RHR: Is Bipolar Disorder Caused by Chronic Inflammation?

In this episode we’ll cover:

• 06:14 Could inflammation be the key?
• 10:28 How inflammation is connected to bipolar disorder
• 15:22 Common causes of inflammation
• 21:53 Recommended diet and lifestyle changes
• 27:20 Use caution when stopping medications

[smart_track_player url="http://traffic.libsyn.com/thehealthyskeptic/RHR_-_Is_Bipolar_Disorder_Caused_by_Chronic_Inflammation.mp3" title="RHR: Is Bipolar Disorder Caused by Chronic Inflammation?" artist="Chris Kresser" social="true" social_twitter="true" social_facebook="true" social_gplus="true" ] Chris Kresser: Hey everybody, it’s Chris Kresser. Welcome to another episode of Revolution Health Radio. We’re going to head back to a Q&A format for a little while. As you know, if you’ve been listening to the show for a while, I like to mix it up. We’ve been doing a lot of interviews, which is great and really educational for me and hopefully for you as well. But I've been missing the Q&As and I know that some of you have as well based on the messages you sent and we’ve got a nice buildup of questions since we haven’t answered any for a while. So, I think for a little while, we’ll do some Q&As. Of course, I still may do some interviews here and there, but I think I'm going to stick with this format for a little bit. Okay, so with that in mind, I’d love to answer a question from a Reem. Let’s give it a listen. Reem: Hi,Chris. First I want to say thank you for everything that you do. You’re work has made a huge impact on my life and I honestly, truly cannot thank you enough for that. So you have my sincere gratitude. I want to ask about my dad who has been on medication for bipolar disorder for decades now. He sees a psychiatrist regularly and because of the drugs that he’s taking, he hasn’t been hospitalized in years. And we’re very thankful for these drugs for allowing him to live a normal life. At the same time, these drugs have very serious side effects and just last year he started complaining about being slow. And we didn’t really do anything about it, but it’s just gotten worse and worse. And now when you talk to him, it’s obvious that it takes him extra time to process new information and to then respond. His creativity and his productivity have gone way down, he’s experienced serious cognitive decline, his critical thinking, analytical, even reasoning skills I’d say have been very much impaired. And this actually cost him his job. He was laid off two weeks ago and in this state, I really worry about him finding and sustaining another job. We’re going to be looking for a different psychiatrist, but I’m very interested in lifestyle changes that we can make to mitigate these side effects and to perhaps even eliminate or at least reduce the need for these drugs. He’s currently on the average American diet, he does not engage in that much physical activity. And I know that Paleo is good for everybody, but I’m really interested to hear about why it would be good specifically for him and what other natural remedies that we can engage in to hopefully stop things from getting worse and maybe even improve them. Thanks so much.

Six ways to treat bipolar disorder with diet and lifestyle changes

Chris Kresser: Okay, thanks so much for sending that question Reem. It’s a fantastic question. It’s something I've been wanting to cover for a while and I have covered in various ways although not directly with bipolar disorder. You may be aware that I wrote an article back in 2014 called “Is Depression A Disease—or a Symptom of Inflammation?” And then I wrote an entire series on depression several years ago, I think as far back as 2010 or 2011, maybe even before that, where I argued that the dominant paradigm of understanding depression as a disease caused by an imbalance of chemicals in the brain that in turn should be corrected with drugs that affect those chemicals, is fundamentally flawed. It turns out there are several holes in that theory including that reducing the level of norepinephrine, serotonin, and dopamine—which are neurotransmitters that have been implicated in depression—does not necessarily produce depression in humans, although it appears to do that in animals. We know that some depressed patients have low levels of serotonin and norepinephrine but the majority do not, and in fact, several studies indicate that only about 25 percent of depressed patients have low levels of those neurotransmitters, and we know that some depressed patients have abnormally high levels of serotonin and norepinephrine, and some patients with no history of depression at all have low levels of them. And even if there is an imbalance of neurotransmitters in the brain, which I'm not even opposed to the idea of that being true in some people, the question is, why did those neurotransmitters become imbalanced in the first place? So, when we look at things through a functional medicine lens, we’re always trying to get to the root of the problem and that was never really explained in this chemical imbalance theory of depression.

Could inflammation be the key?

