Personalized Psychiatry: Using Blood Tests to Find the Right Mental Health Treatment

Alexander: 
What we’ve discovered is that when you match the right patient to the right medication, you can use very low doses because it’s a right fit. When you don’t have a good match, you need to ram in high doses to start to get an effect, right? But when it’s the right fit and it clicks in, low doses usually work.

So, a lot of the patients and doctors that have used our testing start with the low dose, and often times, that’s all they need.

Bret: 
Welcome to the Metabolic Mind Podcast. I’m your host, Dr. Bret Scher. Metabolic Mind is a nonprofit initiative of Baszucki Group where we’re providing information about the intersection of metabolic health and mental health and metabolic therapies such as nutritional ketosis as therapies for mental illness.

Thank you for joining us. Although our podcast is for informational purposes only, and we aren’t giving medical advice, we hope you will learn from our content and it will help facilitate discussions with your healthcare providers to see if you could benefit from exploring the connection between metabolic and mental health.

Dr. Alexander B. Niculescu is a professor of psychiatry at the University of Arizona where he focuses on personalized psychiatry, and he’s also the founder and CEO of MindX Sciences, where they really are on the cutting edge of trying to transform psychiatry from just a subjective diagnostic and treatment type field to an objective field where you can actually take blood tests and measure and understand better about someone’s symptoms and what treatments they may respond to.

It sounds futuristic, but according to Dr. Niculescu, it is the present and it is here today. So let’s dig deeper into this in our interview.

Dr. Niculescu, so great to see you. Thank you for joining me here at Metabolic Mind. 

Alexander: 
Thank you very much, Bret, good to be with you. And good to reconnect after all these years, after doing our internship together way back at Mercy Hospital. 

Bret: 
Yeah. Such a great story, right? We started off, I won’t say how many years ago, but quite a few years ago as interns just starting on our medical journey.

And then I went off to finish my internal medicine residency, and you went off to finish your psychiatry residency. And now our paths crossed once again. So I really.. 

Alexander: 
Are converging, right? Are converging, the mind and the body are one. And all the sort of work that you’re doing and the path you took and your current program and approach are converging with what we’re doing in terms of brain health, what we’re discovering in terms of precision medicine and so on.

So it’s great to have this conversation. 

Bret: 
Yeah, it really is. It really is. And I want to kick it off with an article you wrote at Psychiatry Online talking about Precise, Personalized, and Preventative Psychiatry. And I just love all those words: precise and personalized and preventative.

So I want to dig into that and all the concepts. But first, before we do that, give us the brief rundown on who you are, where you are, what you’re doing, how you got to this point. I know you’ve done a lot and you have your, a lot of irons in the fire, but see if you can sum that up for people.

Alexander: 
Yeah, sure. So, I’m a physician scientist. I still see patients to this day. In fact, this morning, I had my weekly clinic. And I’ve done academic research for the last two decades in developing this field of precision psychiatry. Really, we’ve pioneered it for the last, 20 years.

And five years ago, we decided to take the plunge and help move from the ivory tower into doctors and patients and families hands, some of the discoveries that we made. So I’m the founder of MindX Sciences, which is a precision mental health company that’s based in Indianapolis. We grew it through COVID without missing a beat.

We have tests on the market that are used by early adopting doctors and patients. We have some collaborations with pharma for drug development, and It’s very fulfilling to see some of the, your life’s mission and some of the work actually helping people directly. Because as academics, sometimes we publish, the university makes a press release, everybody’s excited, and then nothing happens.

You can’t, those tests are not available. I can’t use them in my own patient and so on. So it’s been a journey, and it’s great to interact with a lot of great people along the way, learn from them, and move things forward. 

Bret: 
Yeah, that’s such a great, and a very crucial point about research. Not just for research sake, but taking that leap and making that connection of the research to the patient because that’s what the research is there for, to eventually help people live better lives.

So, I think that’s such an important point that you bring up there. 

Alexander: 
Yeah, and you and I are doctors. So, our mission really, our raison d’être, is to help patients. And we can help them, one at a time, when we treat them as clinicians. Or we can have sometimes a broader impact at scale when we get involved, like you do with the organization that you’re affiliated with, that I’m a big fan of by the way. And like we do with our research, and then more recently with getting products out on the market so people can use them.

