Depression is a common mental health disorder, and its emotional and psychological symptoms are well known. Perhaps less known are the various biological factors that give rise to it.
In a recent public lecture, Dr. Lena Brundin, a professor in Van Andel Institute’s Department of Neurodegenerative Science, explored the link between inflammation and depression.
Dr. Brundin, her lab and her collaborators at other institutions have found certain inflammatory markers in people with depression, and they are working toward new ways for clinicians and mental health professionals to diagnose and treat the disorder.
If you or someone you know are struggling with any of the topics mentioned in this lecture, please call the 988 Lifeline.
Watch the lecture below:
Video transcript
Note: The following transcript has been edited for readability. Click a timestamp to jump to that part of the video.
Maranda [0:05]:
Good afternoon and welcome to Van Andel Institute’s Public Lecture Series. I’m Maranda, and I am so excited to be here to guide us through today’s presentation. Today we’re exploring an important topic. Nearly one in 10 adults in the US experience major depression each year, making it one of the most common mental health disorders. Depression can significantly disrupt day-to-day life. And although the emotional and psychological aspects of depression are well known, we’re beginning to better understand the complex biological factors at play. By better understanding those biological factors, we can develop more effective ways to diagnose and treat severe depression.
Today we are joined by Dr. Lena Brundin, a psychiatrist and scientist who seeks better ways to diagnose and treat depression and reduce suicide risk. By studying inflammation of the nervous system, Dr. Brundin will highlight the ways in which biological factors, specifically inflammation, contribute to depression and suicide risk, and detail how new research offers hope for improved care.
Before we get started, we want to remind everyone that if you or someone you know is struggling with any of the topics we discuss today, please know the 988 Suicide Crisis Lifeline provides confidential, free, 24/7 support. We’ll take time for a Q&A session after the lecture, so feel free to think of questions during the presentation. You can use the chat function to share your questions, and we’ll do our best to make sure we answer as many as we can. Due to the sensitive nature of the questions that might arise, feel free to enter “anonymous” as your chat name so we can help protect your privacy. Now, please join me in welcoming Dr. Lena Brundin.
Lena Brundin [2:03]:
Thank you so much for the introduction. I am so glad to be here today to talk about this important topic. And before I start, just like Maranda said, just a reminder, we will touch upon some sensitive subjects today, so please dial 988 in case of need.
And today I will first talk about what the depression is and how it can be defined, before moving on to discuss potential causes and the current treatment options for depression. I will then talk about how inflammation can trigger depression and moving on to describe some of our previous and ongoing studies that we’re working on.
So, first of all, let’s think about what it really means to have depression and what depression is. So, the World Health Organization defines depression as a disease that is characterized by a low mood or a loss of pleasure for longer periods of time. And this is a state that is regular, or different from our regular mood or our feelings about everyday life.
Depression is also a very common disorder. The statistics from the CDC from last year shows that there were over 15 million physician visits with a primary diagnosis being depression. And at this very moment, there are around 650,000 adults in the United States that are experiencing significant feelings of depression.
You can also look at the numbers a bit differently. So if you look at the lifetime risk for depression, that’s a bit harder to collect that information. But the Gallup Institute has done a large survey over many years, and you can see here that as many as 30% out of all Americans say that they have ever had depression diagnosed by a health professional, and around 18% are saying that they are currently being diagnosed or currently under treatment for depression. You can also see that these numbers have been increasing over the past years.
If we look at the numbers based on sex, we have known for some time that depression is more common in females, we have about 25% of all men ever being diagnosed with depression and around 33% of all women. So that would be the pre — it makes depression one of our most common illnesses. It’s very common in both sexes, and it does have a significant morbidity, which means that it causes significant suffering and a large loss of birthdays. And in fact, depression is recognized as one of the very top contributors to the overall global burden of disease by the World Health Organization.
And depression is a peculiar disease in terms of that there are no specific tests. There are no blood tests or brain imaging that you can take that will show who has depression, but instead, the medical professionals have to use a number of criteria to be sure of who has depression. And to do that, we use diagnostic manuals. And this is one of the most commonly used manuals. It’s called the Diagnostic and Statistical Manual of Mental Disorders. It’s written by the American Psychiatric Association, and in order to get a diagnosis of depression, the symptoms should have been present nearly all the time, every day, and they should also have been going on for at least several weeks. There are two main symptoms of depression, and at least one of these need to be present, depressed mood or a diminished pleasure or diminished interest.
