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Exploring the Future of Psychiatry with Dr Martijn Arns: From Biomarkers to Brain Stimulation · Hardiness with Dr Paul Taylor

• 0:09
  Speaker 1: Martain Arnes, Welcome to the podcast.
• 0:11
  Speaker 2: Yeah, well thanks a lot for inviting me.
• 0:15
  Speaker 3: Look, the reason I invited you is I saw a
• 0:17
  Speaker 3: post of yours on LinkedIn, and I dove into the
• 0:21
  Speaker 3: post and end I looked into your background, and as
• 0:24
  Speaker 3: soon as I look into your background, I'm like, this
• 0:27
  Speaker 3: is the guy that I want to get in onto
• 0:28
  Speaker 3: my podcast because of the research that you're doing. But
• 0:33
  Speaker 3: you describe yourself as a biological psychologist, not a clinical psychologist.
• 0:40
  Speaker 3: So tell our listeners the difference between that those two things.
• 0:45
  Speaker 2: I think. I think that's quite a big difference. I mean,
• 0:47
  Speaker 2: at the time when I started studying, it was like
• 0:49
  Speaker 2: from the say three four hundred psychologists students a year,
• 0:52
  Speaker 2: that would only be like three to four maybe a
• 0:55
  Speaker 2: handful that would opt for studying physiological psychology or biological
• 0:59
  Speaker 2: psychology as we name it nowadays. And usually I tell
• 1:03
  Speaker 2: people I don't talk to people. I just want to
• 1:05
  Speaker 2: see their brain activity. So biological psychology is more really
• 1:09
  Speaker 2: the biological side of psychology where we're more interested in
• 1:13
  Speaker 2: interrelating behavior to brain. So it's not about checking checklists
• 1:19
  Speaker 2: or just talk therapy. I mean, although it could be
• 1:22
  Speaker 2: part of the interest when you want to see how
• 1:25
  Speaker 2: it works at the brain. But the primary viewpoint is
• 1:29
  Speaker 2: coming from the brain, which is been quite different from psychology,
• 1:33
  Speaker 2: which is more than a clinical psychology, which is more
• 1:36
  Speaker 2: the reverse.
• 1:38
  Speaker 3: Yeah, and so given our listeners a bit of a
• 1:42
  Speaker 3: journey through your background and spoke in academia and then
• 1:46
  Speaker 3: in the work that you do.
• 1:48
  Speaker 2: So when I finished my study, which is let me
• 1:51
  Speaker 2: count a long time ago, there was somewhere ninety ninety eight,
• 1:55
  Speaker 2: after having spend also some time and down Under and
• 1:58
  Speaker 2: some other research places. When I started studying, my specialty
• 2:03
  Speaker 2: was mostly educating people off to mostly get a role
• 2:07
  Speaker 2: in farmer industry because there was a lot of pre
• 2:09
  Speaker 2: clinical research going on where behavior of animals was very
• 2:13
  Speaker 2: important to inform if a drug would be an antidepressant
• 2:16
  Speaker 2: drug or an anti psychotic rug, etc. So I've worked
• 2:19
  Speaker 2: there for a very brief bit at that point in
• 2:21
  Speaker 2: time as well, But over and over again I was like, well,
• 2:25
  Speaker 2: I want to do more translational research. I want to
• 2:27
  Speaker 2: better understand how we can benefit from knowledge from the
• 2:31
  Speaker 2: brain and applying that to humans directly in order to
• 2:35
  Speaker 2: make a difference from treatment perspectives. So after I spent
• 2:40
  Speaker 2: doing research at various research institutes. For example, I did
• 2:43
  Speaker 2: my studies in Name and the Netherlands. Then I had
• 2:47
  Speaker 2: a tour in Sydney, Australia and the Westmead Hospital. I
• 2:51
  Speaker 2: joined the group of Evian Gordon and lie and Williams.
• 2:54
  Speaker 2: I think she joined it later.
• 2:55
  Speaker 3: Actually I know Evan Garden and lay Valliums so Avian
• 3:02
  Speaker 3: with the brilliant Resource Institute. I used to work with
• 3:04
  Speaker 3: those guys a decade ago.
• 3:06
  Speaker 2: Yeah, exactly, I find exactly. I mean that was also
• 3:09
  Speaker 2: a little bit of the way how I got started
• 3:11
  Speaker 2: several years later because ninety seven ninety eight I did
• 3:14
  Speaker 2: a project at the westmin Hospital and the supervision of
• 3:17
  Speaker 2: Evan Gordon. They really learned about applying collecting EG data
• 3:21
  Speaker 2: and lots of people. And then I made a bit
• 3:24
  Speaker 2: of a detour. I also went to the Max Plunk Institute,
• 3:26
  Speaker 2: which was more like memory research, and then I started
• 3:30
  Speaker 2: a PhD in Glasgow and in Scotland together with Oreganaude,
• 3:34
  Speaker 2: which was a farmer company at that time. And that
• 3:37
  Speaker 2: all results in effect of me realizing like, well, it's
• 3:41
  Speaker 2: all this fundamental research is too far away of where
• 3:44
  Speaker 2: we are going. And then after a couple of years
• 3:47
  Speaker 2: spending time in the it. This was like beginning of
• 3:49
  Speaker 2: the two thousands, where even a psychologist could get a
• 3:52
  Speaker 2: job in it and would all be over a good
• 3:55
  Speaker 2: salary and the car. I spent one and a half
• 3:57
  Speaker 2: years there, because of course scientists traveling the world doesn't
• 4:00
  Speaker 2: make you a lot of money, so I needed to
• 4:01
  Speaker 2: pay back some of my dad's at that time. So
• 4:04
  Speaker 2: then Evian Gordon indeed went IPO with the Brain Resource
• 4:07
  Speaker 2: Company and approaching again like if I was interested in
• 4:11
  Speaker 2: setting up at least in a Netland slash the some
• 4:14
  Speaker 2: of the European parts of the Brain Resource Company. And
• 4:16
  Speaker 2: that's how I got started with brain clinics in the
• 4:19
  Speaker 2: very early days. So I made a business plan at
• 4:22
  Speaker 2: that time, and the conclusion was like this no money
• 4:25
  Speaker 2: to be made me. So I thought, well that's a
• 4:27
  Speaker 2: great business plan, let's start doing it. So I jumped
• 4:31
  Speaker 2: into it and we started collecting some data for the
• 4:34
  Speaker 2: Brain Resource Company. But very early on I already realized like, well,
• 4:38
  Speaker 2: we have this brain scanning technique, we can compare brain
• 4:42
  Speaker 2: scans to a database and we have more objective information,
• 4:46
  Speaker 2: and therefore realizing like this could be a very interesting
• 4:50
  Speaker 2: jumping platform to branch out to other applications. And one
• 4:55
  Speaker 2: of the ideas I had at that time already is like,
• 4:57
  Speaker 2: rather than making a diagnosis on the outside based on
• 5:01
  Speaker 2: behavioral checklist like raiding, depression, etc. We need to look
• 5:05
  Speaker 2: under the hoods to better marry a patient to their
• 5:09
  Speaker 2: treatment or their drug of treatment, if you will. And
• 5:12
  Speaker 2: that's been the primary motivation ever since, and I think
• 5:16
  Speaker 2: we've come a long way across the journey ever since.