Bret: 
Yeah, yeah. So let’s dig in a little bit. So, in this article, Precise, Personalized, and Preventative Psychiatry, you started off with a quote that I thought was super interesting, that psychiatry is still practiced in most places as 19th century medicine. That basically saying that it’s focusing on the subjective and the qualitative.

And then you make the analogy to cardiology, which I think was great, of course near and dear to my heart as a cardiologist, that if we practice cardiology as just subjective and qualitative without actually measuring and being objective, it would just really set us back so far. So tell me a little bit more about that. Dig deeper into that, about how psychiatry has practiced in so many places as 19th century medicine.

Alexander: 
Yeah, back in the day, cardiology, you know that better than me, you had a stethoscope a hundred years ago. You relied on talking to the patient, a superb clinical sense, which is becoming a bit of a lost start nowadays. Some of our professors were superb clinicians, did a physical exam where they could pick things that we need advanced technology nowadays to pick up diagnostic pattern recognition.

But still, that’s very hit or miss, right? So you can be a superb clinician. You can have pattern recognition. Even the best clinicians miss things without the objective component. So, cardiology over the years developed the electrophysiological component with EKGs that became validated part of clinical practice, developed the laboratory test component with a lot of the routine panels that are being done, including for acute scenarios like for myocardial infarction, where you get enzyme levels and so on to really nail things, developed an imaging component.

That’s great, you do all sorts of imaging exams to look from ultrasound to MRI to all sorts of things to look at structure, function of the heart. All those things I think are probably very helpful in your practice, right?

When you, treat your patients, same psychiatry. The electrophysiological bit is not yet fully validated and used in clinical practice. So we have EEGs, those are good for seizure detection for sleep studies. There’s no real routine clinical use of EEG in clinical practice for psychiatry.

There are some attempts to use it for clinical trials, developed some electrophysiological markers, early days. We don’t have imaging used as part of routine clinical practice. So, there are studies being done with MRI, structural, functional, some PET scan and so on. Those are, those made it to clinical practice more for neurodegenerative disorders, for Alzheimer’s, other dementias and so on.

They’re not used written in psychiatry. It’s hard to actually pick signal and find unambiguous findings, have things that are unambiguous, useful reproducible and so on. Long story short, we don’t have imaging in clinical practice. Until recently, we didn’t have laboratory tests in clinical practice.

And that’s been my life’s work to develop a liquid biopsy for the mind to be like cancer. In addition to the Scripps Mercy history that we have together, I also did my graduate work, my PhD at Scripps Research, the other Scripps in San Diego. And there a lot of the work that I did as part of my PhD was genetics, cancer genetics.

I thought later when I went back to brain and eventually to psychiatry, could we be like cancer? Could we be like cardiology? Could we have molecular tests help us assess patients, help us match them to the right treatments, help us monitor response to treatment, remove some of the precision?

So it’s been a journey. Took two decades to develop those types of tests, but we managed to do it. And I think this will change everything in terms of how things are practiced. Now, a lot of the work that remains is not just the science and improving products part, but it’s also convincing payers, insurance companies, Medicare and so on, that there is value to paying for these advanced testing to, in terms of better outcomes, for patients reducing overall healthcare costs because hospitalization ER visits are very expensive. There’s work to do in terms of educating doctors. The newer generations are grew up more with this stuff, with the genomic revolution and so on. So they are more amenable with the digital revolution.

They’re more amenable to understanding and using these approaches. A lot of the, our more senior colleagues, are less familiar with this thing. So we have work to do in terms of educating them about how they could be used and so on. So usually I try to keep it very simple. It’s some data to help you with diagnosis and some data to help you choose a medication not based on metabolism, pharmacokinetics, but based on biology of patients.

So that’s the sort of the precision bit, the personalization, because different people have different biomarker that light up or elevated. So then, that leads to matching to different medications. Some are lithium patients, some are valproid patients, some are fluoxetine patients and so on. Some are combination patients. 

Bret: 
Yeah, so it’s really revolutionary what you’re talking about because right now a patient comes in to see the psychiatrist. They talk about their symptoms. They talk about their experiences. And then based on that alone, the doctor will prescribe one or more medications.

If they put them into like a bucket, your bipolar disorder, your psychosis, your depression, whatever bucket DSM five bucket they get into, that usually dictates sort of the prescription. It sounds simplistic, but I think that’s often how it happens. So what you’re saying is the additional level would be, okay, now I’m going to send you for these blood tests to measure specifically for you what’s going on so I can tell which medication or maybe which lifestyle intervention. Now, in a way that sounds futuristic, but you’re saying, no, it’s here.

