Reward- and threat-related neural function associated with depression

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In this podcast, we hear from Dr. Johnna Swartz, Assistant Professor of Human Ecology at the University of California Davis.

The focus is on the JCPP paper ‘Reward- and threat-related neural function associated with risk and presence of depression in adolescents: a study using a composite risk score in Brazil’ (doi.org/10.1111/jcpp.13496), co-authored by Dr. Johnna Swartz.

Johnna sets the scene by explaining why she opted for Brazil to conduct her research, and provides us with a summary of the paper.

Johnna then details why it is important to study low risk, high risk, and depressed adolescents, rather than just low risk versus high-risk adolescents or non-depressed versus depressed adolescents, before highlighting and explaining the key findings of her research.

Furthermore, Johnna also discusses the implications of the findings for professionals working with young people and their families, and whether the risk scores used in the study are being adapted for use in clinical settings to help assess depression risk for young people.

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Dr. Johnna Swartz
Dr. Johnna Swartz

My research interests include identifying genetic and brain markers that predict psychological functioning, including the development of mood and anxiety symptoms, in adolescents and young adults. I also examine environmental factors, such as stress, that moderate these associations to determine the environmental contexts that increase or mitigate risk. (Bio and image from Department of Human Ecology at UC Davis)

Transcript

[00:00:27.610] – Jo Carlowe: Welcome to a different type of In-conversation podcast from the Association for Child and Adolescent Mental Health, ACAMH, where we will look at the paper ‘Reward- and threat-related neural function associated with risk and presence of depression in adolescents: a study using a composite risk score in Brazil’, recently published in the JCPP. I’m Jo Carlowe, a freelance journalist with a specialism in psychology, and I have with me Dr. Johnna Swartz, Assistant Professor of Human Ecology at the University of California Davis. Johnna is co-author of the paper we’ll be discussing today.

[00:01:02.010] 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 review and do share with friends and colleagues. Hi, Johnna, thank you for joining me. Can you briefly introduce yourself?

[00:01:16.700] – Dr. Johnna Swartz: Thank you for having me here. My name is Johnna Swartz as you introduced me. I’m an Associate Professor of Human Ecology at the University of California Davis. My research primarily uses a neuroimaging technique called functional magnetic resonance imaging, which we abbreviate as FMRI to study the way the brain works, and I’m primarily interested in using FMRI to study activity in the teenage brain or the adolescent brain and also sometimes in young adulthood, and using that to study how the patterns of the way the brain works and how the brain develops across adolescents, across those teenage years, how that can potentially increase or decrease risk for developing different types of mental health problems.

[00:02:00.910] – Jo Carlowe: Johnna, what prompted your interest in young people’s mental health?

[00:02:04.420] – Dr. Johnna Swartz: So, in terms of what prompted my interest in studying mental health in general, I think one of the big motivators for me and things that got me interested is just how many people in the population develop a mental health problem across the lifespan. So to just take one example of anxiety disorders, which is one of the types of mental health problems I’ve looked at in my research estimates suggest that anywhere between 25% to 30% of the US population, just looking at the US will develop an anxiety disorder at some point over their lifetime.

[00:02:39.350] And so we think about that. That’s more than a quarter of the population that’s experiencing just this one mental health problem of anxiety disorders, and if we factor in other mental health problems like depression and substance use disorders, schizophrenia, we’re really looking at a very large percentage of people who are affected by this in one way or another at some point in their lives. So I think everybody has a personal connection in some way to mental health, whether they themselves have struggled with a mental health problem or they know a family member or a close friend who has, so I think that leads to a lot of personal connections with mental health that’s motivating as well.

[00:03:16.880] Then in terms of why young people’s mental health and why the period of adolescents, we study that period because I’m primarily interested in anxiety disorders and depression, which this paper is about, and research suggests that especially for depression the risk of developing depression greatly increases during those teenage years. That period of adolescence. So that’s a really interesting time to study the emergence of mental health problems, because that’s when many often emerge for the first time. So that’s why we look at that period in particular, as we want to kind of look at what’s contributing to that first development of that mental health problem.

[00:03:54.340] – Jo Carlowe: Thank you. Well, let’s turn to the paper, ‘Reward- and threat-related neural function associated with risk and presence of depression in adolescents: a study using a composite risk score in Brazil’, which was published in the JCPP. Most neuroimaging research on adolescent brain development and mental health has focused on high income countries. Why did you opt for Brazil to conduct your research?

