David Scheiderer, MD, MBA, DFAPA is board certified in psychiatry and neurology. He specializes in psych-neuro-immunology (PNI), the primary theory of which is that life and its attendant stressors, combined with unique genetic endowments and early life experience, cause progressive imbalances among neurotransmitters, hormones, growth factors, metabolic parameter, and immune function..
Michelle Maddux, ND, received her doctorate of naturopathic medicine from Southwest College of naturopathic Medicine in Arizona. She has completed additional training in integrative and functional medicine, laboratory medicine, eating disorders, meditation, and mindfulness.
Dr. Michelle Maddux: Having trained as a conventional medical doctor specializing in psychiatry, what drew you to integrative and functional medicine?
Dr. David Scheiderer: Keep in mind that I still consider myself largely mainstream conventional, Western allopathic clinician. I have my foot firmly in that world every single day, and when I lecture nationally, it’s largely in my role as a mainstream psychiatrist. At the same time, I have been introducing the “darker arts” of complementary, alternative, functional, integrative, preventative, and curative medicine into my own practice.
It’s probably been almost two decades now that I’ve been doing that, largely because of my growing dissatisfaction with the outcomes I’ve been able to achieve with just mainstream approaches. I’m just not able to help enough people enough. And that’s what got me looking into other models, other ways of conceptualizing symptoms, the human condition, suffering and diagnoses. And then certainly other ways of treating them. Largely, it was because I wasn’t doing a good enough job using just the tools that I was given and that I had cultivated in the early part of my career.
Dr. Michelle Maddux: You have a theory that chronic degenerative conditions, and it’s a category in which you classify most mental health disorders, have been significantly influenced by environmental changes, which are leading to chronic low-grade systemic inflammation. One of the terms that I’ve seen and I’ve heard you use is a meta-inflammation. Can you summarize what these environmental factors are and also give us a little bit more detail into what meta-inflammation is and how it impacts the brain?
Dr. David Scheiderer: My mantra has been, over the years, a personalized treatment for the most personal of all illnesses. No one suffers like those who have mental illness: depression, anxiety, bipolar, mood disorders, degenerative disorders, Alzheimer’s, early dementia, etc. So, while I want to personalize treatment, at the same time, I’ve got to have some peg board onto which to place new data.
One of the most useful peg boards, and I’m calling it my unifying theory of mental illness and diseases of civilization, would be this meta-inflammation notion. And it stems from the converging lines of evidence that strongly suggests, perhaps proves, that chronic degenerative conditions (diseases of civilization) including most mental disorders, have been rising now steadily for quite some time and they have overtaken infections as the leading cause of death and illness.
Even with COVID, it’s not really the infection that kills us, but our own bodies’ overly exuberant immune reaction to the stimulus (virus) that is actually killing us. It leads to the same common final pathway, which is decreased gut microbial diversity. That’s intestinal hyperpermeability. And then you get this flooding of inflammation, and this is bidirectional, mind you. So, in a circular pattern where you’ve got inflammation in the gut, you soon have inflammation in the brain.
This epidemiological transition from infections that used to kill us before the Civil War because we had no antibiotics nor adequate sanitation has shifted to these chronic smoldering inflammatory-based diseases of civilization. And we think that epidemiological transition is due to environmental changes that conferred disease liability on genetic profiles that historically have been benign.
We think that transition is associated with low grade, chronic, systemic meta-inflammation. Not the big hit, but the thousand little cuts. The meta-inflammation that takes place over many, many days, months, years, decades perhaps, that leads to that slow rot of pretty much any of our organ systems.
We also think that much of that chronic inflammation starts in the gut, and then once it gets to the gut, it gets to your brain. Hence, all of my disorders. Now, also we think that this inflammation causes myriad perturbations in that psycho-neuro immunological set of parameters: neurotransmitters, hormones, growth factors, immune reactivity, etc. Mainstream medicine is not thinking that way, but I measure those things as often as I can. I need some measure of my patient’s inflammation. I look at neurotransmitters, I look at adrenal output, I look at growth factors. I look at all kinds of things. That’s what I’ve added to my practice beyond prescribing medication, which I still value and do every single day. But I like to combine these various approaches.