We’ve got it, we’ve developed it and it is available. Yeah, so what level of research backing do you have to say this works and this is going to impact care? 

Alexander: 
Yeah. So, first of all, coming from academia, all these biomarkers that are going to the panels for the different disorders that then become part of the single liquid biopsy.

We have one or multiple studies in high impact journals detailing the science behind them, how they were discovered, prioritized, validated, tested for clinical validation and independent cohorts. What’s the data be behind them? What’s their ability to predict to track and so on?

How do you match with medications? Currently, there are eight panels that are for eight disorders that are part of this liquid biopsy: stress, pain, anxiety, mood disorders, psychosis, memory, longevity, and last but not least, suicidality risk for each of those panels. And each of those panels have about 24 biomarkers in them.

For each of them, there’s at least one publication. In some cases, multiple publication describing the science. So we first do the science and then we roll it to the clinic after that, almost like a phase four. Once you start using them, you collect data, like you have a phase four with a drug, right?

Phase one to three to get the drug out there. And then phase four, collect afterwards once it starts getting used. So we’re collecting the data now from patients and doctors who have used it, and we have over a hundred complex treatment refractory cases that were, that used the liquid biopsy with life changing results.

So it’s very gratifying to see how just by bringing some clarity to the doctor about what happened, what exactly is happening in that patient. Essentially, differential diagnosis in a test tube because you get results for this multiple disorders. So you can see it’s mostly anxiety. It’s mostly depression.

It’s not depression, it’s bipolar. There’s some psychosis. So it’s differential diagnosis in a test tube, it helps you with that. And then we do this overall integration given the multiple things that light up multiple abnormalities. What are the medications that best match you? So you’re treating the person, you’re not treating just their anxiety or their mood, you’re treating their multiple comorbidities.

Multiple things that they have. We’re very big believers that nutritional approaches and nutraceuticals are as important as medications and not just for cultural reasons that some people prefer them and so on, but biologically, they modulate disease. They modulate our biomarkers, on par with, almost on par or on par with the medications.

So, when we provide a report to doctor, we have sort of a risk clock there, which we, there’s a number of zero to a hundred, a traffic light, the green low risk, intermediate risk yellow, red. And also we provide a one year short-term risk after the time of testing. So they know if there’s something that they need to follow, not just acutely, but in terms of the year ahead.

And then two lists: one of medications and one of alternative treatments, for lack of a better term. And in alternative treatments, we have nutraceuticals. A lot of our biomarkers match to things like Omega-3 fatty acids, magnesium, things like that are very useful for patients to have and fairly innocuous.

So then the doctor, the patient, we always share the results with the patient, the family, and the doctor. We believe there should be another “P” added to all those “P,” which is participatory. We believe that patients, families should participate in their care and be informed because it’s their health. Okay, so we always give the results to the patient, the family and the ordering clinician.

Then, we have follow-up discussions to interpret them, to help with a plan of action. So now we have one year follow-up on a lot of those cases so we can look at, what’s called in the regulatory area, clinical utility. So, we have analytical validity for these markers from our studies.

We have clinical validity from our publications and so on. Now, we look at clinical utility, meaning if a doctor uses this in the real world in a patient, does that move the needle? Does that change care, and so on? Because the doctors have, the doctors make the diagnosis. The doctors prescribe the treatment.

So does it influence, does it lead to change in practice, better outcomes and so on? So we’re compiling that data, writing it up for insurance, do CS for publications. We always publish everything we do. And hopefully we can get some reimbursement for these tests so more people can afford them.

Right now, they’re out of pocket and one of my missions is to make these widely accessible, not just for people who have the means for them, although they are cheaper than a day of hospitalization. They’re cheaper than the copay might have for some ER visits. 

Bret: 
Before we continue, I want to take a brief moment to let our practitioners know about a couple of fantastic free CME courses developed in partnership with Baszucki Group by Dr. Georgia Ede and Dr. Chris Palmer. Both of these free CME sessions provide excellent insight on incorporating metabolic therapies for mental illness into your practice. They’re approved for a MA category one credits, CNE nursing credit hours, and continuing education credits for psychologists, and they’re completely free of charge on mycme.com.

There’s a link in the description. I highly recommend you check them both out. Now, back to the video.

So let me drill down on one specific aspect. So the differentiation between depression and bipolar disorder, I think that’s one that’s so crucial, because if you treat someone just for depression and you unmask mania because they really had bipolar disorder, that can be catastrophic.

