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Stephen Manlove – the next decade in psychiatry

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The Histroy of Psychiatric Therapies

Hello, my name is Stephen Manlove. I’m a psychiatrist in Rapid City, South Dokata. And I’ve been thinking about psychiatry, where it’s going, where it’s been and I’m going to do a little presentation on that today to share my thoughts. The purpose is to get some cross-pollination going, to get other people thinking about these things and looking for feedback, looking for new ideas because we need more. We’ve gotten stuck in old ideas. So let’s just start by talking about the past of psychiatry a little bit.

The beginning of psychiatry in the modern era was really Sigmund Freud and this slide says, “Psychiatry is the art of teaching people how to stand on their own feet while reclining on couches.” A famous Sigmund Freud quote or at least one that’s attributed to him. Freud was a genius, one of the most important intellectual figures of the 20th century. His biggest breakthrough, from my perspective, was identifying that there are unconscious things that are going on in our minds that we are not aware of. He began a process of psychotherapy that has evolved over time and I’m going to show you some examples of some different kinds of psychotherapies as they’ve evolved.

This slide says, “In my dream, I catch the car and the driver turns out to be a cat. I chase him up a tree, steal the car and then run over the postman.” So this would be an example of psychoanalysis. This slide says, “Nervous little dogs face their fears at an anxiety management seminar.” This would be an example of exposure therapy. In this cartoon, it says, “Are you aware that when you said that your tail went between your legs?” This is an example of Gestalt therapy, being in a moment with your feelings. This cartoon says, “And for future reference, Mr. Glynn, you don’t need to “get in character” for regression therapy.” So this would be an example of regression therapy. This is a little cartoon about a borderline personality disorder, “I prefer to not think of myself as having Borderline Personality Disorder. I prefer to think of it as being really awesome and letting everyone know through outbursts of emotion.” So how do we treat that?

This is a slide that gives an example of that. It says, “Today I will live in the moment unless the moment is unpleasant. In which case I will eat a cookie.” This would be an example of a dialectical behavioral therapy that we use to treat borderline personality disorders. And here’s an example of scream therapies – a person in the emergency room and the statement says, “It’s our new method for determining who we should treat first. We take the people in order of how loud they scream.” Another example of exposure therapy, “Professor Gallagher and his controversial technique of simultaneously controlling the fear of heights, snakes, and the dark.”

I will move into a little bit more newer kinds of therapy including marital therapy. In this cartoon it says, “He’s handsome, sincere, intelligent, supportive, patient, successful, romantic, strong, funny, energetic, thoughtful, sensitive and kind but sometimes he leaves the cap off the toothpaste.” Does that sound familiar to anybody? And then there’s family therapy. This is a family of rabbits. They’re very complex families as you might guess but they’re looking at a family tree.

So while this development of psychotherapy was going on, there was also some biological therapies that were in process and these began in the early 1900’s, the early 20th century. They tried a variety of ways of changing the brain to try to treat psychiatric illness. One of the first ones was malaria-induced fever which was used to treat neural syphilitic paresis in 1917. Then they used insulin-induced coma and convulsions to treat schizophrenia in around 1927. When I was a resident, I had a psychoanalysis mentor who told me about doing insulin shock therapy. He said they would make people go into a coma and then they would slowly bring them out. He said the doctor would sit on the edge of the bed and feed them jam as they were coming out of their coma and they would sort of have this rebirth experience with the psychiatrist, as sort of the feeding them and taking care of them. And apparently, there was some therapeutic benefit from it.

Later they developed Metrazol-induced convulsions to treat schizophrenia and effective disease. The problem with Metrazol was that they couldn’t stop the convulsions sometimes. People continued to have convulsions afterward and that created some of its own issues. And then electroconvulsive shock therapy was discovered by Ugo Cerletti and Lucio Bini in Rome in 1937. That was one neurostimulation that really caught a toehold. That was, as you know, right during the beginning of World War II and as people came out of the war when it ended, there were lots of veterans who had lots of psychiatric problems and there were really no treatments for them in the 1940s, except electroconvulsive therapies. So if you talk to psychiatrists who were practicing in those days, they weren’t doing psychoanalysis. Many of them were doing electroconvulsive therapy. I have one friend who is a psychiatrist who’s about 99 years old now. He told me that during the 1940s, he did 15,000 electroconvulsive therapy treatments in Omaha.

