Associate Professor Johnna Swartz  Hello, my name is Johnna Swartz,   and I’m an Associate Professor of Human Ecology,  at the University of California Davis, and,   today, I’m going to talk to you about the  association between inflammation and brain   function in teens. So, a little overview  of what I’m going to talk about today,   I’m going to start by talking about, what is  inflammation? And then I’m going to talk about,   what is the amygdala? This is the specific  part of the brain that I’m going to focus on   today. And then I’m going to talk about a study  that we conducted in my lab, that looked at the   association between inflammation and the  brain, and findings from our research. And   then I’m going to conclude by talking about,  what does this mean for teens and Researchers? So, starting out, what is inflammation?  So, at a very basic, simplified level,   when we get sick or injured, inflammation  helps us fight off viruses and bacteria. So,   in the short-term, when we’re actively sick or  actively injured, inflammation is generally a good   thing, because it’s helping to fight off those  viruses and bacteria and keep us healthy. But   research suggests that other things can increase  inflammation, even when we’re not actively sick. And so, some examples of these things  include eating certain types of foods, like,   ultra-processed foods, so, think  fast foods, or packaged foods,   where you don’t understand the ingredients  on the label. Research suggests that eating   those types of ultra-processed foods regularly in  the diet has been associated with higher levels   of inflammation. Chronic stress has also  been associated with higher inflammation,   and by chronic stress, we’re talking about  stress that happens on a pretty regular basis,   so on an everyday or repeated basis over time.  Not getting good quality sleep is often associated   with higher levels of inflammation, and obesity  has also been associated with higher inflammation. So, in these cases, these  are more day-to-day things,   and when inflammation is higher  on a day-to-day, regular basis,   even when we’re not actively sick or injured,  this type of inflammation often increases risk   for both physical and mental health problems.  And so, this type of day-to-day inflammation,   that’s not due to being sick or injured,  but just due to these lifestyle factors,   this is the type of inflammation that I’m  going to be focusing on in the talk today. And so, as I mentioned, inflammation is  associated – this day-to-day inflammation   is associated with higher risk for a range  of health problems, and one of those health   problems is mental health problems. So,  in teens, higher levels of inflammation   have been associated with higher risk for mental  health problems, such as depression. And there’s   still more research that needs to be done in this  area, but there are some studies suggesting that   higher inflammation might even contribute to  the onset, or the development of depression.   So, there’s this important link between  inflammation and risk for mental health problems. And that has led Researchers, like myself and  others, to ask, “Why do we see this connection   between inflammation and our mental health?  What are the pathways that can explain why we   see this connection?” And so, we’ve started  looking at the brain as a potential pathway   that could explain that link between inflammation  and our mental health. And throughout this talk,   I’ll occasionally refer to what’s called  “peripheral inflammation,” and this is   inflammation that occurs throughout our bodies,  which is separate from the inflammation that’s   occurring in our brains. And one of the  reasons that it’s separate is that we have   something called a “blood-brain barrier.” This  prevents most of the things that are circulating   throughout our bodies from crossing over and  reaching into our brains, so it’s protective,   and it protects our brains from other things  that might be circulating through our bodies. But some of the inflammatory messengers that  our own bodies produce can actually cross   that blood-brain barrier, and can cross from our  bodies to our brains. Once they have crossed to   our brain, they could potentially interact with  our brains, and other messengers in our brains,   to influence the ways our brains are functioning.  So, this is a potential pathway through which   the inflammation that’s happening in our  bodies can potentially cross to our brains,   and influence how our brains are functioning,  and that’s what we’re interested in. So, in my research, as I mentioned, I’m  interested in understanding how inflammation might   be associated with the functioning of our brain.  