[MUSIC PLAYING] We are the Association for Child and Adolescent Mental Health, or ACAMH for short. And this is ACAMH Learn. Welcome to Mind the Kids, a podcast series dedicated to exploring the latest advancements in child and adolescent mental health research and practise. I'm Clara, an academic clinical fellow in child psychiatry, and I'm passionate about understanding and addressing the diverse mental health challenges faced by young people globally. In this series, I will be joined by renowned researchers and clinicians worldwide to discuss their cutting edge research, their innovative interventions and best practises in child and adolescent mental health. So today, I have the pleasure of receiving Professor Nathalie Auger from the University of Montreal and Professor Howard Steiger from McGill University, and we will be discussing their paper, maternal anorexia nervosa and risk of mental and neurodevelopmental morbidity in offspring, that was published in the Child and Adolescent Mental Health Journal. So it's an honour to have you both here, Nathalie and Howard, and I wanted to start by saying that we know that anorexia nervosa is increasingly prevalent among women of reproductive age. And in your study, you take a really important perspective. So you look at outcomes in the offspring of these women using a very large cohort of over a million people, which is super exciting from an epidemiological perspective. So to start off, I wanted to ask you, what was the key question or knowledge gap that you were hoping to address with this study? That's an excellent question. Thank you so much for asking it. We have a research programme in our institution, essentially, looking at the outcomes of pregnancy and issues surrounding the health of children in childhood and adolescence. One of those things is essentially the mental health of mothers, how mothers' mental health influences child's rearing and so on. At the population level, what we found, looking at the literature, was that there didn't seem to be much information out there on how anorexia, comprehensively, was associated with the outcomes of children later on in life. That's why we carried out this study. We wanted to see if we could tap our data to look more closely at all the different kinds of outcomes that could be linked with a mother's anorexia status. Do you want to add anything, Professor Steiger? Yeah, yeah. I think what's important about this study too is it-- increasingly, we become aware that anorexia nervosa, of course, has a sociocultural basis, and it can be influenced by familial factors, but it also has very strong biology and association with many other things that are quite far removed from eating. And so examining these sort of associations and the transmission of not only eating disorders, but mental health problems and attentional problems and neurodevelopmental problems really helps inform our understanding of what this disorder really is about. In current thinking, most experts in eating disorders understand anorexia nervosa to be, in fact, a metabo-psychiatric problem that has a large genetic component as well. And so I think the study by Nathalie's group really points, in many ways, to the way in which, yes, perhaps we're talking about some influences of a psychosocial nature, mothers transmitting vulnerability and that through those pathways to children, but also likelihood of biological connections that are very important to understand. Absolutely, and you mentioned the metabolic component. And it's not the focus of the discussion today, but I know there is another really interesting paper by both of you and your team looking at gastrointestinal outcomes I believe, gastrointestinal problems in the offspring of mothers with anorexia, using, I think, the same cohort. And I think it's just really interesting because your group is really advancing our knowledge that actually the outcomes we see in patients and in their offspring is not just about the mental health or the behaviour, as you said, it's about much more than that. So basically, we were talking about cohort studies before. And I know that there are other cohort studies also looking at maternal anorexia and offspring outcomes. One inclusive was using a UK cohort. But your study really stands out because, as you said, it's really comprehensive and you were able to follow-up those children for a very extensive period of time. And you also include neurodevelopmental outcomes. So what would you say are the main headline findings, and were there any results that particularly surprised you? Yes, another very good question. I'm not sure how you felt, Howard, but I was particularly impressed by the substance-related outcomes in the kids, especially neonatal abstinence syndrome and the childhood poisonings, where we weren't expecting those kinds of findings as much. We weren't expecting that we'd see such a strong association with neonatal abstinence syndrome. So that happens when the, at birth of the child and in those first few months, the child goes into withdrawal. We usually often don't know that the mother was taking substances. But it occurs because of the withdrawal of those substances. After the delivery of the child, can be discovered incidentally and reflects either an unreported or unknown substance use disorder in the mother. Same thing with childhood poisonings, where unexpectedly, there were a lot of poisonings in the child, suggesting that there are substances lying around in the house that the child is accidentally ingesting and leading to these requirements to go to the hospital and be seen for the child. I was particularly surprised by that, because those were substance