So again this is a picture of Ugo Cerletti who started electroconvulsive therapy. They introduced electricity into the brain to trigger a seizure and that’s how it worked. Now This is an example of a more modern view of electroconvulsive therapy (showing a new slide). It’s very safe, very effective but it has some morbidity associated with it, including memory problems, and it’s also complicated to do. You have to give people anesthesia and you need to have it done in a very controlled environment for it to be safe.

Medications for Psychiatry

So how about medications? It seems like we’ve had medication forever but actually, that’s not true. The first medication for psychiatric problems was developed in the early 1950s called Thorazine. It was the first drug used to treat psychosis. They were trying to develop an antihistamine and they developed this Thorazine, which not only had some antihistamine properties but it also treated psychosis. When it was developed in those days, people who had chronic mental illnesses lived in state hospitals. There were these huge state hospitals all around the country that had several thousand people in each of them and there were little communities of mentally ill people. When Thorazine was developed, the psychiatrists who were using it then, they thought that they were going to lose their jobs because everybody got better it seemed, and people were just walking out of the mental hospitals because they no longer were psychotic.

So there’s an advertisement for Thorazine, “Help keep your patients out of mental hospitals”. Another one – they began to use them for everything because they didn’t have anything else – but, “Doctor, what can you do for Pop?”. For an obstreperous older person, Thorazine was a godsend. And then how about the oppositional kid, “In the child with a behavioral disorder, take Thorazine.”

Now we don’t even use Thorazine very much anymore. It’s very rare that we use it. Here’s another one, it looks like it is used to keep people from dancing but actually, it’s trying to detect agitated people and this medication helps. Around the time that Thorazine was being developed, there was a medicine that was developed to treat hypertension that was called Reserpine. This guy, Robert Wilkins, was studying that and he noticed that Reserpine had remarkable effectiveness in the management of hypertension, but also had mental status changed, it calmed people down. Somebody said, “I haven’t felt this good for years. Nothing bothers me anymore.” So that got people’s attention and they began to think about other medicines that could do that, that are related to, or the same. It turned out that Reserpine, though it did have a calming effect, paradoxically also caused depression, so that was a reason they stopped using it for the most part. But because it did help – and the way it worked for hypertension was that it affected Monoamine neurotransmitters – it generated a hypothesis that maybe other medicines that affected these same neurotransmitters like serotonin, norepinephrine, and dopamine – which are almost household words now – might be able to be affected by some kinds of medications.

So what are the three monoamine neurotransmitters that affect mood? I just told you; Serotine, Dopamine, Norepinephrine. And where do they come from? This is a slide that shows that these monoamine neurotransmitters actually come from nuclei in the brain stem. There are projections from the brain stems, into the frontal lobes, and all through the brain that are projections from these nuclei. These are distributing serotine, norepinephrine and dopamine around the brain. And that’s how we think that antidepressants ultimately work – not just by stimulating the release of monoamine neurotransmitters from cells in specific parts of the brain, but from these nuclei in the brain stem.

Around the time they were thinking about Reserpine – I mentioned the deinstitutionalization of psychiatric patients – there was another deinstitutionalization that was going on back in the 1940s and early 50s and that was that of the tuberculosis asylums. Back before the 1940s, they didn’t have any medicines to treat tuberculosis, so people would go to asylums and they would just wait until their body either fought off the illness or they died. There still are some asylums around the country that you can visit, but they really are only of historical interest. In the 1940s and during that timeframe, they developed a series of drugs that you could treat tuberculosis with. One of those was called Iproniazid. This drug helped tuberculosis, but they serendipitously observed that it helped depression also. So people who had TB who were depressed, not only did their TB get better, but their depression also improved. So they began to wonder if medicines like Iproniazid might help depression, and that led to the development of monoamine oxidase inhibitors, which iproniazid was one of the first of.

And this (slide) just kind of shows some of those medications, where they came from and when they came around. Isoniazid in 1952/53 and Iproniazid, which were monoamine oxidase inhibitors. Then later on in the 50s, the tricyclic antidepressants were developed, which were Imipramine and Amitriptyline. And these were the medicines that I grew up with. I did my residency from 1982 to 1987. Those were the medicines we used for depressions then. We had that and electroconvulsive therapies. These were fairly dirty medicines, meaning they had quite a few side effects, so you really needed to treat it in order to put people through the toxicity of these medications.