So what’s, can I ask you specifically, what are the markers that you use to determine if someone is more likely to be unipolar depression or bipolar disorder? 

Alexander: 
Yeah, yeah. Very good question. And that’s one of the most common things that we encounter in people who come and get tested.

And a lot of people get, and I sometimes get on a soapbox about this, I feel so strongly about it, they get labeled as treatment-resistant depression. Okay. So they get tried on 1, 2, 3, 4, 5 different antidepressants. They don’t respond well or not completely or they do worse. They become agitated, suicidal.

That should be a clue right there without futuristic state of the art testing that is not depression, that it could be bipolar, but it often gets missed because people usually present initially for the depressive component, even if they’re on the bipolar spectrum. That’s when they’re mildly euphoric or hypomanic or so on there.

They don’t want to see a doctor so it often gets missed. And as you exact, as you pointed out, treating with antidepressants, just antidepressants, somebody who’s on a bipolar spectrum, it’s counterproductive, can backfire. They can, they get into this agitated mixed taste. They can become suicidal.

They don’t respond. So, a lot of the cases that we see that are labeled as treatment refractory are, in fact, undiagnosed bipolar disorder. So, on our mood test, we have a panel for depression and low mood and depression risk, and a panel for high mood and mania risk. So, we look at the signal in both clocks.

If you’re have high signal only on the depressive markers and not a high signal on the mania, high mood markers, then it’s depression. And if you have a high signal on both, it’s especially in terms of trait risk, the one year risk, you’re at one year risk of depression and also at one year risk of mania episodes, then it’s bipolar.

And interestingly, there’s a probably a new nosological thing that we need to describe and publish out there in our next study. There are people who are mostly have a high signal on the high mood side in mania. They don’t have a lot of signal for depression. These might be these, fortunate or unfortunate, individuals who we see in the news who sleep, three, four hours a night are always high energy.

Always, in the news, do all sorts of things, entrepreneurs, politicians, CEOs, that type of thing. So there’s that mirror image, right? Because currently the diagnosis is MDD, major depressive disorder, bipolar two, which is mostly depression with occasional hypo maintenance and bipolar one where you have the big mood swings, full-blown mania, full-blown depression.

It could be a mirror image, which we could call bipolar three or bipolar four, where it’s mostly mania, high mood with occasional couple of days a month of low mood depression, where they hide in their office. And we see that data as well.

So it’s a spectrum. Knowing where you are on the spectrum is important because the treatment is different and should be different. So if you have depression and also risk for the mania side, you should definitely be on a mood stabilizer in addition to an antidepressant or just on a mood stabilizer, if it’s most long term, if it’s mostly mania. 

Bret: 
Yeah. That’s what I find so interesting about this. As someone who wouldn’t have otherwise been diagnosed with bipolar disorder, if you see this signal say, okay, I’m not just going to put you on an antidepressant, but I’m going to put you on lithium or a mood stabilizer plus an antidepressant. But I can already hear either the skeptics or the people who maybe aren’t so familiar with this and say, we’ve been here before with all this genetic testing and genes may tell you that you’re a little more predisposed to something. But I don’t know. It seems like the direct line from genes to expression of that, of that genetic predisposition is not a straight line, and the percentages are pretty low. So how would you compare these testings that you’re doing to the reliability or the specificity of genetic testing?

Alexander: 
Yeah. It’s, I think, it’s an important point to clarify for people. Before we do that, I would like to mention also that it’s not just looking at where the risk signal is if it’s just for depression, if it’s both for depression and mania, both. So then you have to watch for bipolar, that sort of thing.

But the medication matches that you get for this panel are very interesting and revelatory. So, these patients that are labeled as treatment-resistant depression, when you run the test on them, their top matches for medications are invariably mood stabilizer. Their best matches are mood stabilizer. And very low on the list, actually, you have the SSRIs that they were tortured with. 

It doesn’t mean you shouldn’t be on an antidepressant if you’re, have a lot of depression along with your occasional upswings and everything. But it should always be, if you’re on the spectrum, it should always be moderated with a mood stabilizer. And if you have big mood swings or you’re mostly on the high mood mania side, the mood stabilizer is enough. A lot of the old medications come up in these reports, so things that are not promoted or advertised anymore that are sort of oldies but goldies.

