The Link Between Metabolism and Mental Health, with Dr. Christopher Palmer

In this episode, we discuss:

• What led Dr. Palmer down this path of research and to this theory
• The problems with how we currently treat and understand mental illness
• The connection between metabolic health and the brain
• How mental states differ from mental disorders and why this is crucial to understand
• The evidence that mental disorders are really metabolic disorders of the brain
• Why classifying mental disorders as separate conditions exacerbates misconceptions about them
• Whether some psychiatric medications are causing harm and keeping people ill
• What kinds of new treatments might offer more hope of long-term healing, as opposed to symptom reduction

Show notes:

• Dr. Chris Palmer’s website
• Brain Energy website
• Brain Energy: A Revolutionary Breakthrough in Understanding Mental Health–and Improving Treatment for Anxiety, Depression, OCD, PTSD, and More by Christopher Palmer, MD
• “The Chemical Imbalance Myth of Depression“ video by Chris
• “The serotonin theory of depression: a systematic umbrella review of the evidence” study by Dr. Joanna Moncrieff, Ruth E. Cooper, Tom Stockmann, Simone Amendola, Michael P. Hengartner, and Mark A. Horowitz

Hey, everyone, Chris Kresser here. Welcome to another episode of Revolution Health Radio. The latest statistics suggest that one in 10 Americans suffer from depression, and anxiety is also extremely common both in the [United States] and in other countries around the world. There was a recent study published, which I did a Tuesday Tip video on, which found conclusively that, contrary to popular belief, depression is not caused by a simple chemical imbalance or low serotonin levels. It’s really important that we expand our understanding of what contributes to depression. I’ve written about this for many years. We’ve talked about the gut–brain axis and the connection between gut health and inflammation in the gut and depression. We know that nutrient deficiency can contribute [to depression], [as well as] sleep deprivation, chronic stress, lack of exposure to natural light, too much exposure to artificial light at night, which disrupts our circadian rhythms, and, of course, life events and circumstances and trauma. All these things can contribute to depression.

There’s another very interesting theory that’s gained traction over the past several years, and one of the biggest advocates of this theory has been Dr. Christopher Palmer, who is a Harvard psychiatrist and researcher working in this field. His theory is that depression is very often a metabolic disorder in the brain. That is the subject of this show. Dr. Palmer is going to tell us more about his research and how he came to believe that depression is a metabolic disorder of the brain, what [you] can do about [it] if you are experiencing depression or you know someone who is, [and] how we can leverage this new understanding to create better mental health. I really enjoyed this interview, [and] I think you will, as well. Let’s dive in.

Chris Kresser:  Dr. Christopher Palmer, it’s such a pleasure to have you on the show. Welcome.

Chris Palmer:  Thank you. It’s an honor to be here.

Chris Kresser:  I’d love to start with how you came across [the] idea of depression and other mental health disorders being metabolic issues in the brain. This is obviously not the standard theory of what causes mental illness, and perhaps we can talk a little bit about some of the problems with the conventional theories, particularly the study Dr. Moncrieff published recently. How did you arrive at this idea?

Dr. Palmer’s Path to the Brain Energy Theory of Mental Illness

Chris Palmer:  It’s a great question, and I think it’s, in some ways, been a work in progress for over 25 years as an academic psychiatrist. But the pivotal moment for me was in 2016, when I used the ketogenic diet to help a patient of mine with schizoaffective disorder lose weight. That was really my only goal. I had no concept that it might help his psychotic symptoms or other symptoms. I was simply trying to help the guy lose weight. I’d been using the ketogenic diet for people with depression, or even just low-carbohydrate diets or getting rid of junk food. I’d been using those approaches for almost 20 years, I think, at that point. But depression is very different [from] schizoaffective disorder. So this man tried the ketogenic diet, [and] within two weeks, not only did he begin to lose weight, but I started to notice an antidepressant effect in him. He was becoming less sedated, making better eye contact, [and] talking a lot more. But the most astonishing thing was that, at about six to eight weeks into the diet, he spontaneously told me that his auditory hallucinations were going away, his long-standing paranoid delusions were going away, [and] he began to realize that they weren’t true and probably never had been.

This man went on to lose 160 pounds and has kept it off to this day. He was able to do things that he had not been able to do since the time of his diagnosis. He was able to go out in public and not be terrified that everybody was trying to mess with him or harm him in some way. He was able to complete a certificate program. He was able to perform improv in front of a live audience. These things would have been impossible for him prior to the diet. Seeing schizoaffective disorder, which is a version of schizophrenia, go into nearly complete remission from a diet in many ways completely upended everything that I had been taught as an academic psychiatrist, and it forced me to do a deep dive into a tremendous amount of science to try to understand what just happened.

Chris Kresser:  That is fascinating and a powerful experience to have as a clinician. It’s, of course, not evidence that looked at a large number of people, but I know from my own experience as a clinician [that] when something like that happens right in front of my eyes, it is very difficult to ignore and it changes everything. It sounds like it did for you.