So, what if depression isn’t actually caused, at least at the root level, by a chemical imbalance after all? More specifically, we might ask, what if depression is not a disease but a symptom of an underlying problem? And this is exactly what most of the recent research on depression is telling us. In fact, there is a new theory called the Immune Cytokine Model of Depression, sometimes known as the Inflammatory Cytokine Model of Depression, which holds that depression is not a disease in itself, but instead, it’s a multifaceted sign of chronic immune system activation. So, to put it in more plain language, depression may be a symptom of chronic inflammation, but this is not only true for depression, it’s also true for all kinds of other mental and behavioral health disorders like bipolar disorder, which is what Reem’s question is about, schizophrenia, anxiety, OCD, ADHD, and autism spectrum disorder in this growing list of cognitive behavioral disorders that we’re seeing in children, and there is quite a bit of peer-reviewed research to support the connection between inflammation and all of these mental and behavioral health disorders. There is a great review paper by Burke et al. We’ll provide a link to it in the show notes where the authors presented several lines of evidence supporting the connection between depression and inflammation. For example, depression is often present in acute inflammatory illnesses, higher levels of inflammation have been shown to increase the risk of developing depression later, and administering endotoxins that provoke inflammation to healthy people has been shown to trigger classic depressive symptoms. So, they actually do experiments where they give people these toxins that provoke inflammation, and those people then go on to have depressive symptoms. About a quarter of patients who take Interferon, which is a medication used to treat hepatitis C and the way that the medication works is by causing significant inflammation in order to help the body deal with the hepatitis C infection. About a quarter of patients who take that drug develop major depression. It’s a notorious side effect of that medication. In fact, in many people who have hepatitis C believe that the treatment in that case has worsened the disease. And then finally, remission of clinical depression is often associated with normalization of inflammatory markers. So, if patients are being followed in a study and they have depression and then that depression resolves, when they get certain inflammatory markers tested, the researchers will observe that those markers have gone down in the patient’s that have gotten better. So what’s happening here? What is this connection between inflammation and depression all about? Well, during an inflammatory reaction in our body, there are chemicals called cytokines produced and they have a whole bunch of really technical names including tumor necrosis factor alpha or TNF-alpha, interleukin-1, interferon gamma, and interleukin-10 among others. And researchers discovered as far back as the early ‘80s that inflammatory cytokines, like those I just described, produce a wide variety of psychiatric and neurological symptoms which perfectly mirror the defining characteristics of depression. So, in other words, the presence of these inflammatory cytokines causes the very symptoms which we refer to as depression. Interestingly enough, antidepressants, particularly SSRIs, have been shown to reduce the production of proinflammatory cytokines like TNF-alpha and interleukin-1 and increase the production of anti-inflammatory cytokines like interleukin-10. They also change the gene expression of some immune cells that are involved in inflammatory processes. So, this suggests that SSRIs may work when they do work and that’s a whole another topic. They're not very effective as you may know, but when they do work, it may be because they are reducing inflammation rather than altering brain chemistry.

