms of the different types of patients that are there. And they might need different types of treatments, then, potentially. And you had another point, as well? It could also be that we just didn't know enough yet about the way those processes go. Yes. For example, we talked about the various components of subjective behavior, physiological ones. And I feel like in therapy, we normally tend to look at the subjective points, maybe the physiological, as well as the research parts For example, it might take multiple patients. It's a factor. It's most often multiple patients. So that could also be a factor. Right. So we don't have sufficient understanding yet of the different processes that underlie these disorders. Is that a way of putting it? Yeah? Thank you. Other thoughts that came up? Yeah? This kind is also kind of what you just said. Or maybe it's the idea that we can only measure the size of illness from a subjective perspective. So it's like asking the patient, what kind of illness do you have? And I feel like with any other illness, you can usually look at the material matter of the organ. Or you can, I don't know. Of course, with brain scans, I can't interpret them very well when it comes to psychophysiology. And so, yeah, I think that was a very good point that was also just diagnosed. Yes. Thank you. Yeah. Indeed. So a bit related also to what the gentleman was saying, that there's these different fundamental aspects that we're not sufficiently grasping yet and that are very hard to target, that we don't know, that we don't have the tools for to target very well. Yeah. OK. Any last burning thoughts? Yeah? I think that sometimes mental disorders are hard to distinguish from each other because they have many common similarities. Right. And this would take more time. And why? So indeed, that's absolutely the case. Very important point. So there's overlap between the different disorders. They're not completely separate. And why does that lead to lack of efficacy of treatments, you think? It could be that there's a focus on the disorder, on the label that we put, but not so much on the symptoms, perhaps, or the specific characteristics that they manifest through the disorder. So there are different patients that have different characteristics, potentially. Yes. Maybe, I think, we should focus more on what we see that's related to the disorder, through the patient, and not what, generally, this disorder consists of. Right. So the more attention for the personal story, the personal symptoms of that specific patient, and then really try to focus your treatment on those specific personal symptoms that that person has, the individual story. Thank you. OK. Briefly, before we go to the break, I think there are two main aspects to this that you guys already mentioned. Great. Clinical heterogeneity, indeed. And indeed, what falls under the umbrella term of one diagnostic category is so heterogeneous. My favorite example is PTSD, where someone calculated the different types of symptom profiles that you could get. According to the DSM-5. So looking at all the different types of symptoms that are part of PTSD, what different combinations you could have, and how many different profiles you could have. And there are 636,120 different ways to get PTSD. And if you don't believe me on the math, then you can look at that reference over there. If you think about that, it makes total sense, indeed, that we don't have a treatment that works well for all of them. Especially because we have this lack of mechanistic understanding. And that also came back in a lot of answers that I saw already. These disorders are not like the flu, where we know, ah, you caught this and this specific virus. And we have a quite good understanding of the pathophysiology of what that virus is doing to your body. And this is why you get these and these symptoms. That is something we simply don't have yet. And it's, indeed, related to the fact that we still need much more research to really understand what are really these mechanisms that trigger these symptoms for these individuals. Because then we can start thinking about, oh, if this is the problem, if this is mechanistically what is going on, if this is what makes this person have these symptoms, then it would be much easier to come up with a fitting treatment. Now, I want to illustrate this also with a case example. But I'm going to do this after the break, because it's right about time. But we'll finish in time. Let's have a 10-minute break. Be back at 9.30. Thanks so much for being this lively already, even though it's this early in the morning. See you in 10 minutes. All right. OK, welcome back. We're going to get started again. We're going to get started again. So I got some questions in the break about whether I'm going to talk about the assignments, also for the course. And yes, absolutely, I will talk about the assignments at the end. So I'm going to first finish this lecture. And then I'm going to talk about the course structure and also cover the assignments. And you can ask questions. So that will be fine. I also put out this little poll here. Some of you might have seen it, where you can just scan the QR code if you want and answer a few questions. And then also, in the moment when I'm talking about the course, it's nice to know a little bit about you and who you are and what you're interested in. But that will come later. So we were discussing reasons for why we have a limited understanding of psychopathology and, therefore, limited effects of treatment. And one of the things that was also mentioned is that sometimes it's not really that easy to discriminate between different types of diagnostic categories, different diagnoses. And I think it's illustrated by this case that I'm going to talk you through. So I'm going to take you through this case. And then I want to hear your diagnosis, what you think. Of course, this is very limited to do this in a classroom. But I'm curious what ideas you have for a diagnosis. So it's a hot July day as Bill walks, Bill is the patient, hesitantly down his local high street. Today, like most days over the last two years, he expects to be attacked by a stranger when walking around outside. Most of the time, when he's out, he keeps his eyes to the ground. He doesn't want to meet eye to eye with another man in case the eye contact is taken as a provocation. A little later, he notices that he's feeling hot and sweaty in his leather jacket. He thinks, other people are thinking I'm an idiot wearing a leather jacket on a hot day like this. He wants to take his jacket off. But if I take my jacket off, he gets a fleeting image of himself, fearful, wide-eyed, with thin and pasty arms, weak and vulnerable. This makes him feel anxious. And then he catches the turn of someone's head out of the corner of his eye. And he speedily scans around at the people in his vicinity. He sees two men walking towards him and looking at him. His eyes meet their eyes. And for a moment, his gaze is transfixed. I'm in danger. I must get out of here, he concludes. Bill then looks around for an escape route. Ah, an alleyway. He swiftly turns down the alleyway and heads in the direction of home. When he gets home, memories of this frightening event flood back into his mind. And he spends several hours worrying about whether the people he had seen would follow him home and attack him. OK. So this person is clearly not feeling well. But what might be a diagnosis for this person? Based on this, of course, very limited, superficial story, what would be your ideas about this? Anyone? Yeah? Schizophrenia. Schizophrenia. Can you say why? It seems somehow delusional or having no soul. Delusions? Paranoia? Yeah. Maybe slightly hallucinating? Sorry? Maybe slightly hallucinating? Slightly? I didn't hear the last thing. Hallucinating. Hallucinating. Hallucinating, even. Could be. Could be. Thank you. Are there other options that you had in mind, essentially? Yes? Maybe it's PTSD, because he developed it during the last two years. Yeah. So it's something that developed more recently. And why do you think that that is related to PTSD? PTSD can also involve paranoia and worrying if he panics and goes outside. Absolutely. And it could be that two years ago, something extreme happened to him. And the symptoms started from there. Thank you. Yeah? He also had anxiety disorders. Yeah? He also had all sorts of variations that were catastrophizing. Catastrophizing. Classical anxiety symptoms. Absolutely. Clear anxiety also during the walking outside. Avoidance, even. Yeah? Absolutely. OCD. OCD? OK. Why do you think OCD? Well, he