use disorders in the mother that coincided with anorexia nervosa and were not detected. They only came to light when we saw the effect on the child, either at birth or in childhood. I thought that was particularly important and unrecognised. Yeah, I think that, that is really an interesting association to identify. I guess the stereotype of people who have anorexia nervosa is people who are very rule-governed, perfectionistic, overcontrolled. And so that image doesn't include, often, the reality, which is that many variations on anorexia nervosa include people who are highly dysregulated, impulsive, maybe a little bit more prone to being substance users, and that sort of a thing. And so, yeah, it was a bit of a surprising finding for me too, But I guess, as you're pointing out, Natalie, it really highlights the importance to consider detecting those kinds of things in clinical work. Also, I guess, there's another reality. I mean, not to try to malign or blame people who have anorexia nervosa, but suffering a severe eating disorder means people are very overly absorbed in the problems of managing eating and not eating and the consequences of starvation. And I think it is not unlikely then that we're talking about mothers who, at times, may be so distracted or so caught up in the realities of the disorder, that they may not always be attentive to things like stuff that's left around that their kids might be consuming and so on. So important stuff. I also thought it was really fascinating to see how clearly the results showed not only a mother-child transmission of anorexia nervosa, but of things that are very frequently concurrent with anorexia nervosa that people don't always consider or aren't always aware of, such as the neurodevelopmental angle. The results showed it wasn't so much autism, but, I guess, probably much more attentional problems and things like that. There is a very clear clinical connection comorbidity between anorexia nervosa and attentional problems. Some of the substrate would be common neurobiology dopamine-related systems, for example, that are involved in both anorexia nervosa and attention deficit disorder, things like that. And so that was pretty striking as well. Yeah, there were so many interesting findings. Speaking of the maternal transmission that you just mentioned, Howard, one of the findings that really stood out to me was the strong association that you found between anorexia nervosa and the risk of anorexia nervosa in offspring-- and particularly hospitalisation. I remember it was quite a large hazard ratio. And I think this question also applies to the other findings you just mentioned, because we know, as you said in the beginning, Howard, that there is a really strong genetic component to anorexia nervosa. But what I'm also wondering is about the role of the environment in the sense that growing up with a parent who is unwell, and potentially being exposed to certain behaviours or attitudes around food-- and equally, you just mentioned, for example, the inattention. And we know that ADHD, for example, has a very strong neurobiological basis. But I also wonder if the fact that if your parent has ADHD and you're constantly being exposed to disorganised behaviour, or if that's your reference level, I wonder how do you make sense of that balance between genetic and environmental influences in your findings, considering that we're talking about outcomes, really, later on in life. I think you followed up the kids up to the age of 17, if I'm correct? Well, actually, we're looking at kids who are hospitalised up to the age of 17, right? Because don't forget, the findings are really based on a database that reflects hospitalisation for anorexia nervosa in the public record. Of course, that brings things close to what has been a real interest of mine as a clinician, scientist, researcher throughout my career, which is epigenetics, the science about how the environment turns on or turns off genetic susceptibilities. And anorexia nervosa is a fascinating example of the ways in which we have clear heredity. But then an environment has to activate vulnerability. For example, you can't develop anorexia nervosa without doing too much calorie restriction or too much dieting. So you need an environment that, if nothing else, induces people to feel that they're overweight and feel that they should be restricting food intake. And we have some fascinating findings that really talk about the way in which nutritional factors, directly, can be involved in activating genetic susceptibility. So one of our recent studies points to not only the way in which genes that are involved in brain function, or that would be influential over mental health, can be turned on by malnutrition-- we were studying B12 deficiencies and things like that-- but also genes related to the metabolic side of things, insulin function and other stuff. So to get more back directly to your question, Clara, eating disorder's-- it's very difficult to know how to disentangle that, both in our data in this study, but in all areas, to really try to tease out the ways in which-- what is very likely is that both psychosocial influences and genetic influences are involved. Kids with anorexia nervosa, classically, are people who worry about others welfare to the neglect of satisfying their own needs sometimes. Psychodynamic law. We talk about parentified children who have to worry about their parents instead of worrying about themselves sometimes. And maybe there is some aspect of this, which might be about a mum who has attention deficit disorder and needs to be organised by the child in some ways. So that could be one factor. But I think we