The Problem With How We Currently Understand and Treat Mental Illness

Chris Kresser:  Let’s talk a little bit about some of the problems with the conventional idea of what causes depression and other mental health disorders, especially in light of a study that was published by Dr. Moncrieff and colleagues in Molecular Psychiatry in late July. [It] was an umbrella review that looked at a whole bunch of systematic reviews and meta-analyses, and found no evidence to support the idea that depression is caused by low serotonin or chemical imbalance. What did you make of that?

Chris Palmer:  It’s really interesting because that study got a lot of press, which I think is fantastic. But, as you mentioned, she was reviewing other studies and meta-analyses. I had long realized well over 15 years ago that the chemical imbalance theory, especially the chemical imbalance theory for depression, was just not true. One of the strongest pieces of data all along has been that we know that [selective serotonin reuptake inhibitors] (SSRIs) [like] Prozac, Paxil, [and] Zoloft increase serotonin levels immediately. Within 24 hours, we can measure that serotonin levels are higher in the synapses, exactly where we want them to be in human beings. And yet, they don’t improve symptoms right away. It can’t be a chemical imbalance due to serotonin because it’s increasing serotonin right away, and it’s not improving the symptoms of depression right away. That doesn’t make sense.

I think one of the biggest challenges in the mental health field is that, right now, if you really get into specifics with the leading neuroscientists and psychiatrists in the world, they will tell you that no one knows what causes mental illness. We don’t know. All we know are risk factors, or some of the factors involved, and we usually lump them into the biopsychosocial model. We say that there are biological things like neurotransmitters, hormones, [and] genetics. There are psychological and social factors like trauma and stress. Throw substance abuse in there, whether you consider that a social thing or a biological thing. All these things come together to result in mental illness. And that model applies to all mental disorders. It’s not just specific to depression or anxiety; it also applies to bipolar disorder, schizophrenia, eating disorders, all of them. But nobody knows how they all fit together. Nobody can make sense of it. It’s this huge, overwhelmingly complex puzzle. So most of our treatments are just based on empirical observations. A lot of the antipsychotic and antidepressant medications were discovered serendipitously. They weren’t purposefully designed. We saw that they sort of helped reduce symptoms, at least in some people, and that was better than nothing. And that’s our field right now. That is the field of psychiatry.

We have psychotherapies that can be useful for some people. But again, they’re not a cure-all either. We’ve got all these treatments that we know are only partially effective in some people, and I think people in the mental health field, and certainly people suffering from these disorders and their family members, are frustrated and exasperated because nobody knows what to do. Nobody knows how to make things better.

Chris Kresser:  I completely agree. This is not my field. I don’t have the expertise that you do by any stretch. And yet, I’ve been aware of this for 15 years, as well. It seemed to me, even with my cursory reading of the literature back then, that the evidence base had moved on. There wasn’t any compelling evidence to support this idea. Yet, here we are 15 years later, and I saw a news report about [a] study that came out [showing that] 85 to 90 percent of the general population, if you ask them what causes depression, [will] answer “chemical imbalance and low serotonin levels.” We have this gap between what the people who are experts in the field, like yourself and others, believe about depression and mental health disorders, and what the general public believes. It’s a pretty big gap. What’s your sense of why that has persisted over the past 20 years, despite the fact that the scientific consensus has moved on in a lot of ways?

Chris Palmer:  It’s interesting because I think, at the end of the day, it’s because that’s what people are being told by their prescribers. The prescribers have it in their mind, whether it’s psychiatrists, nurse practitioners, primary care [doctors], your OB-GYN, [or whoever is] prescribing your psychiatric medications. These are prescribed to a huge percentage of our population, and prescribers have it in their mind that, if somebody’s depressed or anxious, the treatment is a pill. They pull out the prescription pad and they want to write a prescription. The logical question from the patient is, “Why are you giving me a pill?” They need a quick, easy answer, and the quick, easy answer is, “Oh, because your neurotransmitters must be imbalanced, and this pill is going to balance them for you.” It’s a nice, quick answer. It’s unfortunate that it’s not at all based on science, and actually, the science has proved it wrong.

Chris Kresser:  False, yeah.

Chris Palmer:  If that model was really working for the world, I would be all for it. I am all for helping reduce suffering in the world and treating illness. And if a pill can do that, I am all for it, especially if that pill doesn’t come with too many side effects. The hard reality, unfortunately, is that well over 50 percent of people who seek treatment for depression or any other mental illness are not getting better with our current treatments. And if people don’t believe that, I will just share a couple of quick statistics. Mental disorders are increasing in prevalence. They’re not even staying the same; they are getting worse in the United States and throughout the world. In fact, mental disorders are now the leading cause of disability in the United States and on the planet. And it’s not because people aren’t getting treatment; it’s because our treatments fail to work for far too many people. I am a psychiatrist. I’m not here to bash the mental health field. I’m not here to bash other psychiatrists. But we need to do a reckoning of the facts and the science and our abysmal outcomes [with] the current treatments.