Dr. Michelle Maddux: In the case of depression, specifically, you posit a microbiota hypothesis. What’s the most compelling evidence to suggest that the gut microbiota plays a foundational role in both the development and alleviation of depressive symptoms? I know it’s a huge issue right now, as people are coming up for air post COVID, and we’re seeing a huge increase, not just in anxiety, but I’m struck with how many people are coming out of this in a very profound depressive state.
Dr. David Scheiderer: There are no easy answers. That trend however does fit nicely and is wholly consistent with this theory, this peg board. The COVID virus would be the stimulus amongst a lot of other contemporary life slings and arrows: urbanicity, the pace at which we attack our days, bad diets, we don’t get outside and walk and get natural sunlight, we’re not getting enough sleep. So, there are many, many things that are feeding this pro-inflammatory motif that plagues so many of us, and what is partly responsible for not only an acute response to COVID or another infection, but this long haul set of symptoms that we’re seeing.
And it’s not just the anxiety, anxiousness, fretfulness, existential angst, what’s it all about, meaning of life, “Oh my gosh, I’m going to die,” kind of stuff, which is there and you’ve got to treat that too, but brain inflammation leads to profound, what we used to call ‘sickness’ symptoms. Those would include brain fog, lethargy, no energy, no focus, no concentration, no vigor and vitality: basically, a lack of joy. These symptoms are very consistent with an inflammation endophenotype. Now keep in mind, back to depression for a second, I’m a DSM-5 guy. I have to be because I’m a board certified psychiatrist here in the United States. If you check five of nine boxes, that set of criteria to make the diagnosis of major depression, how many different combinations of symptoms (endophenotypes) can you come up with?
The answer is 227, 227 different endophenotypes of depression. For example, you can meet criteria for depression and not be able to sleep or sleep all the time, not be able to eat or eat all the time, not be able to sit still or not be able to move. So, which of those endophenotypes, those 227 unique presentations, is associated with inflammation?
The answer to that question is the old ‘atypical,’ now being called immunometabolic depression: sleeping all the time, eating all the time, fatigue, fatigue, fatigue, lethargy, brain fog, no joy in Mudville, Debbie downer, Eeyore, slug leaving a trail, co-morbid PTSD, fibromyalgia, and chronic fatigue. And what happens early in life sets you up for this overly exuberant immune-reactivity to whatever the stimulus is, for example COVID.
Now back to the early part of that question, “Well, what makes me think that has anything to do with the gut?” Interestingly enough, we know that if you give somebody who has depression a fecal material transplant of a healthy person, you can treat their depression. Which kind of depression? Well, you know which kind. That immunometabolic, atypical, inflammatory depression. Similarly, I can take a normal person and inject them … Don’t try this at home, okay? Inject them with fecal material transplant of a depressed person and make that individual who was previously not depressed, now depressed. It’s interesting. Who thinks of these things?
Actually, the concept goes back over 2000 years. The Bedouin Arabs were using fecal material transplants to treat a host of illnesses, including mood disorders. Now, again, that was warm camel dung. So we’ve known about this for quite some time. It has just recently been considered more prime time. Now we have a lot of other datasets. In certain types of depression, treating inflammation and the gut seems to work. I use a lot of probiotics, a lot of fish oil, a lot of D3, a lot of L-methylfolate right on top of my antidepressants. Right on top of psychoactive medications for those people who I believe to have intestinal hyperpermeability and neuro-inflammation because of that leaky gut.
Dr. Michelle Maddux: You mentioned that you do testing for inflammation markers. When you’re addressing the patients who present with both depression and their blood work shows that they have inflammation, what is your first line of treatment?