• 5:20
  Speaker 2: And that's basically how it got started, in starting my
• 5:23
  Speaker 2: own private research institute at that time, on the one hand,
• 5:27
  Speaker 2: collaborating with Brain Resource, but also getting to go with
• 5:31
  Speaker 2: our own research lines and advancing applied neuroscience. So that's
• 5:36
  Speaker 2: in a.
• 5:37
  Speaker 3: Nutshell, yes, very interesting because I actually studied in Glasgow
• 5:42
  Speaker 3: University as well. I did a master's in nutrition at
• 5:45
  Speaker 3: Glasgow Uni. Jesus, it's a cold, wet place in the
• 5:49
  Speaker 3: middle of winter, isn't it. Yeah.
• 5:51
  Speaker 2: You know. The funny thing is I've spent quite some
• 5:53
  Speaker 2: time in all these places, and to be honest, Munich
• 5:57
  Speaker 2: was my least favorite place, at least at that time
• 6:01
  Speaker 2: as a student. It's really hard to get integrated in.
• 6:03
  Speaker 2: Glasgow was the funniest place. Sorry, even above Sydney.
• 6:06
  Speaker 1: It's a lot of things.
• 6:07
  Speaker 2: It's a lot of people really go good, no matter
• 6:11
  Speaker 2: how dark and depressing it was outside inside of the
• 6:13
  Speaker 2: bars in places, they're really friendly, welcoming people. I had
• 6:17
  Speaker 2: the greatest time in Glasgow, to be honest.
• 6:21
  Speaker 3: Yes, yes, Meeter Ashton Lean a bit of time in there.
• 6:24
  Speaker 3: I'm sure I'm sure you've forquented ashtle Leon once or twice.
• 6:27
  Speaker 1: Tell me this before we dig into this.
• 6:28
  Speaker 3: Did you ever come across doctor Roy Sugarman in your
• 6:31
  Speaker 3: time in the Brilliant Resource company?
• 6:33
  Speaker 1: He worked with heavy Yeah.
• 6:34
  Speaker 2: I know, well exchanges with him. I mean this is
• 6:37
  Speaker 2: probably like more than twenty twenty five years ago that
• 6:40
  Speaker 2: that we had so lates.
• 6:42
  Speaker 3: Yeah, nah, very cool.
• 6:45
  Speaker 2: The name rings the bell for sure.
• 6:48
  Speaker 1: So so let's talk.
• 6:50
  Speaker 3: You mentioned something there about with psychiatric disorders the checklist.
• 6:56
  Speaker 3: Now my listeners will have heard me, Steph. Your listeners
• 7:01
  Speaker 3: say before that that psychiatry is the only branch of
• 7:04
  Speaker 3: medicine where people are diagnosed with conditions without a biological
• 7:10
  Speaker 3: signature at all. And are we any closer to biological signatures?
• 7:17
  Speaker 3: And and and if you could explain what that means
• 7:20
  Speaker 3: to people, you'll explain it a lot better than me.
• 7:23
  Speaker 3: And are we getting any closer to biological signatures for
• 7:28
  Speaker 3: different psychiatric conditions? And then and and how do we
• 7:33
  Speaker 3: use the brain and the information from the brand to
• 7:36
  Speaker 3: inform treatment. There's a few questions in there, take them
• 7:39
  Speaker 3: any order you want.
• 7:41
  Speaker 2: Well, it's going to be a longer answer. Yes and no,
• 7:43
  Speaker 2: it's the short answer, and the longer answer is indeed,
• 7:46
  Speaker 2: like you're suggesting, the running joke is a little bit
• 7:49
  Speaker 2: like the psychiatrist. You know, that's the only MD that
• 7:51
  Speaker 2: doesn't first inspect the organ he's treating. And that's that's
• 7:56
  Speaker 2: how it is in current medicine, and especially in PSYCHAI.
• 8:00
  Speaker 2: We take a checklist, we rate specific behaviors, we measure
• 8:05
  Speaker 2: to the DSM four very important. It's not the set
• 8:09
  Speaker 2: of behavioral criteria that make a diagnosis of depression or ADHD.
• 8:14
  Speaker 2: It's the final question. And the final question is clinical impairments.
• 8:18
  Speaker 2: So someone can have meet a list of criteria and
• 8:21
  Speaker 2: not being able to concentrate, impulsive, et cetera. But in
• 8:26
  Speaker 2: the end, if there's no clinical impairment, then the diagnosis
• 8:31
  Speaker 2: will not be made. And remember this because this is
• 8:33
  Speaker 2: a very important notion, because let's visualize two people. We
• 8:39
  Speaker 2: have one person with a CEO and a company, very impulsive,
• 8:44
  Speaker 2: very inattentive, probably has a PA to cover up for
• 8:47
  Speaker 2: all that inattentive behavior, et cetera, but this impulsiveness, et
• 8:52
  Speaker 2: cetera is one of his core strengths. Now let's take,
• 8:55
  Speaker 2: on the other hand, this other person white collar workers, say,
• 8:58
  Speaker 2: very inattentive in PILM and well, his job is, his
• 9:02
  Speaker 2: boss is not really happy with it, and therefore gets
• 9:05
  Speaker 2: reverred out to an MD or to a psychiatrist. They
• 9:08
  Speaker 2: do the checklist, and that they will note some clinical
• 9:11
  Speaker 2: impairment because his complaints are impacting on his job and
• 9:16
  Speaker 2: therefore this clinical impairment. So therefore that person might receive
• 9:20
  Speaker 2: a diagnosis of ADHD, of course a bit more complicated
• 9:24
  Speaker 2: like I'm painting the picture right now. But the CEO
• 9:27
  Speaker 2: on the other end will not get a diagnosis. And
• 9:29
  Speaker 2: this automatically will already tell you that a biomarker driven
• 9:33
  Speaker 2: psychiatry will be impossible because with my biomarker, I might
• 9:38
  Speaker 2: pick up on the level of inattention impulsivity. I could
• 9:41
  Speaker 2: pick up on all those complaints, maybe very reliably, but
• 9:44
  Speaker 2: I will never pick up on the clinical impairment, which
• 9:47
  Speaker 2: is more situational environmental, and that's why by definition, a
• 9:52
  Speaker 2: biomarker will never work. And this is the most important reason.