Imipramine was one of the first tricyclics discovered in 1951. Again, it was an antihistamine they thought they were developing and it turned out to be a major tranquilizer that really helped depression more than psychosis. And it’s a norepinephrine and serotine reuptake inhibitor, so it elevated those in the brain. And then in about 1990 – this was in my life when I was just starting my practice – Prozac came out and this really changed the landscape of prescribing medicine for psychiatry. Prozac just didn’t seem to have any side effects compared to the other medicines, and it was rapidly the most commonly prescribed drug in the United States within a few years. It was helpful and it worked well. It worked just by inhibiting serotine reuptake, so it had fewer side effects than the other medications had, and so we had found the happiness store when we found Prozac.

This cartoon says, “His few friends had told him he could never buy it, but Mr Crawley surmised that they just didn’t know where the store was.” And this seemed to be where the store was, it was the Prozac store, but this didn’t turn out to be perfect either. So that’s around 1990 that Prozac was developed and around 1985, a few years earlier, this guy named Anthony Barker began to play around with using electromagnetic fields to stimulate neuronal conduction, and that was the beginning of transcranial magnetic stimulation, which is an event that ultimately has really changed psychiatry. I think we need to pay attention to this because I think this is where psychiatry maybe going over the next decade as we get better and better at utilizing this for focal treatment of different brain disorders, not just in psychiatry disorders.

This is an example of a TMS machine. There are other places that you can see lectures just on TMS so I’m not going to go into that in depth, but suffice to say, it became an important part of our practice once it was FDA approved in 2008. We began to have different options of strategies for using it.

The Human Genome Project

While this was going, there’s this other thing happening that I’m calling psychiatric genetics. As you know, in the 1990s and ending in 2003, the human genome was going on and it was completed in 2003. So we had this vast amount of genetic information that we’ve been sifting forever since then. That is another thing that is really beginning to inform how we make decisions, and we’ll inform that more and more over the next decade.

So we did DNA analysis and now we’re trying to figure out how to analyze the DNA analysis. “God, the human genome code’s been unravelled.” And God says, “Damn hackers!!! Now I have to change the password.” So one of the examples of what the human genome project has shown us – and genetic studies for mental health – is that there is a gene called MTHFR, or methylenetetrahydrofolate reductase gene, that makes an enzyme with the same name. There’s a meaningful percentage of the population that is deficient in that, and f you look at people with treatment-resistant depression, it’s a much higher percentage. In our clinic, it’s around 70 or 80 percent of our patients that are deficient in it. Finding that out is important because we can bypass the gene that’s absent and give people Methylated Folate to address that issue. We believe that is one of several things that is helping our patients do better than they were before.

This is just an example of what happens with folic acid and what’s missing when you have that MTHFR gene being abnormal. Folic acid, which you get in many foods and that you can get by vitamins too, is methylated by the MTHFR enzyme and creates what’s called Methylfolate. This is the active form. Folic acid itself doesn’t do much, Methylfolate is what you need. So if you don’t have that gene that turns folic acid into Methylfolate, then you don’t have the full complement of it that you need because it is important for making our transmitters; serotonin, norepinephrine, dopamine.

So if you don’t have as much Methylfolate as you really need, it’s like having a pipe in a well to pump water out. If you have got six inches, you can get some water, but you’re going to very quickly be pumping air. If the pipe is down six feet into the water, then you’re going to get a bunch of water and you’re not going to pump air very quick. If you don’t have much Methylfolate, you’re pumping air fast when you’re trying to make more of these neurotransmitters.

Now, this (slide) just shows that if you don’t have the gene, you don’t get methylated folate. I’m going to skip over this one. I pretty much described this already.

So that’s kind of the past of psychiatry and a brief synopsis, but some highlights anyways. You can see that there’s been a phenomenal improvement. I mean, where would we be if we didn’t have anything to treat people with psychosis. We’d still have these thousands of people in these hospitals. The unfortunate part is that all of these medicines have caused side effects. So for instance, why we don’t use Thorazine much anymore is because it made people have all these anticholinergic side effects like; dry mouth, sedation, weight gain and also Tardive dyskinesia. So you fix a problem, but you create other problems. So what we’re hoping is that in the next decade, we’ll find more specific treatments that don’t create so many problems when we’re treating illness.

The Benefits of Exercise

So in my mind, I kind of walked through this process over the past few years of trying to develop a practice that will begin to utilize some of these strategies. So just to tell you a story – about five years ago, I began to think, “You know what, what I’m doing is okay, we’re helping some people, we’re not helping other people, but I really am frustrated with this process of basically 30 percent of people with depression not being treatable using the strategies that were used, which were medications.” And I had been watching the TMS literature, seeing different products come out and I finally got excited enough to try getting a machine.