Dr. David Scheiderer: That’s tricky because that’s just not how we’re thinking in mainstream psychiatry yet. We don’t have biomarkers. But there is an old study that tries to approach the idea of optimal first line therapy. It looked at the use of escitalopram, Lexapro, a very good SSRI, compared head-to-head against nortriptyline branded as Pamelor. So, it was really not evaluating the specific drug nortriptyline versus escitalopram, but rather the effectiveness of a serotonin dominant reuptake inhibitor versus a norepinephrine dominant reuptake inhibitor.
Which did better? And it turned out it depended on a single measure of inflammation and that was high sensitivity CRP, C-reactive protein. I measure this on all of my patients because it does indeed inform my treatment recommendations. So, for example, if I have somebody that comes to me and they meet criteria for depression and they have an elevated CRP and other evidence of inflammation, they’re going to get a norepinephrine dominant treatment strategy, medication-wise, not a serotonin dominant strategy.
We know that if we support serotonin (SSRIs, SNRIs) unilaterally or disproportionately for any length of time, we see a compensatory decrease in dopamine and norepinephrine. A serotonin dominant strategy then is going to make those negative, immunometabolic symptoms, those ‘lack of’ symptoms (lack of: joy, motivation, get up and go, vim, vigor, vitality, clarity of thought, executive function) worse. I really use this thought process, my unifying theory so to speak, to guide my treatment decisions, whether that be medication, psychotherapy, or lifestyle. Get a life people, right? Go get some sleep. Go walk in the sun. Eat a handful of nuts. Whatever those life hacks are. Have a relationship. Change your evil ways. Brain transplant, if you need one. But when I’m going to use medications, that individual will get something that’s not serotonin dominant.
Now that’s outside of mainstream psychiatry, but in somebody that has atypical metabolic depression, and I coach my mainstream colleagues about this all the time, “Do not use an SSRI (selective serotonin reuptake inhibitor ) or even an SNRI (selective serotonin norepinephrine reuptake inhibitor) for these patients because all of them are serotonin dominant treatment strategies that at best will only treat certain symptoms and will ignore, maybe even make worse, all of these other humanity robbing negative symptoms.”
Another good measure would be salivary cortisol. Is this a high cortisol depression or a low cortisol depression? That’s interesting. So, you get those three symptom-based subtypes among the 227 endophenotypes way over here to my right. You’ve got the can’t sleep, can’t eat, can’t sit still, weeping and a’ wailing, doom, despair and agony, comorbid OCD and panic, high anxiety. You want to take a benzo before you see them. Now they’re the ones that have high cortisol which is different than this person over here, Debbie downer, Eeyore, slug leaving a trail, sleeping all the time, eating all the time, fatigue, fatigue, fatigue, lethargy, brain fog, comorbid PTSD, fibromyalgia. They’re the ones that have the low cortisol.
Low cortisol equals high inflammation. They’re the ones that have the increased gut microbial change, that decreased gut microbial diversity, and thereby the leaky gut. Those are the ones who are going to get a norepinephrine dominant treatment strategy and then also some of my best inflammation right sizing treatment strategies: fish oil, D3, L-methylfolate, N-acetyl cysteine, probably a probiotic and they’re going to get some very direct dietary lifestyle suggestions as well.
Dr. Michelle Maddux: As far as probiotics go, there are an enormous number of products on the market. There is really quite a plethora of options. Do you have a favored psychobiotic or a probiotic formulated specifically for its impact on mental and emotional health?
Dr. David Scheiderer: I do certainly have my favorites. We all have our favorites and there is a wide degree of variability. So where in the world do you start? I start with reputable manufacturers who have good data, including data in humanoids and that’s really hard to find with supplements and nutraceuticals, including probiotics. But there’s more and more and more all the time.