Chris Kresser:  I couldn’t agree more. This reminds me of a quote I came across when I wrote about this 12 or 13 years ago. Dr. Elliot Valenstein said, “A theory that is wrong is considered preferable to admitting our ignorance.” Unfortunately, that’s the history of a lot of our theories. One way to look at that is, that’s just science doing its thing, right? We’re going to be ignorant a lot of the time, and it’s better to admit that than to perpetuate a theory that’s not correct just because it’s convenient in some way or another. But anyway, I want to talk more about your story. So you had this patient, you put him on a ketogenic diet for reasons other than improving his mental health, [and] found that he had an improvement that, correct me if I’m wrong, exceeded what would usually be possible with medications in that situation. [With] any of the standard care that you would give, you wouldn’t expect to see that dramatic of a result. So that sets you on the path of, “Why? How did this happen?” What did you learn? What is it that you’ve discovered in all those years of research on the connection between metabolic health and the brain?

The Connection Between Metabolic Health and the Brain

Chris Palmer:  So, a couple of things to highlight. One is [that] I started using this intervention in many other treatments and I started collaborating with researchers from around the world. We now have a whole metabolic psychiatry consortium funded through philanthropy, [and] we’ve got many case reports. So this man was not an isolated case. We have many people who have overcome schizophrenia and bipolar disorder and chronic depression and put those disorders into full and complete remission off [of] psychiatric medications. We’ve got at least five controlled trials now underway. So that propelled me even more. This man is not an outlier. This wasn’t a highly unusual case, [where] maybe he had some vitamin deficiency that the ketogenic diet was replacing for him, or maybe he was allergic to gluten. Because those are common questions that I get like, “Did he really just have celiac disease that never got diagnosed? You put him on [a] keto [diet], and that helped it; maybe that’s what it was.” No, that is not what it was.

When I started diving into the science, I already knew the ketogenic diet [was] a weight loss intervention and can be highly useful and effective for people with diabetes or insulin resistance. What I did not know at the time is that it is [also] a 100-year-old, evidence-based treatment for epilepsy. And that was really important to me as a psychiatrist because we use epilepsy treatments all the time. So the great news about that is that we have decades of neuroscience research telling us how and why the ketogenic diet appears to stop seizures. And many of those mechanisms of action are highly relevant to people with mental disorders. People have demonstrated that it can change neurotransmitter activity, it decreases neural inflammation, changes the gut microbiome, changes gene expression, all sorts of things. Initially, I was still just dumbfounded and confused because I’m trying to understand why one diet [would] help people lose weight, and at the same time help people who have type 2 diabetes, and at the same time help some people with epilepsy, and at the same time help people with depression, and at the same time help some people with schizophrenia. Those are all completely different illnesses. There’s no way in hell that I [can] connect these.

But that was the task that I set out to do, to understand what [connects] these. And at the end of the day, that led me to this broad concept that we call metabolism and, more specifically, it led me to do a deep dive into the science of mitochondria and all the different roles that they play in cells [and], more importantly, all the different roles [that] they play in all those disorders. It turns out [that] the ketogenic diet is a very powerful treatment to improve mitochondrial health and the quantity of mitochondria in your cells.

Chris Kresser:  I would love to spend a good chunk of time talking about that because I know [it’s] foundational to your approach and this theory. Before we do, I want to talk a little bit about defining some terms and some key differences. For me, from my Functional Medicine training, we came to see diseases as being expressions of underlying dysfunction. It’s a systems-based approach, where the dysfunction is at a deeper level, like the mitochondria, for example, or it could be cellular energy production, or some other kind of underlying mechanism that can then manifest in many different ways, according to that patient’s unique genetics, epigenetics, diet, lifestyle, [and] so many other different characteristics. Is that what’s happening here with mental health issues, as well? [Where] you have the same underlying dysfunction of the mitochondria, but in one person, it leads to depression, in another person, it leads to anxiety, [and] in another person, it could lead to schizophrenia or a more serious mental health disorder. What is the connection between different mental states, different mental health disorders, and these underlying mechanisms?

Mental States vs. Mental Disorders

Chris Palmer:  Yeah, so that last part is a huge topic.

Chris Kresser:  I’m sure. We’d need to spend many hours [to cover it]. But maybe just a 30,000-foot view.

Chris Palmer:  The 30,000-foot view is [that] the first thing I distinguish is the difference between a mental state and a mental disorder. Right now, the field of psychiatry does not necessarily do a good job of distinguishing those. What I mean by that, to give you some clear examples—let’s take a man who is married and has two kids. His wife and two kids are tragically killed in an automobile accident. That man is going to get clinically depressed when that happens. In fact, if he doesn’t get depressed, I think all of us would say [that] there’s something wrong with him. He’s abnormal. Or like, “Did he kill them? How can he not be depressed?” That man, if he’s a normal human being, is going to be severely depressed. According to [the Diagnostic and Statistical Manual of Mental Disorders] (DSM), he’s allowed to be depressed for 13 days. If he’s still depressed on day 14, he now has a brain disorder that we call major depressive disorder. And what causes that? Well, that’s probably a serotonin imbalance, or there’s something going on there. So [on] day 13, he’s just a normal human being going through grief, and on day 14, he’s now got a brain disorder.

