[MUSIC PLAYING] We are the Association for Child and Adolescent Mental Health, or ACAMH for short. And this is ACAMH Learn. My name is Kelsey Hagan. I am a licenced clinical psychologist and assistant professor of psychiatry at Virginia Commonwealth University in Richmond, Virginia in the United States. I am also an affiliate editor for the Journal of Child Psychology and Psychiatry, or JCPP for eating disorders, and I conduct research on adolescents with eating disorders, and especially in the space of the neurobiology of adolescent bulimia nervosa. So adolescence is a time of the dynamic brain restructuring such that there are changes in white and grey matter, and there's also changes in how the brain and brain regions communicate with one another, known as functional connectivity. And then there's also changes in hormones. So during adolescent brain development and puberty, hormones come online. And hormones can influence how major neurotransmitters implicated in eating like dopamine, for instance, are impacted. So adolescence is really a prime time for major reorganisation of the brain. And different hormones can influence appetitive hormones that impact eating. And so during this time, you see a lot of mental health disorders coming to be. And so while the brain and the body are doing what it's supposed to do in terms of development, what can happen is things can go a little bit awry. So there are several key brain systems that appear to be quite relevant to eating disorders. The first of which is the limbic system or the negative affective systems. This is because negative affect or negative emotionality like depression, anxiety is shown to be a precursor to the onset and also can perpetuate the expression of eating disorders. So that's a key brain system. Another key brain system is the reward processing system. So things like the striatum and the orbitofrontal cortex, for instance. Reward is really important in eating disorders because food is a natural reward. And in some cases, food might be especially rewarding. In other cases, food might be aversive and less rewarding. So in cases of binge eating, foods thought to be especially rewarding or have altered reward value, whereas in restrictive eating, reward is-- our food is thought to have perhaps less reward or maybe even be punishing. Another relevant brain system is the interoceptive system or the arousal and regulatory system. So interoception is how we sense feelings in our body. In eating disorders, there is an idea that interoception is altered so that feelings of fullness are altered. Some might be insensitive to feelings of fullness, which could promote binge eating, and some might have heightened sense of fullness which could promote restrictive eating. So that's another really important system is the arousal system that encompasses interoception and the interior insula, for instance. Another really important key system is the cognitive control system. So this regulates things like attention, memory, overall cognition. Why we think this is important is because in some cases, such as in restrictive eating, there's elevated cognitive control that comes online. And in other cases like binge eating and bulimia nervosa, states of control alter. So sometimes there's excessive cognitive control and states of restriction, and other times, there is low cognitive control or cognitive slips, if you will, and states of binge eating. So those are the main brain systems that we think are relevant. Surprisingly, we have several neurobiological models. And yet, these have not been tested straightforward with our current research. So some of our neurobiological models, for instance, include the three-dimensional neurobiological model of Avoidant Restrictive Food Intake Disorder, or ARFID. And that really encompasses different systems and different subtypes of ARFID and how they might be affected by neurobiology. In bulimia nervosa, we have affect type models of eating disorders or bulimia nervosa and binge eating and purging. And those have not been tested robustly with our current research. And anorexia nervosa, a very prominent model is the habit hypothesis of anorexia nervosa, which is this idea that restrictive eating initially is rewarding. And then becomes more habitual over time. And that is a really prominent neurobiological model. It has been hard to test, however, in neuroimaging studies because it's hard to actually implement a task that measures habit in the scanner and within that short period of time. So those are just a handful of our neurobiological models that give us some idea about what might be driving restrictive and binge eating behaviours, but they've been difficult to test. The current research on the neurobiology and neural mechanisms of eating disorders in youth has mostly centred on anorexia nervosa. And this is important because anorexia nervosa is a very lethal disorder. And one of the most robust findings that we have seen across studies and has been consolidated in a meta-analysis published by the ENIGMA working group on anorexia nervosa, is that brain volume and structure decreases over time with anorexia nervosa. And then there's some evidence that some areas recover versus don't. Another major finding is that there are reward processing differences in teens with anorexia nervosa versus those without anorexia nervosa. And the direction of these reward processing differences is altered and not one way or the other. It depends on the domain of reward processing that we're talking about. So for instance, reward learning looks a little bit different than delay