[00:04:17.120] – Dr. Johnna Swartz: There’s kind of two answers to that question. One is the kind of more theoretical, research-oriented question of why should we conduct research in low- and middle-income countries like Brazil? There’s a couple of really good reasons that we should be, kind of, more inclusive in our research and conduct research in different countries. I think one is that actually the majority of the children and adolescents on the globe live in low- and middle-income countries. So if we want to have our research apply to the majority of children and adolescents in the world, and we want it to be useful for people across the globe, we have to include participants in our studies who are from those countries.

[00:04:55.060] I think also kind of from the theoretical end it’s useful for researchers in high income countries to test and compare results in low- and middle-income countries, because that can tell us how well our theories of adolescent brain development and our theories around how the brain contributes to mental health problems, whether those apply in other countries and cultures and settings as well. So are some of these patterns of mental health risk and brain development are they pretty universal, where we see them across the globe and across different countries?

[00:05:24.810] Or are some of these patterns we’ve detected in high income countries that signify depression risk? Are those more kind of context specific and really only predicting depression risk in high income countries? So that’s just good to know for our theories and understanding the role of adolescent brain development in mental health. In terms of the more kind of practical reason of why Brazil specifically, that was a more, kind of, practical consideration in terms of this is where we established a really strong collaboration and the way we established this collaboration in Brazil was actually this really unique opportunity that we got through the foundation MQ, which is a British Foundation that is funding research to promote mental health and quality of life.

[00:06:06.710] And they held this innovation workshop a few years ago where they invited investigators from across the globe who are interested in adolescent mental health to travel to London, and we got together in teams and then over the course of a few days put together a grant proposal, and then they funded one at the end of the innovation workshop, and our proposal got funded. So that’s actually what got this research started. So in my team one of the investigators there was Christian Kieling, who’s my current collaborator, and he is a researcher in Brazil.

[00:06:36.990] He’s a child and adolescent psychiatrist. So we were able to form this strong collaboration, working together and that’s really important when you’re doing research in a foreign country to have somebody on the ground level who speaks the language, who knows the regulations of research in that country, who knows the culture of the participants you’re working with. So that’s kind of why Brazil specifically is that we were able to form that collaboration through that innovation workshop and then have that strong connection there that allowed us to do that research.

[00:07:06.170] – Jo Carlowe: Johnna, can you give us a summary of the paper? What did you look at?

[00:07:09.590] – Dr. Johnna Swartz: So the goal of this paper was to look at how brain activity differs in adolescents who are at risk for depression, and in adolescents who currently are depressed have a current depression diagnosis compared to adolescents who have low risk for depression, and specifically we were looking at this in Brazil, which, as we just discussed is a country where not much neuroimaging research has been conducted so far. So the goal was to look at this in a different location than from a high income country. An additional kind of innovative component of this study was how we recruited participants into the study, and our goal was to again look at adolescents who are at different levels of risk for depression.

[00:07:47.660] So to do that we had the adolescent participants complete a risk questionnaire that consisted of a number of different questions that assessed different risk factors for depression that we know of from prior research. So things like failing a grade at school. Getting into fights at school. Running away from home. Feeling socially isolated from peers, having poor relationships with parents or between your parents and other questions. So they answered all of these questions on the risk questionnaire and using their responses for each participant a risk score was calculated telling us their kind of relative risk for developing depression in the future.

[00:08:24.640] And this was, of course, based on prior research in previous cohorts of adolescents where the risk score had been tested and had shown to predict depression risk. So using this risk score that we had for each participant, we recruited a group of 50 adolescents who were considered at high risk for developing depression. So they had relatively high risk scores on this risk calculator, but they were not currently depressed and had no previous history of depression. Then we recruited a group of 50 adolescents who were currently depressed and also had a pretty high-risk score on this risk calculator.

[00:08:57.520] So they were high risk and currently had a depression diagnosis, and then we recruited a third group of 50 adolescents who were low risk for depression. So they had pretty low scores on our risk calculator, and so a low risk of developing depression in the future, and all of these 150 participants completed an FMRI scan, and the goal was to look at differences in brain activity across the three groups to see if we could pick up on differences in brain function that could tell us a little bit more about how brain function might be related to risk for depression and developing depression.

[00:09:31.130] – Jo Carlowe: Most previous studies compare low risk versus high-risk adolescents or non-depressed versus depressed adolescents. Why was it important to study those three groups, low risk, high risk, and depressed adolescents?

[00:09:45.920] – Dr. Johnna Swartz: So that allows us to make stronger conclusions about results and, kind of, gives us the complete picture. So if you think about comparing low risk versus high risk adolescents, if we just had those two groups and we found a difference between those two groups and brain function that would tell us that the high risk adolescents differed in some way in brain function from the low risk adolescents, but what we don’t know is if that’s actually going to predict the development of depression in the future since they’re not currently depressed.