So I got a TMS machine in 2015. We started using it and we had really great results very quickly. This was in people we knew statistically had a very small chance of responding to antidepressant medications. What I noticed almost immediately within the first couple of months of treating these people, was that people who exercised while contemporaneously with the TMS seemed to do better. We thought, “Well okay, so maybe they’re feeling better, so they’re now willing to exercise, or they’re activated enough to exercise, or maybe the exercise is helping the TMS work better.”

And so I began to do some literature research on exercise and what it does to your brain, and I found that exercise increased a hormone called ‘Brain-Derived Neurotrophic Factor’ or ‘brain growth’ or ‘neuron growth factor’. So this actually stimulates brain growth. One of the theories about TMS is that it also stimulates brain growth, so I thought, “Aha, there’s some synergy. Exercise stimulates brain-derived neurotrophic factor. TMS stimulates brain growth. Maybe the combination gives a synergistically better response.”

This is a slide that just kind of shows something about brain-derived neurotrophic factor. You can see up in the left-hand corner, exercise is one of the things that trigger a release, but also, so does dietary energy restriction. Ketogenic type diets, where you restrict sugar and some carbohydrates, and cognitive challenges can also stimulate brain-derived neurotrophic factor. BDNF goes to several areas all over the body really, but specifically, the hypothalamus and the hippocampus – the autonomic nervous system and the peripheral nervous system and makes them all work better basically.

Why does that happen? We think that exercise triggers the release of a chemical in your liver called ‘Beta-hydroxybutyrate’ or ‘Beta-hydroxybutyric acid’ that gets into the bloodstream and goes to different parts of the brain. It’s metabolized through some histones and causes expression and brain-derived neurotrophic factor. That’s exciting.

So what does BDNF do on a chemical level, on a cellular level? There are some studies that suggest that it makes cholesterol, which is all through your body. You need to have cholesterol in your body and it stimulates synapse formation, so we think that BDNF at least stimulates synaptoplastic activity that is making synapses. And we want your brain to have a robust activity in both synaptoplastic making synapses and synaptoplastic which is reducing synapses, so that your brain will adapt to your environment by doing those things.

So knowing that, you know you should get out and exercise regularly because you want your brain to be dynamic and plastic. So okay, brain exercise, that seemed like an important factor. The next obvious question was, “What else might improve brain growth, program dynamics, neuroplasticity, make your brain function better so that you either don’t get depression or you don’t get dementia or brain disease as easily or so that you can be treated more easily when you do get them?”

So that led to sifting through the scientific literature because there really isn’t much in the medical literature on what can stimulate brain growth and brain plasticity. And in doing that, I got into the dementia literature. That’s where a lot of the research is being done and I found lots of different factors that can affect brain plasticity, brain growth. I also found that after 30 years of trying to treat Alzheimer’s disease, after the disease had established itself, virtually no progress had been made, so there’s an argument that I began to look at from this dementia literature that we need to be thinking about preventing illness rather than waiting until you get an illness. So, really it doesn’t look like we can treat dementia but we can maybe prevent it. Depression is also possibly a disease of poor neuroplasticity and if we can enhance this, not only may we prevent it, but we may make it easier to treat and that’s what I think that we’ve seen in our data, which I’m going to show you in just a minute.

TMS and Brain Health

So what we began to do in our office was, we did a combination of transcranial magnetic stimulation and brain health. We would assess brain health by looking at people’s behavior and their symptoms, that sort of thing, but then looking for biomarkers, suggestive of factors that might cause poor brain health. We found that in the population that we did TMS on, we were finding lots of abnormal biomarkers and they varied from person to person. We checked about 50 different variables and we found that, compared to the general population, this one had many more abnormalities. Things like Zinc deficiency, elevated homocysteine levels, metabolic syndrome, subtle kinds of hypothyroidism or adrenal problems. We believe that when we addressed all those problems and then did TMS, we had possibly better results, both in response rate and less recidivism than maybe we’re seeing in the general community.

So just as an example and in some large studies, this has been the kind of the response rates of TMS: 56.4 partial response. That would be like a 50% drop in their depressions scale and a 28.7% remission rate. Now I know lots of clinics are doing better than that and they’re probably doing things kind of like what we’re doing or maybe different things too.

This is just a slide that shows those numbers and a bar graph presentation. I’m really interested in the patients rating because what I think they’re doing, who cares? Really, what matters is how the patients think they’re doing.

