In this podcast Professor Anne-Laura Van Harmelen talks about her new appointment of Professor of Brain Safety and Resilience, the work of Risk and Resilience Group, and its work on HOPES project and RAISE Study.
Within this Anne-Laura discusses how the brain responds to stress, the idea of a ‘developmental time window’, and the importance of taking a complexity science approach.
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Anne-Laura van Harmelen is a Royal Society Dorothy Hodgkin Fellow and PI of the Risk and Resilience Group at the University of Cambridge. Group Director & Principal Investigator, RAISE study, REACT study & HOPES project. The MQ funded HOPES project investigates the social and neurobiological mechanisms of adolescent suicide. The Royal Society Funded RAISE project aims to understand the neuro-immune mechanisms of stress resilience. For her work, Anne-Laura was awarded a ‘2020 Rising Star’ award from the Association for Psychological Science. Anne-Laura is on Twitter @DrAnneLaura and can be found on Linked In, and Google Scholar.
Interviewer: Hello and welcome to the In-Conversation podcast series for the Association for Child and Adolescent Mental Health or ACAMH for short. I’m Jo Carlowe, a freelance journalist with a specialism in psychology. Today I’m interviewing Anne-Laura Van Harmelen who has recently taken up the appointment of Professor of Brain Safety and Resilience at the Institute of Education and Child Studies at Leiden University in the Netherlands. Anne-Laura is also a Royal Society Dorothy Hodgkin Fellow and leads the Risk and Resilience Group at the University of Cambridge and Leiden University. Today we’ll be focusing on mental health resilience after childhood adversity.
If you’re a fan of our In-Conversation series please subscribe on iTunes or your preferred streaming platform. Let us know how we did with a rating or overview and do share with friends and colleagues. Anne-Laura welcome. Thank you for joining me. Can you start with an introduction?
Professor Anne-Laura Van Harmelen: My name is Anne-Laura Van Harmelen and I work in Leiden. I’ve recently moved to London from Cambridge where I was a Royal Society Dorothy Hodgkin Fellow and do research on the effects of child adversity on adolescent mental health and trying to better understand why some young people go on to develop mental illness after having experienced really negative events in early life, whereas others don’t.
I mean, I’ve always been very interested in child health and mental health. It’s actually one of the reasons why I wanted to study psychology. Before I studied psychology I did a Bachelors in physical education. During my Bachelors I ended up specialising in special needs and that kind of really sparked an interest in, kind of, what it was that made these children so special and unique and I wanted to better understand, kind of, their genetic and their cognitive mechanisms.
So I then decided to study psychology in Harmelen, in the Netherlands. During my studies I did some periods of studying abroad in Oslo and I did my Master’s Thesis in Richard McNally’s lab in Harvard where we studied the effects of early experiences on memory processing in adults, and there I became kind of fascinated with the really long lasting effects of trauma can have.
I did a PhD in Leiden studying the effects of emotional maltreatment on mental illness and trying to better understand why a lot of individuals who have experienced such negative events and why they go on to develop mental illness and whether their brain mechanisms or cognitive mechanisms and how they are related to mental illness.
After I did that I, kind of, noticed that whenever I gave talks to clinicians and people with lived experiences they would always be like, yeah but that’s nice all these nerve cognitive mechanisms, but what does it mean for us, and kind of are we now stuck because you see these changes in the brain. Does that mean that we’re now doomed? So then I really wanted to kind of better understand resilience and how we could help people.
So I decided to focus on better understanding resilience and resilience what it meant. How it worked. So that’s what I’ve been working on for the last, I don’t know, eight years.
Interviewer: As I mentioned in the intro you recently took up the new appointment of Professor of Brain Safety and Resilience. Why was this role created and what will be its main focus?
Professor Anne-Laura Van Harmelen: The role is created within a new funding stream at Leiden University to kind of help aid social safety and resilience and that’s, kind of, because of the fact that as our society becomes increasingly more complex it is really important that we better understand how we can deal with such fundamental issues, such as social and personal security or resilience against threats to our security.
Adolescence is such an important time period with major neurodevelopmental changes. Changes in the brain and major hormonal changes, major changes in just social environments.
Adolescence is usually also start when children go from primary school to secondary school and all these changes they’re happening whilst the brain is still very much in development during that time and also very sensitive to such changes. Adolescence is also the period of time where the majority of mental illnesses first emerge and behavioural difficulties first emerge. So the aim of this funding is really to better understand how we can increase social resilience in young people to help their transition from childhood to adulthood in a good way.