[00:10:15.870] So we’re not certain that that pattern we’re seeing in the high risk adolescence is really going to contribute to the development of depression, and likewise if we look at non-depressed versus depressed, if we see a difference in brain activity in the depressed group, we don’t really know if that pattern existed before they developed depression and contributed to their depression risk or maybe that pattern of activity we see in the depressed group developed after they developed depression and is kind of a response to developing depression, and since we’re interested in risk we want to see patterns of brain activity that may exist before people develop depression that could have contributed to their risk.

[00:10:52.880] So if we get all three groups together, low risk, high risk, and depressed, and we see a difference in brain activity that is similar in our high risk and our depressed adolescents, and that differs from our low risk adolescents that increases our confidence that that pattern of brain activity is potentially a risk factor for depression, since we see it in that high risk group and is also contributing to the development of depression because we see it in that depressed group as well. So it just allows us to draw those stronger conclusions about the patterns of brain activity that we see.

[00:11:23.490] – Jo Carlowe: Right. That’s really helpful actually and what did you find? Can you highlight and explain the key findings.

[00:11:29.910] – Dr. Johnna Swartz: There are several findings. So I think the main summary or take away. So one of our questions was are we going to see the same patterns of brain activity associated with risk for depression and presence of depression in these adolescents from Brazil? As has been shown previously in FMRI research in high income countries like the US and the takeaway is that we did see some patterns that were similar to what have been shown in the US and then we saw some patterns that were different. So one example of a pattern we saw that was similar to what has been shown in the US is that we found that higher connectivity or correlation activity between the prefrontal cortex and the amygdala during a task when the participants were viewing emotional faces, negative emotional faces when those two regions were more connected or communicating with each other better that was associated with lower depression symptoms across our entire sample, combining across all three groups.

[00:12:24.020] And that pattern of stronger connectivity or communication between the prefrontal cortex and the amygdala being associated with lower depression has been found frequently in other studies, for example in the US. So we think that that pattern is suggesting that better emotion regulation and regulation within this circuit might be helping with lowering depression or lowering risk for depression. So the amygdala is kind of the emotional hub of the brain, and it responds strongly to things that are threatening, stressful, negative in our environment and it can then activate the stress response, and we think one of the patterns of brain activity that contributes to risk for depression and anxiety is if the amygdala becomes overactive and it starts responding too frequently or too strongly to things that are stressful or negative in our environment.

[00:13:14.300] Then maybe it activates the stress response too often. The prefrontal cortex can send signals to the amygdala to regulate it or turn down that activity. So when we’re actively trying to control our emotions or work through emotion regulation, prefrontal cortex can then send signals to the amygdala to lower that activity. So we think that when there’s strong communication between the prefrontal cortex and the amygdala that can help with supporting better emotion regulation, better regulation of the amygdala, and then that might be why it’s associated with lower depression symptoms. There’s kind of better control over this emotion region in the brain.

[00:13:51.190] So that’s one of the things we found that was consistent with the research in high income countries. We also found lots of results that were not consistent with research in high income countries, and as just one example, we also had participants do a task in the scanner where they won or lost money. So we could look at the brain when you’re winning rewards and the brain when you’re losing things, which is undesirable and we had used this task because in previous research in the US and other high income countries, when we look at adolescents with depression they tend to show lower activity or blunted activity in a region of the brain called the ventral striatum when winning money. So winning rewards doesn’t seem to register as strongly in the brain in that region for them and that part of the brain processes rewards and helps us, kind of, notice when we’re doing well or winning things.

[00:14:41.810] In the Brazilian adolescence we found that the high risk and depressed groups showed blunted activity in the brain when winning rewards, but actually in a different region, in a part of the brain called the lateral prefrontal cortex, which is more involved in kind of our conscious decisions around motivation and rewards and what types of rewards we want to go after. So we’re not certain why we saw blunted activity in different parts of the brain in our high risk and depressed adolescents in Brazil as compared to other countries, but we saw several findings like that where there were kind of differences in what had been found in previous research in high income countries.

[00:15:18.850] – Jo Carlowe: Do you have any suggestions as to how you account for the differences you’ve described?

[00:15:24.030] – Dr. Johnna Swartz: There’s a couple of things. One is, I always say the caution is that we did not actually have a comparison group in the study of adolescents from a high-income country, and that would have been the ideal study if we had had more funding and a larger study because then we could really, more strongly say that this difference was really in the Brazilian adolescents. So there could be methodological differences in our study, like the way we designed our tasks, the way we recruited adolescents into the study using our risk calculator which hadn’t been done in prior research.