This is our data and the first 43 people we treated. For the first two years of our TMS treatment, we treated 43 people. They were all severely depressed based on their score on the PHQ9 or the MADRS, and all had failed at least five antidepressants. Some had failed as many as 20 antidepressant trials, so lots of tries, not very many hits. Out results were 21 out of 43 people, or 72% had a greater than 50% drop on their depression scale, which is pretty good. And 15 of the 43, or 35% reported complete remission based on their rating scales. So a little better than what I showed you on the bigger studies, not necessarily better than other clinics are doing but I think there’s a message related to the brain health issue. I think that may have been what made the difference. I don’t have our data on recidivism yet but our recidivism rate had been much lower than what we would see if we were treating people with antidepressants. When people respond well to antidepressants, they have something like a 50% recidivism rate within the year. We were right around 20% of the recidivism rate. We just need another course of TMS so much better than meds. Maybe related to the brain health stuff.

And if we’re doing nothing else with the brain health stuff, we’re making people healthier and we’re reducing their likelihood of other degenerative health problems. Because when we treat brain health, we’re actually treating the whole body health. There’s really very little difference between what you do.

This just compares us versus large studies. I showed you this before. We think our data is a little bit better than the large studies, not dramatically better but maybe better enough to at least make you wonder if it might not be being helped by something else we’re doing. In our case, it seems to be brain health.

Prevention is Better Than Cure

So another story in the past year: I had the opportunity to have to go to the Mayo Clinic. My wife had a health problem that required some intervention. She had melanoma, skin cancer and she had surgery. We went to a clinic which is sort of one of the classic medical model places and we got great care. Everything turned out fined. It was all wonderful, using standard medical model strategies. When we were done, we talked to the doctors who were running this and they reported that we’d gotten everything and everything was good.

The next question asked was, “Well okay, so how do I prevent it from happening again?”
And they said, “Well, you know, skin cream and stay out of the sun.”
“Okay yeah, we know that. I mean, that’s pretty common knowledge, but what else can we do?”
“Well, there’s really nothing else that helps.”

That’s what they told us and so I’m sitting there thinking, I know that we get cancers, to some degree, a disease of the immune system. Your immune system is no longer getting rid of cancer cells, they proliferate and you get what we call cancer. We are always pairing out cancer cells from our body and keeping that from occurring. So something is not going right in your immune system when you develop cancer. At least hypothetically, that’s the case. This is really first-year medical school information. This is not something that you need to be a scientist to understand. But they didn’t mention that and so I wondered why they didn’t talk about that, or about ways that you might improve your immune system so you could prevent maybe melanoma or some other cancer occurring. It struck me that, despite that, they had a different way of thinking about medical information, they wanted a high degree of proof that something would be helpful before they would suggest it to you. This, I think, they didn’t feel that they had a high enough level of proof that other things could be helpful and that, therefore, they wouldn’t share it with us, so they were missing out on some thoughts about how you prevent disease. I mentioned, we know that cancers to some degree are a disease of the immune system.

This (slide) shows a pyramid that looks at different kinds of studies and levels of certainty. The highest level of certainty is, ‘systematic review/meta-analysis’. The lower level is, ‘Expert opinion’. But I think that I was reading between the lines when we talked with the docs. The information about improving your immune response to help prevent cancer was not a high enough level of certainty for them to recommend it to other people. And I thought, “Well that’s good, I understand that you don’t want to recommend things, especially dangerous things to people that could be helpful to them, but you don’t have a high level of certainty. But how about things that aren’t dangerous to you.”

So if an intervention is dangerous, like toxic chemotherapy, a high degree of proof is needed before recommending the intervention. If an intervention is not dangerous, like Vitamin D to improve one’s immune system, just as an example, a lower level of proof may be sufficient before recommending it. I think this is a problem that the medical community has, that we are locked into this high level of proof before we’re suggesting people do things which are really benign to prevent illness.

So that made me begin to think more about medicine in the future, as well as psychiatry and mental health in the future. Around that time, this was in August of 2017, a guy named Dale Bredesen came out with a book called ‘The End of Alzheimer’s’, which showed that prevention can work in treating Alzheimer’s disease. Dale Bredesen was one of the people that did a lot of that research on dementia that I was mentioning, him and other people. He compiled this in a book and began to do studies looking at if you address all these biomarkers that are off, could you prevent dementia and he found good results. So the question that arose: Should we not be doing that with other illness, certainly with brain illnesses but also with other illnesses all through the medical community? Should we be working more on prevention, rather than waiting for people to get the disease and then just doing disease treatment?