• 9:56
  Speaker 2: There's multiple other reasons of reliability that even raters could
• 10:00
  Speaker 2: could vary well in rating, and there's also environmental societal
• 10:07
  Speaker 2: changes where some behavior is seen more easily as deviating
• 10:11
  Speaker 2: from the norm than it would be ten twenty years ago.
• 10:14
  Speaker 2: But apart from that, I think this is the most
• 10:16
  Speaker 2: crucial reason why a biomark can never be used for
• 10:22
  Speaker 2: diagnosis as they are today. So we need to develop
• 10:25
  Speaker 2: ourselves to a new framework now with the other question
• 10:30
  Speaker 2: you asked, and I think this is a way more
• 10:31
  Speaker 2: important question, because why would we want to stick a
• 10:34
  Speaker 2: label to someone's forehead in terms of a diagnosi as well.
• 10:38
  Speaker 2: According to the DSM for DSM five, the only reason
• 10:42
  Speaker 2: to have these terminologies of depression, ADHD etc. Is to
• 10:47
  Speaker 2: foster communication among professionals. So it's only meant as a
• 10:51
  Speaker 2: language that if you and I talk about depression, that
• 10:56
  Speaker 2: we both understand what we're talking about. The DSM four
• 10:59
  Speaker 2: and five never developed to be a diagnostic framework to
• 11:02
  Speaker 2: be used to develop treatments upon. It was never designed
• 11:06
  Speaker 2: for insurance companies to exercise upon that was never behind it.
• 11:11
  Speaker 2: But still there was all industry that started building anti
• 11:13
  Speaker 2: psychotics and anti depressants, et cetera. Wherever, whereas it was
• 11:18
  Speaker 2: never intended intended for that purpose. Now it's just there
• 11:23
  Speaker 2: to foster.
• 11:24
  Speaker 1: So it's been so some margins.
• 11:26
  Speaker 3: It's my understanding though, that it's kind of it's been
• 11:30
  Speaker 3: hijacked a little bit by industry for them to develop
• 11:34
  Speaker 3: specific treatments.
• 11:36
  Speaker 2: What you're saying, yeah, I mean that's that's one one
• 11:38
  Speaker 2: way to look at it. I may not maybe purposely.
• 11:40
  Speaker 2: I mean, on the other hand, developing a drug. I'm
• 11:44
  Speaker 2: not saying hijacked in a negative sense. I mean, if
• 11:46
  Speaker 2: you develop a drug, you would like to ting onto
• 11:48
  Speaker 2: something to make understandable what it is that drug is doing.
• 11:51
  Speaker 2: So it's very understandable. But it's also I think has
• 11:55
  Speaker 2: put us on a trajectory where we are currently are
• 12:00
  Speaker 2: that the effectiveness of most treatments are very very low.
• 12:05
  Speaker 2: If we look at depression, and I can paint the
• 12:07
  Speaker 2: whole landscape from you ranging from psychotherapy, all anti press
• 12:11
  Speaker 2: and medications, brain stimulation techniques, ketamine psychedelics, et cetera. Overall
• 12:17
  Speaker 2: the response for mission rates on the group level are
• 12:20
  Speaker 2: roughly thirty forty forty five percent when you look at
• 12:23
  Speaker 2: the largest studies around. So if you go to the
• 12:26
  Speaker 2: casino and you know you're winning chances or a dead low,
• 12:29
  Speaker 2: I'm not sure that casinos will do good business well.
• 12:31
  Speaker 2: In psychiatry, that's what we have to deal with, and
• 12:33
  Speaker 2: that's why we have this stepped care model that we
• 12:36
  Speaker 2: keep on putting people on new drugs until we have
• 12:39
  Speaker 2: found a treatment that will benefit the majority, and when
• 12:43
  Speaker 2: going through four different steps, only two thirds of people
• 12:46
  Speaker 2: are actually helped. So it's a very excruciating process knowing
• 12:51
  Speaker 2: that you're dealing with patients that have co morbid suicideality
• 12:54
  Speaker 2: that are very impaired in their lives. So this is
• 12:57
  Speaker 2: really the worst discipline I think from an effectiveness point
• 13:02
  Speaker 2: of view. Maybe in the hall of metasine.
• 13:06
  Speaker 3: And yeah, look, I think that's pretty clear from the
• 13:10
  Speaker 3: data that the interventions in psychiatry are pretty poor compared
• 13:17
  Speaker 3: to other branches of medicine and unacceptable for some branches
• 13:22
  Speaker 3: of medicine.
• 13:23
  Speaker 1: But how is neuroscience helping?
• 13:27
  Speaker 2: Oh, this is I think the topic where we have
• 13:29
  Speaker 2: to be more optimistic because knowing that on the group level,
• 13:35
  Speaker 2: a treatment is only effective in thirty to forty percent,
• 13:39
  Speaker 2: and also knowing that if people that do not respond
• 13:42
  Speaker 2: to one treatment might be responding to another treatment. That's
• 13:45
  Speaker 2: where the real hope is and that's really really where
• 13:48
  Speaker 2: I think we can make a difference and consistently throughout
• 13:51
  Speaker 2: all the data we have collected in our lives. So
• 13:54
  Speaker 2: we've been part of the I spot D study that
• 13:56
  Speaker 2: was this large study that was funded by by Evan
• 13:59
  Speaker 2: Gordon and Brain Resource, the largest biomarker study to date,
• 14:04
  Speaker 2: and that study has been confirming what I just said.
• 14:07
  Speaker 2: If we make correlations between symptom profiles and baseline EG,
• 14:12
  Speaker 2: we never found something. But if you start making correlations
• 14:17
  Speaker 2: between brain activity at baseline and behavior in the future,
• 14:22
  Speaker 2: so like the symptoms in the future, we did find
• 14:25
  Speaker 2: a significant association. So that's already telling you that your baseline,
• 14:31
  Speaker 2: the way your brain activity is at this point in time,
• 14:33
  Speaker 2: is predictive of the trajectory to responding to a drug.
• 14:38
  Speaker 2: So if you're responding to a drug, you have a
• 14:40
  Speaker 2: different type of EG then relative to when you're not
• 14:44
  Speaker 2: responding to a treatment. So in the first quest, we
• 14:48
  Speaker 2: really started to asking the question can we predict people
• 14:51
  Speaker 2: that are responding and non responding to treatment? And the
• 14:54
  Speaker 2: simple answer is yes, and we can do quite some
• 14:57
  Speaker 2: substantial degree predicted.
• 14:59
  Speaker 3: However, when you develop what sort of accuracy, sorry, Mark,
• 15:04
  Speaker 3: what sort of accuracy are we talking here in terms
• 15:07
  Speaker 3: of predictive.