And in addition, as you probably are aware, there are several other typical criteria of depression, including significant weight or appetite changes, insomnia or hypersomnia, the feeling of fatigue or a loss of energy, feelings of worthlessness or guilt, and also indecisiveness and a diminished ability to concentrate.
So, one of the main criteria for depression is the inability to feel pleasure. And I want to talk a bit more about that because that’s a difficult symptom to experience, and often it’s not well-recognized. Inability to feel pleasure means a lack of the feeling of joy or happiness when doing things that normally would make a person happy. And examples of that could be that maybe a usually outgoing person doesn’t enjoy social activities anymore, somebody who withdraws and doesn’t want to do sports or watch movies or games anymore. And the lack of ability to feel pleasure can be exceptionally hard. For example, when somebody cannot experience happiness from seeing their children or grandchildren, and sometimes, as you might be aware, this symptom can also affect new mothers that just had a baby. As you can imagine, this lack of feeling joy can trigger many more negative thoughts and emotions such as guilt, worthlessness and severe emotional pain. And this can lead to social isolation. And the affected person might even start to think that there is something wrong with them, (that) they might be evil or others might even be better without them.
This thought spiral of negative thoughts and emotion in depression can escalate to thoughts of death or even suicidal behavior. So, it’s very important to try to recognize this escalating spiral of thoughts and to recognize it. And because somebody who has depression might not be aware of it themselves, or they might not want to talk about it, it’s very important for others to be observant and to look for signs of depression. Some of the signs and symptoms that I talked about can be fairly easy to pick up, whereas others can be more subtle. So, for example, a lack of engagement can be a sign of depression. Somebody who doesn’t accept your invites or somebody who seems to pull away could be struggling with depression. And anger and irritability can also be symptoms of someone not feeling well and struggling internally. So, remember, you don’t have to take that personally. You can try and take a step back and try to understand what is lying behind the anger. And being tired and distracted can also be a sign of depression.
So, what do we do when we see signs that tells us that somebody might have depression? You can try to be forgiving when somebody seems to be hostile or angry because, remember, it might not have anything to do with you. And don’t stop inviting somebody who says they can’t come. You can keep trying. You can call up your friends or family members again, even if it, if it felt like they had nothing to say the last time you tried to talk to them. So, even if your conversation is brief, call them again and again. And you can suggest low-energy activity. That could be perhaps just hanging out, watching a movie together, something that’s easy to do. And also remember that depression is a disease that can be treated.
So, why, why do I say keep that in mind? Well, depression is a disease that comes very close to our identity, and it’s a very cruel disease because it changes the way that we behave and how we experience emotions such as joy. And it also causes isolation from loved ones. And when these things happen, it can be helpful to remind ourselves that depression is actually a disease affecting the biology of our brains, but it’s not really us.
So, what do I mean by that? Depression can have a profound effect on how we handle situations and challenges, as you can see here on, on my illustration, because the depression alters our emotional and behavioral responses to what we are experiencing, but it can really never affect who we are. So somewhere above those biological functions and those responses and challenges, depression is still something very distinct and very different from our self-awareness, from our souls and from our identity.
So, how do we help someone when we think that they really do have depression? First of all, like I said, it’s really important just to be there, to keep calling, to keep coming by. And try to open up a conversation about depression with the person in question, and perhaps talk to their family and talk to other friends.
Seek professional help, because it’s really important to know that there are many options available, and you can help by reaching out to take the very first step to book an appointment. That’s something that’s often extremely hard for a person with depression. So if you can be there, if you can help, look up the number, if you can help dial the number and even make the appointment, if you can go with them to that first appointment, those are extremely important first steps that somebody can help with.
And now that we have talked about some symptoms of depression and how common depression is, I will move on to talk more about the actual causes of depression.
Many researchers agree that depression is what we call a multifactorial disease, which means a disease that can develop from several factors or from combinations of factors. And this could be, for example, somebody going through a difficult life situation and also having some kind of biological vulnerability at the same time. But depression can actually hit somebody at the very height of their career or somebody who’s having a wonderful family life. And it’s very possible for a person to be affected without any external circumstance. And that part is really important to remember, because it’s hard for somebody with depression to hear that they have nothing to be depressed about. Thinking that way could actually contribute to feelings of guilt and shame about having depression at a time in life when everybody thinks that they really shouldn’t.