And the trick there is to use low doses because a lot of these older medications have acquired this reputation for toxicity or side effects, and rightly so at high doses. The dose makes the poison. At high doses, they’re very toxic and a lot of people have side effects and just stop them.

What we’ve discovered is that when you match the right patient to the right medication, you can use very low doses because it’s a right fit. When you don’t have a good match, you need to ram in high doses to start to get an effect, right? But when it’s the right fit and it clicks in, low doses usually work.

So a lot of the patients and doctors that have used our testing start with the low dose. and that’s all, often times, that’s all they need out of the sort of recommended list. Obviously, they pick and choose depending on comorbidities, allergies, medical, things that we don’t know anything about.

We don’t diagnose or treat people. We’re part of the conversation. So coming back to this very important issue of genetic testing. We don’t do genetic testing, actually. We look at gene expression mRNA. So how active a gene is, and that is actually gene and environment coming together. So you have your DNA, you have all your environmental influences, medications, nutrition, ketosis, stress, drugs, sleep deprivation, you name it.

Pollution, all those things interact. And then you have gene expression, which is where the rubber meets the road. The expression of genes is modulated by your DNA makeup and by the environmental factors. So we go where the action is. We look at messenger RNAs, which are these molecules that are expressed of genes, depending on how active or inactive that gene is.

So very different than DNA genetic testing. And the way to, one way to look at that is DNA testing is, it’s like those guys in basketball, college players one and done. If you test once, that’s it, it doesn’t change, right? Whereas these markers, how expressed the genus are very dynamic.

They change with your biology, with disease severity, with response to treatment with environmental factors. They’re more like glucose and hemoglobin A1C and so on. They’re not, so it’s not really genetic testing that we’re doing. The other issue, which is very important that you alluded to, is the issue of power and reproducibility predictive ability.

DNA is so far removed from the phenotype. And there’s so much variation in the letters of DNA in you and I and everybody that very few disorders just tested at the DNA level can have some sort of like diagnostic or predictive, but there’s Huntington disorder, things like that. Huntington disease, very few, most mutations in DNA have a very weak effect by themselves.

So what my colleagues in genetics, I’m a car carrying genetics as myself, but since we’re doing gene expression, so what my colleagues in genetics are doing, they’re stringing together thousands, hundreds of thousands of those letters in the DNA that have some signal for them into polygenic risk scores.

So those polygenic risk scores where you have hundreds of thousands of genetic letters, polymorphisms in them despite putting every all that together, have very little predictive ability. The odds ratios are 1.1, so maybe like a, 5%, 10% increase even when you put all those risk mutations together and so on.

Not yet ready for clinic, in my opinion, whereas the odds ratio of one of our mRNA biomarkers, the best biomarkers are twofold, threefold odds ratio, which is really high and actionable. We also make sure that we look at reproducibility. I’m a biologist, in biology, reproducibility in independent experiments or cohort is key in genetics.

There is this strong sort of statistical bias. People are statisticians more than biologists, and they are Fisher more than Bayesians, that’s inside baseball. But they look at P values, they look at P values on P test. So, if they see an astronomical P value, they’re happy and they say, wow, we found something.

It doesn’t matter what the P value in the discovery study is. If it doesn’t reproduce or is predictive in independent studies, I always bring that point up with them. It also doesn’t matter clinically to you or I, if the odds ratio are infinitesimal. So it can have a great P value because they did it in a million people, but the odds ratio are 1.002 or something.

So what we’re doing is not genetics. There are some useful genetic tests, and in fact, I use them in clinic. They are out there on the market. Those tests are, the VA offers them routinely to all veterans. So the VA healthcare system is, as usual and as little appreciate, is ahead of the curve.

So those tests just look at cytochrome P450 mutations, Bret. \They tell you whether you’re a fast or slow metabolizer or the patient is a fast or slow metabolizer, which is useful to doctors like you and I because then we know, if it’s a slow metabolizer, we should start at the lower dose with the, with a given medication that we would like to use.

If it’s a fast metabolizer, start a higher dose because it goes right through their body. So, those genetic tests, they’re called pharmacogenetic tests, are useful, but that’s all they can do. They can inform you given a certain medication that you want to use, whether you should start low or higher with the dosage.

Our biomarker tests don’t give you direct information about dosage, but based on biology, they match people to medications like you’ve mentioned, lithium or fluoxetine, or aripiprazole. So we have actually curated all the psychiatric medications, develop experimental data sets and databases for them so that if we can match people, depending on what biomarkers light up in them are elevated or decrease below normal, to different medications.