• 15:07
  Speaker 2: Yeah, that's why I wanted to get to get into
• 15:09
  Speaker 2: because it was not like in the eighty ninety or
• 15:12
  Speaker 2: a ninety plus kind of sensitivity, so we would still
• 15:15
  Speaker 2: be on the lower end of sensitivity and specifict you
• 15:20
  Speaker 2: have more like sixty seventy percent, which that's what I
• 15:24
  Speaker 2: wanted to explain as well, which indeed is clinically very
• 15:27
  Speaker 2: challenging because if you cannot be absolutely accurate that someone
• 15:32
  Speaker 2: will or will not respond, then you also cannot make
• 15:35
  Speaker 2: a decision to prescribe or to withhold a treatment. And
• 15:40
  Speaker 2: to prescribe a treatment can ethically be justified quite easily,
• 15:44
  Speaker 2: but you cannot very easily tell someone like, well, my
• 15:47
  Speaker 2: biomarket tells me you're not going to respond to this
• 15:50
  Speaker 2: treatment with an eighty percent accuracy, that still means that
• 15:54
  Speaker 2: someone has likely to twenty percent to respond to the treatment. Ethically,
• 15:58
  Speaker 2: you cannot make that, not until you have an alternative
• 16:02
  Speaker 2: to offer, and that's where we have also based on
• 16:06
  Speaker 2: a lot of the studies we conducted based on I SPOT,
• 16:08
  Speaker 2: based on these ethical and moral decisions we needed to
• 16:11
  Speaker 2: make as well, and that's why we've shifted to a
• 16:13
  Speaker 2: different way. Many people talk about precition psychiatry, personalized medicine
• 16:18
  Speaker 2: that deals with such questions, and we've moved away to
• 16:21
  Speaker 2: a model that we call stratified psychiatry and in stratified
• 16:25
  Speaker 2: psychiatry in depression. For example, we take the whole family
• 16:29
  Speaker 2: of antidepressant treatments and what we'll do will develop a
• 16:33
  Speaker 2: biomarker that might predict some responsiveness to say, antidepressant A,
• 16:39
  Speaker 2: and as long as the same biomarker does not predict
• 16:43
  Speaker 2: impaired response to another one, then we have a winner,
• 16:46
  Speaker 2: because what we can we can gain with one drug.
• 16:49
  Speaker 2: But if we have to then tell someone you cannot
• 16:52
  Speaker 2: use this drug, however we stratify you to the other
• 16:56
  Speaker 2: drug that at least is equally effective as the group
• 16:58
  Speaker 2: level response remission, then we still win because we take
• 17:03
  Speaker 2: away the drugs so of say that people are less
• 17:06
  Speaker 2: responsive to, and then we will never have to make
• 17:09
  Speaker 2: the life or death decision of withholding someone from a treatment,
• 17:14
  Speaker 2: and so it's a slightly different perspective, but clinically very important.
• 17:19
  Speaker 3: Yes, yeah, now that that that is important and it's
• 17:23
  Speaker 3: worthwhile excuse me, it's worthwhile just dubbing clicking on that
• 17:27
  Speaker 3: in that you can with what you're saying now is
• 17:30
  Speaker 3: you're moving towards well. Actually this is saying that this
• 17:34
  Speaker 3: treatment may not be good for you, or you may
• 17:38
  Speaker 3: not respond well to this treatment, so instead you should
• 17:42
  Speaker 3: have this one. Now that's important because a you can
• 17:46
  Speaker 3: potentially increase the effectiveness, but b the patient doesn't go
• 17:50
  Speaker 3: on to a drug that is not helpful, that often
• 17:55
  Speaker 3: has very very significant side effects. And I've been you
• 18:00
  Speaker 3: Professor John Reid on my podcast, who's done large studies
• 18:04
  Speaker 3: of real people with antidepressants and find that sixty plus
• 18:09
  Speaker 3: percent of them have a whole host of side effects,
• 18:13
  Speaker 3: including suicidal ideation. So if we can can basically go
• 18:18
  Speaker 3: this drug is not useful for you, or or are
• 18:21
  Speaker 3: our information is saying don't take this drug. Whereas if
• 18:25
  Speaker 3: they'd just gone to the doctor, the doctor could have say,
• 18:27
  Speaker 3: well let's try you on this one first, and they
• 18:30
  Speaker 3: go and they have a bad outcome and then they
• 18:33
  Speaker 3: have to go on to another treatment, but they could
• 18:35
  Speaker 3: potentially be worse off than when they started right exactly.
• 18:39
  Speaker 2: So, rather than patients coming to a psychiatrist and a
• 18:43
  Speaker 2: psychiatrist having a whole range of first line choices, have
• 18:47
  Speaker 2: first line treatments of psychotherapy and SSRIY in ten different
• 18:52
  Speaker 2: kinds and as NRI in several kinds. And then there's
• 18:55
  Speaker 2: second line treatments which is more like OURTMS for example,
• 19:00
  Speaker 2: treatment used for more treatment resistant patients. So rather than
• 19:03
  Speaker 2: doing a random pick out of one of these, you
• 19:07
  Speaker 2: take a simple biomarker, which most consistently we've shown with EG,
• 19:11
  Speaker 2: and you pick the one that someone is most likely
• 19:14
  Speaker 2: to respond to. And what we've seen is in replicated
• 19:17
  Speaker 2: studies that we've been publishing out there, and we've seen
• 19:21
  Speaker 2: that you could enhance based on a cop one or
• 19:25
  Speaker 2: two very simple biomarkers, enhance your remission rates from say
• 19:29
  Speaker 2: forty fifty percent to sixty sixty five percent. So we
• 19:32
  Speaker 2: see about a thirty percent gain in the remission rates
• 19:36
  Speaker 2: by simply using one biomarker and stratify people between an
• 19:40
  Speaker 2: evident between two evidence based treatments.
• 19:44
  Speaker 3: And that is really significant, right, that's thirty percent uplift.
• 19:48
  Speaker 2: And that's also what these studies have shown. If we
• 19:50
  Speaker 2: look at I spot where people were actually randomized to
• 19:54
  Speaker 2: three different drugs, two SSRIs, one s and ri I
• 19:57
  Speaker 2: and one drug with even a completely slightly different working
• 20:00
  Speaker 2: mechanism on the group level, remission rates were completely identical
• 20:05
  Speaker 2: for all all three groups. So the psychiatrist could as
• 20:08
  Speaker 2: well roll the dice and vside on a treatment based
• 20:12
  Speaker 2: on rolling the dice. And we know it doesn't make
• 20:14
  Speaker 2: a difference from any studies.
• 20:16
  Speaker 3: That's crazy and can you just let the listeners know.
• 20:20
  Speaker 3: So you mentioned ssrright, selective excuse me, serotonin reoptic inhibitors
• 20:25
  Speaker 3: and selective neurepinephron tell our listeners how those drugs are
• 20:30
  Speaker 3: different in terms of their mechanisms of action.