And in the study I’m going to talk about today,   I’m going to ta – focus on one brain region, in  particular, which is called “the amygdala.” And   even though we call it “the amygdala,” singular,  like it’s one region, there’s actually – everybody   has two amygdala; we have a left amygdala and  a right amygdala. So, you can see an example   of this in the image below. This is an MRI – this  is an image from an MRI scan, so, kind of, taken   from the perspective of somebody looking straight  on, and the amygdala is highlighted in those blue   clusters right there. So, you can see there’s a  left amygdala, and a right amygdala. So, this is   the brain region that I’ve studied a lot, and that  we focused on for looking at teen mental health. So, what does the amygdala do? It has a couple  of different roles, but one of the main things   that the amygdala does is that it is, kind of,  scanning our environments when we’re interacting   with the world, and it will activate in  response to anything in our environments   that’s potentially emotionally significant to us.  So, a good example of this are emotional faces,   so if we’re out interacting with people,  and we see somebody with a happy, smiling   facial expression, that’s emotionally significant  information, and that tells us that that person is   probably going to be friendly towards us, they’re  happy, and that provides us important information. In contrast, if we see somebody who’s frowning  at us, or looking angry at us, that’s emotionally   significant information, as well, it tells us  that that person might not be friendly towards us,   and they might be angry. And so, the  amygdala would activate in response to   both of those emotional faces, because they’re  telling us important emotional information.   The amygdala will also activate to things that are  stressful to us, to things that are threatening,   or potentially dangerous, all of these things  convey important emotional information,   so the amygdala activates in response  to those emotionally significant things. Once the amygdala has activated to something,  it will then send signals to other parts of   the brain that will then change how  we respond to it. So, for example,   if the amygdala activates to something that  we perceive as stressful or threatening,   it will then send signals to other parts of the  brain that will activate the stress response,   and trigger a stress response. It can also send  signals to other parts of the brain that might   focus our attention on something, or it might  influence our emotional reactions to something,   so we might start to feel more anxious, if the  amygdala is activating to something strongly. And so, this is why we’re interested in the  amygdala when we’re interested in mental health,   because research has shown, through  repeated studies, that people who have   mental health problems, including  anxiety disorders and depression,   often have an overactive amygdala  response, that’s higher than someone   without these disorders. And we think that  higher, or overactive, amygdala activity   might actually contribute to some of the  symptoms that we see in these disorders. So, for example, with anxiety disorders, one of  the key symptoms or characteristics of any anxiety   disorder is having an overactive anxiety response,  or an overactive stress response, to something   that’s – that we’re perceiving. And we think that  that overactive anxiety, or overactive stress   response, could be tied to having an overactive  amygdala response. Likewise, for depression,   some of the key symptoms that we see there can  often include heightened negative emotions. So,   for example, with depression, there’s often  heightened sadness, or guilt, or shame,   or frustration, and we think that that might also  be tied to having an overactive amygdala response. So, in both of these disorders, we see that  there’s often that overactive amygdala response   which might be contributing to some of those key  symptoms, and so that’s why we’re interested in   studying it when we study teen mental health. So,  to just summarise what I said on the last slide,   research has shown that heightened amygdala  activity to negative emotional stimuli has   been associated with both major depression and  anxiety disorders. And this has been shown both   in adults and teens, and so that’s why we  focus on this brain region in our research.  And so, Researchers, kind of, seeing  all these different studies coming out,   have suggested that maybe this heightened  or overactive amygdala activity could be   a pathway that could explain why inflammation in  our bodies might influence our mental health risk.   So, as I mentioned at the beginning of  this talk, inflammation is associated   with increased risk for mental health problems  in teens, and higher amygdala activity is also   associated with increased risk for mental health  problems in teens. And so, if inflammation from   our bodies is crossing that blood-brain barrier,  and influencing our brain function, potentially,   it could be contributing to this overactive  amygdala response, and that might be why we   see – or one of the reasons we see a link  between inflammation and our mental health. And so, this has been a proposed pathway, but  it hasn’t really been tested much in research,   or it hadn’t been tested much in research. And so,   one of the first things we need to do to test  whether this pathway might explain the link,   is to test whether there’s a correlation  or an association between inflammation and   amygdala activity, that’s really the first  step to know if this pathway might exist. And so, research has done this, in adults mostly.  