Interviewer: Before we go on it would be really important to give a definition of what you actually mean by resilience.
Professor Anne-Laura Van Harmelen: Resilience in general refers to the ability of an organism to adapt to a changing environment and to cope with the environmental challenges, but even in my field, in mental health research there’s considerable heterogeneity in what people mean with resilience. However, and there’s over 60 years of research on resilience, like vast literature there. There is an emerging consensus in the field that resilience really refers to a process of positive adaptation in response to stress.
So that means that when you then apply it to, in my case, individuals with a history of early life experiences where you can’t really measure the process of adaptation during stress, because that would mean that you’ll be measuring individual’s responses during maltreatment, during abusive episodes. What we really refer to with resilience is functioning after such experience that is better than expected or better than others with similar levels of adversity, and because of the fact that early life experiences have such a big impact on a whole range of domains, be that from academic to mental health to personality to behavioural aspects of functioning, it’s really important to kind of look at how well someone is doing across all those domains.
We know that such resilient functioning is aided by factors or we call them resilience factors and those resilience factors say they are found within the body, such as your genetic profile or how your brain responds to stress, but they’re also found outside the body in the form of social support or social structures in which you grow up and they’re all important in determining or aiding resilient functioning.
Interviewer: Globally I think over 50% of children and adolescents experience dramatic and stressful events in early life and yet not all of those young people will go on to develop mental health disorders. So why is that? What separates the ones who do from the ones who don’t?
Professor Anne-Laura Van Harmelen: That’s the million dollar question. That’s the I would say key aim of my research group is to better understand why some young people develop mental illness and others don’t. We don’t know is the short answer. We don’t know exactly what differentiates those who go on to develop psychopathology from those who don’t.
But we do know that are a lot of important factors that may contribute to this in the form of risk factors or resilience factors. We also know that there is not one factor that rules them all, rather that they each have a really small contribution and they interact together. You can think about your family environment is incredibly important for how you cope with stress in later life and your family environment has a big influence on, kind of, the friendships that you form and the way you interact with people. So these factors they’re both related to each other.
Interviewer: Is there some kind of resilience biomarker that can help identify who is at greatest risk? So perhaps you can talk through some of these influences that intersect.
Professor Anne-Laura Van Harmelen: There are resilience biomarkers. I mean, there are important aspects within your biology that can aid how you respond to stress, how you respond to active experiences, but there is not one of them. There actually are a lot of them and they are all inter-related and they change over time.
So it’s important to look at the whole system of biomarkers. I don’t really like the term biomarker. It suggests that you either have resilience or you don’t which I don’t really agree with. So what we know, for instance, is that the way that your brain responds to stress is really important. We’ve just finished a review paper where we looked at all the literature, looking at those kind of three key regions in the brain that are important for emotion, regulation and stress responsivity.
We looked at what the findings were of studies that compared those individuals who had experienced maltreatment remained mentally healthy throughout their lives and compared them with those individuals who had experienced childhood adversity and who were currently mentally ill or had developed some mentally and mental illness in their life, and what kind of differential changes, not necessarily that people who were more vulnerable in their functioning that they had stronger stress responses, but it was rather the case that those who were currently more functioning, more resilient, that they had stronger dampening of the initial stress response.
So the stress response was kind of the same, but it was more the modulation of the stress response that was a bit stronger in individuals who were at that point, more functioning, more resiliently, but other than that there are indications that the signs of the hippocampus might be different, where a larger structure is associated with, kind of, more adaptive functioning. So these are two clear biomarkers, if you will, in your brain, but then we also showed that those adolescents who reported higher friendship quality in adolescence that that was related with more resilient functioning in adolescence.
Another paper where we looked at resilience we found that if adolescents were able to recall more positive memories that were specific, so a specific positive memory is a memory where it’s kind of locked in time and place. So a good example is that time where someone helped me when I fell and they were really nice about it, and then that gave me a good kind of feeling, and if you are able to remember really specific positive memories we found that that kind of helped young people and lowered their, kind of, risk for mental illness.