So I’m going to work with a company that’s keeping up and really cutting edge. I want a product that has been selected, not only for individual species and strains, but the synergies enjoyed by combining these strains. I want something that’s going to be stable on the shelf. And I want to have something that’s going to go in me and it’s going to get to where it needs to go-alive. There are a lot of things I’m going to look for in a probiotic preparation, not unlike the due diligence I hope that I’m doing with the sourcing of any of my nutraceuticals and supplements. I think it’s particularly important, however, with probiotics, because there’s a lot of, dare I say, misinformation. That’s wrong. There’s just a lack of information, which is probably more accurate.
I don’t use just one medication. So, I’m unlikely to use just one type of supplement, especially a probiotic, but certainly Omni-Biotic would be what I use the most. It’s what I take personally, for example. I like the fact that we’ve got data in humans. I like the fact that I’m able to travel with it as easily as I do. I don’t want to be one of those that buys my own hustle, but certain companies help me by providing up-to-date research and educational materials. I think all of that is attractive, too.
So, partner yourself with a good company with good science and good company support. That would be my recommendation. So, the specific species and strains, and not only that, but the synergies, I want them to have been studied extensively, preferably in humans. And I want them to be good for my own disease states including anxiety, depression, weight, and cognition.
An interesting study looked at people admitted for (bipolar) mania. They’re stabilized in the hospital and then in a double blinded fashion, they’re randomized to receive upon discharge that same medication that stabilized them versus that same medication that stabilized them plus a probiotic. The double blinded phase was that they received an adjunctive placebo or adjunctive probiotic when they left the hospital.
And what they found was that those who got the adjunctive probiotic performed significantly better than those who did not with respect to the primary outcome measure of re-hospitalization. Now, what was interesting was the effect size of that intervention. It was greater in those individuals that had inflammation at baseline. So you present inflamed, you’ve got this psychiatric syndrome, you’re given a probiotic, and you’re less likely to be re-hospitalized if you took that, rather than just your medication. You see where that data is really intriguing to a mainstream shrink type.
I’m usually going to use probiotics in my inflammatory, immunometabolic depressions. That’s the most common form of depression. You see it every single day. We’re going to see a ton of that post COVID. And that leads us back to where we started. We used to say, “What is triggering neuroinflammation in the modern world? Well, it’s either someone you met or something you ate.”
So interpersonal strife and diet are the two biggest drivers. Infection is still not as common as dietary and interpersonal stress-related neuro-inflammation. But it doesn’t matter what the stimulus is. It’s your own idiosyncratic immune reaction to that stimulus that creates the problem. It’s kind of simple. And that starts with the gut, of course.
Dr. Michelle Maddux: So many people who have had COVID long ago are still experiencing brain fog, cognition issues and mood changes. Can you dive into that gut-brain axis specifically with this, and describe how are you helping your patients who have contracted this disease and are still struggling with these symptoms?
Dr. David Scheiderer: Well, go back to square one and say, “Well, what is driving these at a psycho-neuro immunological level?” Long haul is just a description of symptoms. All psychiatric diagnoses are what is referred to as descriptive methodology. What that is really telling us is we don’t know what’s going on at a molecular level with any of these illnesses.
Your genes, uterine environment, early life adversity, current choices and habits combined with life slings and arrows, COVID, what have you, bring about progressive imbalances among various physiological systems to include neurotransmitters, hormones, thyroid function, adrenal output, immune reactivity, growth factors, etc. So that’s your psycho neuro-immunological perturbations (PNIPs). When you come to me with those symptoms, I’m going to look to see what is out of whack. And if it is inflammation, then I’m just assuming that it’s going to involve your gut.
They’re the ones, then, that are going to get my best agents to accomplish roughly the following things: I’m going to seal and heal your leaky gut. I’m going to right-size inflammation. I’m going to resuscitate your tired adrenals. I’m going to rebalance your hormones, neurotransmitters, thyroid, reproductive, insulin, whatever. And then hopefully, once all that’s working, I’m going to teach you some lifestyle tricks to maintain the gains that we make. Now how do I do that? Behavioral changes, nutraceuticals, vitamin supplements, minerals.