How inflammation is connected to bipolar disorder

Now, I want to specifically address the connection between inflammation and bipolar disorder since that’s really what Reem’s question was about, and there was a new paper published in 2016 which reviewed the mechanism linking chronic inflammation and bipolar disorder, again, we’ll provide a link to this in the show notes, and the authors said in the abstract, “Knowledge about the neurobiology of bipolar disorder is increasing steadily and evidence from several lines of research implicates immunoinflammatory mechanisms in the brain and periphery in the etiopathogenesis of this illness and its comorbidity.” So, that’s a big mouthful, but to translate, they're saying there’s a whole lot more research now linking both immune and inflammatory mechanisms to bipolar disorder and what causes bipolar disorder. And they go on to say, “The main findings are an increase in the levels of proinflammatory cytokines…” so increase in inflammation during acute episodes of bipolar disorder. So, when they see someone actually having an acute bipolar episode, they can measure those inflammatory cytokines and see that they're elevated “and a decrease in neurotrophic support…” so there are changes that are happening in the brain that are not favorable, and then “activation of glial cells,” so the glial cells are like the immune cells of the brain and when they're activated, that leads to neuroinflammation or inflammation of brain cells. And just doing a quick search for bipolar disorder and inflammation in PubMed, there are a whole bunch of very interesting titles, and you can quickly see that this is a pretty active area of research. So for example, there is a title, “Is bipolar disorder an inflammatory condition? The relevance of microglial activation,” and “Can bipolar disorder be viewed as a multisystem inflammatory disease?” is another one. “Imbalance between proinflammatory and anti-inflammatory cytokines in bipolar disorder,” “Inflammation and the phenomenology, pathophysiology, comorbidity and treatment of bipolar disorder – a systematic review of the literature,” and then finally, “Pathways underlying neuroprogression in bipolar disorder – Focus on inflammation, oxidative stress, and neurotrophic factors.” So, you can see, I'm not making this up. There is a well-established connection in the literature between inflammation and bipolar disorder, and as I've said, a very active area of research and we’re learning more and more about it every day. So, the question is, what do we do with this information and how would it change how we might approach bipolar disorder clinically? So the conventional paradigm, as I'm sure you know, is bipolar disorder is caused by a chemical imbalance, so we need to take drugs that alter that chemical imbalance. And these drugs can be effective in certain ways, as Reem said, the drugs have allowed her father to function and have taken the extremes out of... I'm kind of reading between the lines here and certainly working from my experience with other people with bipolar disorder... the drugs can have a lifesaving and life-changing effect in that they enable somebody to function who was not able to function before. So certainly, they're not all bad, and they can—I mean, if they're lifesaving, of course, they're not all bad and they literally can save lives. So, we have to acknowledge that these drugs can play a role, especially in really acute episodes. But, these drugs are also notorious for the kind of side effects that Reem described which is a really dulling of affect, reduction in cognitive function and sharpness, a flatness of mood, and a lot of patients describe feeling numb and just unable to really feel any highs or lows in their life at all. And in fact, these side effects are potentially very serious because they often lead to the patient stopping the drug even against the advice of their caregiver, and that of course, can have serious consequences. So, the other problem stepping back and looking at it from the perspective of the paradigm or the lens that we view this condition through, the bipolar drugs really don’t address the root of the problem. If the root of the problem is inflammation, then yes, SSRIs might be anti-inflammatory, but that doesn’t mean that they're addressing the causes or triggers of inflammation in the first place, and some of the other bipolar drugs that are used in that condition may or may not even have anti-inflammatory effects.

Common causes of inflammation

So, from a functional medicine perspective again, we always want to address the root of the problem and use a simple analogy I've used many times, I'm sorry if you're tired of it by now, but it’s really clear and easy to understand for people, but if you have a rock in your shoe and it’s causing your foot to hurt, you could take Advil and that will help with the pain, but if you really want to get rid of the pain, the safest way would be to take off your shoe and dump the rock out. And so, if we use that analogy here with bipolar disorder and treatment, the drugs that you can take for bipolar disorder may help with the symptoms and that may be really important to do especially at certain phases of that condition, in acute flare-ups, but if you really want to make long term lasting progress, you have to address the mechanisms that are leading to that chronic inflammation and activation of the immune system since that really is the underlying cause of these as far as the recent research is suggesting. So, if a patient comes to see me with a complaint of bipolar disorder, depression, OCD, anxiety, ADHD or any of those kinds of mental or behavioral health disorders, because I know this, because I'm familiar with this research, the very first thing I'm doing is looking for sources of chronic inflammation. And in my experience, the most common culprits are:

1. The Standard American Diet which is an inflammatory nutrient-poor diet, food intolerances, nutrient imbalances, so either excesses of certain nutrients or more commonly deficiencies of other nutrients.
2. Gastrointestinal pathology, so things like SIBO or dysbiosis, disruptive gut microbiome, or GI infections like H. pylori or fungal overgrowth, parasites, etc.
3. Then, we have chronic stress which I think is a really overlooked factor in our current culture as well as lack of social support which is shown to be a greater predictor of early death than even smoking 15 cigarettes a day, so two really huge factors that are often under emphasized.
4. Circadian disruption, so too much exposure to artificial light at night and not enough exposure to natural or bright light during the day. This is a huge issue that has been shown in a large body of evidence over the last 20 years to be a major trigger for inflammation and all kinds of other chronic disease states.
5. Lack of physical activity, which is probably the biggest issue in our culture but also too much physical activity which is an issue in certain subpopulations of people, you know, CrossFit for example.
6. Chronic infections, so things like tick-borne illnesses like Lyme or Bartonella or reactivated viral infections like Epstein-Barr.
7. And then, toxic burden, so exposure to heavy metals or mold or other biotoxins.