thought if something happens, like he was like, all right, then maybe the provocation happens. So it goes from a very mundane situation to a very big consequence. So it might be that he has a very specific compulsion about. Yeah. That's what he had. All right. Yeah. OK. Thank you. So many different diagnoses possible, clearly. And this person, this is from a real case. And this person, if I remember correctly, had four different diagnoses consecutively. PTSD, paranoid schizophrenia, generalized anxiety, and the fourth one I forgot right now. But that only illustrates how difficult it is. So real case. And you might think, well, this is a very specific, complex case. Is it really that realistic? Well, we know that people typically have many disorders at the same time. So this is, for example, the overlap between depression and anxiety disorders in terms of their comorbidity. And it's huge. It's really huge. So for example, from these numbers, 67% of people who have OCD also have depression at the same time. And I think the more recent numbers are that, on average, patients who get diagnosed have 2.1 disorder. So it's really quite typical, in fact, that people can have multiple DSMD and diagnoses at the same time. So this really goes back to what some of you said earlier, that it's really hard to discriminate between different disorders, and that there's a lot of overlap. So why is there this overlap? Well, there could be different reasons for that. One is that we just don't have the right tools to discriminate between these different disorders, so that they are, in fact, different. They are categorically different. We just can't really make the difference, because we don't know how. So that would be poor discriminative validity. It could also be, and that happens. We know that happens. That actually, the disorders are really related, in the sense that one disorder leads to the other. Sometimes referred to also as things like primary versus secondary disorders. In the case of anxiety, people, when they have very serious anxiety for a longer period, often also spiral into a depression, for example. So there could be these relations underlying this comorbidity. And it could also be related to common risk factors. And to illustrate that, there is this graph here. So you can have risk factors for different disorders at different disease stages. And these are the different disease stages. Baseline acute. So acute is the moment where the disorder first emerges. And then you have the early period after that, and then the chronic period, potentially. And at these different stages, there is different types of risk factors that can play a role. So before the onset of the disorder at baseline, there can already be predisposing factors that overlap between different disorders. So they are transdiagnostic risk factors, in the sense that, for example, having experienced something very negative in your childhood can predispose you to anxiety, as well as depression, for example. So there is overlap in these risk factors. And that is why these disorders come together. But also at later disease stages, you can have precipitating risk factors that overlap. So risk factors that, for example, in the acute phase lead to the triggering, the onset of the disease, but can lead to multiple diseases. And you can have perpetuating risk factors that also overlap. For example, we know that stress, in many cases, contributes to the continuation of many different types of disorders, whether that's schizophrenia, for example, or depression. OK. Many different reasons, then, why there is so much overlap. But what should we do with this? Well, it might be the case that when we have the DSM, our diagnostic system, as a starting category, that is not necessarily the best way forward if we really want to better understand psychopathology for research. Because the goal of the DSM was, of course, to develop a very robust and reliable system to come up with diagnosis based on clinical experience. And it's been highly, highly successful in that, because it is quite reliable. And a lot of effort has been put in there that people, in the end, if they just follow all the criteria in the book very, very specifically, they do quite often come up with the same reliable diagnosis. So in that sense, it works well. But the problem, as we have discussed, is that it doesn't necessarily, this diagnosis can be very broad. And it doesn't necessarily link back to a specific mechanism that we can try to find with research and that we can try to target with personalized treatments. So if we want to make that step, we actually need to focus on symptoms rather than syndromes. So rather than focusing on these broad diagnostic categories, like depression, we have to talk about the individual story of the patient, like we discussed. What are their specific symptoms that they have? And how can we deal with that? But because we had this traditional DSM-based focus, where we said we're going to take this group of patients with DSM diagnosis A and we're going to compare them to super healthy controls, that hasn't been really done. And there is a gap between the goals of diagnosis and scientific studies. And it also has led to the fact that research very often has been isolated on specific disorders, whereas, for example, there are conferences on PTSD. And there are other people that are going to conferences on depression sometimes. These things really exist. Whereas actually, there's so much overlap and so much knowledge that could be shared between the scientific studies. But due to this DSM-based system, people have been used to doing their research in a very isolated way. OK. So what we want to do is go from a disorder focus, something that has been driven very much by the diagnostic system, the DSM, to a different focus. And again, the DSM has many different advantages. It causes us to have a common language for communication. You all roughly have an idea what I talk about when I talk about depression. And that is easy to communicate between clinicians, scientists, et cetera. But it has these disadvantages. And because this overall category can come at the cost of the actual complex clinical reality at the level of the patient, the personal story that we discussed. It treats implicitly each disorder as something that is completely independent when we know they're not. It also assumes that if you become diagnosed with a specific disorder, you're somehow very distinct from all the people that don't have that disorder, that have another disorder, but also people that don't have that disorder, so the people that are healthy, quote unquote. So in that sense, it's also really not helping in terms of stigma. And that is especially important also because we know these cut-offs, where you say, oh, you need to tick these and these and these boxes. And then you have the disorder, according to the DSM. Well, unfortunately, these cut-offs are not so extremely evidence-based as you would hope. So there's an arbitrary nature to them. And I think you all agree that's suboptimal. And what will be better is to have a transdiagnostic focus where we focus on the processes that contribute to the etiology. Etiology is always a bit difficult word. But etiology just means how things arise, how things developed. So we need to understand better the processes that underlie the development of the disorder and the maintenance of the disorder across these diagnostic borders because there is so much overlap. And then we can use a functional approach where we dissect the syndromes into component parts, look at that individual patient, their central problematic behavior, their specific symptoms. And we can look how that patient compares to other patients that have that common processes of etiology, those same processes that contributed to their symptoms, to look at how we can develop treatments. Does that make sense to people? And this is called a transdiagnostic focus. And again, it's something that's been around now for about 10 years or so. But it's still relatively new compared to all the traditional work. And still, there is a lot of DSM-based research going on. But this has been a huge new development over the years. Clear? Yeah? Yes, question? I have a question about when you take a more transdiagnostic focus, isn't research just also way more complicated and it's way more complicated to focus on people more individually? Because you would have to, in a way, study each person. Yeah. Yeah. Yeah, I see what you mean. I'm going to go over an example. And then let's see if your question is resolved by that. But it's