[00:15:56.130] Just the FMRI scanner that we were using. All of these factors could have contributed to the differences we saw. So one explanation is just that there were methodological differences in our study that contributed to those findings and if we had done the same exact methods in the US maybe we would have seen the same exact results. So I want to put that big caution out there. If it is a true kind of country or context specific difference, one big difference in Brazil is the levels of stress that some of the adolescents may be exposed to.

[00:16:25.360] So we know that the socioeconomic conditions can be much worse for some of the adolescents in Brazil and that there can be high levels of crime in certain parts of Brazil as well. So they might just be exposed to different environmental factors, different levels of stress and risk factors that may shape the brain in different ways and contribute to depression risk in different ways. So I think both of those are equal possibilities, either differences in the methods or kind of true differences based on the context that those adolescents are living in.

[00:16:54.220] – Jo Carlowe: Are there any other key findings? I’m wondering about when you talked earlier about adolescents who had high risk in comparison with those that were actually depressed, where the high risk automatically led to actual depression.

[00:17:07.690] – Dr. Johnna Swartz: I think, for the most part, most of our findings that we found in the high-risk group we also found in the depressed group. So that was the case with that finding I mentioned with the reward processing where both the high risk and the depressed group showed this blunted reward related activation when they were winning rewards in the lateral prefrontal cortex. We also had another finding that was similar with the emotion processing tasks we did, where they were looking at negative emotional faces and we had some additional findings where the high risk and depressed groups both showed weaker connectivity between the amygdala and several other parts of the brain that hadn’t really been found as well in high income countries. Parts of the brain that are involved in kind of integrating information that we’re receiving from different senses in our environment and that are also involved in what are called mentalising or theory of mind abilities where you have to kind of think about what another person’s emotional state might be or what they might be thinking.

[00:18:06.350] So in the high risk and depressed groups they showed weaker amygdala connectivity with many of these different regions and different parts of the brain that do these different kind of higher order processing, and I think what’s interesting about that is then we can conclude that possibly all of these patterns that we’re seeing are actually contributing to risk for depression. Since, as I mentioned earlier on, if we see that pattern is consistent in both high risk and depressed adolescents then that suggests that might actually be a risk process that is contributing to the development of depression.

[00:18:36.620] We can’t firmly conclude that until we do a longitudinal study where we follow participants over time and check whether these patterns of brain development are actually predicting future development of depression or future changes in depression symptoms, but this gives us kind of an initial clue that these patterns might actually be contributing to depression risk.

[00:18:56.230] – Jo Carlowe: It makes me think that young people identified as at high risk of depression may come away with a sense that depression is hardwired and inevitable for them. What’s your message to young people who fall into that category?

[00:19:11.470] – Dr. Johnna Swartz: I would say the message is that much of our neuro imaging research actually suggests the opposite, that nothing is really hardwired into the brain and that the brain is what we call really plastic. So it’s very open to influences and can change quite a bit across development, especially during the period of adolescence. It’s a very plastic period where a lot of changes in the brain can occur, but even following through adulthood we see that changes in the brain continue to occur. So what that means is that anybody can kind of change the function of their brain, and there are different interventions that we know work for that.

[00:19:47.150] So one example is research on cognitive behavioural therapy or CBT and there have been some neuroimaging studies that have looked at participants before going through CBT, and after going through CBT and the process of going through cognitive behavioural therapy can actually change the brain. So one example is a research study has shown that when people go through CBT at the end they actually have stronger connectivity between the prefrontal cortex and the amygdala, which again, was a pattern we thought is associated with better emotion regulation and better ability to kind of control the stress response.

[00:20:21.110] So everything we’re doing kind of throughout our lives and even on a day-to-day basis can shape our brain, and there’s always kind of room to change the way we think and change the way our brains are wired. So I think nothing’s really hard-wired, especially for adolescents.

[00:20:35.370] – Jo Carlowe: That’s good to know. A very hopeful message. Coming back to your paper what are the implications of your findings for professionals working with young people and their families?

[00:20:46.990] – Dr. Johnna Swartz: So one of the main takeaways was that we did see some patterns of brain function associated with risk for depression and depression that were consistent with previous studies in high income countries. There are some patterns of depression risk that might be relatively universal and might predict depression across different populations, but we also saw that there were several patterns of brain function that were pretty specific to this Brazilian context, and that had not been shown in previous research in other countries. So this probably suggests that there’s a combination of kind of universal risk factors for depression and then some maybe country or culture or context specific risk factors.

[00:21:26.990] So I think the implications are if you’re a professional working with children or adolescents and their families, it’s really important to get to know the specific population you’re working with and to, as much as possible, read research in which people from your population are represented in that research so that you can be really aware of what are those specific concerns and risk factors in that population and, kind of, target your approaches towards being sensitive to the differences that we see across different populations and cultures and context.