Now, I think everybody knows that defies common sense. And yet, [the] DSM does not tell us to even consider the possibility that this might be a normal reaction to adversity. Instead, we take people who maybe are severely depressed in a crippling way for years or decades, who I believe really do have a brain disorder [and] that there’s something wrong with their brain or body that’s causing those symptoms, [and] we’re lumping those people [in] with this guy on day 14. I think we’re missing the common sense boat on that front. Another common sense issue is, if we went to Ukraine right now, there would be a lot of people who would get diagnosed with a brain disorder we call post-traumatic stress disorder (PTSD). It doesn’t matter [that] their country is still being bombed, [and] it doesn’t matter that their lives are still in danger. [The] DSM doesn’t take that into account. It just says they’ve got [PTSD].

So I think step one is [that] we have to distinguish normal reactions to adversity and normal human responses from disorders. Once we get to disorders, it’s really interesting. Because if you look at all the risk factors, whether it’s hormonal imbalances, medications, trauma and stress, or even if it’s specific genes that we have identified that confer higher levels of risk for mental disorders, they all overlap. All the risk factors overlap with all the mental disorders. I am not the first [to discover this]; I’m just building on decades of research from other researchers who have argued, based on all this science, that mental disorders all appear to share one common pathway to mental illness. But right now, the field can’t say what that common pathway is. I am arguing that [the] common pathway is metabolism, and more specifically, mitochondria.

Are mental disorders really metabolic disorders of the brain? New ways to understand and treat mental illness are on the horizon. #chriskresser #brainenergy #metabolicpsychiatry

Evidence That Mental Disorders Are Really Metabolic Disorders

Chris Kresser:  What is the evidence that you came across? Aside from your own clinical experience, which I do value. I’m not one of those people [who] believes that’s worthless and [that] everything needs to be in a randomized, controlled trial. Of course, [there are] several potential lines of evidence here that we could talk about. What was the thing or set of things that really solidified this for you and brought you to this belief that metabolic dysfunction is the root cause of mental health issues?

Chris Palmer:  It’s interesting because, in some ways, people might think this sounds radical or new or like I’m making something up. In fact, I’m not at all. All I’m doing is taking almost two centuries of data, of research studies, clinical studies, epidemiological studies, basic science studies, neuroimaging studies, genetic studies, all of it, and I’m putting it together in one coherent way. In the 1800s, researchers in the mental health field knew that people with mental disorders had much higher rates of diabetes, and people with diabetes had much higher rates of mental disorders. So it’s not a coincidence that [in] the 1930s, psychiatry was using insulin coma therapy within years of insulin being discovered. The mental health field knew that there’s a connection between diabetes and mental illness. Since the 1940s, we have an abundance of data showing metabolic abnormalities in the brains and bodies of people with mental illness. All those neuroimaging studies that we’ve been doing for decades, functional [magnetic resonance imaging] (MRI), [single-photon emission computerized tomography] (SPECT) scans, [positron emission tomography] (PET) scans, guess what they’re measuring? They’re measuring brain metabolism.

In all these ways, it’s really just taking the entire body of evidence that we have in the mental health field and putting it together in a clear and coherent way. The evidence that mitochondria are involved in mental illness is more recent. The first mental disorder implicated with mitochondrial dysfunction is autism, and that was in the 1980s. Since about 2000, numerous researchers have been studying mitochondria and mitochondrial dysfunction, and their relationship with bipolar disorder, schizophrenia, depression, and other chronic mental disorders. So again, in many ways, this is just taking all the evidence that we have in the entire mental health field, and putting it together in one clear, coherent way.

Chris Kresser:  Well, it makes sense to me because if you look at other brain-related conditions that don’t manifest with changed mental state but clearly indicate an issue with cognitive function or motor function like Parkinson’s [disease], there [are] tons of studies on mitochondrial dysfunction being a root cause of Parkinson’s disease. There [are] studies on mitochondrial dysfunction and dementia and Alzheimer’s [disease] and most other neurodegenerative conditions that I’ve seen. It wouldn’t make sense to me that [mitochondrial dysfunction] would be something that caused all those types of problems in the brain, but then had nothing to do whatsoever with changes in mental states or mental health. So, even from that perspective, it seems like there’s probably decades of research supporting that connection.

Chris Palmer:  Absolutely. Especially with the neurodegenerative disorders [like] Parkinson’s [disease] and Alzheimer’s [disease]. For people who don’t know, people who have mental illness are at a much higher risk of developing Alzheimer’s disease. In fact, some of the earliest signs and symptoms of Alzheimer’s disease are mental symptoms [like] depression, personality changes, [and] panic attacks. Once Alzheimer’s disease gets underway, almost 100 percent of patients will have mental symptoms. They have depression, agitation, insomnia, [and] 40 to 50 percent will have hallucinations and delusions. And those are the hallmark symptoms of what we call schizophrenia. So you really can’t talk about Alzheimer’s disease without talking about mental illness and vice versa.