The two main treatment options for depression are therapy and pharmacological treatment. And cognitive behavioral therapy is one form of therapy that works by changing how we think and behave by consciously interrupting negative emotions and behaviors. And an example of that is to work to interrupt this negative thought spiral of depression that I showed you before. And this is really hard work, but it’s important and it can be really powerful to learn how you can be in charge of your own behavioral and cognitive responses.
When it comes to pharmacotherapy, serotonin reuptake inhibitors — this is abbreviated SSRIs — are often the first line of choice. And these medications work by building up the amount of serotonin between nerve cells to increase the serotonin signaling. And there are also many combination medications available. They work with increasing both serotonin, dopamine, and noradrenaline and other neurochemicals. And the majority of people who get depression will respond to and recover after one or combinations of these treatments. So you might need to try several different medications, but the odds are on your side that you will feel well again. So never hesitate to seek help.
Unfortunately, the treatment of depression though is not always a smooth ride. And one problem is that we don’t know who will respond to what treatment, and therefore there’s often a trial-and-error period before a good treatment and a dose has been established. And for each medication tried, we also have to wait several weeks and sometimes months before we know if it works or not. And a portion of patients don’t respond sufficiently even after several trials of different medications. This is about one-fifth or so of patients. And for those patients, there are definitely more options to try. We have some very powerful neuromodulatory treatments such as ECT and TMS, for example, that you might have heard of. But the fact that some people are experiencing this treatment resistance, trying many different options of medications, is, of course, very difficult. And the fact that we have these difficulties finding the optimal — the best treatment for depression is, of course, one of the strongest reasons why we’re doing really intensive research in the field of biological psychiatry. We’re trying to find out what biological factors cause depression.
So, is inflammation an underlying biological factor that can lead to depression? The answer to that question is yes. And in the next few slides I will explain what we know about that.
“Sickness behavior” is a term you might have heard. It was first defined in the 1980s, and it describes emotions and behaviors that people with infections typically exhibit. And if you have had an infection such as the flu or COVID, for example, you might remember that you also felt a depressed mood, that you had some changes in your sleep and in your appetite, and you also had decreased concentration ability, in that you felt a lot of fatigue at that time.
And so, interestingly, if you think back to the beginning of my talk, I showed you the symptoms, the symptom criteria for depression, and they are actually identical to these symptoms of sickness behavior. And the difference is that sickness behavior usually goes away when the disease has passed. And you also have symptoms such as cough or sore throat or a fever that makes you recognize that this is an infection that I’m having. But the fact that the symptoms of depression and sickness behavior are so similar, this of course leads to the idea that the underlying root biological causes could be similar as well.
So, what really is inflammation? Well, inflammation is the body’s response to injury that could be to any type of injury, to a bug bite, or a scrape, or a wound or to infections. And the inflammatory process has several components, and they can act locally at the site of injury and as well as being released into the bloodstream.
And some of the important mediators of inflammation are called cytokines. Those are very small inflammatory molecules that are circulating in the blood, and they can also reach the brain from the peripheral sites of infection. And once they come inside of the brain, certain cell types within the brain react strongly when they can sense that these inflammatory cytokines are present. And these cells are called the microglia cells. So the microglia cells become what we call activated, meaning they change the way they look and they start secreting inflammatory factors themselves. And that way the inflammation can start and be sustained within the brain.
The hypothalamus is one of the first places within the brain where the inflammatory cytokines first can enter. And nerve cells in your hypothalamus, they mediate some of the very first physiological responses to inflammation, and that includes developing a fever and feeling, in general, illness and malaise and fatigue. And if then the inflammation continues, there will be more far-reaching effects throughout your brain because many circuits connect in the hypothalamus. So these signals will transmit throughout your brain, and altering the reward systems of the brain, the decision-making and many other functions.
And we know for sure that cytokines can trigger depression when they reach the brain, because when cytokines and similar factors that are called interferons are given clinically as a treatment for some infections, for example, a very high percentage of these patients develop depression — as many as 70%. And there has also been some studies in human volunteers that were injected with an inflammatory substance, just a short-lasting challenge. And when they did that, they quickly developed depressive symptoms in response to the inflammatory challenge.
The next question we’re asking is then, is all of the patients that have clinical depression also having inflammation, or is this something specific that happens only to those — very, this very small group of patients that received the interferon treatments? And there have been many studies done that have measured inflammatory factors in patients with depression. And my research group has done several of them, and the general consensus is that among all the patients with depression, a substantial amount actually has inflammation.