Prior research in adults has shown that higher   levels of peripheral inflammation were associated  with higher amygdala activity to negative stimuli.   This is what we would expect if we ha – do  have this pathway from inflammation to amygdala   activity influencing our mental health. But not  a lot of research has looked at this question in   teens and, actually, before the study that I’m  going to talk about in my talk, only one other   study had looked at this question in teens, and  had found that higher inflammation was associated   with higher amygdala activity in teens, but not  much other research had been conducted in teens. And so, that was the goal for my study, was to  look at whether higher inflammation is associated   with higher amygdala activity to negative stimuli  in teens. And you may be wondering, why is it   important to test this question in teens, if it’s  already been tested in adults? And there was a   couple of reasons why it’s important to look  at this specifically in teens. First of all,   for the mental health problems that I’m interested  in, anxiety and depression, these often first   develop during the teenage years. So if we want  to understand what’s contributing to the onset, or   the development, of these mental health problems,  we have to look during the teenage years. The second reason to look at teens specifically  is that teen brains are a little bit different   than adult brains, and so we can’t assume  that what we’re seeing with an adult brain   is going to be the same as what we  would see with a teen brain. And so,   we have to actually look in teens, specifically,   to know what’s going on in the teenage brain,  and so that was the goal for our research. Alright, so, our research question was, “Do  higher levels of peripheral inflammation relate   to how the amygdala activates in response to  emotional faces in teens?” So, for this study,   to measure peripheral inflammation, we looked  at three markers of inflammation, which were,   C-reactive protein, or CRP, interleukin-6, or  IL-6, and tumor necrosis factor-alpha, or TNF-α. And the way we measure peripheral  inflammation is very simple,   it’s with a blood draw through your arm. So, if  you’ve ever gone to the Doctor or an annual exam   and they’ve done a blood draw to look at your  health markers, it’s the same exact process   we used in our study. So, we did a blood draw  with a vein in your arm, and we were able to,   from that blood sample, measure these  different markers of inflammation. So,   that’s a really, kind of, simple way to get  at this measure of peripheral inflammation. So, participants in our study included  88 teens, between the ages of 12 to 15   years old. As I mentioned, we measured  inflammation with a blood sample, and   we also measured amygdala activity. So, how do we  measure amygdala activity in a research study? We   use an MRI imaging technique called “Functional  Magnetic Resonance Imaging,” or, for short, fMRI.   And you might have had an MRI scan before, if  you’ve ever had, you know, back pain or a health   problem, and they’re often pretty common  for imaging different parts of the body. If you’ve never had an MRI scan before,  the picture below is an example of what   an MRI scanner might look like. And in a research  study, or just, you know, for medical diagnostics,   we would have a participant lie in that scanner  bed that you see that’s coming out of the scanner,   and then they would go inside the scanner, which  is what we would use to take pictures of their   brains. So, an MRI scan takes structural images  of the brain, so it helps us image all of those   structures that are inside your head. What’s  special about a functional, or an fMRI, is that   it also allows us to measure activity levels  throughout the brain, so we’re able to measure   how active different parts of the brain are, when  you’re thinking about or doing different things. So, for our study, we showed participants,  while they were in the MRI scanner,   pictures of emotional faces that were  either positive emotional faces, so,   happy, smiling faces, or faces with negative  emotional expressions. So we also showed   pictures of fearful faces and angry faces,  that are displaying more negative emotions.   