Laura Machlin Hi, I’m Laura Machlin. I am  currently a Postdoctoral Fellow at Harvard   University, in the Department of Psychology,  and I’m excited to share some of my work today   with you, focusing on the Dimensional  Model of Adversity and Psychopathology,   which is one model of  conceptualising early adversity. And so, my programme of research focuses on one  component of the early life environment and how   it shapes how children grow and develop, and  that is early adversity. And so, the way that I   define early adversity is experiences that are  likely to require a significant adaptation by   the average child and that are a deviation  from the expectable environment. And so,   experiences of early adversity can include  experiences like physical and sexual abuse,   experiencing neglect, chronic poverty,  direct exposure to community violence,   like in your neighbourhood. And  it can include other hardships,   as well, for example, like what some children  experienced during the COVID-19 pandemic. And it’s really important to understand early  adversity and how it shapes how children grow and   develop, because these experiences are extremely  common. So, more than half of children experience   some form of early adversity by adulthood, making  it a really important topic to understand and   research. And one reason that it’s really  important to understand early adversity   within the context of development, as well,  is because it’s very strongly associated   with risk for psychopathology. And so, if  you look at the X axis of this graph here,   you can see the number of experiences of early  adversity that a child has had on the X axis and   the odds of mental health disorder onset on  the Y axis. And so, what you can see here is   that as a child has experienced a greater  number of experiences of early adversity,   their risk for the onset of a mental health  disorder systematically increases, as well,   making it really important to  understand this relationship. And in fact, early adversity statistically  accounts for 32% of all psychological   disorders in adolescence and 44% of all  psychological disorders in childhood. And so,   these are really strong patterns of association.  I’ll also add here that this is a really broad   pattern of risk. So, early adversity here,  it’s impacting risk for both internalising and   externalising psychopathology, with similar  strength of association across disorders. So, early adversity is a really broad concept that  includes many different types of experiences and   so, part of what I’ll be doing today is talking a  little bit about how Researchers model and measure   early adversity. And so, I’m going to be talking  about three different models of early adversity   today. And so, the first model is the specific  type, or specificity model, and historically,   this has been a common approach that Researchers  have taken. And so, what it means is that   Researchers may focus their body of work on one  specific type of early adversity. So, for example,   focusing on childhood sexual abuse or focusing  on specifically institutionalised samples. And so, when you think about potential mechanisms  that may account for why experiences of early   adversity may increase risk for psychopathology,  what these models imply is that there may be   specific mechanisms related to specific types  of early adversity. And so, sexual abuse may be   associated with one neurodevelopmental mechanism  that accounts for some of the relationship between   sexual abuse and psychopathology. Whereas  institutionalised samples may have a different   mechanism through which institutionalisation  may impact risk for psychopathology. So,   that is the first model of early adversity that  Researchers have used, that specificity model. The second model that’s been commonly used in  the literature is an ACEs model, but stands   for adverse childhood experiences, or a cumulative  risk model. And so, the way that this model works   is that Researchers typically sum the number of  different types of early adversity that a child   has experienced, and then it – their – shows that  their risk for psychopathology increases. And so,   you can see this relationship, just like what  I showed before, whereas overall risk for all   different types of early adversity increases,  risk for psychopathology increases, as well. And so, there’s been a number of devel –  neurodevelopmental mechanisms that have   been studied using an ACEs or cumulative risk  approach, and some of those mechanisms include HPA   axis dysregulation, such as measuring cortisol as  a potential mechanism, linking adverse childhood   experiences and psychopathology, or the concept  of allostatic load. And so, there’s good evidence   to support these models of early adversity and  those mechanisms. But really importantly here,   these models of ACEs or cumulative risk  implicitly assume that all experiences of   early adversity impact neurodevelopment through  the same underlying global mechanisms. However,   if we think about it, there are  likely other mechanisms, as well,   for how early adversity impacts risk for  psychopathology that are at least partially   distinct, and I’m going to be talking  about some of those mechanisms today. And so, we covered, kind of, a specific model,  looking at specific types of early adversity.   