also want to strongly consider, it's not bad moms and it's not bad parenting that causes eating disorders. These are disorders that have a really clear basis in real physical susceptibility that then gets turned on by real environmental exposures. Some of them are stresses during development. But for sure, the ultimate one is the stress of being malnourished or calorie involved, subject to marked calorie restriction. So I don't know, Nathalie, if you have thoughts on how to disentangle those things, but clearly, any kind of research always has to bear in mind the reality that we're really talking about a biopsychosocial phenomenon that has a biology and an environmental context. Yeah, I agree with that. I think it's a general issue in-- when you're working with large data sets and doing epidemiological analysis, it's hard to address the cause. What is the underlying factor? Is it the biological factors, environmental factors, genetic factors? Those things are hard to disentangle. Sometimes there are some methods that can be used, like working with the family unit, to try to control those kind of environmental influences within the family, genetic factors within the family. In this particular study, we didn't use that approach. We were looking mother-child-- so there was no siblings as controls. But definitely, it's another research-- I consider it as another research question or the next step. What is the next thing that a researcher could look at, which is to try to disentangle using some different methods that are out there? Something for the future, I'd say. It's very, as Nathalie, saying, very difficult to devise methodologies that separate these things. But maybe we can infer some things, even just by patterns that are found in the data. What was very interesting was the finding that suggested that you had different effects, whether the mum was hospitalised for her anorexia nervosa while pregnant, or subsequently to or prior to. One of the things that I'm thinking of, as I'm saying this, is that the moms who were hospitalised while pregnant tended to be associated with mental health outcomes in the offspring. Makes me think of numerous studies that talk about maternal stress during pregnancy as being a correlate or an antecedent to mental health outcomes, or negative mental health outcomes in kids. We have a study that looked at the outcome for kids whose moms were pregnant with them during a very famous ice storm that happened in 1998, in Quebec. It was considered Canada's worst natural disaster. And so although it's a bit weird to think in terms of the effect of ice storms on anorexia, we were talking about moms who lived a horrible environmental stress. And strangely enough, those kids whose moms were exposed to marked environmental stress during pregnancy have a higher risk of anorexia, or eating disorder related symptoms, when they became adolescents many years later. Again, suggested the effect of, perhaps, mum's stress levels during pregnancy. Now, clearly, moms who are hospitalised for anorexia nervosa while they're pregnant, not only are they actively malnourished, but they're clearly undergoing a high level of distress. And so these are important factors to bear in mind even before people are born. The risk for developing things like eating disorders is kind of being prepared. I was going to say that it's really fascinating to think that even before someone is born, there are so many factors-- and I'm not in obstetrics and gynaecology research, but I know that it's also a very trending area of research right now, like the intrauterine environment and all those influences in the development of the child. And yeah, the ice storm study. I'm going to read that one. I didn't know about that one. Yeah, that's really interesting. Yeah, if I can say as a clinician, I think it's really important, because if there's one thing that-- I mean, there's huge stigma attached to eating disorders. If there's one thing that people who have eating disorders experience strongly, it's shame. And same for moms of kids, or parents of kids, who develop eating disorders. And these kinds of findings demonstrate that it's not so simple as all that. That there's a lot of biology that's acting even before you're born. You don't develop an eating disorder because of moral weakness. You develop it because of real physical susceptibilities that get turned on by real environmental exposures that are active throughout one's lifespan, even prior to one's lifespan, prenatally. 100%. And I think another element, also to add and to link with my next question, is it's also-- we know people have access to treatment at different times in their lives, and some people struggle to have access to treatment. And a really interesting finding of your study, for me, was the timing of the maternal anorexia that mattered. So you found that anorexia treated in later adolescence or adulthood was actually associated with increased risk in offspring, but, actually, anorexia before the age of 15 was not associated with increased risk. And I was going to ask both of you, but maybe Howard, you can contribute with your vast clinician experience, if that aligns with what we understand clinically about anorexia, or if that finding raises new questions, because in my mind, I felt that someone who may have anorexia earlier in life, they might have a more serious course of illness. But yeah, but that was just my musing. Yeah, I really scratched my head around that finding. I'm not sure how to interpret it. I hope Nathalie has a better interpretation than I'll have. But the thoughts that occurred to me were that-- I mean, we know, clinically, that forms of anorexia that