Treatment, Intervention, Prevention

So I began to think of the medical community and the way we think about things as being a three-legged stool that’s missing one of the legs. The 2 legs that we have – that are pretty good and we certainly wouldn’t want to do without – are the treatment of the disease once it occurs and more dramatic interventions for disease, like surgery, electroconvulsive therapy or transcranial magnetic stimulation. We are getting better at those things. There is still progress to be made of course, but we’re not doing the third leg, which is prevention. It turns out, from my perspective, that even when people have a disease, if you begin to work on prevention or the preventive kinds of strategies, you make the disease more treatable.

We know that for instance, in let’s say a person with COPD, they’ve got it, they’ve already got the illness. We know that if you take that person with and get them into an exercise routine – which would be a standard preventative kind of strategy – and stop smoking, you can make their disease more easily treated, so there’s good data about that. So prevention isn’t just before they’re sick. It’s also a strategy you can use to enhance current treatment.

So my vision of the medical system psychiatric treatment of mental illness in the next decade is that we work on developing the three-legged stool, that we enhance our psychopharmacological approaches. We get better at our interventions with TMS, ECT and other neural stimulating strategies that can actually treat brain illness without causing systemic side effects, and that we add prevention to the process. So that’s kind of a synopsis of where I think we need to be going and I’m going to describe a little bit more about that in the next part of this talk.

So again, the three legs disease treatment using medication, psychotherapy, disease intervention, procedures such as surgery, TMS, ECT and then disease prevention, using genetic markers and biomarkers to begin to asses when a person is developing a disease and trying to stop it before it gets out of control.

I wouldn’t want to get rid of disease intervention. When I have a serious infection, I want to take antibiotics under the right circumstance, so the great anti-psychotics have really helped people with psychotic illness. Obviously, insulin has saved countless lives for people who have diabetes. The list goes on. Disease treatment using psychotherapy, it helped people gain insight into their behaviors, enhances the functionality of the frontal lobes. It’s very helpful for people. So I’m not putting down what medicines do add, I just want to add a third leg.

Disease interventions, like surgery: My wife’s cancer was cured with surgery, I like that.
Stent placement: When I have a heart attack, I don’t want you to talk to me about prevention, I want a stent placed or surgery doing.
Transcranial magnetic stimulation or ECT: When somebody’s severely depressed and they are suicidal or not living a life with any meaning, I want to do something to help that now.
I don’t want to just talk about prevention, but if I add improvement of their biomarkers and understand what’s going on genetically with them, I think that I can treat them better.

So how do we do disease prevention? These are a couple of bullets to think about with that. First, disease prevention is different than early detection. Early detection is good. I’m not opposed to it, but we want to prevent illnesses before their detectable and that’s what disease prevention is trying to do. We want to look at genetic susceptibility. There are no gene panels that you can do that will tell you. It will give at least some prediction about how likely you are to develop heart disease, obesity, depression or GI problems and there are genetic markers that could alert you to the fact that you have a propensity for developing those problems, and that you need to do something different to prevent that from occurring. You need to not just follow your impulses. You need to have some discipline if you don’t want those things to happen.

Behaviors, like exercise or what you eat, is another way of doing disease prevention. Diet, thinking about environmental triggers. Who are you with? Where are you? What are you breathing? What are you eating? All those environmental things that are impinging on our bodies. And then finally, biomarkers is what I call this last group, level of hormones, vitamins, minerals. Examples of early detection like pap smears, PSA, skin monitoring or blood lipid testing. Those are all early detection and they’re important. A prevention reduces the likelihood that a disease will occur.

Now let’s talk about genes. We start with our genes. That’s like the blueprint that we’re starting with. That tells us our genetic susceptibility. We can get that by getting a family history. That is very useful genetic information or we can do that by genetic testing. Genetic testing gives us the real blueprint. Our family history tells us something about how that blueprint has evolved, based on environmental factors that the person has had to deal, with.

So genetics, again, is just the genes and it’s about the cord in the genes. Epigenetics focuses on how those genes and the DNA is regulated. It is, again, what you eat, where you live, who you interact with, when you sleep, how you exercise, even aging. They all eventually cause chemical modifications around the genes that affect if they’re turning on or off. In certain diseases like cancer or Alzheimer’s disease, various genes will be switched into an unhealthy state from a healthy state, depending on different environmental triggers.