Chris Kresser:  Right. And then, of course, there’s been a theory for many years that Alzheimer’s [disease] is essentially type 3 diabetes of the brain. [Meaning] there’s a problem with how the brain processes glucose. Maybe we could get into that a little bit. Is the mitochondrial dysfunction happening systemically throughout the entire body in these situations? Or is there a unique problem with the brain’s ability to process glucose? In other words, and maybe another way of getting at this is, is it possible in this framework that somebody is lean, has normal glucose, [and] normal insulin, but for whatever reason, their brain has an issue processing glucose or has some issue with mitochondrial dysfunction? Or is it much more systemic? Or both?

Chris Palmer:  It’s a great question. The answer is that every cell in our body is unique and different from the other cells in the body. So, cells are dying every day. And mitochondria control cell death. Whether it’s from a heart attack because that cell isn’t getting enough oxygen, or whether it’s programmed cell death, or apoptosis, mitochondria are controlling that process. So all the cells are different. We know from numerous studies, whether it’s on schizophrenia, depression, bipolar disorder, or Alzheimer’s disease, that sometimes people can have metabolism problems in brain cells and yet, if we check a fingerstick blood glucose, it’s normal. What that means is that not everybody who has type 3 diabetes necessarily has insulin resistance or type 2 diabetes. A lot of people with Alzheimer’s disease, for instance, can have normal blood sugars, but researchers can measure glucose hypometabolism, [which is a] metabolic problem [of] not being able to use glucose effectively in the brain. We have the same exact types of studies that have been demonstrated in people with depression and in people with bipolar disorder and schizophrenia.

Chris Kresser:  That’s definitely been my experience, as well. I’ve had a lot of patients over the years [who] didn’t have any obvious signs of diabetes or glucose disorders. They weren’t overweight, they had normal fasting glucose, normal insulin, normal post-meal glucose, and yet they were still experiencing anxiety, depression, other mental health issues, and, in some cases, early dementia, Alzheimer’s [disease], or Parkinson’s [disease]. It sounds like it is possible to have a defect in processing sugar and mitochondrial issues in one part of your body and not in another.

Chris Palmer:  I think that’s correct. And we actually have really good hard evidence of that. On neuroimaging studies from some colleagues of mine at Harvard Medical School, they did exactly that. They studied patients with schizophrenia, their normal siblings, and normal, healthy controls. What they found [was] that both the patients and the siblings had insulin resistance in their brain compared to the healthy controls. So insulin resistance seemed to be a risk factor in that family, but mitochondrial dysfunction is what pushed the people into psychosis. I do want to say [that] there’s a lot more to mitochondrial dysfunction than just glucose and insulin and using glucose as a fuel source. Hormones can affect it, vitamin deficiencies can affect mitochondrial function, stress and trauma, the gut microbiome, [and] inflammation. There are lots of factors that can play a role in mitochondrial function. I don’t want people to come away thinking it’s all about insulin and glucose.

Chris Kresser:  Yeah, I think that’s important to mention. There’s a risk that we were too reductionist for so many years with the chemical imbalance theory, [thinking that] all depression just comes down to low serotonin, which ignores all the complexity that you mentioned earlier. But it is interesting that what you’re saying here is that there’s a unifying mechanism. It doesn’t mean that there aren’t multiple different triggers of that mechanism. Nutrient deficiency has lots of effects, but it causes mitochondrial dysfunction. Inflammation has lots of effects that cause mitochondrial dysfunction. Chronic stress can cause mitochondrial dysfunction. Sleep deprivation can cause [mitochondrial dysfunction]. We know all these things are well-established triggers of mental health disorders in the scientific literature. What you’re saying here is that there’s a shared mechanism between all these different things. And that, of course, opens up new avenues for how we might address mental health disorders with this kind of framework.

Chris Palmer:  Absolutely. It’s really interesting because it aligns perfectly with the Functional Medicine field. It really does. It gets to, “Let’s think about root causes. Let’s do an analysis of everything that we can think of that might be playing a role, and let’s try out some interventions to see if we can make a difference.” I think, as an academic psychiatrist, one of the most powerful messages of this theory is that I’m arguing that schizophrenia and bipolar disorder do not need to be chronic, lifelong, untreatable disorders. They should not be disabling people for life. We can find answers. Although the science is complex, once you understand it and can take a 30,000-foot view of it, you can see and understand that we can do something for this person. We should not simply be putting them on antipsychotics and calling it a day, knowing that these medications aren’t going to put their illness into remission. Knowing that these people are likely to be disabled for life. Instead, I think we need to be taking more of a Functional Medicine approach of, “Let’s look for some root cause problems for your diagnostic label, and try to heal this person and return them to full health.”