Of course, there are other sources of inflammation but these are the primary ones that I see most consistently in my practice and if we’re going to break those down into even more common, we’re talking, in terms of the standard American lifestyle, we’re talking of course about poor diet, nutrient deficiencies, gut pathology, and stress. I would say those are the big four. So, if you think this through, there is good news and bad news. The good news is that if you identify and address these mechanisms, you can potentially reverse and heal depression and other mental health disorders instead of just suppressing the symptoms with drugs, and what that means as a clinician, or if you're someone who suffers from one of these conditions yourself, is that there’s actually hope. And I think hope is crucial especially for patients who are suffering from these kinds of conditions and for clinicians that treat them, and that’s what has been lacking so much in the treatment of these problems is—patients are typically told that they need to take a psychiatric drug and they’ll be on that drug for the rest of their life and if the drug has really onerous side effects which they often do particularly with bipolar disorder, schizophrenia, and conditions like that, then sometimes patients look at their future or people who have these conditions who are faced with taking these drugs for the rest of their life and the side effects are really terrible, and I know at least a couple of people in my own life who have chosen to take their own life instead of face the future like that. So, the stakes are incredibly high here and it’s a really serious problem, and offering patients hope and a light at the end of the tunnel, a way that they may be able to at least partially heal and reverse these conditions, that should not be underestimated. That’s a fundamental paradigm shift and it offers something completely different than the conventional model does, and as I just described, the energetic effect of that can't be underestimated. The bad news of this is that identifying and addressing all of the mechanisms that can lead to chronic inflammation is not always easy. Certainly, in some cases, just switching to a healthy diet, making sure that you're getting enough sleep, you're getting adequate amounts of physical activity, and you're managing your stress, that’s probably 80% of it for many people. But for others who are dealing with GI pathologies like SIBO, parasites, dealing with chronic infections or heavy metal toxicity, or things like that, figuring that stuff out often requires working with a functional medicine practitioner who’s skilled in that kind of diagnosis and treatment. And unfortunately, at this point, it’s still not easy to find a knowledgeable practitioner in that area, which is of course the reason I've launched the Kresser Institute and I'm busy trying to train as many of those practitioners as I can. It can be expensive to work with a practitioner like that. It’s not always in reach for people, especially because these tests and treatments in functional medicine are often not covered by insurance.