The ACEs or cumulative risk model, which is  really looking at global mechanisms of early   adversity and then, the last model that I’ll talk  about, which I’ll spend some more time on today,   is the Dimensional Model of Adversity and  Psychopathology. And this model was created   by my graduate school mentor, Margaret  Sheridan and my postdoctoral mentor,   Kate McLaughlin. And so, what this model  hypothesises is that there’s two dimensions   of experience and each of those dimensions  of experience are going to be associated with   more specific neurobiological changes  and associated changes in behaviour. And so, if you look at the two axes here,  you can see that on one axis is threat,   which is one of the dimensions of  experience, and on the other axis,   the Y axis, is deprivation, which is that  other dimension of experience. And so,   by ‘deprivation’, what I really mean here is  reductions in expected cognitive and social   inputs that you would expect a child to  get. And so, experiences that are going   to be high in deprivation are going to include  things like neglect or institutionalisation. And then, on the threat axis, which  is the X axis here, so, by ‘threat’,   what I really mean is exposure to interpersonal  violence that’s going to either result in harm   to a child or threat of harm to a child, or to a  close other, like a parent or caregiver. And so,   experiences that are going to be higher in  threat are going to include things like direct   exposure to community violence, domestic  violence, and physical and sexual abuse. And so, the idea behind this  model is that when you have   a specific kid who’s experienced  early adversity in front of you,   that you would be able to understand their  experience and place them somewhere along   these two axes to understand the level of both  deprivation and threat that they’ve experienced. And so, I’ll provide just two examples here.  So, for example, you could see a kid who is in   a single parent household, with one sibling, and  their parent is really loving and supportive of   them. They’re not experiencing violence in other  areas of their life, like in their neighbourhood.   But their parent has to work three jobs to  financially support their family and as a result,   isn’t able to spend a lot of one-on-one time  with that child, or has to leave that child at   home alone just in order to work those jobs and  make ends meet. And so, if you think about that   specific child, that would be characterised by  a high deprivation and lower threat environment. And so, now, I’ll give a second  example. So, there might be another   kid in a similar neighbourhood that  financially, the family is doing well,   but parents are physically fighting at home and  that is making that child feel afraid. And so,   that type of experience would be characterised  by high threat and low deprivation. And so, when I give these examples, I think it’s  easy to see that when we think about the types of   early adversity and the experiences that these  children have had, that we might expect these   experiences to impact children in different ways  across development. And so, that’s really what the   Dimensional Model of Adversity and Psychopathology  is really helpful for, is that you can examine   experiences of deprivation controlling for threat,  experiences of threat controlling for deprivation,   and link that with more specific neurobiological  changes and changes in behaviour. And so, next,   I’ll present some evidence in support of  this model, and in all of those examples,   I will be examining deprivation controlling for  threat and threat controlling for deprivation. And so, based on prior work that’s been done,   we know that using the Dimensional Model of  Adversity and Psychopathology, that deprivation   has been associated with deficits in executive  functioning, like working memory and inhibitory   control, and then, it’s also been associated  with differences in language development. So,   in particular, that dep – experiences of  deprivation may be associated with deficits in   receptive language, specifically. And we know that  experiences of threat have been associated with   both behavioural and neural measures of emotional  reactivity and emotional regulation and also,   differences in fear learning, so, in how  children learn about new fearful stimuli. And so, I can’t go over all of  this body of work today, and so,   I’m going to choose to focus on just  a few components of this work. And so,   what I’ll talk about more – in more detail  today is associations between deprivation   and executive functioning and associations  between threat and fear learning. And then,   I’ll also touch on some changes in brain structure  associated with both deprivation and threat,   as well. And I do want to emphasise here that  I’m picking out just a few papers within this   larger body of work to highlight today, but  there has been a lot of work done in this area,   includer – including additional studies in  the areas that I’ll be presenting today. And so, the first piece that I’m going to go  over is associations of deprivation and threat   with brain structure, and I just wanted to start  by providing a little bit about – of background   about brain structure across development.  