a good question, indeed. Because indeed, it was kind of easy to just say, OK, I'm going to take all these people with depression. I'm going to ignore all the differences. But now you say, OK, I only want to look at this specific patient that has exactly these and these symptoms and this level. Yeah, then you kind of only have a case study. It will be very hard to compare. I get your point. So let's first go over what could be potential advantages of doing this transdiagnostically. Well, you can deal better with this comorbidity. That's something that we discussed. And patients are rarely pure, like I said. And actually, the overlap among patients within a diagnostic category is sometimes smaller than the overlap between categories. So sometimes a disorder can be so broad that there's so much heterogeneity that this variance is larger within the category than between, arguing why it's important to just not keep them completely separate. And another advantage is that you can deal better with the fact that we, of course, know that it's not an all-or-none phenomenon to have a disorder, to have a disease or not. It's not the case that only if you tick these and these boxes, then suddenly you have the disorder. And before that, you're completely healthy. That doesn't make sense to anyone, right? So this is a clear case where the DSM is a bit oversimplified, leading to stigmatizing also. Because what we know from many scientific studies is that all these processes, all these symptoms that we see, actually occur on a continuum typically, right? They're not all-or- none. You can have no symptoms. You can have maybe something mild, moderate, severe. It's a continuum. And it's not really captured by the current DSM-based focus. Another advantage would be, for a transdiagnostic perspective, where you say, I'm going to look beyond diagnostic categories. I'm just going to look at symptoms, is that there would be potential advantages for treatment development. That's the third point. Because there can be transfer between advances that are made across different disorders. And you can really find that, hey, actually, this type of treatment that was traditionally used, for example, for this diagnostic category, also works fine for people with this in the symptom profile that have another diagnosis, right? So as long as there is a link between the treatment and the problems that people have, why should you keep them as separate? Yeah? So how are you then going to do the research is a great question. And the people that have done a lot of development in this direction are the people that worked on the so-called RDoC initiative. So how many people know? Do people know this term, RDoC? Some people know it? Yeah? Can you raise your hand high, just to have an impression? Many people do know it. OK. Just quickly then, because I don't think everyone knows it. So the research domain criteria was an initiative that was started a bit more than 10 years ago by the directors of the National Institutes of Mental Health in the US. So they have a huge mental health institute in the US with a lot of funding. And the directors at some point said, we want to do transdiagnostic research. We want to really make a change in how we do research. And the way, the framework for this, they called RDoC, Research Domain Criteria. So it's very much transdiagnostic. But how are you going to do this? Well, this is one potential way of doing research. So you start out with all these different people with different types of disorders. Let's say it's depression, different forms of depression. And you can see from the different colors, these are people with different backgrounds, with different experiences, with different symptom profiles. There is a lot of heterogeneity. There can also be other types of diagnostic categories here. So this is all depression related, but you could also, for example, have anxiety here as well. And you just put them all together, one big group, as you can see. You put them all together. And then you can study them. You can study their symptoms, specific behavioral processes, effective bias, subjective experiences. You can put them in the MRI scanner, scan their brains. You can test them genetically. You can do all the different types of research that you want to try to get at things that you think might be potential mechanisms underlying their problems. And then based on what you find, based on these data that you gather, for example, here the example is brain activity in the insular cortex is one. You're going to cluster people according to what you find. So let's say insular cortex activity would be a very, very important phenotype. Based on how much insular cortex activity they show, you could categorize them in these different clusters that you can see here. So the idea is here you're starting from the mechanism. And the insular cortex activity is just one example. It could be anything. It could be a behavioral experiment that you've done with these people. It could be measures of subjective processes of symptoms, life experiences, et cetera, et cetera. But you're going to cluster them according to these proposed mechanisms. And now you have them on the right ordered according to those mechanisms. So you have a group that shows absolutely no insular cortex activity. You have one that shows mild, one that shows moderate, and one that shows extreme insular cortex activity, for example. It could also be combinations of different mechanisms that you look at. It could be anything. So now you have different groups, not based on their original diagnosis, but based on what you think is a potential mechanism. And then you can start to look at, hey, do I find that these groups are differently affected by different treatments, for example? Is this related to other types of mechanisms, et cetera, et cetera? So you can run these prospective trials and see, is this mechanism really telling us? Is it really helpful in terms of personalizing their potential treatments? So this is one way of doing it. And of course, you still have the variability because, again, the colors are not the same within one cluster either. You can see that. But at least people are put into broader categories that are really based on their specific problems that they have, their specific symptoms. Does that make sense? OK. Two others as well? Yeah? Great. So there are also disadvantages to this. This is not the solution to everything, unfortunately. And we still have to see how much this really pays off in the end. 10 years ago, a bit more of this was started. But still, these are very large studies, typically. So we still have to see what the advantages are. And there are some problems with this potential triangular diagnostic approach. They are covered also in the second paper for this week. So you're going to read about that. It's a paper by Nolan Hoeksema. So very briefly now only, one of the problems is, well, it's interesting that typically different psychological disorders seem to present themselves very differently. And it could be that even though there is overlap in terms of their symptoms, for example, two patients could be very, very similar. They could still have a very different trajectory over time. So even though we nailed their mechanisms, apparently, still there might be a lot of variability. Because we know that there are these differences, what is called divergent trajectories between people. So why would that be? Even though they have the same potential diagnostic risk factors, why would there still be differences between people? Why couldn't we still explain everything with that, So that's divergent trajectories. And another point that is talked about is multifinality. And I'm, in view of the time, going to keep it short now and just let you read about that. And then I'm sure we'll discuss it on Thursday in the interactive lecture. So we've covered learning objectives. We've reflected now on the current state, the recent state of affairs in clinical science, clinical practice, and how effective science might contribute to that. That's the second point. And we've also covered the third point, talking about transdiagnostic models and how they potentially can help us a bit further with further understanding the origin and maintenance of psychopathology, even though it's not going to be perfect. Now, are there any last questions about this? Because otherwise, I would like to go on and talk about the core structure. Yeah? About the transdiagnostic approach, do you want to adopt it in a clinical setting? Don't we have to change it for all the healthcare