discounting. And other findings that we have seen in terms of binge eating and bulimia nervosa are that it appears that reward anticipation might be a little bit lower among those with binge eating and binge type eating disorders, but the literature is very mixed. We also don't know a lot about ARFID, so there's very little research out there right now on ARFID. So again, the most robust findings are in the field of anorexia nervosa. As I mentioned in the previous question, the evidence remains really limited around adolescents with bulimia nervosa and adolescents with avoidant restrictive food intake disorder. ARFID was introduced in the DSM in 2013, and so it's only been around for about 13 years as of this recording. So we don't know a tonne about the neurobiology yet. There's research being conducted right now and we're really looking forward to those findings. And then with respect to bulimia nervosa, we don't know actually a whole lot about bulimia nervosa in terms of its neurobiology and adolescence. Most of the studies have been in adults. And so work is underway now to better understand adolescent bulimia nervosa. Although, there is a hint that self-regulatory systems are impacted in this group. So what is key in terms of the existing neurobiological evidence? One thing that really stands out is anorexia nervosa and the reduced brain volume that we see as a result of malnutrition and the disorder. And so for clinicians, what's really important to understand is that someone who's presenting with anorexia nervosa and their brain is quite compromised and their ability to make decisions because of this low brain volume is going to be compromised. And so what's really important, and I think a really important goal is to increase nutrition and make that a top priority in the beginning of treatment, because there is some evidence that brain volume can recover over time with treatment and things can get better. And once brain volume starts to come back online, then some more psychological interventions might be meaningful with this group. Another key thing that we see and a key clinical implication of from what we know about adolescents with-- or bulimia nervosa, is that self-regulatory systems appear to be diminished. And so what this limited evidence tells us is that perhaps, we need to be thinking about ways to help an adolescent with bulimia nervosa, promote self-regulation, what supports can we provide them as they're going through treatment and working on reducing binging and purging. So that might be more parental or caregiver supports, helping them plan their days so that self-regulation can be at its optimal function. And then for ARFID, again, we don't quite know yet what it's going to look like there. And so we look forward to seeing some of the results of our colleagues. So I think the most promising directions for future research on the neural mechanisms of youth with eating disorders, there are several different avenues. One is that small sample sizes have precluded our knowledge of adolescent eating disorders and their neurobiology. We've got some really great big cohort studies going on across the world now. So in the US, we have the adolescent brain cognitive development study that is following adolescence from childhood all the way into young adulthood when eating disorders really start to come online. So we'll really be able to start to see some longitudinal neurobiological factors that show up, perhaps even before with-- before an onset and through the disorder. And we've also got the imagined cohort and other cohorts across the United-- or across the world. So longitudinal is going to be really important. And within that, studying at risk populations is going to be really important as well. There has been some work on this, but I think even more is needed to help us understand the neurobiological vulnerabilities to eating disorders in this group. I think other important areas for future research are just more work on understanding adolescent binge eating and adolescent ARFID and what neurobiology looks like there because we don't know yet. We've really lagged behind understanding of the neurobiology in these key populations. And more understanding of the neurobiology will really help us to inform treatments that are mechanistic and precise. And then I think a final really important future direction is going to be to increase representation in our samples. So most of the samples that we reviewed in our paper were comprised of female participants. And the rationale behind that was solid and made sense. It was that they wanted a more homogeneous group when they're conducting these smaller research studies. But we do know that eating disorders impact males and boys. And so it's going to be really important to see whether there are differences in neurobiology across boys and girls, and whether that impacts eating disorder symptom expression. We do know a little bit about how eating disorder symptoms like binge eating, restrictive eating can feel and be experienced qualitatively differently across boys and girls. So it's going to be really important to help us better understand the neurobiology of how gonadal hormones might be coming into play with this symptom expression. And so all of these things, longitudinal studies, including at risk populations, including more representation and including a more of a focus on binge eating and ARFID are going to be really important. And then I also think what's going to be important is including how neurobiology might change with treatment. 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