we see early in adolescents tend to be much more treatable, and they tend to be a little more likely to be transient problems or problems that can be resolved quickly clinically, whereas eating disorders that persisted later into the life cycle tend to be a little stickier or more-- So maybe one possibility is we're talking about, really, milder forms of eating disorders that were present in these moms who were hospitalised early on. That's one idea. I mean, I suppose another one is that if she was treated early, maybe she was recovered before she gave birth. And so the consequences of an active eating disorder during gestation wouldn't have been active, that sort of thing. Or maybe mum's adjustment was better by the time the kid was born. Yeah, I had similar thoughts, that younger girls with anorexia, it was a different process as opposed to adult women with anorexia, where the underlying driver might be a bit different. I don't really know the extent to which young kids in social media are-- I don't know if there's an element of that in the disease. I felt like there was also another interesting finding, which was that women who had been treated had shorter treatment stays for anorexia nervosa, who may have been less receptive to treatment, checking out of the hospital early, and so on. Those ones were also having more of those kinds of outcomes in their kids later on. I felt like under treatment, or the early treatment of those 15-year-olds, the threat threshold might be lower also in hospitals. Clinicians might admit children more easily when they're very young, give them necessary treatment early on in life, that those factors are actually a good thing. Treating anorexia nervosa seemed like a good thing for her later children. Yeah, I guess that also points-- if you want to think even in terms of epigenetic factors, then we might be thinking about moms who gave birth later to their children have a greater accumulation, perhaps, of those kinds of mechanisms that might be transmitted to the foetus epigenetically. So who knows. But these are all issues for speculation, and really challenging to try to unravel. And speaking of challenges, Nathalie, you touched on that earlier a little bit when you spoke about sibling analysis. But one of the outcomes your study also looks at is at neurodevelopmental outcomes. And we know that those tend to cluster in families. So I was going to ask, how did you account for that in your analysis, and how confident you are that the associations you found regarding the neurodevelopmental outcomes specifically, they're just not reflecting broader familial risk. I see. That's another really good question. I see these issues as interconnected. Another question where we can't answer using the kind of data we have. And so it's, I guess, a little bit disappointing, where the answer is, again, I don't know. But I think that they're all important issues for the next phase of research, other researchers that may have different kinds of data, different kinds of details in their data sets to address this. What is the underlying cause? Is it maternal anorexia nervosa that's causing the problem, or is it other underlying or surrounding issues in her environment that are driving the other kinds of less expected outcomes like the neurodevelopment? No, it's not a disappointing answer at all. And I think that, actually, it's really interesting when you think about methods that you can use to try to disentangle those associations. And as Howard mentioned, what is epigenetics and what is really driving that effect? Is it epigenetics? Is it the genetics? Is it, as you said, the environment that is triggering that genetic vulnerability? And I think that really matters when we think about what interventions we can use from those findings. Yeah. Also, I think Nathalie's on the right idea when she says these things are interconnected. And so I think almost invariably true in all kinds of studies, whether they be clinical studies, population level, whatever, is that we can't disentangle these things easily. And it's probably because they don't disentangle. Eating disorders are not just about eating. They represent a multi-dimensional convergence of various kinds of vulnerabilities, some of which include attentional problems, personality traits, metabolic traits, other stuff like that. So maybe it-- well, I mean, this is speculative rather than based on the data I suppose, but my bet, if I had to bet, would be that they're part of the same vulnerability that's being transmitted. That's a really interesting take. Thinking about implications for clinical practise, and based also on your knowledge as clinicians and epidemiologists, what do you see as the main implications of your findings for supporting women with a current or past history of anorexia, who are maybe thinking about having children and they're worried about their reproductive future? Yes. I think, on the DNA analysis and what we saw or see in the data, is that eating disorders, they're not something that's affecting only you, and that there is a connection with your future descendants, your future families, and that they should be treated, not ignored, not let to become more severe, but treated early on to the extent that's possible and that this early treatment is not only beneficial for you, but your own children as well. That's the key takeaway that we sensed in the data itself. Yeah, I guess they point also to how important it is for people to be well-informed and well-educated about the realities of some of these kinds of problems. Again, it's not a shameful thing to have anorexia nervosa. It's something that exists for real reasons. And people who