systems? Absolutely. Absolutely, yes. So that is an interesting question. When would you need to change that in a clinical setting? For now, I would say the goal is to mainly change the research. So those are different goals that you can have. But once we think that the knowledge that we've gained from these transdiagnostic studies is robust enough, then, of course, that is the time when we completely have to rethink the way the clinical system works. But we're not there yet, I think. I feel like a lot of psychologists already don't support machine disadvantages in the TSM. You can see they didn't bring it down to vulnerability. So in clinical practice already, people are adopting a more transdiagnostic approach. I think you're right. I think you're absolutely right, yes. But they don't really have the tools, usually, to decide how then to choose a specific treatment for a specific patient. So that is where a lot of steps still need to be made, I think. And people try their best, of course, to individually cater their treatment to a specific person. It's not like they're just sitting there, oh, depression, we're going to do behavior activation therapy, whatever. That's not how it goes, of course. These people are doing their best. They're working very, very hard to try to resolve these problems. But we're not there yet that we can offer them, really, guidelines for how to select which treatment to take. Sorry? They have to do it without patients. It's difficult to do it without. And whether they have to is a bit dependent on the setting, I guess. But we haven't offered a very good structured alternative yet, I would say. Thank you. Other questions on this? No? OK. Have you guys filled in the poll? Some of you did, hopefully. If not, you can quickly scan it now. Because it's nice to see a little bit who is in the course this year. It's just a couple of very brief questions. I'm sure you can answer really quickly. But since we're talking about individualizing treatments, let me see if we can cater to your interests also a little bit in this course. I still see people looking at it. I think everyone scanned it. OK. So we're going to look at the results before. Who am I? So my background is in clinical psychology. But before that, actually, I was trained in neuroscience. So I have a neuroscience background. And currently, I'm working as an associate professor in the clinical psychology section. So I actually made the step towards more practical, applied implementation of what we know about the fundamental neurobiology of emotion, and particularly anxiety and stress. So that's why I love teaching this course. I really believe in this. So you've met me already. Who you haven't met is Nina Dijkstra. She's going to be the course assistant for this course. And I'm very happy that she's helping me with all kinds of things. And she's also your first point of contact. I'm here during the lectures. I try to be here also during the other lectures so that you can always talk to me. There is the opportunity to email Nina. But given that we are a larger group than ever, I really want to emphasize that it is always important to first ask your question in a discussion forum on Brightspace. Why is that? Because otherwise, you get a lot of questions via email. But the knowledge doesn't really spread. So for example, you might have a very good question about an assignment, something that's unclear to you. Post it in a discussion forum. We can answer it there. And then everyone can see it at the same time. So that just works so much more efficiently. So please, please, always go to the discussion forum first. And only if you have something that's very personal, very specific, something you can discuss online, then, of course, you can contact Nina. OK? So the course goals, you can read in the manual. I'm not going to cover them all now. But you can read all the details. But the general gist that we try to get with this course is typically when you read about research, for example, in general, newspaper, media, social media outlets, you kind of get. WEEK 2 - Emotion Control Almost all our actions and decisions are guided by our emotions. So imagine you have to go, you are the one who has to cook tonight. And you go to the Albert Heijn Excel. How can you make a selection among all these thousands of brands and cans? Well, there is something that is guiding you. Like, hey, I feel like eating this tonight. Or how on earth can you select a romantic partner among all the millions of people in this world? So we are guided by a lot of motivational, emotional systems that help us to make very complex decisions. If we would have to make rational calculations, our brains would be completely overheated. So they guide our decisions, our actions, our attention. But sometimes we have to control these emotions, because they may put us in the wrong track. For instance, if I would have social phobia, and I would be asked to give a lecture here, my first tendency would be to run away. And that is not good, because somebody has to teach this lecture. So sometimes we have to control these emotions. They are very helpful, usually, but sometimes we really have to control them, just to make sure that we behave in an adaptive way. So there's many ways we can control and regulate our emotions and emotional actions. And one is just attentional distraction. So if I'm very nervous now, I can also think a little bit about my shopping list, and maybe then I'm a little bit less. Or extinction learning. If I would do this often enough, maybe the fear will slowly fade away, or I learn that actually people don't kill me when I stand here. Or reappraisal. If everybody starts to laugh, I could think, oh, they're laughing at me. Or I could think, hey, there's something funny now on social media that they're picking up. So there's ways of reinterpreting things that are going on. So there's many ways. By the way, you will get all the slides, so there's no need to write anything down. You can just relax and interact, because you will get the slides. But there's also other ways. We can also control our emotional actions. And actually, actions, the whole action system, is very important when we think about emotion. Emotion is actually something that sets us into motion. And action tendencies are often activated before we even know how we feel. So there may be a very immediate leaning backwards, or before we even have the subjective feeling. So action tendencies are very important. And when we are scanning somebody, and we elicit an emotional experience, we see all the motor areas lighting up. So there's a very strong connection with action. So we can control our full body actions. Like I was saying, I shouldn't avoid this, then I should walk in, approach it. But also our gaze behavior. Some people who are a little bit more anxious, or if you're in a state where you feel less comfortable, you start to avoid direct eye contact. So there's many ways we can actually control emotional actions. And that is what I will focus on today, mostly. Yes, please. What is the difference between eye gaze and walking away? Yeah, so I could still walk towards you, but for instance, look at your neighbor, or look in between the chairs. So eye contact, eye gaze aversion, or looking away, is also a way of avoiding. But it can also be the distance, the full distance. Yeah? Other questions? OK. Well, and then a statement of something that we think is going on, but of course we have to prove that. And that is that many forms of psychopathology are actually associated with problems in controlling these automatic action tendencies. So imagine you see something nice. And this is beautiful work by Nico Vrijda. He was a very famous emotion psychologist. Unfortunately, he passed away. But in his book, The Emotions, it's also in English, he gives a very nice background on why, actually, action is so important. So when we see something nice, like this nice cat, we want to approach it. But if we see something aversive, we want to go away from it. That's a very basic principle, these automatic action tendencies. And as I said, they're often activated before we even know it. So now let's think, let's do a little mental exercise. Let's think about different types of psychopathology, like anxiety, depression, and think about this in terms of approach avoidance tendencies. What do you think would be going on in anxiety? Yeah? More avoidance. Depression. Avoidance, yes. So also more approach behavior or less? Yeah, an approach of what? Yeah, and I'm really approaching it, or do you mean more cognitively, mentally? Yeah. Yeah. Yeah, it's interesting. Of