Chris Kresser:  Wow. That’s a powerful frameshift because, as you know probably better than anybody, that kind of diagnosis, particularly with a more serious disorder like schizophrenia, is often seen as a life sentence. Once you have that diagnosis and once you start on that path of taking medications and treatment, it’s not commonly understood that that’s something you’re ever going to not be dealing with. I would say [that] people who have either suffered with those conditions themselves or know someone in their life that has suffered with them [probably] don’t have a lot of examples that they can point to of [a] complete resolution, where somebody [had] schizophrenia for two years or something and then, for the rest of their life, they didn’t have [it]. So even that alone, just the possibility [and] the hope that those conditions [could] be cured, is pretty remarkable.

Chris Palmer:  It is a complete paradigm shift in many ways. As a psychiatrist, I’ve seen many cases along the way of people who had psychotic symptoms for more than six months, and they went into full and complete remission and lived happily ever after, off psychotropic medications. We in the mental health field use circular logic, meaning that we say, “Well, that person couldn’t have had schizophrenia because if they had schizophrenia, it would have been a lifelong brain disorder and they would not have gotten so much better. Certainly not off medications.” But the way that I view it now is that we are defining treatment resistance in response to our current treatments, which we know are not all that effective. We define treatment resistance with a label, and we call it schizophrenia or bipolar disorder, and then we tell people, “You’re going to be sick for the rest of your life.” Why are they going to be sick [for] the rest of their life? It’s because our current treatments aren’t working for that person. The problem with that approach is that we write those people off. We aren’t looking for root causes anymore. We think we’ve identified the root cause. The root cause is this thing called schizophrenia, and there’s not much hope for it.

Although this may sound really far-fetched, and some people might think that I’ve gone off the deep end, I just want to do a reality check for people. The National Institutes of Health (NIH) abandoned the DSM diagnostic labels over a decade ago. This includes labels like bipolar disorder and schizophrenia. The [NIH] has acknowledged those diagnostic labels are not valid constructs. They are not valid biological constructs, based on numerous amounts of research and evidence, whether it’s genetic, basic science, [electroencephalograms] (EEGs), brain scans, [or] clinical questionnaires. They are not valid constructs. We have to wake up to that reality. I think the people at the NIH are struggling because they don’t know what it is. They’re still kind of perplexed about [it]. It’s overwhelming, it’s complicated, [and] we don’t know what it is. I’m saying, look it in the eye and see what it is. It’s metabolism. It’s mitochondria. Once you see that, everything fits together and makes sense. More importantly, we can actually do something. We can help people right now, today, based on current approaches and things that are available today.

Why Classifying Mental Disorders as “Separate” Conditions Is Misleading

Chris Kresser:  Yeah, that is a huge paradigm shift. One analogy that I don’t think [is] perfect but I’d like to explore with you is autoimmune disease. I’ll frequently have patients come to me, and let’s say they have multiple autoimmune conditions, which is not unusual. They might have celiac disease, rheumatoid arthritis, and Hashimoto’s [disease]. The conventional model [is] three different doctors, right? The gastroenterologist for celiac [disease], the rheumatologist for rheumatoid arthritis, and the endocrinologist for Hashimoto’s [disease]. And they’re going to get different drug treatments for all those different conditions. Nobody’s looking at the root cause [that] underlies all of those, which is autoimmunity, the body essentially attacking itself, and asking the question, “Why is the body attacking, in this case, the joints, the thyroid gland, and the cells in the intestine?” It seems to me that the distinction between the mental health disorders might be even less significant because at least in the three different autoimmune diseases, you have evidence of different tissues being attacked and involved even if there’s a shared underlying mechanism. But in the case of bipolar depression and other mental health disorders, is there even that? Or is it just a question of how the underlying biological process manifests, in terms of symptoms? Is there anything that can be seen biologically that’s different between those conditions?

Chris Palmer:  There’s not, unfortunately. And it’s not for a lack of looking. There’s been this long-standing conundrum of, number one, heterogeneity. If you have two people with the same diagnosis, and we do brain scans on them, the brain scans can be very different. One person with autism, for instance, can have [a] very different brain scan and blood biomarkers than another person with autism. Same for schizophrenia. Same for depression. Same for [obsessive-compulsive disorder] (OCD). Same for anorexia. People are very different from each other, and that means they’re unique, and we know that. But the other challenge with mental health disorders is that all these disorders are often comorbid. If you look at people who are getting mental health treatment, on average, they have about three and a half diagnoses. Just like you described for autoimmune disorders, people have more than one. When it comes to mental illness, people getting treatment usually have more than one. The person with schizophrenia can also have anxiety, or a substance use disorder, or OCD. The person with anorexia can also have PTSD, or a substance use disorder, or other things. When you start to look at real people with these disorders, these disorders are no longer distinct entities. They overlap, they share biological factors, they share risk factors, and at the end of the day, they’re really just different manifestations of similar pathological processes.

Are Psychiatric Medications Causing Harm?