have it need to know that it may have consequences for their own future adjustments and for the adjustments of their kids and so on. It's funny. Probably a million times, I've been asked by somebody who has an eating disorder, do I have to worry about this? Am I going to transmit it to my children? What's really important there is epigenetic counselling. My answer to that one is really, you know what, genes are innocent until the environment turns them to a life of crime. And so don't think that just because you carry genes that could be associated with a certain vulnerability, that means necessarily your kids are going to have this problem. There's a lot of influences that will either protect or accentuate risk. And it's one of the reasons also to be careful to make sure you favour their development. But that there's nothing so determinant that means you have to feel that you're carrying some kind of awful legacy that you're going to pass on. And I think that perspective that both of you brought, that perspective about risk not being a sentence but something that actually can be modulated, when we speak about eating disorders, but mental health disorders more broadly, is so important because it's something people really care about. As you said, oftentimes patients ask, oh, will I pass this on to my children? And actually, the answer is much more complex and much more nuanced. And also just to highlight, because I know sometimes we have a lot of people with lived experience listening to this podcast, yeah, just to highlight, I thought that was a really hopeful finding about how if you actually are treated earlier before the age of 15, that was associated with much better outcomes for offspring. So to wrap up, looking ahead, if each of you could highlight one area of research you would really like to see developed further in this field, and especially using large population cohorts that we now have available, what would it be? I don't have necessarily correct answer, but in my mind, I always wonder about men with eating disorders, how that can influence the family and outcomes of their children as well. They aren't pregnant, obviously, but I feel like that might be an under-addressed issue that could potentially be important, as important as the mother. So I feel like that's something that could receive more attention in future research. Yeah, on that note, in fact, we have to be careful about not doing mum-blaming. Dads matter too. And, even in an epigenetic sense, there's a lot of data to suggest that dads transmit susceptibilities through the sperm line in a way that means they're involved in these things too. But no, I guess my answer to your question, Clara, is going to be obvious and predictable because of my clear interest in gene environment interactions and things. I think that, Nathalie, you have to get into population level studies that look at the influence of environmental impacts on people who have certain kinds of susceptibilities. And also, I don't know if those data can even be obtained. It seems to me that's what's a really key area that we have to explore in the area of eating disorders among some people. Not everybody. But there's a subset of people who go on to have very long-standing eating disorders that can sometimes persist throughout one's lifespan. And I'm pretty convinced that people who were struggling to-- what new treatments can we offer that will prevent these things or help these people recover? And I have a feeling it's almost, maybe, naive to think it's going to be some new treatment, rather than thinking about the trajectory of use of the treatments that we already have, And whether we can study the ways in which sometimes it's because people had a treatment that was time limited, and then a huge gap, before they received any further care, or weren't able to access the right level of care at the right time. And so I think it's really important if we can do that at a more population level and really study the trajectories through which people go in treatment. Bingo. I think that might reveal a lot of very important things about how to help people better. I mean, I could stay here all day talking about this just because I'm in the UK right now. There is a really big debate on assisted dying. And some people who have long-standing eating disorders, mainly anorexia, have become a part of this debate. And there's a lot of conflicting views because lots of people, and myself included, share your view, Professor Steiger, that eating disorders are definitely not terminal illnesses. And actually, when we look at these people with really long-standing eating disorders, I think about asking what happened. And often as well, there are other comorbidities involved. And as you said, oftentimes it's just that they weren't treated for long enough. But I understand it's a challenge. And it is a very contentious issue. But it would be really interesting if you could look at it with large population of data sets. It would be really interesting looking at outpatient outcomes as well. Just because when we look at inpatient outcomes, oftentimes there is the selection of bias that we are selecting for the most severe cases. But actually, what happens with people who maybe received brief psychosocial interventions and actually never engaged with services anymore? But that's just me musing. I just wanted to say a huge thank you to both of you. This has been so interesting. And to be able to discuss the findings of your paper in more detail and to hear from you both. Thank you so much. Thank you so much. Thanks for talking with us. Thank you from here as well. It was a pleasure to be with you. [MUSIC PLAYING]