course, there's multiple answers. But what they typically show is less avoidance, sorry, less approach. So the reward system is a little bit less activated. So what they also show is actually a reduction in approach behavior, approaching of appetitive things. So and of course, increased avoidance is definitely something that we're we see as well. There's 70% comorbidity between anxiety and depression. So yeah, but you're right. Of course, there's also approach of maybe negative things, and especially thoughts, thinking. Aggression? Any ideas? How would you think in these dimensions of approach avoidance if you think about? Yeah? The approach of? Aggressive situations. Yeah, yeah. So maybe if there is something threatening, or a person who looks really angry, instead of avoiding it, you would actually approach it. You feel challenged. Yeah, yeah, great. Addiction? Any ideas what is going on there? Yeah? Yeah. Approach of the bottle, or? Yeah, yeah. So there is a strong reward sensitivity and a strong tendency to approach. And even difficulties to inhibit that approach behavior. So this is an interesting way to think about this dimension of approach avoidance if we think about motivational behavior and different types of psychopathology. So what I will do is mostly focus on anxiety and avoidance. Yes? And depression. Yeah, that's definitely also going on. So we consider the lack of approach, so especially in the more, yeah, anhedonia, the people who really feel, have blunted feelings. And so there is also no approach of appetitive situations anymore. But you're completely right. There's definitely also avoidance. So this is not mutually exclusive. Yeah, yeah? Yeah. And for addiction, there's more. Absolutely, absolutely. So I'm really talking about action tendencies here. But when you think about the experiential, like we were just discussing also for other conditions, experiential, the fact that you actually do approach the bottle or all the substances, that may actually mean that you're avoiding something else. That could be experiential avoidance or cognitive avoidance. But in terms of action tendencies that are immediately generated when they see it, that is often the approach tendency. So here we really focus on the action tendency. Yeah, but you're right. This is not like set in stone and that this is the only thing that is going on. Yeah. So and why do I think this is so interesting, avoidance? Because so one question we had is like, how on earth is it possible that even when it's really counterproductive, for instance, it's so important for your career to go to this interview for an internship or whatever and then not going because of fear. So how are our brains able to overwrite persistent avoidance, costly avoidance? That is something that we have been puzzling with and that I would like to take you along to today. I have a question. I'm grappling with the position of avoidance. But would, for instance, procrastination also be avoidance when you push tasks to your best? Absolutely. That's a cognitive type. Like we have experiential avoidance. There is avoidance of doing something, of experiencing when you are actually doing that task. Here I'm really talking about automatic action tendencies that are often generated before we even know how we feel. Yeah. So it's really the action tendency that I take here. That is this very first thing that we are kind of, that is a very strong automatic tendency that we have. But of course, these terms are broader and can also be used for more cognitive instances that are less directly related to action tendencies. Yeah. Yeah. Good questions. Great. So how is our brain able to, so we can have very strong avoidance tendencies that we really like, but how are we able to override that? How does the brain do that? So that is one of the questions that I would like to address with you today. So we do this in light also of RDoC because avoidance is something that is a transdiagnostic phenomenon. It is not that we have one disorder, one DSM classification that is called avoidance disorder. That is not the case. So avoidance tendencies are actually a transdiagnostic phenomenon that goes along all kinds of classifications that we can have. And of course, we all know the DSM-IV, a statistic manual that describes disorders, mental disorders, as we call them. But at some point, NIH, the National Institutes of Health, said, listen, let's not just think about disorders, but let's think about dimensions that are cutting across these disorders. And the RDoC was a system that was introduced at some point. NIH is actually the National Institutes of Health where the DSM, the Bible of psychopathology, is written. It's a very important institute. They said, well, we are only going to fund research that covers mental disease in a transdiagnostic fashion. We stop just studying depression, just anxiety. Why? Because we think that there's important dimensions that play a role in many disorders. And they came with five systems. One, and I have to wear my glasses to even see what is here. One is the, can you read it? Is it large enough on the slides? So negative valence systems, so negativity. Think about fear, avoidance. The opposite pole would be fearlessness. And they also describe what kind of neural substrates would be involved there, like the amygdala, but also hormonal systems, like cortisol. So the negative valence system is like a multimodal system that can play a role in many disorders. Of course, also in depression, also in PTSD, not just in anxiety. There's a positive valence system. Think about approach motivation. We were just talking about this. The opposite would be anhedonia, something that we see in depression a lot. Dopamine plays an important role. Mesolimbic system, where dopamine does play a role. Then the third would be cognitive systems. Think about working memory, cognitive, all kinds of efforts-related things. Think about chronic fatigue. The opposite would be impulsivity. Think about ADHD. So it's across disorders. You take a dimension. And here they say, well, we lump the cognitive systems. The systems for social processes. So they thought this is a separate system, worth mentioning. Think about social dominance. Dominance versus submissiveness. That is a dimension that is also relevant. And interestingly, hormones play a big role in social interaction. For instance, testosterone is a very socially-driven hormone. Serotonin, facial expressions play a role. And then they point to the neural mechanisms where facial expressions are processed. And then the fifth dimension would be the arousal and more regulatory processes. Think about stress regulation. How much of these stress hormones do you create and how do you regulate it? So instead of just thinking of disorders, they said, think more in a horizontal fashion, cross disorders, about these five dimensions. And I think it's an interesting exercise to do this. And avoidance, the way I was just talking about it, fearful avoidance, is of course something that would fit very nicely in the first dimension, but would have a lot of hints and connections to other dimensions as well. And my goal for today is not to give absolute knowledge about things, but to show you how we play with these dimensions, what kind of questions we address, what kind of methods we use to try to come a little bit deeper in understanding the mechanisms behind psychopathology. So that's my goal. So when we study transdiagnostic mechanisms of psychopathology, how do we explain psychopathology? You can do that in many ways. You just heard me talking about a phenomena, but we can also think about other dimensions. So what the DSM does is describing what we see, a phenomenon. For instance, a person feels, looks really scared and doesn't show up. That's a phenomenon, that is something that we describe. That is the way the DSM actually describes an anxiety disorder. But you could also describe it at the level of what we call endophenotype. So not the phenotype, what you see, but an endophenotype, which is actually an intermediate phenotype. It says more about the mechanisms, the underlying mechanisms, what is going on in the brain and cognitive systems. And of course, we have pieces of hardware. We have a genotype, genetic information, that interacts with the environment. So for instance, you could have a certain genetic variation that makes you very sensitive to environmental influences. Sometimes people say serotonin plays an important role there. The serotonin transported gene polymorphism. If you have a short allele, doesn't matter, then you're more sensitive to