• 20:34
  Speaker 2: Well, the drugs usually impact on a specific neurotransmitter, and
• 20:38
  Speaker 2: a neud transmitter is like a small chemical in the
• 20:41
  Speaker 2: brain that facilitates communication between between urins, and some of
• 20:45
  Speaker 2: them are communicating via means of serotonin, other via means
• 20:50
  Speaker 2: of neu adrenaline. And we have very often heard about
• 20:52
  Speaker 2: dopamine as well, So some antidepressants have a preference for
• 20:56
  Speaker 2: more dopaminergic neurotransmitters. So we have multiple, maybe tens more
• 21:04
  Speaker 2: close to one hundred different antidepressants and they all have
• 21:08
  Speaker 2: a slight different preference for one of the other neurot
• 21:10
  Speaker 2: transmitted systems. However, on the group level, people are equally
• 21:15
  Speaker 2: responsive to one or the other. And that's really sobering
• 21:18
  Speaker 2: because in the old days we used to think like, well,
• 21:21
  Speaker 2: maybe we are more dealing with a subgroup of people
• 21:24
  Speaker 2: that have a more certnergic depression and other people have
• 21:28
  Speaker 2: a more say no other nergic depression. Well, all the
• 21:31
  Speaker 2: research in that specific area has not indicated any evidence
• 21:34
  Speaker 2: for that, and at this point in times, psychiatrists have
• 21:37
  Speaker 2: no means other than their gut feeling, other than their
• 21:42
  Speaker 2: experience with patients to prescribe people with a better treatment.
• 21:46
  Speaker 2: But overall, still you could as well randomize people to
• 21:50
  Speaker 2: the treatments because on the group level it's not going
• 21:52
  Speaker 2: to make a difference at all. And even this is
• 21:56
  Speaker 2: within antidepressants, but even if you would add psychotherapy or
• 22:00
  Speaker 2: TMS to it as well, we know tms relative to antidepressants,
• 22:04
  Speaker 2: tms relative to each other. There's multiple tms producols as well.
• 22:09
  Speaker 2: For the for rights prefrontal or less prefontal cortex, and
• 22:14
  Speaker 2: on a group level, they have identical results as well.
• 22:16
  Speaker 2: So it's not only true for for drugs, but for
• 22:20
  Speaker 2: any antidepressant treatment. We see group level remission rates being
• 22:25
  Speaker 2: quite identical.
• 22:26
  Speaker 1: And that's that's going to be really confusing.
• 22:31
  Speaker 3: Me as well for researchers when you're looking at different
• 22:35
  Speaker 3: drugs with different mechanisms of actions, and then when you
• 22:39
  Speaker 3: take a thousand people, same effectiveness, and so that that
• 22:46
  Speaker 3: begs the question as to when they are effective, what
• 22:51
  Speaker 3: is the mechanism of action. I've heard some people talk
• 22:55
  Speaker 3: that they think that it's nothing to do with the
• 22:57
  Speaker 3: serotonin and orap and effort, but it might be that
• 22:59
  Speaker 3: the these drugs are increasing BDNF and and helping the
• 23:04
  Speaker 3: brand that way. Any comments on that or have you
• 23:08
  Speaker 3: got any insights into this?
• 23:10
  Speaker 2: Yeah, I mean that's the final common pathway of any
• 23:13
  Speaker 2: antidepressant treatment, including electro convilsive therapy, psychedelics rTMS. The final
• 23:19
  Speaker 2: common pathway is b D and F or nerve growth
• 23:22
  Speaker 2: factors expressed in the hippocampus that supposedly can facilitate neural
• 23:28
  Speaker 2: growth and functioning of specific networks in the brain. So
• 23:34
  Speaker 2: they all have that. So it's not true. Serotonin it
• 23:38
  Speaker 2: was thought to be a final part of what was
• 23:41
  Speaker 2: explaining depression, and now we know it's not actually has
• 23:44
  Speaker 2: more specific networks and specific parts of the brain where
• 23:49
  Speaker 2: these nerve growth factors play play an important role. But
• 23:55
  Speaker 2: I think that the honor sensor is how do all
• 23:57
  Speaker 2: these treatments work. I mean, we know there's a final
• 23:59
  Speaker 2: common part way in BDNF, for example, but still knowing
• 24:04
  Speaker 2: that some treatments will be very ineffective, they might still
• 24:08
  Speaker 2: have this downstream effect that maybe you're not strongly enough.
• 24:11
  Speaker 2: I think the first question I would and that's why
• 24:14
  Speaker 2: I'm an applied neuro scientist. The first question I would
• 24:16
  Speaker 2: like to answer, can we first improve the remission rates
• 24:20
  Speaker 2: by using a stratified psychiatry approach before we start understanding it,
• 24:24
  Speaker 2: because our understanding will even get way more complicated. Where
• 24:28
  Speaker 2: we assume the whole family of treatments we have the
• 24:30
  Speaker 2: same effect. We're now seeing that within that family of treatments,
• 24:34
  Speaker 2: one drug has a supposedly different working mechanism relative to
• 24:39
  Speaker 2: another drug, even if it's the same family. So we're
• 24:42
  Speaker 2: complicating the whole story much more by taking individual variation
• 24:46
  Speaker 2: into account and that's really where we need to go to.
• 24:49
  Speaker 3: Right, I think what you're saying, so you're saying nis like,
• 24:53
  Speaker 3: let's let's do stratification, find the drug that is working better,
• 24:58
  Speaker 3: and then explore the mechanisms, rather than as what happened
• 25:02
  Speaker 3: twenty thirty years ago, propose a serotonin mechanism, make a
• 25:06
  Speaker 3: drug that has an action on it, and then use
• 25:10
  Speaker 3: that drug. So it's a kind of bit of reverse
• 25:14
  Speaker 3: way of doing things, which I get.
• 25:16
  Speaker 1: I actually get that.
• 25:18
  Speaker 3: But the BDNF story probably at least partly explains why
• 25:25
  Speaker 3: I would imagine you're a ware of the British Medical
• 25:27
  Speaker 3: Journal our BMJ studies comparing a whole different type of
• 25:33
  Speaker 3: exercise interventions to antidepressant therapy and find that every single
• 25:38
  Speaker 3: form of exercise had a greater effects size than antidepressants.
• 25:43
  Speaker 3: And we know that exercise is very potent at stimulating BDNF,
• 25:49
  Speaker 3: particularly more vigorous exercise, so that would kind of seem
• 25:53
  Speaker 3: to play into BDNF being the ultimate thing that might
• 25:57
  Speaker 3: make a difference.
• 26:00
  Speaker 2: Yeah, I mean, in that sense, it's not really surprising.
• 26:02
  Speaker 2: One of the most powerful psychological treatments is called behavioral activation.