So, it’s a very different approach that genetic, we’re not really doing genetics. It’s more closer to diabetes, I would say, or closer to cardiology where levels of dynamic markers are changed. And those markers can change again when you retest, if the disease evolved or if you treat it properly.

Bret: 
Yeah, that’s really interesting to hear that sort of the difference between genetic testing and sort of the expression of the genes and more like clinically useful, I guess you could say, measurements. But I’m curious though, the way we.. 

Alexander: 
It’s related to that point, if I may, 

Bret: 
Yeah, please. 

Alexander: 
It’s a very important point that you zero in because people hear all this genetic testing, epigenetic, what about epigenetic testing? What about gene expression? One way to look at it, there are other ways, is so genetic testing, properly defined as DNA epigenetic testing is, the DNA sometimes is covered or naked.

If it’s covered with those methylation patterns and so on that are, that you acquire during development or with nutrition, environmental changes, if it’s covered as silence so that gene doesn’t get expressed, if the gene is not covered naked, it can get expressed more. So, in some ways it’s closer to expression, the epigenetic markers, the changes are more valuable because they’re closer to expression, but they’re not very dynamic. Then expression, the RNAs that are produced of these genes are the reality and where action is. I joke with my colleagues in genetics that DNA testing is bronze metal, silver medal.

We went for both mRNA expression. We’re not going, we’re not necessarily the best. There might be a platinum level protein. So you could go directly for the proteins that are made of those messenger RNAs. They’re just harder to discover at the protein level, but we are taking that direction for the future.

Our best mRNA biomarkers, we want to study their protein correlate because you could develop then simple eLISA-based immunological tests that can be done point of care, or even at home, like with COVID, where you something colorimetric, it colors up. And then you come for additional screening.

Bronze, silver, gold, maybe platinum in the future. 

Bret: 
So, it seems like the way we’ve been discussing this is almost is for its use if someone comes in with a clear psychiatric diagnosis or psychiatric symptoms, and you’re using this to help diagnose the condition and determine treatment. But in the article I referenced, you used the word precise, personalized, and preventative.

Yeah. So do you think this could also help bridge the gap to the next step before someone’s really had symptoms? They just go to see their primary care doctor for general screening, or maybe they’ve had some real mild symptoms that you could use this type of test to say, yes, you are at high risk for major depression, for schizophrenia, for bipolar disorder, and then institute either lifestyle or medical therapy for prevention?

Could you see that happening? 

Alexander: 
Yeah. No, I think that’s exactly where things should be moving. \When a new approach or technology is adopted, you first have to address where the pain point is. And the pain point is are these sort of complex treatment refractory cases where patients are suffering, the doctors don’t know what to do.

The insurers are unhappy because those people are in the hospital all the time and so on. So, we went after where the maximum pain was to offer some help over there treating acute cases. It’s not ideal in medicine, just like in cardiology. You’re treating DMI, but what, why not have in the future be a bit more upstream?

So, stage one is demonstrating that these things work in the most severe cases, right? Just like a Land Rover, if it works in the hills of Afghanistan or wherever it will work on the streets of Beverly Hills. You go first for the extreme scenario, and if it works there, will work for milder cases. But really, they should become part of annual exams where people, you go to your annual exam once a year, you get an extra tube to also do your mental health labs, basically. And in this way, maybe you’re past an acute episode, things have been improved. And then, at your followup, six months, one year, you get another test to see how things have improved, if there’s still optimization to be made and so on.

That’s stage two. Stage three is actually screening population, part of routine primary care, pediatric care. And with the caveat that we don’t have yet a lot of data on younger people with all of majority of our work today that we’ve published has been in adults. But part of primary care where people get as part of their routine annual exam screen.

And you might catch things really early, just like with diabetes, you might catch things really early before they develop the clinical symptomatology. And that’s the best medicine because when you intervene early, you can, it takes much less effort to fix and prevent things, to intervene there and prevent a full-blown illness.

It’s much better for the patients, for their families. They don’t have all that disruption when a disease manifests itself fully and it’s, it explodes to clinical attention, it’s a bit harder to treat. You might not get a hundred percent remission, although you might get, there’s, some sick well, right?

The damage, there’s some damage that’s been done. So prevention is really the best medicine for everybody, for patients, for families, for society. Because otherwise you go bankrupt, as a society, if you’re just treating a sort of expensive severe, end stage type cases. And that’s why prevention is very important.