So all these examples are brain and cognitive aspects and social aspects and we also know that friendships are incredibly important in determining how your brain responds to stress. Research studies by, I think Ann Masten and Megan Gunnar who show that in animals social support can actually lower stress responses and there’s a really interesting paper where the number of friendship interactions in adolescence they predicted how these young people responded to social exclusion a few years later, and that clearly shows the link between social experiences and how your brain responds to stress.
So all these mechanisms they might help a presenting functioning, but they’re also kind of inextricably intertwined. Social experiences can actually help shape the way you respond to stress, and it’s not just social experiences, but also really simple things like the amount of sleep you had last night and you have a healthy diet shapes your stress response and that, kind of, also really nicely shows that small changes in when you had a bad night or not kind of really can have a big effect in how you respond to stress the next day.
I think it’s also highlights the kind of dynamic nature of resilience and how you respond to stress. If you have a really good social network but your best friend moves away then you might, at that point of time, you might have been really, really resilient, but you might be more vulnerable because of the fact that your friend has just moved away, or if you had a really bad night you might respond to a stressor the next day in a very different manner than when compared to when you had like a solid night of sleep.
That kind of highlights the dynamic nature of resilient functioning where if you haven’t been resilient in the past it doesn’t mean that you can’t be resilient in the future. It just means that at that point of time you were a bit more vulnerable.
Interviewer: Anne-Laura, I understand that some of your findings though suggest that there may be a developmental time window. So where children may be especially sensitive to the impact of maltreatment or conversely, sensitive to positive influences. Can you tell me a little bit about this?
Professor Anne-Laura Van Harmelen: What we found is that resilience factors and the way that they interact with each other they remain relatively stable over the adolescent time period, but that they are slightly more different in the way that they’re connected to each other in early adolescence, suggesting that they’re more plastic, more amenable to change in early adolescence and that’s, kind of, the period of 14 years of age.
So that suggests that that time period might be an especially crucial time period for intervention and prevention efforts, and there’s some some other research called the life course model of stress theory that when there is a stressor in certain developmental time period where certain brain regions are developing that those brain regions are especially vulnerable to that stressor.
We haven’t really been able to fully corroborate that in research yet, but it would also be interesting to see whether or not those brain regions are equally sensitive to positive influences during those kind of developmental time periods, and that is something that we don’t know and I really want to better understand and investigate.
Interviewer: I want to look at some of your research. As we mentioned in the intro you lead the Risk and Resilience Group. So what’s the main focus and aims of this research group?
Professor Anne-Laura Van Harmelen: The aim of the research group really is to better understand how resilience can be achieved in young people who experience really negative things in early life. What we do specifically is we investigate mechanisms of risk. Some of my group for instance are examining what the neurobiological mechanisms are that underlie really vulnerable functioning in the form of suicidality and suicide and how those brain mechanisms how they interact with the social environment.
That is kind of one aspect of our group, but then we also look at mechanisms of resilient functioning. So then we’re studying individuals who have experienced really negative things but went on to do quite well, and in that population we really want to investigate what it is that sets them apart at that point of time and whether or not that changes over time.
So if the kind of mechanism for resilience are the same across the developmental time periods, whether they’re the same for early adolescence versus late adolescence or whether or not they might change, and if so what is it exactly what changes and when should we intervene and which processes and which mechanisms.
Interviewer: I notice on your website it states that the approach that’s taken is a complexity science approach. So what does that entail and why is that approach so important?
Professor Anne-Laura Van Harmelen: So complexity science really suggests that there is not one mechanism that determines how someone becomes resilient or not. Rather it suggests that there are many different influences and that those influences are all interrelated and that they might change over time and complexity approach really focuses on these interactions and their dynamic changes over time.
So instead of just focusing on or zooming into the brain or zooming into specific aspects of the brain we investigate the brain in interaction with other factors or with the social environment and look at how those factors predict change over time. That’s kind of the approach that we take.
Interviewer: Do most studies examine and integrate these complex dynamics or is there a lack?
Professor Anne-Laura Van Harmelen: I think that there are really good new efforts where labs are starting to appreciate the importance of not just looking at the brain in isolation or social experiences in isolation but rather at the interactions, but the problem with that is that you need lots of data for it. Lots of data meaning lots of individuals coming to the laboratory, doing these neuro tasks or going into the brain scanner and you also need to have lots of data from every individual over time.