If we understand the genetic problems we are susceptible to, we may be able to make lifestyle changes to affect epigenetics, how the genes are actually expressed, and decrease the likelihood that negative genetic problems would be expressed.

Meditation, Exercise and Diet

So how about lifestyle: behavior/exercise, meditative experiences, diet. Everybody knows these, nobody does them, but we should all be doing these. We should all be thinking about ways of integrating these into our lifestyle, because these all have possible effects on genetics and thus, epigenetics.

Standard behavioral recommendations; 30-60 minutes of aerobic exercise, 4-6 times a week. Our strength training a couple of times a week – not easy. This guy says, “This morning I spent an hour on the bike. Tomorrow I intend to start peddling.” Yeah, start somewhere, right? And in my office, we are working with people on developing exercise programs. Everybody who does TMS in my office, we are also developing an exercise routine. We’re coaching them, starting with where they’re at and developing some kind of routine to improve their exercise physiology.

“Refusing to go to the gym is not the same thing as resistance training”. Yeah, remember that. So it is hard to get people to exercise who arent exercisers. It’s easy if you’ve been an exerciser or if its part of your lifestyle. You know it makes you feel good, you do it. If you haven’t done it, you don’t know it, and you’ve got to learn it, but you can start in small steps and build.

Meditative experiences: transcendental meditation, focused attention, mindfulness, effortless transcending. There are different words that people use. There are lots of different styles of this. Prayer – within a religious context – music, tai chi. I know that my days are better, my brain is quieter if I have taken the opportunity to meditate, so I do that as part of a personal exercise and meditate every day unless there’s some catastrophe that day. And they balance me. They keep me able to focus, to be engaged with other people, by doing other things that I really love to do. And I am just encouraging people to figure out some way that works for them, that they can enter that state where they can calm their brain on a regular basis. Hopefully daily, doesn’t need to be forever. It could be a half hour or 15 minutes if you can get it. 15 minutes is a lot better than nothing.

Then diet: standard recommendations that we give are minimized consumption of processed sugar. I don’t know if you know this but sugar’s poison. You’ve got to think of it like that. And if that’s the case, then we’re flooded by poison right?. You walk into any grocery store and any coffee shop, the sugar is calling you, right? We want to minimize the consumption of grain products. I can talk about that a little bit but gluten, in particular, appears to have some negative effects on especially the development of inflammation. Take Omega-2 fatty acid and/or eat more fish, preferably small fish. Big fish tend to accumulate mercury and small fish, like sardines, and even fish like trout and salmon can have less mercury in them. Big fish, like tuna, have more mercury in them.

They ask for 12 hours a day. That can be a little bit challenging if you’re like me, but you can work towards it. That means don’t eat between dinner and breakfast. So for me, I often get home at 6 o’clock. We might have dinner by 19:00. I like to go at least until 07:00 the next day. Really, what I like to do, is go until about 09:00 or 09:30. I’m getting 14 hours and that would be optimal. I get hungry, I need to function, my brain feels like it can’t engage as well. Sometimes I eat, but I’m working towards that.

Take vitamin D. Almost everybody – especially Northern latitudes like South Dakota – is vitamin D deficient. Virtually everybody that we’ve tested – and we’ve tested over 200 people – has been vitamin D deficient.

So this sugar consumption business: natural sugars in fruits and vegetable, and unsweetened dairy products seem to be okay. You just want to limit granulated sugars, processed sugar, high fructose corn syrup – which is in every processed food almost – honey, maple syrup, things that have highly concentrated sugar. So fruits and vegetables – especially fruits – have sugar in them, but you’re also eating fiber. That reduces the glycemic index, and that makes them less likely to trigger an insulin response. We’ll talk about the problems with insulin response in a minute. And this is it, so high sugar consumption results in a hyperinsulinemic state. So insulin follows sugar because it’s trying to put the sugar in, itself. We are more hyperinsulinemic now as a culture than at any time in the history of the world, because we’re eating more sugar. Our bodies aren’t used to that.

Chronic hyperinsulinemia and elevated blood sugar are toxic to the brain, so when you have your next candy bar, remember you’re doing some toxicity to your brain. It doubles the risk of Alzheimer’s disease, hyperinsulinemia does, due to excessive sugar intake. Again, we’re probably more hyperinsulinemic than at any point in the history of mankind.