• 26:07
  Speaker 2: As you imply any type of activation, especially in depression,
• 26:12
  Speaker 2: could be very powerful. Even so strongly, and I recall
• 26:16
  Speaker 2: this from a long time ago. There was the big
• 26:19
  Speaker 2: professor who was specialized in cogitive behavior therapy, and in
• 26:23
  Speaker 2: order to do concuaitive behavior therapy it requires a lot
• 26:26
  Speaker 2: of training, right, and he explained behavioral activation as being
• 26:30
  Speaker 2: so simple that you can even teach a psychiatrists how
• 26:33
  Speaker 2: to do it. Then he was a psychiatrist at that time.
• 26:36
  Speaker 2: As a behavioral activation is much simpler to do, and
• 26:38
  Speaker 2: they actually have done had to head studies in very
• 26:41
  Speaker 2: large numbers where behavioral activation is non inferior to CBT,
• 26:47
  Speaker 2: and so it's much simpler to do. And even there
• 26:49
  Speaker 2: that's similar to possibly medications, behavioral activation is a very
• 26:53
  Speaker 2: powerful technique to at least get some initial antidepressant benefit. Again,
• 26:58
  Speaker 2: if that's just to be f I think we should
• 27:02
  Speaker 2: also be cautious by just similar to in the past
• 27:05
  Speaker 2: saying oh, it's a bit of a certain one thing slow,
• 27:07
  Speaker 2: we're going to increase it. I think we need to
• 27:09
  Speaker 2: be cautious about it and not oversimplify things. It's probably
• 27:13
  Speaker 2: more complicated. Let's be humble, let's only start focusing on
• 27:16
  Speaker 2: all the mechanisms. Once we have identified the various subgroups,
• 27:20
  Speaker 2: and that makes more sense in my view, and anything
• 27:23
  Speaker 2: is simplification beforehand.
• 27:25
  Speaker 3: Yeah, no, that makes sense. So let's not talk about TMS. So,
• 27:29
  Speaker 3: because you have done a lot of work in the TMSPS, firstly.
• 27:34
  Speaker 1: Explain what it is and high and.
• 27:38
  Speaker 3: Actually what's its mechanisms of action? And then what sort
• 27:43
  Speaker 3: of conditions is it being used for?
• 27:46
  Speaker 1: And what the hell does heartbeat have to do with it?
• 27:50
  Speaker 2: Interesting question. I'll finish off with a heart rate and
• 27:53
  Speaker 2: keep the most exciting to the end. I think TMS
• 27:56
  Speaker 2: is a very exciting technique. And this was so remember
• 28:00
  Speaker 2: that what with brain clinics, we're onto doing EG research
• 28:05
  Speaker 2: and with EG we pick up the activity that's projecting
• 28:09
  Speaker 2: perpendicular to your scope. So at that point in time
• 28:13
  Speaker 2: two thousand and five, two thousand and six, I thought like, well,
• 28:16
  Speaker 2: there's this technique TMS, which is a very vocal, strong
• 28:20
  Speaker 2: magnetic field and it works in exactly the opposite direction
• 28:23
  Speaker 2: as the EEG that we're picking up. So I very
• 28:25
  Speaker 2: naively thought like, oh, that's interesting. I can see an
• 28:28
  Speaker 2: EEG where something is different and maybe I can use
• 28:31
  Speaker 2: this technique to then specifically in an individualized way modulate
• 28:37
  Speaker 2: brain activity. And so we bought our first TMS machine
• 28:40
  Speaker 2: in two thousand and six and we got started and well,
• 28:44
  Speaker 2: in the end it turned out to be completely different.
• 28:47
  Speaker 2: So with transcranial magnetic brain stimulation, and we generate a
• 28:51
  Speaker 2: magnetic fields in the strength of roughly one point five
• 28:54
  Speaker 2: to two testa that's very strong and very quickly build setting.
• 28:59
  Speaker 2: And because it's the magnetic or the decay of the
• 29:02
  Speaker 2: field is in the order of nanoseconds, we have a
• 29:06
  Speaker 2: very quick change which can elicit a small current in
• 29:11
  Speaker 2: the brain. And just to illustrate this, if I hold
• 29:14
  Speaker 2: it above my hand, my right cortex, so they say,
• 29:17
  Speaker 2: and I'm stimulating the area that's responsible for my left hand,
• 29:22
  Speaker 2: then I can also elicit a movement in my left hand.
• 29:25
  Speaker 2: So it's wow, physical stimulation exactly. So it's physical stimulation.
• 29:30
  Speaker 2: There's no people have done magnet therapies and stuff like that,
• 29:32
  Speaker 2: there's nothing related to that. This is really like physical
• 29:37
  Speaker 2: brain stimulation. So on the other hand, that's also the
• 29:40
  Speaker 2: only outcome we can get. We can stimulate your motor
• 29:43
  Speaker 2: areas and see motor movement, and that's it. So it's
• 29:46
  Speaker 2: always been very surprising to me if I move the
• 29:50
  Speaker 2: stimulation well to my prefrontal cortex where my high higher
• 29:53
  Speaker 2: order thinking processes that take place, that I can stimulate
• 29:57
  Speaker 2: whatever I want, but there's no conscious recollection. Get It's
• 30:00
  Speaker 2: not that I think like, oh my brain is working different,
• 30:03
  Speaker 2: my cognition is impaired. You really need to do very
• 30:05
  Speaker 2: very sophisticated behavioral algorithms to get some kind of a
• 30:09
  Speaker 2: readout from the prefrontal cortex on your Ownand we do
• 30:13
  Speaker 2: know that if you move your coil five centimeters interior
• 30:17
  Speaker 2: in the prefront or quartex and stimulate for say twenty
• 30:21
  Speaker 2: to thirty sessions, we know you get a very strong
• 30:24
  Speaker 2: and robust antidepressant effect in quite a number of people. Again,
• 30:28
  Speaker 2: on a group level, you get remission rates to say
• 30:31
  Speaker 2: forty to fifty percent, which is still meaningful. Also, and
• 30:36
  Speaker 2: this is a very important distinction taken into account. This
• 30:39
  Speaker 2: is mainly investigated in treatment resistant people, so people that
• 30:43
  Speaker 2: have filled all most other treatments before and getting such
• 30:48
  Speaker 2: a remission rate in that subgroup of patients, I think
• 30:51
  Speaker 2: it's very very encouraging because for these people the only
• 30:54
  Speaker 2: thing left will be electroc convulsive therapy or shock therapy,
• 30:58
  Speaker 2: which is not something you want to be considering too lightly, So.