Now that is time consuming for your participants, but also really expensive and therefore people haven’t been able to do it as much as they would have liked to just because it’s really expensive and you need to have lots of funding to be able to do it, and a new way to address that problem is to work together as scientists. Maybe I have some data on, say, 40 individuals and a colleague of mine in Scotland had data on 60 individuals, and we all work together and we kind of address them or assess the same things where we can pull all this data together and then examine it in a more comprehensive manner and that’s what lots of new projects are actually doing.
One good example is the Enigma Project focusing on the genetics and brain mechanisms of mental disorders, and another good example of that is the HOPES Project where we’re looking at how the brain interacts with the social environment and making individuals more vulnerable to adolescent suicide, and those projects are kind of setting themselves apart by the big collaborative nature of those projects and by scientists really working together.
Interviewer: I wanted to ask you about the HOPES Project. As you say it investigates the social and neurobiological mechanisms of adolescent suicide. What are the takeaways so far from this important work?
Professor Anne-Laura Van Harmelen: We’re really still in the baby phase of the HOPES Project because what we’ve done at the moment is we’ve established, kind of, the largest data set on adolescent suicide which means that we’ve made the database and have about 60 research institutes who have contributed data, and at the moment we’re putting all that data together and we’re still analysing. So there are no, as of yet, no real clear results, but we have been looking at some data in my lab in Cambridge and that data-set it was a really small data-set.
We were looking at how the brain factors that we know that are important for suicidality how they relate with how specifically rumination. So rumination refers to really the tendency of people to repetitively think really negatively about certain things and the social environment in this case early life experiences.
So we looked at how these three aspects of brain ruminative tendencies and the social ferment and of how they were related with suicidality, and what we found is that there’s a really strong link between ruminative tendencies and suicidality. The way that the brain was related with suicidality might go through increasing ruminative tendencies.
Another outcome from the HOPES Project is we did a really big review which is, kind of, we read all the literature examining the brain and its relation to suicide and what we found is that there are some vergence in the literature that suggests that there might be two big networks at play that might be altered in the individuals who are more sensitive or more vulnerable to suicide and where you have, kind of, the prefrontal regions or the control regions that are really important for people to plan their behaviour and kind of regulate your responses and the more central regions that are really important for how you respond to certain situations, how much you ruminate, how you feel about yourself in relation to others.
There were indications of kind of alterations in the functioning of these networks in individuals who are vulnerable to suicide and suicidality, and that we feel that if both networks are altered that might lead to really high risk situations where people might feel really negatively about themselves or in response to certain events and then don’t really have the capacity to regulate those emotions or to control or plan their behaviour or plan alternative actions that might make them especially vulnerable to suicide.
We also did a really big special issue in a journal where we invited all the leading suicide researchers to contribute their latest findings and we published that special issue in the Journal of Affective Disorders and what we found is that there’s lots of indications of small mechanisms across a whole range of domains, again social experiences, but also genetic contribution that might make individuals more vulnerable, but again we don’t really know how those interact.
Interviewer: I suppose the critical question then is how do you take something like the HOPES Project? How do you then go about translating research of this kind into practice to support adolescent mental health resilience?
Professor Anne-Laura Van Harmelen: That’s a really important question. You need to have the foundations to build good therapy that addresses or that is helpful to different individuals and a better understanding, the kind of, the groups of individuals that might have different risk mechanisms and how we can help each of those groups is incredibly important at the moment, but at the moment research kind of suggests that there’s one preferred way to go about for certain therapies.
And I think that harnessing this complexity science method, better understanding of the various mechanisms that might be there that might make individuals more vulnerable and might give us more new pathways to intervene and better understanding how people might be more vulnerable will hopefully lead to new insights into how we can help them.
So I think my research really lays the foundation on which research or intervention studies and prevention studies can build on.
Interviewer: The R&R Group as a number of other ongoing studies I understand, including the RAISE Study and react. Can you tell us something about these.
Professor Anne-Laura Van Harmelen: Yeah, of course. So the RAISE Study stands for Resilience after Individual Stress Exposure, and that study looks at how the brain interacts with the immune system during stress and whether or not that kind of helps a resilient functioning. So what we do for that study is we invite individuals with a history of adversity to come to the laboratory and then we put a cannula in their arm and then we bring them to the brain scanner and in the brain scanner they are undergoing something that is a bit stressful, but can’t tell you what because we’re still scanning people, but all individuals do know that they’re undergoing something that is stressful in advance of coming to the lab.