And one study used a marker called CRP to look for that. The CRP is one of the most well-known clinical markers for acute inflammation. And that study found that at least 50% of patients with depression have a CRP above the limit for what is considered inflammation. And the study to the right on your screen was done by me and my colleagues, and we could show that during an episode of depression, the cytokines are increased in your bloodstream, and when the depression has been successfully treated, the inflammation subsides.
But even if we have many studies and even meta-analysis, gathering all the information that’s available showing that there is information in many patients with clinical depression, there are still no clinical guidelines for clinicians in mental health care about how to detect and potentially treat inflammation in depressive patients. And one reason for that, is that we don’t have enough clinical trial data yet to say that it works if we treat depression with an anti-inflammatory medication, but we are working in that direction to gather that evidence.
So, what exactly happens when inflammation reaches the brain? Well, I told you so far that circuits are being activated from the hypothalamus, and microglia cells within the brain become activated and start secreting cytokines to generate inflammation within the brain. And there are other effects that are triggered, too, when that happens.
So, for example, in tissues that are inflamed, the metabolism, or the degree of energy consumption, is changed. And one example of a metabolic chain of reaction during inflammation is the activation of the kynurenine pathway. This is a series of enzymes that we have in our bodies to help break down food, and specifically they break down tryptophan, which is an important component of our diet. There is tryptophan in turkey, in chicken, in bananas, in all of the food we eat. And these enzymes break tryptophan down. And then, along the way, to generate energy in metabolism, there are some small metabolites being formed in the breakdown process and they have neuroactive and immunologically active effects.
So, one of the metabolites of inflammation that we are interested is called, is called quinolinic acid, and we abbreviate it QUIN for simplicity. This little metabolite has several effects that can be toxic for nerve cells, and it disturbs the neurochemical balance in the brain, and it leads to increased inflammation and activation of those microglia cells that I mentioned before.
This is data from our research studies on patients with depression, and it’s a diagram that shows you the levels of an inflammatory cytokine in the blood. On the X axis, it’s called TNF-alpha. And then, on the Y axis, you can see the levels of the metabolite QUIN in the cerebrospinal fluid the — sorry, I raised my hand. So, quinolinic acid is present in the cerebrospinal fluid in these patients that have inflammation in their peripheral blood. And what I wanted to show you with this slide is that when the inflammation in the blood increases, the levels of this toxic metabolite in CSF is increasing at the same time. So, what’s happening around the brain really responds quickly to inflammatory changes in your body. Next slide, please.
So, my research group and our colleagues, we started to measure quinolinic acid and other small metabolites in body fluids from patients with depression and suicide risk. And we found that patients who recently gone through a suicide attempt, they had very high levels of inflammatory cytokines in the CSF, and the very highest levels we found in those that also had a diagnosis of depression. And on this slide you can see measurements of a cytokine called IL-6.
And in these same patients, we also found very high levels of the toxic metabolite QUIN in the CSF. The dots here represent data for the individual patients and the healthy controls, and you can see that more than half of the patients with depression and suicidal behavior had higher levels of this metabolite QUIN in the CSF than the very highest level of a healthy control.
This is an overview of the mechanisms that we think contribute to depression. So, first, inflammation reaches the brain from the periphery in most cases, but it can also actually start in the brain; for example, if you have a case of traumatic brain injury or concussion. So, inflammation takes root in the brain, and this then triggers the activation of the microglia cells that produce more inflammatory cytokines and they become more metabolically active. And now they will use tryptophan from our diet in the inflammatory metabolism, and they produce the toxin QUIN, and QUIN can then bind to receptors on nerve cells, as you can see here. And that way, QUIN actually can alter the neurochemical environment within the brain.
Then, at the same time, as you see to the right here, tryptophan is actually normally used to produce serotonin in the serotonin nerve cells. But when that is used in the state of inflammation for other reactions, there might be a lack of serotonin, too. So, inflammation and the metabolism linked to inflammation really can change the neurochemical environment within the brain. We know, though, that not everybody will become depressed or suicidal even if they have a lot of inflammation going on. So, there must be something that makes certain people more susceptible to inflammation-induced depression than others.