Chris Kresser:  That’s so fascinating. This begs the question, if the model of understanding what causes these disorders is wrong, then we might assume that the current treatment approaches are also not evidence-based at this point. Is it also safe to assume that the current treatments might actually interfere with healing or even, in some cases, make the situation worse? Just as an example, there’s a study that came out and a lot of discussion recently about how taking ibuprofen can make pain chronic. [If] you take ibuprofen for a short-term pain issue, it actually increases the risk [of] that pain [becoming] chronic. There’s a whole mechanism for that, which I won’t go into. [Proton pump inhibitors] (PPIs) that people take for acid reflux can suppress stomach acid, which can increase the risk of bacterial overgrowth in the small intestine, which then can actually cause reflux. There are lots of examples of this in medicine. Are there similar parallels in mental health and the medications that are being used to treat mental health disorders?

Chris Palmer:  That’s probably going to be one of the most controversial findings of my book. And it’s certainly not that there haven’t been a lot of people saying this for decades. A lot of people have been arguing that some psychiatric treatments appear to be harmful, at least to those individuals, and that they might be keeping people ill. For the most part, mainstream psychiatry has not accepted that because we do have randomized, controlled trials showing that, for instance, antipsychotic medications can reduce symptoms in enough people for the [U.S. Food and Drug Administration] (FDA) to approve those medications. And as a psychiatrist, I have seen that with my own eyes. I’ve seen the medications reduce psychotic symptoms or manic symptoms. I’ve seen it; I know it happens. So I’m not here to challenge those observations, because those observations are true.

But I am here to, again, just do a wake-up call to the mental health field. Let’s look at our current treatment outcomes. Let’s look at how many people are disabled by mental disorders despite getting the best treatment available. Let’s look at long-term outcomes. We have a lot of room for improvement. And based on this new scientific understanding of mental disorders as metabolic disorders, this theory and the science to support it raises serious questions about some medications that we’re using, because we know [that] some of the medications we use harm metabolism and, specifically, harm mitochondria and their function. We know that the medications cause weight gain, cause diabetes, cause cardiovascular disease, [and] cause premature mortality, at least in elderly people. Those are all on the package insert. The FDA has mandated that those things be put on the package insert. So nobody can say Chris Palmer is making stuff up, or I’m being a hypocrite, or how dare I say that. Those are facts. This theory [raises] a serious question, and I go into the science to explain how and why those medications probably do reduce symptoms in the short run. But also, [like] in the example you gave with ibuprofen, how that can end up making matters worse in the long run, if you stay on these medications every day, long-term.

Chris Kresser:  Absolutely. I mean, we have so many examples of that. Think of antibiotics for ear infections. We know that most childhood ear infections are actually caused by viral illness rather than bacteria, and yet, antibiotics are often prescribed. Unfortunately, those antibiotics disrupt the gut microbiome, which makes that person more susceptible to future viral illnesses and future infections. It’s this vicious cycle that can happen. In my practice, Remeron is a drug that comes to mind that is notorious for weight gain, and I’ve seen metabolic problems, even if they weren’t present [before], start as a result of using that medication. So yeah, it’s not surprising to me. That’s why I asked that question. But I will leave folks to check out the book for all the details and the mechanisms there because I want to finish up by talking about what this means in terms of future treatment possibilities, the most obvious being taking steps to improve your metabolic function, whether that’s the ketogenic diet, or just a lower-carbohydrate diet, or something like a Paleo-type of diet. That’s perhaps a pretty obvious step that someone could take in this direction. What are the other kinds of treatment pathways that your consortium is exploring as a result of this paradigm shift and new way of looking at treating mental health issues?

A New Treatment Approach Based on Better Understanding of Mental Disorders

Chris Palmer:  It’s a great question. In my mind, this theory really unites the metabolic field with the mental health field. I argue that these things are inseparable and that the relationship goes both ways. If you’re suffering from a mental disorder, it’s not that I’m saying we should throw out all mental health treatments, [or] that we should throw out psychotherapy. I think psychotherapy does help some people. I think some medications can be very helpful to some people. But I want people to start thinking more about metabolic intervention—diet, exercise, sleep regulation, stress reduction, checking hormones, checking for vitamin and nutrient deficiencies, those types of metabolic things. Likewise, I think that this theory is applicable to people who want to lose weight, who want to prevent type 2 diabetes or address their type 2 diabetes, or who want to prevent a heart attack. Because guess what? Mental symptoms or constructs influence those, as well. We know, for instance, people who are lonely are more likely to die early deaths from heart attacks than people who aren’t lonely. And that’s a psychological or social problem, one that most people would consider mental. What I’m arguing is that mental and metabolic are inseparable and that we need comprehensive approaches to treating human beings. We need to treat the whole person, not just one diagnosis, not just one symptom.