And so, I’m going to be showing data of how   deprivation and threat are associated with grey  matter in the brain. And so, from grey matter,   if you look at this brain right here, what you  can extract from specific regions of the brain,   which you can see are segmented here,  is information about cortical thickness,   the thickness of the cortex, cortical surface  area, so this is the peeled surface and then,   these two things, surface area and thickness,  combine to also give you information about   cortical volume. And so, when you look at the  cortex, Researchers typically look at cortical   thickness and cortical surface area. Whereas  when you’re looking at subcortical structures,   like the amygdala and the hippocampus, then  you typically need to use subcortical volume. Now, the reason why it’s interesting to  look at associations between deprivation   and threat with brain structure,  here, is that we know that early   life experiences may change these measures  of brain structure in different regions,   depending on how those regions are typically  developing, because they’re changing just in   typical development across the course of the  lifespan. So, brain structure can provide this   really unique window in under – into understanding  how early experiences may be shaping development. And so, the first study that I’ll present today  is my own work in 65 youth, and what we did is   we brought in children two to five-years-old  and we measured information to assess their   level of threatening experiences that they’ve had,  their experiences of deprivation and also, other   experiences of early adversity that don’t fall  into threat and deprivation, which is captured   here by cumulative risk. And then, brought them  in at five to ten-years-old and looked at their   brain structure to assess cortical thickness,  cortical surface area and subcortical volume. And so, based on prior literature, the  hypothesis here is that threat may be   associated with amygdala and hippocampal volume,  which is – which are subcortical structures,   whereas deprivation would be associated with  reductions in cortical thickness in association   cortex. So, in prefrontal, parietal and temporal  association cortex, we’re going to look at threat   controlling for deprivation and deprivation  controlling for threat here. And so, first,   I’m going to show associations of threat with  sur – cortical surface area, here, and this just   notes that this is controlling for age, gender,  scanner and that other dimension of experience. And so, what you can see here is that threatening  experiences were associated with really widespread   decreases here. So, the green areas here  highlight more highly significant areas.   And you can see here that threat is associated  with some really profound differences in brain   structure in these children, that really  crosses across the entire prefrontal cortex,   including both medial and lateral prefrontal  cortex, here, controlling for deprivation.   And so, this is really quite a dramatic  association that was found here. Now, for deprivation, what I’m going to show  is associations with cortical thickness and so,   I have hypothesised that there might be  decreases in cortical thickness associated   with deprivation. What we actually found was  increases in cortical thickness associated   with deprivation, including in the occipital  cortex, the insula and the anterior cingulate,   here. And so, this is really interesting because  this was one of the first studies that looked at   associations between early adversity and brain  structure in a younger sample of youth. And so,   given that we know that the brain develops  in a complex, protracted and hierarchical   manner that’s influenced by experience, this  association may capture an effect of deprivation   and increased thickness that’s present earlier  in development, even though there’s evidence   later in development that deprivation  may be associated with reduced thickness. And so, overall here, this study and others  have shown evidence that early adversity is   associated with brain structure in childhood. And  then, going back to the Dimensional Model here,   this particular study also provides evidence that  distinguishing between deprivation and threat,   rather than using an ACEs or cumulative risk  approach, may be particularly helpful here   because we found different patterns of association  associated with both deprivation and threat. So,   they were using different measures, cortical  thickness and surface area, and going in   different directions. And so, what that suggests  is that some of the prior literature that may have   measured early adversity in different ways  may have masked some of these associations. And so, going back to the Dimensional Model  here, you can see that this study provides   support for the model by demonstrating  distinct associations of deprivation and   threat with alterations in brain structure  in childhood controlling for one another. So, the second area that I’m  specifically going to focus on today   is associations between deprivation  and executive functioning. And so,   it was hypothesised when the Dimensional Model  of Adversity and Psychopathology first came out,   and there were theoretical papers published  about it, that deprivation would be   associated with deficits in executive  functioning, while threat would not be. And so, a systematic review and meta-analysis  in general paediatrics, done by Johnson and   colleagues, wanted to look at all the work that’s  been done up until this point. Assessing this by   looking at whether or not there are different  strength of associations between deprivation   and threat and associations with executive  functioning, and they specifically focused   on three areas of executive functioning here. So,  cognitive flexibility, so switching back and forth   between different tasks. Inhibitory control, so  being able to inhibit a prepotent response of   something that you’ve been doing, to then do a new  response, and holding things in working memory. And so, their hypothesis, based on the prior  literature and the Dimensional Model here, is   that deprivation would be more closely associated  with executive functioning deficits in all of   those areas, compared to threatening experiences.  