We think our tests can be used for prevention. The signal will be smaller, but that’s great because you, and then you’ll have just a couple of things that you need to watch or address, earlier on. Also, probably, we take a biosocial psychological approach. You need all three to assess somebody, to improve them, to help them function well, function better than well in some cases.

But, maybe the weights are different, right? So when you’re treating, a full-blown complex case, maybe the biological component is at the forefront. You need to fix that, and then you fix lifestyle things, and psychological well-being. But if you’re moving earlier in the chain, you are catching things very early.

You might not need medications. You could just do nutritional approaches like you’re doing. You could do only those, you could do lifestyle changes, remove stressors, negative people, engineer environment better. And then just CBT or other psychological approaches to prevent things from developing.

So the emphasis might be different in terms of how much use or which component, whether you’re at the third, more towards the latter part of the game, or very early on for prevention. All three in everybody. 

Bret: 
Yeah. I think that’s a crucial point when we’re talking about prevention, that it’s not, oh, you’re at risk for this, so here’s your lithium, or that’s probably not the right approach.

But we all know that we should be better about our sleep and we should exercise more and we should eat better. But I think for a lot of people, especially if we’re talking about the age group who are at highest risk of bipolar disorder or psychosis or severe anxiety or in that teenage to young adult age group that they’re like, yeah, I’m young, I’m healthy.

I don’t need to worry about sleep and exercise and eating well yet. I’ll worry about that later. But this is something that could say, actually no, you are the person who really does need to double down on this and really focus on this, that I could really see the utility there. But can it, you’ve talked about nutrition, you’ve talked about lifestyle do you think it would get to the point where it could narrow down more than just sleep better, exercise better, eat better, that it could give more personalized prescription of lifestyle for individuals?

Alexander: 
Yeah. So, for example, let me give you an example. On our reports from the blood testing, we have the medication table list matched rank by best matches to lesser matches. Same thing for alternative approaches. Alternative approaches we have, some people match to sleep, some people match to. Meditation, some people match to, exercise.

So, we have data that is connected to our biomarkers related to lifestyle intervention, too. We would love to get more data from ketosis type studies, from nutritional approaches and so on. It’s fascinating because we do this empirically in non-hypothesis driven, when we develop all of our studies data sets, and algorithms. And then we find they’re on the list things that somebody discovered 2000 years ago or 2,500 years ago in China and Japan and India.

So it’s always fascinating. How did those guys come up with this? Because we’re using the latest technology. How did they figure out that this ingredient in that plant does this and that? Observation over time and who knows? But yeah, and a lot of these things are very powerful.

For example, Omega-3 fatty acids are sometimes in a lot of the patients that we test, almost on par with medications, and some people prefer to do that. Or, for example, during pregnancy, that’s a big problem for clinicians. You have somebody who’s pregnant, and They have, let’s say, bipolar disorder and they’re pregnant. A lot of the standard mood stabilizers, anticonvulsants, even lithium lower risk, but still have a certain risk, right. For genicity, for impacting the fetus? Omega-3 fatty acids have no risk. In fact, they’re in prenatal vitamins. They’re in baby formula, infant formula.

They’re great for the brain development of the fetus. So, and if the person is a good match, you emphasize that, take high doses of that, watch them more closely, get them through the pregnancy and then put them back on medication if need be, and so on. It’s a fascinating area, and I think all approaches have merit in them.

People should be non-sectarian and look at the evidence and use a combined, a combination that fits that particular person. if somebody’s very inclined, for example, in your work and the efforts that your group is doing towards nutritional approaches and there’s evidence for them that they work, by all means they should primarily rely on that, and add a few things here, maybe a little bit of sort of psychological treatment, a low dose of a medication if need be, that sort of thing.

Bret: 
Yeah, I think that would be fascinating to have evidence that says nutrition is first line therapy in this patient, not medications. To have a test that shows that, and certainly no drug company is going to fund that research, but for companies like yours or for philanthropies or so forth to fund that research or to even go even further and say, okay, maybe a low fat Mediterranean diet for this person and a higher fat ketogenic diet for this person based on, this profile.

Yeah. I guess we’re not there yet, but maybe we’re moving that direction. 

Alexander: 
I think all studies that are done for nutrition, and I know you’re involved in some high quality studies, should have an extra blood tube collected for biomarker studies. So, we can look at our biomarkers and see how, what the response is in general.