And when we talk about this, we call it vulnerability factors. So, what could a vulnerability factor be? Well, there is some data that suggests that people who had a severe infection or maybe a trauma during their childhood, they may be more susceptible to depression in adult life. And it seems like this early infection or early trauma can prime the individual’s immune response. So, the immune response will react stronger in the future, and that’s a very interesting mechanism. And the priming of the immune response can happen through something that we call epigenetic mechanisms. And that means that a little mark is left on the DNA after a traumatic or infectious event that regulates the production of different inflammatory proteins later on in life. And so that way, an early event can really leave an epigenetic mark on the DNA that regulates how we can tolerate inflammation in the future. So, that leaves us with some important outstanding questions.
What are our next steps here? Well, for example, can we use those biological markers that we are detecting as risk markers? Can we use those factors that we measure in the blood to see who is at risk for being treatment-resistant? Maybe we should use, use a specific treatment for these patients. And are they even at risk for suicidal thoughts or behavior? Can we tell that from a blood sample? And, of course, another important question is where does the inflammation come from? Because if we find that out, maybe that’s a source of inflammation that we can treat and that will help restoring inflammation to more baseline levels and help with the mood, as well.
So, to answer the first question, can these markers be used to detect risk of treatment resistance or suicide risk? We are conducting a study right now where we follow people with depression over one year, with many repeated samples. And this slide shows the outline of that study. It looks complicated, but what it really shows is that we see patients basically every other month. And every other month, we take a new blood sample, and we do a new psychiatric assessment. And by this study design, we will be able to take a blood sample early on and we will see, will this sample predict what is happening two months later? Can we tell who will develop suicide risk or suicidal thoughts, behavior later on during this year?
And in terms of where the inflammation comes from in the patients with depression, there could be several answers. One very well-known source of inflammation is autoimmune disorders, such as rheumatoid arthritis or SLE, for example. And we already know that people who have those autoimmune diseases, they also have a high prevalence of depression. We and others have also found that a lack of certain important vitamins that regulate the immune response, such as vitamin D; this vitamin is produced in our skin in response to sunlight. And this lack of this vitamin is actually linked to inflammation and depressive symptoms.
We have also seen in our studies that some patients with suicidal behavior and depression have an imbalance in their gut. So, it seems like this imbalance in your gut or in your diet could lead to an increased inflammation in your body that is linked to depression and suicidal ideation.
Pregnancy, I would like to mention, too, because pregnancy is a known risk factor for depression in women, and we have done several studies that suggest that inflammation can be specifically important during that time in women’s life. And here you can see data from our patients showing that the level of QUIN, the inflammatory metabolite, increases significantly more in women that develop depression in pregnancy. So the diagram, you see the green line here, that’s women with depression, and it’s the levels of QUIN that increase pretty drastically in the women that also later on develop depression.
So, based on all this, we can think of several ways that might boost our resistance against depression. So, we can try different ways to live healthy and reduce inflammation in our bodies as much as possible. But of course, remember that this might not be enough — far from it — because depression is still an illness that can hit us anyway, at any time. But it really makes sense to try and build our defenses as much as possible, just as we do when we try to prevent cardiovascular disease, for example.
And things that you can try to do to reduce inflammation would include to prioritize sleep, to exercise more, to eat a healthy diet, you can check anti-inflammatory diets and drink less alcohol. So, these things are all likely to reduce the amount of inflammation we have in our bodies.
And finally, I want to summarize what I have talked about today so far. Inflammation can cause depressive symptoms. The downstream metabolites of inflammation can affect the communication between nerve cells, and some people can be vulnerable to develop depression during inflammation. There can be different sources of inflammation present in individual patients, and it might make sense to think about this and see what could be present in your case. And the inflammatory and metabolic markers could potentially be used to predict the risk for depression, for treatment resistance, and for suicidality in the future. And we should also, of course, do our best to reduce the sources of inflammation in our bodies. And hopefully in the future, there will be clinical guidelines and treatments that will come into the psychiatric clinics.
These are the final points that I wanted you to remember. First of all, remember to be aware of depression. Remember the less-known, less-understood symptoms and signs of depression that I mentioned. Please keep the conversation about mental health and depression going. That really helps. It really helps people opening up about what they’re experiencing. And be proactive about those things we talked about in your lifestyles and maybe encouraging friends and family members, because inflammation can impact the biology in your brain. And then, finally, and maybe most importantly, seek help. Remember, first of all, nobody is alone. This is a huge and very common problem. And remember that there are efficient treatment options available for depression.