The purpose of doing that is so that we can study how the brain responds to stress and how the immune system responds to stress, and the reason for that is we know that early adversity shapes your brain responses. For instance, research from my group has shown that individuals with early experiences have, kind of, sort of hyper responsivity in the amygdala which is a region that is really important for salience detection, for threat detection and that ultimately it’s helpful because if you’re able to quickly detect a threat you’re able to respond to that, but if that kind of threat detection is always there it might make you more vulnerable and what the science suggests that individuals with maltreatment have kind of a hyper vigilant pattern of responding to emotional stimuli, and at the same time we know that early life experiences through changes in diet and sleep but also what happens when when your brain responds to stress, it kind, of activates the HPA axis and the HPA axis then activates your hormones that makes your body prepare to fight or flight.
So what also kicks in is the immune system and your immune system is kind of activated to fight the infection. We know that this is the case in acute stress and we also know that individuals who have experienced maltreatment if they have this kind of heightened inflammatory response still in their blood when you measure them so it seems to be that they have this persistent activation of the immune system.
So we find this hyper responsivity both in the brain but also in the periphery and the immune system and the thing is that the inflammatory markers that we measure they can actually travel upwards through your bloodstream, through your brain, and they can cross what is known as the blood brain barrier and there they amplify stress responses in those brain regions that we just talked about.
So it is thought that individuals who have experienced really negative things they are kind of caught in this positive feedback loop where their brain is more responsive to threats and their immune system kicks in and their immune system is kind of persistently activated and their immune markers travel upwards to the brain and further amplify their stress responses, but this is still a theory that has never been tested.
So I wanted to first test when we can find support for that and then test individuals who are more resilient, but they somehow have some sort of break in that system and where it is it’s at the level of the immune system or is it at the level of the brain, and then if there is some sort of brain system does it actually predict that they are doing better over time in terms of their mental health and wellbeing.
So that is the RAISE Study, but then we were testing individuals in the lab every day. I have a team in Cambridge who are absolutely fabulous. They were working really, really hard testing because this is a really comprehensive study. For every individual in the lab there had to be an immunologist present, bloods, a radiologist to assess their brain. They had to have the research assistants there to help participants. We had to have a clinical research nurse to put the cannula in and to assess the participants.
So every every participant required a lot of, kind of, experts in the lab and then we also took… It took an entire day and of course in March when the pandemic hit we had to stop our research study, but we had all this data on these individuals about their stress responses in the lab. So what we did is we followed up these individuals so that we could see how their brain responses in the lab, how that predicted if at all, how they responded to to to the pandemic, to the stress of social isolation and to the stress in general. So that is the REACT Study, the resilience after the COVID threat study and this is also very much ongoing. The last wave will be assessed in October.
Interviewer: Anna-Laura, what else is in the pipeline?
Professor Anne-Laura Van Harmelen: We’ve mentioned the Social Resilience and Security Research Programme. I’m super excited about that, and one of the things that we’re doing at the moment is studying through Delfi methods which is, kind of, asking experts what they think are the most important questions in the field related to in this case transgressive behaviours.
What I’m really excited about is the plan is to really approach this question from all these different domains of different fields, archaeology, philosophy, education and child study, psychology, neuroscience, law and our plan is to to really come up with a new framework for what is transgressive behaviours in adolescents and importantly also what are, kind of, online behaviours that are considered to be transgressive and what are considered to be normal so that we can then study them.
So that is something that I’m working on at the moment. I’m super excited about because it’s so important. We don’t know anything about online behaviours in young people. What is kind of normal online behaviour? Discuss how important online behaviour because of the huge importance and also kind of time that people spend online it’s super important that we know more about that.
Interviewer: Finally, Anna-Laura, what is your takeaway message for those listening to our conversation?
Professor Anne-Laura Van Harmelen: I think in general when I talk about my research what I find really important is that if you’re feeling low, if you have mental illness it is really important to know that it will change and if you’re not resilient at the moment know that you can build resilience, you can become more resilient in the future. It is not something that you have or don’t have. It is something that you learn and build and become.
Interviewer: Thank you ever so much. For more details on professor Anne-Laura van Harmelen please visit the ACAMH website www.acamh.org and Twitter at ACAMH. ACAMH is spelt ACAMH and don’t forget to follow us on iTunes or your preferred streaming platform. Let us know if you enjoyed the podcast with a rating or review and do share with friends and colleagues.