We were able to show this to the participants  while they were in the MRI scanner, by displaying   them through mirrors, that allowed them to see  the pictures while they were in the scanner. And so, we were able to measure activity  levels in the brain while the participants   were looking at these images of  these different emotional faces. And,   as I mentioned, we really focused  on the amygdala for this study,   and so we focused on measuring amygdala  activity, in response to these different   emotional face expressions that they were looking  at. So, that’s how we measured the amygdala. And then our question was, “Are these  correlated? Is inflammation that we’re   measuring from the blood draw correlated  with levels of amygdala activity?” So,   we looked at the correlation, or the association,  between those two, in our main analyses. And so,   here’s one of our main research findings from  this study. We found that there was a significant   correlation, or association, between one of  the markers of inflammation that we looked at,   which was TNF-α, and amygdala activity to  the negative emotional face expressions. And so, if you’ve – if you’re not familiar with,  kind of, looking at these types of scatter plots,   I’ll briefly walk through, kind of, how to read  and understand this plot. So, on the bottom,   kind of, line of the plot, we’re looking  at levels of TNF-α, and so, in this plot,   zero, right in the middle, indicates average  levels for this sample, and the dots in the   scatter plot represent individual participants.  So, the ones that are right in the middle would   be the teens that have average levels of  TNF-α. Numbers that are on the positive side,   more towards the right of the plot, so one, two,  or three, would be teens that have above average   levels of TNF-α for the sample. And the dots  that fall more towards the left of the plot,   in the negative one, negative two and negative  three range, are teens that have below average   levels of TNF-α for this sample. So, that’s  what you’re looking at along the bottom. And then on the line that’s at the very left of  the scatter plot, is the measure of bilateral   amygdala activity to angry and fearful faces.  And it’s bilateral, because, as I mentioned,   everybody has a left and a right amygdala, and  so we just average activity levels across the   left and the right, to look at bilateral, or both  sides, averaged together, so that’s what bilateral   means. So, we have bilateral amygdala activity to  the angry and fearful faces, and higher numbers   that go more towards the top of the plot indicate  higher levels of amygdala activity in this sample. So, what you can see from the scatter plot is  for the teens that had higher levels of TNF-α,   on average, they had higher levels of amygdala  activity to the emotional faces. And, in contrast,   for teens who are more on the left side of the  plot, who have below average levels of TNF-α,   they, on average, tended to have  lower levels of amygdala activity. And you can see that this was not a  perfect correlation, the dots are,   kind of, spread out around the line, and  so, this means that there’s lots of other   things besides inflammation that might  be influencing the amygdala activity,   but there is this correlation, or this  association, here. We did not find associations   with the other two markers of inflammation  that we looked at, which were CRP and IL-6. And another interesting thing to note about our  findings is that we also looked at the association   between inflammation and amygdala activity to the  happy, positive faces, and we found that there was   a similar positive association. So, teens that had  higher levels of TNF-α also had higher amygdala   activity to the happy faces. So, this suggests  that higher levels of TNF-α might lead to just   higher overall levels of amygdala activity to all  emotional stimuli, whether positive or negative.   And so, that might only be a risk factor for teens  who are living in really stressful environments,   where they’re encountering a lot of  negative things on a regular basis. The last thing I wanted to emphasise about these  findings is that this is just a correlation,   and so, with our research design, we are  not able to say that higher inflammation   is causing higher amygdala activity, or  vice versa. All we can say is that these   two things are correlated or associated,  but we don’t know what’s causing what,   from this research design. So, more research  is needed with different research designs,   to address whether inflammation is  causing higher amygdala activity. So, to summarise, higher levels of  one marker of inflammation, TNF-α,   were associated with increased amygdala activity  to emotional faces. This suggests that higher   levels of this inflammatory marker may make  the brain more reactive to emotional material,   including stressful or negative material,  although, again, more research is needed   to know whether higher inflammation  actually causes changes in the brain. But this initial finding of this association could  help explain the link between inflammation and   risk for mental health problems. If inflammation  is travelling to the brain and influencing how   the amygdala responds to things, that may then  influence risk for those mental health problems. So, what does this research mean for teens?  Overall, the research that I just described,   that we conducted in my lab, and research from  other studies, is coming together to suggest that   higher levels of inflammation may be a risk factor  for developing depression and anxiety. Although,   as I mentioned, more research looking at  whether inflammation causes changes in   the brain and mental health problems is needed.  