positive and negative environmental effects. If people who have that variation are exposed to traumatic events, they are more vulnerable to developing symptoms. So I don't put the genotype here alone. I put it together with environmental factors because they interact. Plus we know that genetic expression can change due to environmental changes. So that is an interaction. But the bottom line here and the take-home message is we can actually investigate psychopathology at many different levels. And we can give many descriptive different levels of how we describe it. So we can think about the genotype with the environment. How does that interact? We can study the systems. Or we can just describe what we see. And everything is fine and good. And we need all of these levels. In experimental psychopathology, which is actually how our department is called, Experimental Psychopathology and Treatment, we tend to focus less, sorry, on the phenotype, but we try to really get a view on what is going on in terms of the intermediate phenotype. What are the cognitive or neurocognitive mechanisms that are underlying what we actually see and observe? Yeah? So that you see a little bit where we think that we are trying to give a description. Okay. Now what will I do today? Just to illustrate how we play with these different lines of explanation, give a short background on the neurocontrol of social avoidance. So I will use social avoidance and social fear as a way to illustrate these levels and how we can study this. Then I will explain and see with you whether there are individual differences in this in terms of symptoms, in terms of genetic makeup, in terms of hormones. Then we will explore a little bit if we can improve certain types of control using brain stimulation, but mostly using hormonal administrations. And if time allows, think about whether this has implications. Can we actually use this fundamental knowledge to do something to improve existing therapies or maybe make them a little bit more efficient? And we have some nice examples. And hopefully I have time to end with a theoretical note. So the working model. And don't be shied away by the fact that I may mention some neural structures. You can forget about them right away. There's a few that might be interesting to remember. But again, this is really to illustrate how we play with these levels of description. So think about social anxiety. The last thing you want to be exposed to as a socially anxious person is somebody who looks angry at you. That is a very potent threat cue. So when we are exposed to a threatening cue, like an angry face, or when we even think about going maybe to the supermarket and seeing the cachet again, or whatever, amygdala will evaluate these emotional cues right away and will send direct connections to very low-level brainstem structure called the PAG that may lead to freezing. We know that from animal research, but humans do that too. We can freeze. We see something and direct connections from the amygdala to this midbrain structure can lead to freeze. And here you see the amygdala. This is the forebrain. So it's like this. Here's my forebrain. And the amygdala are low here and they send connections to the brainstem. So it's very low- level control of motor behavior. Connections to the striatum, which is a little bit higher, can facilitate active fight and flight, these automatic action tendencies. And of course the motor cortex plays a role too. And then it's the role of these more cortical structures, your frontal cortex, really high-level frontal structure, and also more other cortical areas to control these action tendencies. If needed. And they do that mostly by acting on the amygdala. That was the model that was out there based on animal research, mostly when we got into this topic. So that is the model. And again, just forget about it. You will get these slides. Now, there's another piece that I would like to bring to the table here because these brain structures are actually influenced largely by hormones. And steroid hormones like cortisol and testosterone play an important role in the regulation of social motivational behavior. And whether we are more dominant in a social interaction or more submissive. And if we want to learn something about the influence of hormones, steroid hormones, on the brain in humans, we can learn actually a lot from research in primates. Primates have very strong social hierarchies. And one thing that was found, and there is this wonderful researcher, Paul Sapolsky, who runs a research lab, but he also spends almost three months a year in the bush just observing how these colonies behave, who is more socially dominant, who is more socially submissive, who shows all the sociophobic type of behaviors. And then he would always try to get some hairs, some poop, derive some blood from the animals to see how their hormone levels were. And one of the most consistent findings is that those animals that are more socially submissive in these interaction, they have higher levels of cortisol, both at baseline and in reaction to stress. They have a higher peak. And the ones that are more socially dominant, they have higher testosterone levels, both at baseline, but also in reaction to a challenge, to a social challenge. Testosterone ramps up more rapidly, stays higher for a longer time. Now, what is interesting and what many people do not know and we only know testosterone from everything in the media, is that actually cortisol, which is produced by the HPA axis, the hypothalamus pituitary adrenal cortex, the HPA axis is quite well known, has a lot of overlap with the HPG axis that leads to the production of testosterone. And in fact, when we are stressed, both go up together. Cortisol and testosterone go up together. It's more about which one stays high or how high does it go. So the HPG axis is the hypothalamus pituitary gonad axis. And both in men and in women, for us it's in the ovaries, that leads to the production of testosterone. And yes, men have nine-fold higher testosterone levels, but it doesn't mean that testosterone behaves in terms of stress as a stress hormone in a similar fashion, rather similar fashion in women. Of course, there's differences, but in terms of relations and cortisol- testosterone ratio, it's almost similar how it behaves. Now, the HPA and HPG axis inhibit each other on almost every level in the system. So when you are very stressed and you have high cortisol levels, reproductive functions can go down. We have a little bit less testosterone. If we give a little bit of testosterone to somebody, we see that the cortisol stress responses go down. So these two systems are in a mutual inhibition. And the stress, they can go up together, but in the end, they inhibit each other. So it's very interesting to look at the balance in these systems. And you had a complicated paper about that. So now, the triple imbalance theory, and this was the paper that I gave to you. It's an old paper, but it's the only one still out there that covers both cortisol and testosterone and also links that to genetic information of serotonin. And that's the reason that I, plus links it to aggression. And that's the reason I gave it to you. I know it's a little bit complicated, but at least, yeah, I think it's such an interesting topic because it so beautifully illustrates how you can look and how you can think about psychopathology, both at the hormonal level, the neural level, but also in terms of genetic makeup. And that's the reason that I gave the paper to you nevertheless, and apologies. So what does this triple imbalance theory about aggression, what does it say? Well, it says that at the level of the amygdala, and I just mentioned to you that when there's a cue out there and there's a situation, the emotional evaluation often happens in the amygdala. If you have high, the testosterone-cortisol ratio has an impact on how the emotions are evaluated. And what we often see, that if there is a high testosterone-cortisol ratio, we write that down as T-CT ratio. If that is high, that means high testosterone, low cortisol. The amygdala codes for fight. So there's a stronger fight tendency, stronger approach fight tendency. That's the theory based on animal research. Interestingly, there's a second important part in this picture. If we look at the prefrontal cortex, poor serotonin function, which is a neurotransmitter, would lead to reduced capacity for the prefrontal cortex to down-regulate the amygdala, to exert control. So, if you have both, if you have both poor serotonin function and you have this disbalance in these