And with that, I wanted to acknowledge everybody that I would like to thank. And, of course, first and foremost, I would like to thank all the participants in our clinical studies. There are several hundred at this point, probably thousands, of clinical study participants. And without them there would be no research about depression. And I also would like to thank my funding sources, primarily the National Institutes of Mental Health, our colleagues at the National Network of Depression Centers that we are members of, and my colleagues and collaborators at Columbia University, Karolinska Institute and Lund University in Sweden. And, of course, our local collaborators here at Pine Rest Clinical Christian Mental Health led by Professor Nagy Youssef, and, of course, Professor Eric Achtyes at Western Michigan University.
So, thank you very much, also, of course, to my lab — former and current members at the Brundin Lab at Van Andel Institute. So, thank you very much to everybody and I’m happy to take any questions.
Maranda [36:57]:
Thank you so much, Dr. Brundin. So much information. I think we all were hoping you would tell us that one thing we could do to fix the problem, but you’ve given us so much to think about.
I’m very curious what led you to investigating the role that inflammation plays with depression? What caused this?
Lena Brundin [37:17]:
Well, I started many years back in Sweden, and what really started me was my studies where, actually, I looked at microglia cells, and at that time it wasn’t really well-recognized that the brain could be inflamed. This is really a field that has really started up over the past 15 years or so, because for a very long time it was thought that the brain is an organ that sits by itself and it doesn’t react much to what’s going on in the rest of the body.
So, looking at microglia cells, when I did my graduate studies, I saw that these cells in the brain, they can react really strongly to inflammatory stimuli, and they change their entire appearance. They become reactive and start secreting their own cytokines. It made me realize that there is a lot that can actually happen within the brain that is likely to change the neurochemical environment. So, after realizing that, we started up together — with our studies back in Sweden — different clinical trials where we measured inflammatory factors in blood samples and in cerebrospinal fluid from patients with depression and suicidal behavior. And I’ve been continuing that work since the past 12, 13 years or so in West Michigan.
Maranda [38:37]:
We have a question from the chat area. Have you noticed anything interesting from your preliminary data from the ongoing study, or is it too soon to say?
Lena Brundin [38:50]:
Well, it’s a little too soon to say, because it’s a very complicated study that — you saw the slide, it has maybe eight different sampling time points. So, we’re still working to refine the statistical analysis, but we have already done a longitudinal study in pregnancy here in West Michigan, too. And in that study, we could actually confirm that we could predict with a blood sample, we could predict a couple of months later on who would be experiencing severe symptoms of depression.
Maranda [39:23]:
Next question. Do you know of any clinical traits or any clinical trials on these markers that do not require hospitalization? For example, could someone in routine psychiatric or therapy care be tested for these kinds of things, just to know where those markers might be?
Lena Brundin [39:44]:
Well, so, usually, actually, when you go to your regular physical checkups, sometimes the doctor will order CRP for example, which is a marker of how much inflammation you have in your body. And it makes sense to look at the CRP, because it’s also a risk marker for cardiovascular disease.
So, by looking at your CRP level at your annual checkup and see does that look to be high, you can have a conversation with your physician: What factors should I look into in order to reduce the amount of inflammation I have in my body? Try to figure out what is going on that you can, you know, reduce the CRP. So, that is a very common marker and it is often used in health care already.
Maranda [40:31]:
Is that something that we can actually ask our doctors for at an appointment and just say, “I’m very curious about it” and then seek their recommendations? Or is that something that is not common practice?
Lena Brundin [40:43]:
I would say that it is a pretty common factor, but, of course, each doctor has their individual routines and how they handle these checkups and so on. But it’s definitely, it’s worth bringing the conversation up about inflammation with your doctor because, like I said, it’s important in many different ways for your general health.
And, you know, there might be different sources of inflammation that you can actually treat. There might, you know, some people have chronic tooth infections that go on for many years that could be individual source of inflammation that you can actually find some treatment for. And perhaps you will then notice that your mood is also changing because inflammation is being reduced. So, it does make sense to look at your individual situation and see if there could be some individual risk for inflammation there.
Maranda [41:35]:
Next question that has come in, and I think a lot of us are wondering this, is there any research being done on those with long-term COVID, as depression is part of those symptoms as well? What are you seeing in the work you’re doing?
Lena Brundin [41:50]:
Yeah, there is definitely, there’s a risk for depression that goes with long COVID, and yeah, it — long COVID has been a bit tricky to gain a thorough understanding of. And I would have to say that we might feel impatient, but it’s kind of recent that COVID hit us. So, I think we have to be a little more patient, and wait a few more years, because there are a lot of different studies coming out trying to look at long COVID, the risk factors of long COVID and the treatments of long COVID. So I guess my best answer is that yes, after COVID, just as after the flu or other severe infections, there is an increased risk for depression that can be linked to inflammation.