But there are things that we know from research   that people can do to help lower their  inflammation. So, always make sure to   check with your Doctor before making any changes  to your lifestyle or health related behaviours,   but I’ll talk about some things that we know  from research can be associated with helping   to lower that everyday, day-to-day inflammation. So, first, reducing things that we know increase   inflammation is a potential way to try to  decrease inflammation. And I talked about   examples of some things that we know increase  inflammation at the beginning of this talk. So,   for example, I talked about how ultra-processed  foods are often associated with higher levels of   inflammation. So removing ultra-processed foods  from the diet, not eating ultra-processed foods   and replacing those with more wholegrains,  fruits, vegetables, healthier types of foods,   that’s one thing that research suggests can help  lower that day-to-day, everyday inflammation. Another example I gave of something that raises  inflammation is getting poor quality sleep. So,   for individuals who have sleep problems,  or are not getting good quality of sleep,   finding ways to improve sleep  problems and get better quality sleep,   is another thing that can potentially  help lower that day-to-day inflammation. And, in addition to removing things that  raise inflammation, there are other things   that can be added into day-to-day activities  or lifestyles that have also been shown to   reduce inflammation. So, a couple of examples  of these things include, regular exercise,   or physical activity, that’s often  been linked to lower inflammation,   and mind-body therapies, such as yoga or  meditation, these are therapies that help   connect the brain and the body. There’s  some evidence suggesting that these may   help lower inflammation levels. More research  is needed. Results have been somewhat mixed,   but there’s some research suggesting that these  might also be associated with lower inflammation. I think one other interesting thing to point  out here is that all of these things I have   mentioned, like eating a healthier diet, removing  ultra-processed foods, getting good quality sleep,   regular exercise and physical activity, yoga,  meditation, all these things have also been   associated with better mental health and  lower depression and anxiety. And so,   it’s possible that one of the ways that these  things might be associated with better mental   health is by helping to lower inflammation.  Of course, as I’ve mentioned, we need more   research to really test that pathway, and test  whether that’s causing changes in mental health,   but it’s interesting that that might help  explain why we see that these things are   associated with better mental health. What does this mean for Researchers?   So, this also suggests that pharmacological,  or other approaches, to reducing inflammation   could be investigated as a potential treatment  target in helping to treat depression and anxiety   disorders. And there actually have already  been clinical studies conducted that have   tested anti-inflammatory treatments to treat  depression, and some with promising results.   But reviews of this research suggest that  we need more high quality clinical trials,   to really test the effectiveness of these  anti-inflammatory treatments. So, more research   is needed there on potential anti-inflammatory  treatments for anxiety and depression. And then, as I’ve mentioned throughout this  talk, we still need more research testing whether   inflammation causes changes in the brain and  causes changes in mental health, to establish that   pathway. So, lots more research is needed in this  area, but it’s an exciting new field of research.   So, hopefully, we’ll see new studies coming out in  this area in the next few years and in the future. Just – so, to summarise, at the end of my  talk, some of the main points. I started   out by talking about how inflammation is part of  our body’s response to fighting off bacteria and   viruses. But some things can raise inflammation,  even when we’re not sick and, in those cases,   that inflammation might have negative  consequences for our health. Our research,   and others, has shown that higher levels of  peripheral inflammation are associated with   brain activity, including increased amygdala  activity to emotional images. And this could   help explain the link that has been observed  in other studies between higher peripheral   inflammation and higher risk for mental health  problems in teens. So, finding ways to reduce   inflammation could be one pathway to preventing  or treating depression and anxiety in teens. And so, I just want to conclude by acknowledging  all the funders that sponsored the study that I   talked about in the middle of this talk today, and  I want to thank you for listening to this talk,   and I hope you learned something  new from listening to this talk.