hormones, the imbalance, then you might have a slight problem. You might be both impulsive here and show a lot of automatic fight tendencies, but if in addition you have problems with controlling that, it could lead in some instances to problems, yeah? So, that's actually the theory. Now, we were interested in testing this. So, in 2012, they published this and we thought, well, how is this related to anxiety and aggression? I'll talk about both. Well, if you want to test this, then you need a couple of things. As an experimental psychopathology person, you need to do a couple of things. One is, you need to design a task that can capture automatic approach avoidance tendencies. Of course, you could ask somebody, would you like to approach the person, would you like to avoid? Yes, but that does not always say, that doesn't always go hand in hand with the automatic action tendencies that we measure. So, you need a task that is sensitive to picking up these individual differences. The second thing is, you have to relate it to these hormones, so you have to find a way to measure these hormones and to relate it to each other. And ideally, you also relate it to genetics. So, I'll just going to give you an illustration of how we try to do these things in relation to anxiety and aggression. Well, the first thing is, how do we measure whole body approach avoidance action tendencies? Well, we started actually with this setup. This was still at the VU in Amsterdam. We had at Movement Sciences Department, they had this fancy balance board that can pick up really subtle shifts in your motion. And if people step on it, it immediately records already the initiation of an action with a very high temporal resolution within milliseconds. So, that is what you need. For automatic action tendencies, you really need millisecond precision. And as you can see, it was not fancy, there was an IKEA cupboard that we were still using. These days, it all looks a little bit more fancy. And we were simply showing people happy or angry faces. And we said, well, if you see a happy face, step towards it. If you see an angry face, step away from it. We didn't say anything about approach and avoidance. But what was so interesting is that when people can approach a happy face and avoid an angry face, they are quite fast. This is the reaction time. But if we ask them to do the opposite, if we say, step towards the angry face now, there's a reaction time cost. And that is very persistent, particularly with these whole body movements. There is a reaction time cost here. I call this now incongruent reactions because apparently this is not what we want to do. We don't want to step towards an angry face or step away from a happy face. It goes in both directions. There's a reaction time cost. And that reaction time cost is interesting because it signals that you have to inhibit your automatic action tendency to avoid. And you have to select a rule- driven, namely, we told them approach the angry face, reaction. And that requires control and it takes time. And that is something we can pick up in the reaction time. We can also pick it up in the error rates, by the way. They also make more errors for the affect incongruent reactions. Yeah? So it's a very simple task. You can't go more simple. But it works and we can replicate these things. So in the average population at the group level, this is what we see. Now, then we thought we have to do this in the scanner because my question was how does our brain control automatic avoidance tendencies? They can be very persistent. You really want to avoid the threat. But if we want to understand how patients with sociophobia in the end have to approach things that they are afraid of, let's first find out how healthy individuals, or neurotypicals we call them, so people who are not currently meeting the criteria of a DSM-5 disorder, how do they actually control these automatic action tendencies? That was the question we had. So we had to, of course, adapt this task for the scanner. We now give people a joystick. You lay in the tube. There's a little mirror. Via that mirror, you can actually see a full computer screen, so you can play tasks in the scanner. I think most of you have seen this. And here, they will actually play exactly the same task, but instead now of walking towards the face, we tell them push the joystick away from your body or pull it towards your body in response to the happy or the angry face, yeah? And they have blocks where they have to push the joystick away from their body, for instance, to happy faces in congruent or pull it towards your body. Now, we replicated the behavioral congruency effects. Again, people are faster when they can make affect congruent reactions, and there is quite a big reaction time cost when they have to do the opposite, which is interesting that you find that back even in these joystick movements, right? And we were interested in what happens? What is the brain doing here in this condition? Because they were quite able to do it nevertheless. And then we see, and again, this is the forehead. So this is the prefrontal cortex. This is this part. We see a strong activity here when people have to make affect incongruent reactions, when we have to exert control over our automatic action tendencies. And then you can say, yeah, nice, but this is just correlational, and that's true. Yeah, this is just a correlation. They are playing this game, and then we see this neural correlate. This is not causal evidence. It's just a correlation. It's not enough. Okay, then we said, okay, then we are going to manipulate the activity in this region. We're going to deactivate it, and we just have to make it and we see what happens. And that is something you need to do if you really want to build your causal models, if you really want to understand what's going on, and you need that if you want to build neurocognitively grounded therapies, then you need to have causal evidence. Now, so what did we do? We did a TMS study, transcranial magnetic stimulation, because we were very interested in what the frontal brain is doing in terms of control in emotional action tendencies. And this is Bob, and here he has a coil on his forehead. And what we did is we selected a protocol where we sent pulses through the prefrontal cortex. We know that that leads to a deactivation of the frontal regions for about 40 minutes. So no worries, after 40 minutes, you're back to normal. So you can do that for a short period of time. And this protocol had been validated before in all kinds of species, also humans. And we first played it on ourselves, of course, to feel how, to see how it is before we asked people to go, and we got medical ethical approval for these type of studies, so don't worry. But what we did is we used this protocol where we sent pulses through the prefrontal cortex that leads to a deactivation for about 40 minutes, just enough time to put people in a scanner and play the task again. Now, there is a problem with this type of research, which you think could happen. Any concerns? Yeah? Oh, they get poor control, that is your hypothesis. I will get back to the hypothesis, thank you. This is already great, yeah. Well, but one problem is also, if I put a coil on your head, and I tell you this might have an impact on how your frontal cortex is working, and I let you play the task, there are demand characteristics. You think about, oh, what did I read in the newspaper about the frontal cortex? Oh, I probably have less control now, so there are demand characteristics, and your belief about what this could do to you may have an impact on how you actually perform during the task. So there can be a general slowing because you think this should do something to my brain, so I probably get slow. Therefore, it is always very important to be aware that there's a huge placebo effect, huge placebo effect, not just with drugs, but also with brain stimulation. So how did we resolve that? We had three conditions. One condition is where we placed the coil here, and we gave them actually the protocol, the pulses that would lead to the deactivation. It's here in black, it's our intervention, yeah? Then there was a condition. They came to the lab four times, first to get acquainted with all the protocols, then they got this, then they came back. They got exactly the same location, so if they have a belief about what the frontal cortex does, but they got a different pulse. You don't notice the difference, but we gave a different pulse that shouldn't interfere with social motivational behavior, that shouldn't have an impact. Plus, we placed the