Now, once a patient reaches a certain threshold and it’s a psychiatric illness, I’m going to have to use medication, at least temporarily. But I’m hoping that by doing all this other stuff that I can get you on fewer meds, use them for a shorter period of time, and enjoy better efficacy with fewer side effects. So that’s how I try to combine all these things. These folks are also going to get my best neuroprotectors.
We know that inflammation is part of all the neurodegenerative conditions, and we know that most of those neurodegenerative conditions start in the gut, right? Alzheimer’s, Parkinson’s, Lou Gehrig’s. All of those neurodegenerative illnesses really begin in the gut, so that’s where I start. And remember Hippocrates said, “All illness begins in the gut.” I don’t know who that cat was, but it made sense to me. That’s where I’m at with what I try to do behind the scenes. I want not only to reduce your suffering, but I want to prevent or delay onset of these very dreaded neurodegenerative conditions. Then I want to enhance the quality of your life, your pursuit of happiness. Medicines will only help reduce your suffering initially. They don’t really accomplish those other things.
Dr. Michelle Maddux: Do you see better outcomes when you do address the gut with your patients, similar to that head-to-head study that you talked about with medication alone, or medication plus probiotics?
Dr. David Scheiderer: Yes. All the time, but I don’t collect outcomes. I’m a clinician. I have the discussion all the time with my patients. I treat the gut all the time. And not only does this help with their brain symptoms, it helps with many of their systemic symptoms because these are systemic phenomena.
We were taught in that song that the hip bone is indeed connected to the thigh bone. Well, it’s all connected. In my line of work (conventional medicine), there is an organ cartel where you’ve got a doctor for a left big toe, and then you got a doctor for the right big toe, and a doctor for this and that, and no one’s communicating, this kind of systems approach just makes sense to me. And it’s particularly important when we’re talking about the brain, the most cherished of all organs.
With my approach, I’m hoping to help not only with psychiatric symptoms, but also with useable energy and focus. Not anxious energy, but cognition, executive functioning, pursuit of happiness. I want to smooth their relationships and tone that irritability and rejection sensitivity. All of those things can get better and I can get you pooping and peeing better too. Eating, sleeping, pooping, peeing: those are four of my primary questions. Does that sound like a psychiatrist? Maybe not, but it’s a big part of the whole picture. And boy, if you’re gut ain’t working, you’re not doing any of those things adequately.
Dr. Michelle Maddux: As a naturopath, we are taught about the emunctories, organs of elimination. People get squeamish, but I tell them, “Your body is taking out the trash. Think about what happens in your home if someone’s shirks their duty and doesn’t take out the trash. What an unpleasant environment that begins to be.” And it’s the same in our bodies. We have to have those organs functioning at an optimal place.
Dr. David Scheiderer: Amen to that. As American humorist, Henry Wheeler, said, “I’d rather have an operational set of bowels than any amount of brains in the world,” and I think it’s funny because that’s probably true.
The older you get, the more you focus on such things. I’ll tell you what though, Michelle, I’m surprised every day by how many young people I see who are all eaten up with this meta inflammation and also constipated.
Dr. Michelle Maddux: I am constantly surprised by people who seem to follow the “healthy American diet.” It’s still an American diet. They’re trying to be healthy, but they don’t have an understanding of how their emunctories, gut, and all of these things come together to impact how they’re feeling right now.
Dr. David Scheiderer: That’s extremely well said, and I love what you’re doing out there. We’re getting more and more functional medicine, integrated medicine, and naturopathic types in the eastern U.S. You guys have it all over us in terms of your approach and just your fund of knowledge. I’m jealous.
Dr. Michelle Maddux: Thank you so much for your time. And thank you for sharing your knowledge and your expertise with us today.