So how is elevated insulin toxic to the brain? So there’s an enzyme in your brain. It’s called insulin-degrading enzyme, this breaks down insulin – that’s cool. It also breaks down amyloid. This is the plague that develops in the brains of people that have Alzheimer’s disease. You get enough of this; you are more likely to have Alzheimer’s disease. So this insulin degrading enzyme; you want it to be available to break down amyloid. If it’s being used up breaking down insulin, because you’re in a hyperinsulinemic state, then you don’t have enough available to break down amyloid that can be developing, and that is one reason why hyperinsulinemia is toxic to the brain; because it uses up insulin degrading enzyme, and doesn’t allow you to break down amyloid as well.

The second dietary thing that we suggest is that people at least limit consumption of grain products, especially processed wheat. There’s some evidence that wheat increases inflammation throughout the body, including the brain, and we think that inflammation makes your brainsick. Gluten sensitivity seems to be the central problem, and it seems to create more problem for some people than others; people with celiac disease as a gluten-sensitive problem, but probably all of us have some issues with gluten. So it’s worth understanding the problem with gluten. So why is wheat or gluten a problem? Here’s the backstory. There’s a molecule called Gliadin, which is a component of the grain protein gluten, and gluten is found in wheat. Gliadin causes a substance called Zonulin to increase in the intestines, so when you eat gluten and gliadin comes out of the gluten, it causes Zonulin to be released in the intestine.

Zonulin appears to make our gut more permeable. If these are two cells in the GI system (clenches his hands together to represents the two cells), and there’s a pretty tight junction between them, then not much is going to slip through between my fingers. Maybe a little bit; small things. If this is affected by gliadin, those holes get bigger. So bigger things are slipping in between your cells and into your bloodstream. And why is that important? Well, your body is not used to those things and your body recognizes them as being foreign. It says, “these things don’t belong”, so it develops an immune response to these other bigger things that are sliding through in between cells, and causes an inflammatory state. That seems to trigger more autoimmunity.

We kind of have an epidemic right now of autoimmune diseases and hyperinflammatory states, and things like arthritis. Cancer is an inflammatory disease. Coronary artery disease is an inflammatory illness. All of these things may be worsened by that process of allowing bigger proteins into your bloodstream, through your intestines, and your body developing an immune response, and then your body subsequently developing an immune response to things that are sort of like those proteins that are found elsewhere in your body, and thus, you get autoimmunity. So we want to be thinking about that; how to make your GI system as healthy as possible to decrease inflammation, to make your brain healthier. All of these things are connected.

Omega-3, fatty acids, eat more fish; I suggest people start low but aim for about two thousand milligrams twice a day. Why? We’ll go into that in a second. Usually, this is completely benign. Most people have no side effects. On occasion, a person will have an upset stomach. Some people will burp up a fish taste. You can usually get around that by either freezing the omega-3 fish oil and eating the frozen tablets, or just finding a brand that doesn’t do that to you. Omega-3 decreases inflammation and improve hippocampus volume; improves brain health. They ask for 12 hours each day, and that again – we talked about that a minute ago – try to finish eating dinner, and then go 12 hours before breakfast or longer, and especially if you have an APOE4 gene; an example of knowing your genetics. If you have an APOE4 gene – which is a gene that predicts Alzheimer’s disease – probably, if you fast a little bit longer, you can decrease your likelihood of that gene expressing itself.

So why fast? It keeps your insulin level from spiking before bedtime since insulin spikes at that time seem to contribute to insulin resistance. Insulin inhibits the release of melatonin, which actually helps you sleep and inhibits growth hormone, which is good for keeping your brain vibrant. It promotes what’s called autophagy, which is a process in which cells recycle components, and destroy damaged proteins and mitochondria. So when you’re starving a little bit; when you’re a little bit low on blood sugar and your body is looking for food, you will break down old crappy cells that you need to get rid of anyway. So it kind of prunes out the bad stuff, and that’s what we think happens with autophagy. And the last thing that fasting does, is it induces ketosis, which is what we talked about earlier. Ketosis can trigger brain-derived neurotrophic factor release. That, plus exercise.

Take vitamin D. Here’s some reasons; reduces inflammation, reduces auto-immunity, improves brain function, reduces cancer cell growth, improves immunity, enhances mood and sleep, reduces the risk of heart disease. D3 is the most active form of vitamin D, so that’s what I suggest people take. It’s available over-the-counter. Almost everybody needs some, especially at this latitude, and for most people, there’s not a reason to not just take 2,000 units a day. Although, if you know your vitamin D level, you can be a little bit more precise about how much you need.

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