Maranda [42:43]:
In your study, are all 160 participants free from taking antidepressants so as not to influence or impact the blood analysis?
Lena Brundin [42:54]:
That’s a really great question, and the answer is that no, they’re not free from medication, because, for ethical reasons, we can’t really keep somebody off medication for a whole year, or even for, you know, weeks or months. We would want the patients to take the medication, you know, even if they don’t have perfect effects from the medications, most patients still have a benefit from medications.
So, very rarely would it make sense to make a patient completely medication-free for a long period of time. So, we have to try to analyze those inflammatory factors in the presence of medication, and it does look like we can still pick up a signal. So, patients who have more severe symptoms often have higher inflammation even in the presence of those antidepressive medications they’re taking.
Maranda [43:50]:
Are you aware if any individual has an increased risk of depression later in life if they experience severe depression postpartum?
Lena Brundin [44:00]:
I would say that there is an increased risk for depression in later life. If somebody had depression during pregnancy, you know, it’s difficult to say exactly how much higher that risk is, but I would say that any person who has had risk, who has had depression prior, I would be more observant, you know, if the symptoms would reoccur. So yeah, there’s a reason to look out for, for symptoms that could recur.
Maranda [44:35]:
Playing off that, does any of your research include the parallels between menopause and depression?
Lena Brundin [44:43]:
So, we are hoping to start a study on depression in menopause, because that is a very important time in women’s life when the hormones are shifting pretty rapidly and that can impact the immune response. We know that there is a greater risk for women to fall ill in depression and anxiety during menopause and perimenopause. So, it’s really important and we’re hoping to start up a study about that pretty soon.
Maranda [45:15]:
You mentioned some early triggers, and when I think about children playing sports and getting a concussion or, at a very young age, getting RSV or other types of viruses, do you consider those markers that could actually impact depression later in life?
Lena Brundin [45:33]:
It is possible if you sometimes — we call it challenges. If there is an adverse event that could be a trauma, that could be a strong psychological trauma in childhood, or it could be a severe infection in childhood. So, those are risk factors that could lead to a greater risk of developing depression in later life. Yes.
Maranda [46:00]:
Anxiety and depression are often linked. Is there any plan to study the potential influence of inflammation in patients with anxiety?
Lena Brundin [46:10]:
That’s a really great question, too. So, it is true that anxiety is often comorbid, it’s happening at the same time as depression. It’s still considered a distinct disease, so it’s a different disease. And when we have looked at the markers of anxiety, they are not the same as the markers for depression. So, it seems to be a bit of a distinct symptom, anxiety. So, it doesn’t correlate as well with the markers of inflammation that we are picking up as a marker of depression and suicide risk.
Maranda [46:48]:
Next question, similar, what about chronic infections for kids? Is there any increased risk factor for those children to suffer from depression as adults? Do you feel that there, that is one more factor or do you think those are isolated?
Lena Brundin [47:05]:
Well, chronic infections in children, I don’t think I have seen any epidemiological studies. So, the studies that I have seen mostly talked about — a really strong infection such as sepsis or, you know, a very, very strong infection. I don’t know for sure about chronic infections in children.
Maranda [47:30]:
Do you have any recommendations for those suffering from seasonal depression, especially in cloudy West Michigan? Would you suggest vitamin D or anything else? Or maybe a lot of vacations? What do you think?
Lena Brundin [47:44]:
I mean, a lot of vacation would be great, and, especially as a Swede, I can recommend vacation. We take a lot of vacation in Sweden. Sweden is very dark and very, very cloudy, so we need our vacations. But I do think if you can’t get sufficient amounts of vacation, which is true for most people, I think you can take vitamin D supplements. Just be sure, so you don’t take too much of vitamin D, look at the recommendations and take something that’s within the recommendations of daily use, because sometimes, when you go to, to the store, there are some really strong dosing vitamins and that might not always be optimal. In fact, that might be a little risky and dangerous. So take something within the recommended dosage, and that’s probably somewhere among the lower end of what you will find on the shelves in the stores.
Maranda [48:42]:
We often think about things like turmeric and ibuprofen as things to combat inflammation. Do you feel that that would be wise to think about taking something like that to, you know, if there is that link between depression and inflammation?