Recommended diet and lifestyle changes

So, that’s the downside and the bad news, but there are some simple steps that everyone can take no matter whether they have access to a functional medicine practitioner which I'm going to outline for you right now. Diet: The first one would be following a Paleo-type (I use that term loosely), nutrient-dense, anti-inflammatory diet. So, that means focusing on the foods that human beings have been eating for the vast majority of our evolutionary history like animal products, meat and fish, wild fruits and vegetables, nuts and seeds, and starchy tubers. These are the foods that we are well-adapted to and our body knows how to process, and then avoiding the highly refined foods that have come to comprise the majority of the calories that the average American and anyone living in the industrialized world eats today. So, things like flour, sugar, and other packaged and processed and refined foods which have an inflammatory effect. Gut Health: The second thing would be to focus on gut health, so that means eating fermented foods, so things like sauerkraut, kimchi, beverages like beet kvass, and if dairy is tolerated, things like kefir and yoghurt or even water kefir if you don’t tolerate dairy kombucha can be helpful. And then you want to make sure you're eating plenty of fermentable fiber so these are types of carbohydrates, soluble fibers, resistant starches or non-starch polysaccharides that feed the beneficial gut flora and which in turn have a favorable effect on gut health which as we know now favorably affects the brain. Consuming bone broth which is rich in glycine and other nutrients that help heal the gut, and then collagen or glycine rich cuts of meat, the fattier cuts of meat like oxtail and brisket and shanks, that can all be very healing for the gut. Stress: And then we have stress management which, again, is often overlooked, but I think is a crucial part of addressing the underlying mechanism for mental health pathology. So, there are lots of different options here, everything from yoga, tai chi, qigong, meditation, deep breathing, to spending more time in nature. And certainly, increasing social support based on what we said earlier about how lack of social support is such a big risk factor—not only for mental health conditions but pretty much all of the diseases that we know of. Circadian Rhythm: Circadian treatment, so this means reducing your exposure to artificial light at night, like, not reading with your iPad right before bed or using the computer right before bed and then increasing your exposure to bright natural light during the day. It could mean taking a walk in the morning or at lunch time without sunglasses. Exercise: Physical activity, so we have a framework that was inspired by Dan Pardi’s “enduring mover” framework called SWAP which stands for Stand, Walk and Push. So, the idea would be to try to stand for half a day instead of sitting the whole time if you have a sedentary type of job and that can be done with a standing desk, or even a treadmill desk, taking walking meetings, walking or bicycling to work, lots of different strategies there. Walking 10,000 steps a day—anywhere from 7,000 or 8,000 or 10,000 steps a day, and then doing some more intense physical activity like high-intensity interval training, weight lifting, sprints, that sort of thing. Environmental Exposure: Finally then, just reducing your toxic burden using non-toxic personal care products, non-toxic home products, and of course, eating organic food whenever possible and if that’s out of reach financially to eat everything organic, you could focus on eliminating the Dirty Dozen. What the Environmental Working Group calls the Dirty Dozen is the 12 most pesticide-laden fruits and vegetables. And then where you can give yourself a little slack is with their Clean 15, which is the 15 fruits and vegetables that are less likely to have pesticides in them. So, if everyone dealing with bipolar disorder—or any kind of cognitive mental health issues—just did those things, I think that would be enormously helpful in most cases. It may not completely address the problems in all of those cases, but it would be huge step in the right direction and that’s a lot for someone to focus on. So, in terms of resources, my book, The Paleo Cure is a great resource. I cover all of the things that I just mentioned in a lot more detail than I can go into here on this podcast. 14Four.me is my implementation program, so that’s a program I created as a kind of companion to the book to actually help people put this stuff into practice because it’s one thing to read about it, it’s another thing to actually start doing it in your life. And then, the Environmental Working Group has some really good guides on toxin-free home cleaning products and personal care products that you can check out, as well as every year they update the Clean 15 and Dirty Dozen lists.

Use caution when stopping medications

So, a really important reminder before we finish up here which is, you should not stop taking psychiatric meds without discussing it first with your doctor. Stopping these meds requires very careful titration. And in fact, unfortunately, a lot of doctors, even psychiatrists, are not particularly well educated on just how careful and slow this titration needs to be. There’s a psychiatrist named Peter Breggin who has written a lot about psychiatric drugs and has some fantastic resources including a book on psychiatric drug withdrawal and we’ll provide a note to that in the resources section, but I think it’s called Psychiatric Drug Withdrawal: A Guide for Prescribers, Therapists, Patients and Their Families and he talks about how important it is to taper off these drugs slowly because they do alter your own output of these neurotransmitters and your brain chemistry. If you stop them too quickly, that can lead to very serious rebound depression or bipolar symptoms and dramatically increase the risk of suicide and other problems, so it’s not to be taken lightly. And really, if you're on these drugs, you need to understand this because it’s crucial how you taper off this will make a huge difference in your well being. Also, I think it’s really important to start addressing these underlying mechanisms before you start to taper because that’s what’s going to provide you some support in that process. If you just start trying to taper without addressing the underlying causes of the symptoms that led you to take the medication in the first place, then that’s not going to be a very effective strategy. Finally, this is not medical advice, my hope here was to educate you on the connection between chronic inflammation and bipolar disorder, and give you some ideas and resources for how to work with this, and things to explore. But please, do consult your doctor, especially if you're currently on psychiatric medication and you're thinking about stopping. I can't emphasize the importance of that enough. Okay everybody, thanks for listening. That’s it for now. Please do send in your questions especially because we’re going to be going back to this format for a while and I look forward to talking to you next time. If you’d like to leave a question for me to answer in a future episode, you can do that at chriskresser.com/podcastquestion. You can also leave a suggestion for someone you’d like me to interview there. If you're in social media, you can follow me at twitter.com/chriskresser or facebook.com/chriskresserlac. I post a lot of articles and research that I do throughout the week there that never make it to the blogger podcast, so it’s a great way to stay abreast of the latest developments. Thanks so much for listening. I’ll talk to you next time.

from Chris Kresser http://chriskresser.com/rhr-is-bipolar-disorder-caused-by-chronic-inflammation/
via Holistic Clients