• 31:02
  Speaker 3: Every s sorry, before you go any further, can I
• 31:06
  Speaker 3: ask why it is used as second line rather than
• 31:10
  Speaker 3: first line if its effectiveness appears to be as at
• 31:16
  Speaker 3: least effective as some of the first line drugs, and
• 31:19
  Speaker 3: these are on treatment resistant people that you're getting the
• 31:23
  Speaker 3: same effectiveness, So why isn't it used for first line treatment?
• 31:28
  Speaker 2: Yeah, very good question. Yeah, this is usually how research
• 31:32
  Speaker 2: goes have for ethical reasons. You're not going to be
• 31:37
  Speaker 2: experimenting in people that are feel still very likely to
• 31:40
  Speaker 2: respond at an early stage of the depression, and that's
• 31:43
  Speaker 2: why you always start with the toughest cases. But then
• 31:46
  Speaker 2: automatically the insurance mechanism kicks in again, and the insurance
• 31:51
  Speaker 2: mechanism then tells us to only start treating people if
• 31:54
  Speaker 2: they filled a couple of sessions, whereas personally, and again
• 31:58
  Speaker 2: don't take this as official advice, but personally I would
• 32:01
  Speaker 2: consider that we might make it available much more quickly
• 32:07
  Speaker 2: and to maybe first line patients as well. I think
• 32:10
  Speaker 2: in the Netherlands we have one of the few systems
• 32:13
  Speaker 2: where people could qualify for it quite early on, and
• 32:17
  Speaker 2: we require people to have filled two evidence based treatments,
• 32:22
  Speaker 2: which could be psychotherapy and medication. But if people don't
• 32:25
  Speaker 2: want to take medication, they could even have tried two
• 32:28
  Speaker 2: very different types of psychotherapy and then still qualify for
• 32:32
  Speaker 2: our TMS for example. And there's also based on the
• 32:34
  Speaker 2: evidence out there that that will really increase the likely
• 32:38
  Speaker 2: of people to respond to to TMS. But firstly, I
• 32:41
  Speaker 2: do think the future will be going there as well.
• 32:44
  Speaker 2: We will be going to a completely different model. Rather
• 32:47
  Speaker 2: than taking popping a pill every day that's the current model,
• 32:51
  Speaker 2: people will start moving, in my view, more to brain
• 32:53
  Speaker 2: stimulation treatments, short intensive treatment and then you're after treatment
• 32:58
  Speaker 2: for a longer period or maybe with some maintenance treatment
• 33:02
  Speaker 2: once every six months, people can maintain their remission, and
• 33:05
  Speaker 2: I think similar to psychedelics, model is probably going that
• 33:08
  Speaker 2: direction as well, even though the clinical outcomes might not
• 33:12
  Speaker 2: be blowing all the drugs out of the water. But
• 33:14
  Speaker 2: the big advantage of psychedelics is you have a one
• 33:17
  Speaker 2: time psychedelic experience which can keep your remission for at
• 33:21
  Speaker 2: least three to six months, and then you might redo it,
• 33:24
  Speaker 2: which is I think at least better than popping a
• 33:27
  Speaker 2: bill every day, which is all kinds of side effects
• 33:30
  Speaker 2: and other mechanisms associated it.
• 33:33
  Speaker 1: Yeah, yeah, absolutely.
• 33:34
  Speaker 3: And look, I actually know somebody who had treatment resistant
• 33:38
  Speaker 3: depression and did TMS and said, did ten sessions and
• 33:43
  Speaker 3: was like this is doing nothing. Said after the ten
• 33:45
  Speaker 3: session bomb complete and other shift and was just completely
• 33:52
  Speaker 3: blown away by it. And actually I interviewed on my
• 33:56
  Speaker 3: podcast a guy who's running the first sack of psych
• 34:00
  Speaker 3: delic lab in Australia and they're getting some really interesting results.
• 34:05
  Speaker 3: He so they use it with therapy and his words
• 34:08
  Speaker 3: are that the psychedelic the psychedelics act as a rocket
• 34:13
  Speaker 3: ship for the therapy. But he says, if you're going
• 34:16
  Speaker 3: to use a rocket, you need to know how to.
• 34:18
  Speaker 1: Steer a rocket.
• 34:19
  Speaker 3: That's that's his big thing, because he says they're so potent.
• 34:23
  Speaker 3: So so, wh is TMS being used we talked about depression.
• 34:28
  Speaker 3: Is it being used in other psychiatric conditions with any
• 34:32
  Speaker 3: effectiveness at this stage?
• 34:34
  Speaker 2: Yeah, it's for sure. It's being investigated pretty much in
• 34:38
  Speaker 2: almost any psychiatic disorder. I would say, although the effectiveness
• 34:42
  Speaker 2: varies quite a bit. We know there's very strong evidence
• 34:46
  Speaker 2: for a good use of rTMS in the treatment of depression,
• 34:51
  Speaker 2: in the treatment of obsessive compulsive disorder. Those I think
• 34:56
  Speaker 2: are the two main indications. Then when we cross over
• 34:59
  Speaker 2: to neurology, there's some indication in pain, in chronic pain,
• 35:04
  Speaker 2: But the question there is how sustainable are the effects,
• 35:07
  Speaker 2: because you can get an acute suppression of pain, but
• 35:12
  Speaker 2: if you need to do TMS every day, it might
• 35:15
  Speaker 2: not be as clinically meaningful there, And that's I think
• 35:18
  Speaker 2: still the jury is still out on that one. And
• 35:21
  Speaker 2: other than that, I think there's multiple PTSD is also
• 35:24
  Speaker 2: quite effectives as a treatment with with our TMS, using
• 35:28
  Speaker 2: quite similar approaches that we use for the treatment of
• 35:31
  Speaker 2: depression as well. The network seem to overlap to some degree,
• 35:35
  Speaker 2: but I think that's that's why we have the strongest
• 35:37
  Speaker 2: evidence at this point.
• 35:40
  Speaker 3: Okay, can we shift TAC now and and talk about
• 35:45
  Speaker 3: what is probably the fastest growing psychiatric condition that that's
• 35:50
  Speaker 3: just from what I'm observing and hearing, which is ADHD,
• 35:55
  Speaker 3: And there seems to be.
• 36:00
  Speaker 2: They wanted to touch out on a little bit because
• 36:03
  Speaker 2: I think we've now mainly described TMS, but I just
• 36:06
  Speaker 2: wanted to give this example because I think it's a
• 36:08
  Speaker 2: very nice example. Also about I think the field of
• 36:12
  Speaker 2: applied neuroscience I remember that with TMS we want to
• 36:15
  Speaker 2: stimulate the prefrontal cortex, but the current way of thinking
• 36:19
  Speaker 2: is that TMS is more about stimulating specific networks in
• 36:23
  Speaker 2: the brain, and that by stimulating the prefrontal cortex, the
• 36:26
  Speaker 2: signal will be carried through the whole network too much
• 36:29
  Speaker 2: deeper structures that are inaccessible, like the subgenuine interior singlet cortex.