Lena Brundin [48:57]:
Yeah, what I would really wish for is that we could have some clinical recommendations, how to treat inflammation. Well, first of all, I think we should do routine testing to pick it up and then we should have some clinical guidelines how we should treat it.
In the absence of clinical guidelines, it’s really hard to make any clinical recommendations. In fact, we can’t do that, the clinicians can’t do that. So, patients are kind of in a situation where you would try to modulate things that you can, using things that are available over the counter. And, you know, there are vitamins, like I said, there are different ways to alter your lifestyle, your diet, and those recommendations can really have profound changes on the level of inflammation in your body.
So, that might be a better option than taking an anti-inflammatory pill over the counter and having nobody who’s following you up, you know, because even an anti-inflammatory medication can also have side effects. So, it’s important to be observant of that. And, you know, anything you take, it’s best to discuss with clinicians because there might be other medications you take at the same time. So, I would go for adjusting lifestyle factors as the first thing to do because that could really have a profound effect.
Maranda [50:24]:
Are you aware of any research linking childhood seizures to depression or anxiety later in teenage or adult years?
Lena Brundin [50:33]:
Well, I am, I am aware of current seizures and epilepsy being linked to depression. I’m not sure about early childhood symptoms and if that goes away, I haven’t heard anything about that being a risk for future depression.
Maranda [50:54]:
If someone is interested in being recruited as a patient for a clinical study of some sort, are there options available to them? How do they get involved? How do they make themselves available? How does all of that work?
Lena Brundin [51:09]:
Well, when we have recruitment open, the people who are recruiters at the hospitals we work with down at Pine Rest and Western Michigan University in Kalamazoo, other places, they have recruiters, and they have flyers and they provide information. So, I think the best way would be to talk to people at those places and see what research studies are going on.
Maranda [51:36]:
I always want to end these kinds of conversations with a message of hope, because Van Andel Institute celebrates 100% hope with every dollar they receive in the research. What gives you hope in the work that you are doing for those who are suffering from depression?
Lena Brundin [51:55]:
Well, what actually gives me a lot of hope is seeing how much more accepted depression and mental health conditions have become. I hear so many people talking about depression these days, and I see events in our community and people really opening up and just, just telling about their own experience. And I think that’s an amazing progress, because only a few years ago, there was so much stigma and shame about mental health conditions. And, of course, there is still some of that, but I think the community and the conversation about depression has really helped.
So, I see a lot of that in everyday life, in the people I’m meeting in my community. And I’m really hopeful that this will continue by talking more about what we are experiencing. We will be able to help each other and also be observant on these, the less well-known symptoms that I mentioned —about hostility, irritability — and maybe thinking more what is behind the surface of this person. Just increasing that knowledge will help us be more patient. And, you know, reach out again to people that might need help. So, I see a lot of help, a lot of hope about what’s going on in the community.
And I also find a lot of hope, actually, about those studies of inflammation. I think we are making progress and there are more and more researchers acknowledging the impact of inflammation on the brain. So, it is my hope that we will be able to get those clinical recommendations and push more towards the doctors and the mental health professionals actually being able to help the patients: What samples should we take, what factors can we work with and how should we treat this?
So, I hope we’re getting there, and I do sense that there’s a lot of improvement over the past years, for sure.
Maranda [53:51]:
Dr. Brundin, this has been fascinating. I so appreciate the time that you’ve taken to share your work, and please extend our appreciation to your entire team. You are making a difference. You can see we have more and more questions coming in, and we all we wanna know more, so please keep up the good work. Thank you for taking the time to join us today.
Lena Brundin [54:11]:
Thank you very much.
Maranda [54:14]:
Now, if you have been here and you’re saying “Wow, I’ve got a lot of questions, I wanna learn more, I wanna see what else Van Andel Institute is doing,” we invite you to become part of the conversation. We will have lots of opportunities for you. You can go to our website, vai.org, to find out about a newsletter that you can sign up for, what’s happening on our social media platforms.
We also have our final Public Lecture Series of the year that is coming up on Dec. 11. I’m excited about this. It’s a panel discussion on immunity, metabolism and cancer, and you can find out more about that on our website. You can sign up for that as well. Continue the conversation; I really appreciate that you have given us the chance to think about, what are some of those signs and symptoms, and then what can we do in our lifestyle changes that can make those small changes? So again, I hope as you go through the day, you look for ways that you can encourage others. Thank you so much for joining us. Make it a great afternoon where you live.