coil here on the vertex. We gave exactly the same type of stimulation that should be effective for the frontal cortex, so it should feel the same, it should give the same sounds. But again, yeah, the vertex is not really implicated in social emotional regulation. So we had two types of controls, a site control and a protocol control, and that is actually what you need to be certain that if you find something, that it is related to what you did and not to some belief system, yeah? I find it's really important, that's why I'm, because there's a lot of crappy research out there that is not well controlled, and we have to do, if we do research, we have to do it well. Okay, now the question comes, what do you think that would happen? What is the predicted outcome? So, if I would inhibit your frontal cortex, how do you think you would behave on this approach avoidance task? So you already had some hints, yeah, yeah? Yeah, you get more impulsive. How does that look like exactly? Do they break the joystick or do they? Yeah, I hope not. Yeah. Probably, they will be more eager to exert extreme, like more intense avoidance or more intense aggression. Ah, so the automatic action tendencies become stronger. In terms of reaction times or in terms of? I haven't thought of exactly how this would, their behavioral part of it. Maybe, yeah, they'll be more fast in their actions. More fast, yeah? I'd say that the incongruent one should become longer. Yeah. And maybe the congruent one could be smaller or shorter, but eventually, they'll break. Yeah, I saw more hands. That's, it's nice to hear the hypothesis, right? Did I, did I see another hand? No? Mine was the same. Same, okay. Longer reaction time for incongruent. Yeah, that is, I think you're all more or less right. Although, we didn't find it in the reaction times, we found it in error rates, which is even more interesting, I would say. So they, so what are we looking at? This is the prefrontal inhibition. So this is this black, this was actually what we tried to induce. We induced a deactivation in the frontal cortex. And this is a control stimulation. They did nothing typical. We got the same as we would always get. Usually, for incongruent reactions in red, you make a few more errors. But after prefrontal inhibition, the error rates increased dramatically, yeah? So it is not only that they became slower, but they actually made the wrong, so if there was an angry face, and we told them, well, you have to approach it, they avoided it nevertheless. They followed their automatic action tendencies more, and they had problems to actually make the action relate that is incongruent. And that is actually strong causal evidence. So that is, I think it's really nice. Now, the good thing is that we did this in the scanner. I have to look at the time. Oh, it's time for break. Two more minutes, yeah? You mean the blue? Yeah, the blue was not significant. Yeah, that is, yeah. The difference was really here, and yeah, mostly actually within the, yeah. And then I stop, and then we break. Of course, we also did a manipulation check. Because you do something, we actually stimulated on the left side, as you can see here. And that was because in our fMRI studies, our correlational effect was on the left side. So we just, we took the region that we had found before. But there was a lot that, if you think about approach and avoidance in the literature, and I want to warn you there, there is a lot about lateralization. There are a lot of theories that avoidance is on the right side. Well, we never find this, by the way. And also, what happened actually, we deactivated. We did a stimulation here, but our deactivation was on both sides. It's a widespread prefrontal deactivation that we induced. And that is actually what usually happens. Apart from language, usually the two hemispheres really work together. And if you deactivate one, the other one goes along. So the deactivation was widespread here in the frontal cortex. And what was so interesting, this is what we induced. This is what we wanted to, yeah? So nice, manipulation check. But at the same time, we saw a deactivation in action selection regions. So that is interesting. Maybe the frontal cortex is usually talking to action selection regions. Hey, you need to exert a little bit more control during affect incongruence. Plus, we saw increased activity in the amygdala and in the fusiform face areas. And those are the regions that are implicated in the emotional evaluation of the face. So if there's an angry face, so maybe it's the role of these frontal structures to downregulate the amygdala here. And if we inhibit these frontal structures, these amygdala, they become more activated. They react stronger, yeah? So this is an indirect suggestion, but yeah, that is the nice thing about manipulating and see what changes. With that, we can have a break. I would suggest let's not make it too long. Is it fine if we start again at half, 9.30? Okay, see you back at 9.30. Hi, Mariana. So before the break, I set the grounds a little bit about how do we control our automatic action tendencies? Why is it important to look at social avoidance? And now I will move to the topic of individual differences. Do we see individual differences that are perhaps meaningful and bring us closer to the phenomenon of social anxiety or aggression even? I will give an illustration about behavior, but also genetics and hormones. Because I think that nicely fits with the paper that I gave to you, the difficult paper. Okay, the first study was one into genetics. So we had been doing this TMS study that I was just talking about. And then we were actually flabbergasted about these results. Usually when you do research, things don't come out the way you think it should. And this was really actually nice. And then we thought, well, if this paper, if this theory about the triple imbalance, if that is true, if it is true that serotonin plays a role in how well we are able to control automatic action tendencies, we could perhaps put this to test. Because at the Donner Center for Cognitive Neuroimaging, everybody who we scan, we ask them to donate a little bit of saliva. And then we can, and we ask them for permission to do genetics analysis. And many of us actually are S-carriers of the serotonergic transporter gene, polymorphism. That sounds really complicated, but it simply means that in one of the genes that codes for how serotonin works, that you have a variation that in the literature, in animal research and in human research, has been linked to being a little bit more sensitive for environmental changes. So if you grow up in a really fantastic environment, or they do even better, we see that in animals, but if they are exposed to traumatic events, they can do a little bit worse. And this is in terms of group research. So you really cannot translate this on a one-to-one. So if you think, oh, I'm an S-carrier, or oh, I was exposed to trauma, no, this is not how we should think about this. This is group-level research. So it's on averages in a group, doesn't say anything yet about the individual. But it's interesting just to look at these patterns, right, as a good start. So what did we do? We went back to the genetics database, and we asked 24 people who were S-carriers, who had this polymorphism, and 24 who don't have that. And we asked them to do exactly the same task as I just explained to you. So in the scanner, they were doing this approach avoidance task. And interestingly, what we found is that both groups did perfectly well. The reaction times didn't show a difference. Their error rates didn't show a difference. There was nothing different between the groups. No symptom difference, nothing, zero, except for the mechanism by which the brain was resolving the task. So the S-carriers, although their behavior, their performance was exactly the same, what we saw is that they were less recruiting the prefrontal cortex and less downregulating the amygdala. So there was less of a pattern of negative connectivity, the way they crosstalk with each other. And that is interesting because that suggests that as long as you are in a relatively fine situation of doing a task in a scanner, nothing wrong. But perhaps this is what may put people at risk when there is a very challenging environment. Because if the emotions become overwhelming, then perhaps this is a pattern that may put you a little bit more at risk. And then there may be less downregulation possible. So that was the way we interpreted this. In fact, the reason I'm showing it here is because it was so much in line with this hypothesis by Mon