Chris Kresser:  You’re speaking like a Functional Medicine practitioner, Chris. You’re not going to get any argument from me on that. It just always made sense to me that the things that would contribute to [the] reduction of one disease state, let’s say diabetes, or autoimmune disease, or [irritable bowel syndrome], or any number of diseases, are exactly [the] same things that are going to contribute to the reduction of another disease state. We’ve [spent] most of [this] interview talking about how mental health disorders share a common underlying mitochondrial dysfunction. But, of course, mitochondrial dysfunction is not going to limit itself to just causing mental health disorders. There [are] so many other chronic diseases that are associated with mitochondrial dysfunction, from cardiovascular disease to hormone imbalances to osteoporosis. It’s actually hard to find a chronic disease that is not associated with mitochondrial dysfunction. So that just makes a lot of sense to me, that those same steps we try to take to improve our overall health are the same steps that are going to improve our metabolic function and our mental health; 100 percent. I also imagine that, over time, this will lead to some interesting new approaches that we haven’t even thought of yet, in terms of more specific treatments for mental health disorders.

Chris Palmer:  Yes. One of the things that I am absolutely going to be advocating for is more research funding for the mental health field based on this theory and this approach. Because we have a lot of work to do. Getting people off psychiatric medications can be extraordinarily difficult and painful and dangerous, and we need better protocols to help do that more effectively and safely and quickly.

Chris Kresser:  Could we just linger on that for a moment? Because I feel some responsibility. I know a lot of people are going to hear this and be really excited, as they should be, about exploring a different approach to dealing with their mental health disorder. In my experience, a lot of people don’t understand how difficult and challenging it can be to get off psychiatric medications and how important it is to go slowly. Can you just speak to that briefly? So that we don’t have a rash of people who are stopping their psychiatric medication [tomorrow] to go on a ketogenic diet.

Chris Palmer:  In the book, I am outlining tons of strategies people can use, and I am also strongly advocating for helping people get off medications. But I can tell you, I’ve been a psychiatrist for 27 years. If people come off medications too fast, and certainly, if they quit them cold turkey, more often than not, it is a disaster. It is a dangerous disaster. Please do not do that. I’m not saying that to try to keep you hooked on your medicine; I’m saying that because I want you to be safe. These are powerful [medications] that are dramatically impacting [your] brain function, neurotransmitters, hormones, synapses, all sorts of things. When you come off that medication, people have powerful withdrawal reactions, and those need to be managed. One way that I usually explain this to people, because a lot of times, people are like, “Well, that can’t be,” [is] alcohol. If people drink alcohol heavily, they shouldn’t just stop cold turkey either. Because guess what? You can seize if you do that. You can die. You can get delirium tremens. You can certainly have anxiety and the shakes and insomnia and all sorts of horrible, dangerous, life-threatening withdrawal reactions.

Now, does that mean that you shouldn’t come off alcohol? No, you should absolutely come off alcohol, but you need to do it in a safe way with a medical professional. I feel like [with] psychiatric medications, if you make the decision that you want to try to come off them, you need to look at it in a similar way. That it’s going to take some time and effort, and you want to work with somebody who knows what they’re doing to keep you safe and also to get you off as rapidly as possible.

Chris Kresser:  I think in my experience, the slow approach is actually faster in the long term. It’s like the tortoise and the hare. When people go off too fast, they have a rebound, all hell breaks loose, they have to get back on, and they do this bouncing back and forth. Whereas, if you just take a slow, steady approach, you’re more likely to succeed and you probably end up at the destination you want to get to sooner than if you would have gone too quickly in the first place. So thank you for that. I just wanted to put that out there because I know from my own experience that there’s not enough awareness, even among physicians and primary care doctors who don’t spend all day doing this, [about] how carefully this has to be done. And, like you said, under the supervision of someone who really knows what they’re doing, in ideal circumstances.

With that in mind, and with the hope for people who are listening to this that they might be able to get off their psychiatric medication with proper supervision and find a completely different way of addressing their mental health disorder from the root cause outward, tell people where they can learn more about your book and pick up a copy if they’d like to.

Chris Palmer:  There [are] two websites. I’ve got ChrisPalmerMD.com. That’s one easy way to connect with me. I have a BrainEnergy.com website that [has] information about the book, [and] also information for people who want to get involved in transforming the mental health field. I really want to see big changes because far too many people are suffering. Those would be the easiest places to get more information and [reach] me.

Chris Kresser:  Fantastic, Chris. Thank you so much for coming on the show and sharing this important work with everybody. I’ve learned a lot, and I really recommend the book. It’s a real paradigm shift in the understanding of mental health disorders. More than anything, I think it’s a message of hope and empowerment that these don’t have to be conditions that are a life sentence, [where] we are on this treadmill of psychiatric medication for the rest of our lives and there’s nothing that can be done. Which is unfortunately the current status, and how a lot of these conditions are approached and treated. I think your work and your book is going to give a lot of people hope that they can influence the course of their mental health over their lifetime. So thank you for doing that.

Chris Palmer:  Thank you.

Chris Kresser:  All right, everybody. Thanks for listening. Keep sending your questions to ChrisKresser.com/podcastquestion. We’ll see you next time.

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