[00:21:58.160] – Jo Carlowe: Are the risk scores used in your study being adapted for use in clinical settings to help assess depression risk in young people?

[00:22:06.430] – Dr. Johnna Swartz: So that would be a long-term goal of this research. So kind of a long term goal would be to have these risk scores be applied in clinical or even other types of public health settings, but there’s a lot more work that needs to be done first before actually using them in the clinical settings, and there are other investigators in our consortium and our group that was funded by the grant that are working on some of those questions. So some of those are ethical questions.

[00:22:32.990] For example, some of the other investigators in our group are working on the question of what are the ethics of telling an adolescent that they’re at high risk for depression, can that be stigmatising, can that possibly increase their risk for depression if they’re being told they’re at high risk. So what are the potential, kind of, negative consequences of using this risk score? So we have investigators in our group who are interviewing stakeholders and parents and adolescents and teachers and mental health professionals to try to investigate the ethics of that.

[00:23:04.000] So that’s one big question that has to be looked at thoroughly before using the risk scores. Another big question that we have to answer first before actually using these risk scores in practice is once we identify adolescents at high risk for depression, do we have really good quality preventions and interventions that we can give to them that can help them lower their risk because it’s not helpful to tell somebody they’re at high risk for a health outcome and then not have anything they can do to help lower their risk.

[00:23:33.850] So that’s kind of one of the other steps that researchers in our consortium are looking at is looking at different prevention or intervention approaches and seeing if any of those would be effective for lowering depression risk if adolescents are identified as at high risk. So we have to answer these questions first of do we actually have good preventions that will help lower risk before we’d actually use these risk scores in clinical or applied setting.

[00:23:59.650] – Jo Carlowe: Sure, and what about you, Johnna? Are you planning some follow up research yourself that you can reveal to us?

[00:24:05.550] – Dr. Johnna Swartz: Yes, we are doing a longitudinal study in this sample. As I mentioned, we need to follow up these participants over time. So we have a new grant funded by the National Institute of Mental Health that’s currently underway. So we’re currently collecting data for this grant where we’re taking this same sample of adolescents that we measured just at one time point in the paper we’re talking about now, and we’re following them up about three years later. So one of our big questions is, of course, was our risk score accurate in predicting depression risk?

[00:24:37.060] So do we see that adolescents in the high risk group are more likely to develop depression three years later or show greater increases in depression symptoms compared to our low risk groups? Then we’re also having them do another FMRI scan so we can look at changes in the brain over time, and are there any changes in the brain over these three years that are correlated with increases in depression symptoms or increases in developing a diagnosis of depression and that can again give us further confidence that those patterns of brain development that we’re seeing are actually contributing to risk for depression. So we’ll be looking at that in the study that’s currently underway.

[00:25:14.850] – Jo Carlowe: Great, and is there anything else that you’d like to mention that’s in the pipeline for you?

[00:25:19.890] – Dr. Johnna Swartz: I’ve just also recently received one other grant from the National Institute of Mental Health that will fund research in California, kind of, closer to the area where I’m located, and that’s actually another longitudinal follow up in a different sample of children who were followed from the age of ten. They were all Mexican origin children in the kind of area in California around where we’re located and they’ve been followed over time. So we’re planning to do another follow up data collection when they’re at the age of 25, currently. So followed from the age of ten all the way through the age of 25, and we’ll be looking at the development of depression, also different physical health problems and how that might be related to the development of depression, and then importantly looking at different protective factors that might protect against risk for depression for some of the individuals in our study to help identify, what are those things we could improve on or have more of in adolescents and young adults lives that might help protect them from developing depression. So that grant just started on that project is also currently in the works.

[00:26:23.830] – Jo Carlowe: Excellent, and finally, what’s your takeaway message for those listening to our conversation?

[00:26:29.890] – Dr. Johnna Swartz: I think the takeaway message is just on the importance of considering mental health across the globe and that adolescent mental health is something that we should really focus on with our funding and our research, and I think if anything the pandemic has taught us how important mental health is for our day to day function and how disrupted things can be when we’re not functioning well with our mental health. So encouraging more funding, more research and greater improvements in our treatments and interventions for mental health, since adolescents are going to be our next generation of leaders.

[00:27:04.560] So we want to kind of give them the best we can and promote their mental health the best we can, especially in a stressful time like the time we’re living in now.

[00:27:13.330] – Jo Carlowe: Brilliant. Johnna, thank you so much. For more details on Dr. Johnna Swartz 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.

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