And so, what they found is that early adversity   was associated with executive functioning in all  three of those domains, both in early childhood   and in adolescence. And that deprivation was  more strongly associated with deficits in   inhibitory control and working memory. But in  the area of cognitive flexibility, threat and   deprivation did not differ in their association  and so, in the area of cognitive flexibility,   kind of, early adversity more broadly may be  impacting deficits in cognitive flexibility. So, going back to this Dimensional Model, this  work suggests that deprivation, specifically,   may be more strongly associated with executive  functioning deficits, particularly in the domains   of working memory and inhibitory control.  And this may be really helpful in initial,   like, case conceptualisation of youth  who’ve had some of these high deprivation   experiences, like neglect or  institutionalisation. ‘Cause   it suggests that those children are going to be  more likely to have some impairments in working   memory in inhibitory control that could be  targeted through evidence-based treatment. Now, the last area of research that I’m going to  talk about is associations between threat and fear   learning. And first, I’m just going to talk a  little bit about what fear learning is. And so,   fear learning is a type of learning where people,  or in this case children, are learning to predict   aversive events. And so, the idea is you  create a situation when an aversive event   is going to occur, and children should be able  to learn what predicts that aversive event. And so, in a typical fear learning  paradigm, there’s usually three phases   pre-acquisition, fear acquisition and then,  fear extinction, and often, there’s two stimuli,   which is what I’ll present today. So, here these stimuli are going to be shown  as this blue square and this orange diamond,   here. And so, in the pre-acquisition phase of a  fear learning paradigm, you’re going to see these   two stimuli that are randomised and you’re just  going to see them come on your screen one at a   time and nothing happens. This is just a baseline  period. Then, in the fear acquisition phase,   you’re going to see these two stimuli one at  a time again, but one of them is going to be   randomised to be the CS+ or condition stimulus.  The other will be randomised to be the CS-. And   so, the CS+ is going to be paired with that  aversive thing, in this case 80% of the time. And so, for fear learning paradigms that are  used with children, usually the aversive thing   is a sound. So, it’s like a scream, or it  could be the sound of nails on a chalkboard,   something that’s going to be aversive to everyone.  And so, that orange diamond will predict that   that sound will occur about 80% of the time and  through that experience, children should be able   to learn that that orange diamond will predict  that sound, while the blue square does not. Then there’s going to be a fear extinction phase,   where you see those two shapes, one at a  time again. And you have the opportunity   to learn that those shapes are now both  safe and will not predict that sound again. And so, I wanted to look at associations  between threat and fear learning here,   because they were hypothesised in  the creation of the Developmental   Model as one of the deficits that may be  associated with threatening experiences. Another reason here is that it’s really  important to understand fear learning,   because as I said earlier, we know that  threatening experiences are associated with   greater risk for psychopathology in youth and  fear learning is a proposed mechanism for why   some evidence-based treatments may help to reduce  mental health symptoms. So, if you think about any   evidence-based treatment that involves an exposure  and habituation component, so that can include   exposure and response prevention or trauma focused  cognitive behavioural therapy, it’s hypothesised   that the way that these therapies work, in part,  is through underlying fear learning mechanisms. And so, the way that we measure fear learning  is through skin conductance response,   which is the sweat that comes out of your fingers  when you’re wearing electrodes like this. And so,   I’ll present data here that’s looking  at the amplitude of skin conductance   response to the CS+ compared to the CS-, here. And so, here I’m going to just  talk about one study that I’ve   done in an early adolescent sample  of 170 youth, ten to 13-years-old,   where we examined associations of threat and  fear learning controlling for deprivation.   And I was specifically interested in  looking at early adolescence here,   when psychopathology is likely to emerge and  then, in addition to looking at associations   between threat and fear learning, I also wanted  to look at associations with psychopathology. And so, at ten to 13-years-old, these youth  came in and we measured information about   their experiences with early adversity,  such as exposure to threat, and did the   fear learning paradigm and then, also measured  psychopathology. When they came two years later,   we measured psychopathology again. And so,  because of that, we’re able to look at the   emergence of new psychopathology over  time, controlling for current symptoms. And so, what I found here is if you look at this  low threat group on the left-hand side, here, and   this is pre-acquisition and then, the three blocks  of fear acquisition here, with skin conductance   response or physiological reactivity on the Y axis  here. And what you can see is that these youth who   had lower levels of threatening experiences in  the sample show a really expected pattern here. So, there’s no difference in their physiological  response at pre-acquisition, but then,   starting at the beginning of fear learning,  they can clearly differentiate