Just you collect things for metabolic markers, right? For lipid panels, for glucose, for other things but extremes are best avoided. I think, rationality and personalization are key in terms of helping people improve their lives. Each person is unique, has different cultural preferences, biological makeup, a lot of other factors.

So, let’s say somebody has had a bad experience with traditional psychiatry as currently practiced. And there are a lot of people like that. And I’m a psychiatrist, so I take, I’m a part of the problem. I’m also part of the solution. Let’s say they have a bad experience. They were tried on all sorts of medication.

They gain weight, they had side effects. And then, in reaction to that, they say, I’m going to go completely off medications. I’ll just take a nutritional approach and so on. That might work, but there’s no need for extremism. You should tinker with things, see what works, use a little bit of this, little bit of that and so on.

There’s no excuse, in the future, for people being on high doses of the wrong medication and getting side effects. it’s as if, in cardiology years ago, you gave them digitalist toxicity or something. I don’t know; there’s no excuse. I can, I feel for those people. I see them all the time.

We help them all the time. We de-prescribe massively, heavily. They end up on a couple of things at the low dose that have zero side effects and then lifestyle approaches, psychological approaches, and so on, but not completely go from one direction to the other. And conversely, a lot of people in psychiatry say, I should be treated with medications. I’m a biological psychiatrist. This is, these drugs have been studied, FDA approved. Let’s just rely on that, and not adding nutritional approaches, lifestyle changes. Think about the whole person, their well-being, take into account everything.

So, there are extreme extremists on both sides. I think taking a personalized, convergent approach where you treat the person what’s best for them with whatever tools best fit them to minimize any negative impact, maximize positive impacts, and just help them move on with their lives.

And really the best outcomes is when they don’t need you anymore. Our goal is for our patients not to call us anymore, be almost curative or you set them on a road where once a year they get, they come in for a checkup, they get fine tuned and so on. The goal of medicine would be for our patients not to need us actually to move on with their lives and do great and just occasionally come for tuneups. 

Bret: 
Yeah, such a good point. Such a good point. I’m glad you brought up de-prescription and tapering, but doing so in a sort of rational way when you’re monitored and have a purpose and not just doing it at the extreme. I think that’s so important. But this has been a real fascinating conversation, and I’m really interested to see where this goes.

And as it gets used more and adopted more and you get more evidence and more research and hopefully involvement with the payers, I think it really could revolutionize the way psychiatry is being practiced, as you said. So if people want to follow you and hear more about what you’re doing and, read everything else that you’ve written and so forth, where would you direct them to go?

Alexander: 
I’m of, we’re of the same generation. So we didn’t grow up with social media and so on. I’m not a big fan of social media. I think it’s toxic for teenagers, but that’s another discussion. But mindxsciences.com, mindxsciences.com. That’s our company. We put a lot of resources, there are articles, educational things, and so on.

So people should just go to mindxsciences.com, and learn about what we’re doing, become involved, and so on. We’re a mission driven company. We’re doing this for the mission primarily, and wrap the company around it as a vehicle, as opposed to the opposite approach where you want to be a successful commercial entity and you find something cool to take you there.

We welcome people visiting, asking questions. The scientific studies are there. The news articles related to our work are there. You mentioned the psychiatric news article that came out last month on the front page of the newspaper of the American Psychiatric Association.

It’s there. We put links to things so people can access them, download them. And we welcome collaborations with people like you, with other organizations that are fighting the same good fight. There’s so much to do. And if you’re open-minded and collaborative and just look at the evidence as opposed to having dogmatic approaches, then you can make progress and help people if you’re dogmatic or, so we’re doing the science with the small “s”. We’re not the science, like prescriptive, this is the only approach, this is how you should do it.

Now this is the evidence. Maybe this is helpful to you. Let’s look at all sorts of things. Bring your experience, your values. So, mindxsciences.com is a good place to start to look at some of our work. 

Bret: 
Great. Thank you so much for taking the time and I look forward to hearing more from you as this progresses.

Alexander: 
Yeah, I look forward to interacting with you more, Bret. And this is how I should be a cardiologist and a psychiatrist. I’m a sort of a psychiatrist who appreciates cardiology, and you’re very well educated about psychiatry, I have to say for a cardiologist. 

Bret: 
Unusual for a cardiologist. Thank you.

I appreciate that. 

Alexander: 
All right. Thank you very much, Bret. Thank you. 

Bret: 
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