between the   CS+ and the CS- here, which continues  across the course of fear acquisition. So, then higher threat youth in the  sample show the same pattern of response,   but you can see there’s a clear difference  here in the amplitude of that response. So,   what you can see is that high threat youth  here are showing a much greater physiological   response to the CS+ compared to the CS-,  particularly in early fear acquisition. And so,   this can really be conceptualised  as, like, heightened vigilance   to new threatening stimuli compared to  youth with less threatening experiences. And so, I took the skin conductance response from  the acquisition block one and used it to see if it   could predict future psychopathology symptoms  controlling for current symptoms. And what I   found is that that skin conductance response to  the CS+ in that first block of fear acquisition   partially mediated the relationship  between those threatening experiences   and prospective PTSD symptoms controlling for  current symptoms. And so, that’s really the   emergence of PTSD in early adolescence, because  it’s taking into account those past symptoms. And so, what this body of work suggests is that  threat, but not deprivation, here, is associated   with this pattern of heightened vigilance to  new threatening stimuli in your environment   during fear learning. And that this  altered pattern of fear learning   may be one mechanism linking  threatening experiences with   the emergence of psychopathology during  adolescence, in this case PTSD symptoms. And then, as I was mentioning earlier, this  has potential implications to clinical practice   ‘cause it suggests that interventions that  we know that target heightened vigilance to   threatening stimuli, like TF-CBT or  other exposure-based interventions,   may then help prevent the emergence of PTSD  symptoms in these youth. And then, going back   to the dimensional model here provides evidence  that threat specifically, but not deprivation,   is associated with changes in fear learning. And so, overall, what I’ve presented here today is   that deprivation has been associated with deficits  in executive functioning, that are stronger   associations than with threatening experiences.  And threat is associated with these altered   patterns of fear learning, while deprivation  is not. And then, both threat and deprivation   are associated with differences in brain  structure that are at least partially distinct. And so, I just want to wrap up by talking  a little bit about how I see the clinical   implications of some of this work, and some  of this has also been thought about really   well by Rachel Vaughn-Coaxum, who’s at the  University of Pittsburgh. And so, when you   think about the utility of the Dimensional  Model of Adversity and Psychopathology,   one of the things that it’s doing through this  work is it’s identifying mechanisms through which   evidence-based treatments may work for youth  who’ve experienced early adversity. And so,   for example, in the work that I’ve presented  today, it suggests when interventions that promote   executive functioning development, that target  heightened vigilance to threatening stimuli,   may be particularly useful for youth, based  on the type of experiences that they’ve had. The second thing that it does is it facilitates  potential future work related to treatment   matching. And so, you can see here that  I’ve shown some evidence of some disrupted   developmental processes, and you could think  about using that information in the selection   of an evidence-based treatment. And so, for  example, if you have a youth who’s experienced   early adversity and who’s experiencing depressive  symptoms, you might consider what associations are   likely to be associated with their experiences,  whether their experiences of early adversity are   more highly characterised by deprivation  or threat, in selecting an intervention. And we know already that deprivation  and threat can predict worse outcomes   for youth in psychotherapy, depending on  some specific situations. So, for example,   we know that deprivation is associated  with worse outcomes for parent training   interventions and that threat is associated  with worse outcomes for CBT for depression. So,   understanding these experiences and  where a child might fall along them,   may suggest, for example, that youth with  higher levels of threat-related experiences   may better benefit from behavioural  activation, rather than CBT or etc. And then finally, here, it suggests that maybe  in the future, there could be adaptations of   treatment for youth with higher levels of early  adversity, depending on those experiences. So,   perhaps it suggests that youth with higher levels  of deprivation experiences may need increased   repata – repetition of new skills because of  working memory deficits. Or that youth with   higher levels of threatening experiences  may also benefit from unique adaptations. And so, I’ll just wrap up by saying that what  I would advise, based on this model at this   current point in time, is to consider  children’s exposure to both deprivation   and threat along those axes, within case  conceptualisation, along with developmental   timing of those experiences and the severity  of the exposure. And then, hear more about,   kind of, the treatment selection and  modification of that evidence-based   treatments, based on the Dimensional Model  of Adversity and Psychopathology to come. And so, with that, I’ll say thank you   to my mentors who created the Dimensional Model  of Adversity and Psychopathology, Kate McLaughlin   and Margaret Sheridan, along with all my other  colleagues who’ve contributed to this work.