• 36:34
  Speaker 2: We're also deep brain stimulations being done so in TMS.
• 36:38
  Speaker 2: When we talk about biomarkers and improving treatment response, the
• 36:43
  Speaker 2: most often heard way of doing that it's using fMRI,
• 36:46
  Speaker 2: and fMRI scans are very complicated scans where we can
• 36:50
  Speaker 2: look at connectivity from the subgeneral to prefrontal cortex. So
• 36:54
  Speaker 2: although this is the most evidence based at this point
• 36:57
  Speaker 2: in time and most investigated, we've been looking at the
• 37:00
  Speaker 2: for a long time and wanted to achieve a similar
• 37:02
  Speaker 2: kind of outcome, but without using the fMRI because in
• 37:06
  Speaker 2: my view, for clinical practices, it's not always feasible to
• 37:10
  Speaker 2: have an fMRI scan on premise and have every patient
• 37:13
  Speaker 2: goes through in the MRI scan. So this is also
• 37:15
  Speaker 2: where you alluded to that where the heart rates and
• 37:19
  Speaker 2: I think I think it's an interesting topic so by
• 37:22
  Speaker 2: doing a lot of research and also realizing that there's
• 37:25
  Speaker 2: a lot of overlap between the depression network and what
• 37:28
  Speaker 2: we call the frontal Viagel network or the network that's
• 37:32
  Speaker 2: involved in the brain in regulating heart rate, hard rate friability,
• 37:37
  Speaker 2: we realize there's a lot of overlap. And what we
• 37:40
  Speaker 2: found actually was that when you apply TMS acutely to
• 37:44
  Speaker 2: your brain and when you're hitting the right area that
• 37:47
  Speaker 2: you see in acute heart rate suppression. And that's very
• 37:51
  Speaker 2: opposite to what you would think because feeling TMS, it's
• 37:54
  Speaker 2: not painful, but it's also not the most pleasant thing
• 37:57
  Speaker 2: to undergo because muscle shoe will will be stimulated as well,
• 38:03
  Speaker 2: so you would expect herd rate to increase, but not decrease.
• 38:06
  Speaker 2: So we described it a long time ago. It's a
• 38:09
  Speaker 2: good long story short. We've done a lot of research
• 38:11
  Speaker 2: now actually validating it against fMRI based acquisitions, and we
• 38:16
  Speaker 2: found that the overlap by using heart rate as an
• 38:19
  Speaker 2: acute readout of TMS to identify the right connected areas,
• 38:26
  Speaker 2: it overlapped with fMRI with between eighty five and ninety percent.
• 38:31
  Speaker 2: So we have now developed an iPhone app where people
• 38:34
  Speaker 2: can use a simple polar heart rate strap together with
• 38:37
  Speaker 2: an iPhone app, do a five or ten minute procedure
• 38:40
  Speaker 2: with TMS look at the hard rate at the same time,
• 38:43
  Speaker 2: which we call heart brain coupling and apps called heart
• 38:46
  Speaker 2: brain connect and we're using that procedure, you can now
• 38:50
  Speaker 2: indeed target the individualized right brain network and an individual
• 38:56
  Speaker 2: increase likelihood of response and being as accurate as one
• 39:00
  Speaker 2: could be with m right. The reason why I wanted
• 39:03
  Speaker 2: to highlight this because I think this is really the
• 39:05
  Speaker 2: type of innovation that we need in psychiatry to make
• 39:07
  Speaker 2: things scalable as well, and we can have all kinds
• 39:10
  Speaker 2: of advances and over engineering things as we go, which
• 39:14
  Speaker 2: is happening a lot, to be honest, because over engineering
• 39:17
  Speaker 2: making more sophisticated stuff will earn companies more money. But
• 39:21
  Speaker 2: we also have to think in the opposite direction, like
• 39:25
  Speaker 2: disrupting the field of brain stimulation and making it way
• 39:28
  Speaker 2: more accessible. I would like to see that every first
• 39:32
  Speaker 2: line psychology practice would have access at some point in
• 39:35
  Speaker 2: time over a very simple stimulator, maybe only doing one HURTZ,
• 39:39
  Speaker 2: and have very simple targeting techniques like using heart rate
• 39:43
  Speaker 2: to improve the clinical outcomes to a large degree. Already
• 39:46
  Speaker 2: and therefore making it way more accessible to people. And
• 39:49
  Speaker 2: I think that's why I wanted to highlight this as
• 39:51
  Speaker 2: an example of how very sophisticated fMRI based neuroimaging can
• 39:56
  Speaker 2: also be re engineered if you will, to refrisatile clinical
• 40:03
  Speaker 2: clinically based utility using heart.
• 40:05
  Speaker 3: Rate that comes and the cost of a heart rate
• 40:08
  Speaker 3: monitor and an app versus an fMRI machine is a
• 40:13
  Speaker 3: little bit different, isn't it? And so is this is
• 40:15
  Speaker 3: this process mediated to the vegus nerve and because right
• 40:20
  Speaker 3: because it often depressed, people have got very suppressed heart
• 40:25
  Speaker 3: rate variability. Can you just dive into this little a
• 40:28
  Speaker 3: little bit more, that connection between the heart the heart
• 40:32
  Speaker 3: rate variability in the Brian and exactly high are you
• 40:35
  Speaker 3: using heart rate to inform the TMS or guide the tms?
• 40:40
  Speaker 3: This is fascinating, So just ridiculously fascinating.
• 40:43
  Speaker 2: Yes, So when you spend the whole network ranging from
• 40:46
  Speaker 2: the prefioto cortex that's accessible, you then do a deep
• 40:50
  Speaker 2: dive so it's between your eyes and then you go
• 40:53
  Speaker 2: a couple of centimeters to the back of the head.
• 40:55
  Speaker 2: That's where the subgenuale interior signal that is located. The
• 40:59
  Speaker 2: sub genuineteriors England is involved in the treatment of depression
• 41:02
  Speaker 2: because if people do deep brain stimulation, they lower some
• 41:06
  Speaker 2: electrodes into that area and start stimulating that pretty much
• 41:09
  Speaker 2: permanently in order to resolve your depression, which is very effective.
• 41:13
  Speaker 2: And then when we go to the back of the
• 41:15
  Speaker 2: head basically to the brain stem, there we have the
• 41:18
  Speaker 2: vagal nerve that will exit the brain and will be
• 41:21
  Speaker 2: going to your heart but also to the gut as
• 41:25
  Speaker 2: well as the heartbreak access bas And we also know
• 41:29
  Speaker 2: that when we take this vagal nerve and we encapsulate
• 41:31
  Speaker 2: it by an electrode and we start stimulating that called
• 41:34
  Speaker 2: vague nerve stimulation, that can also be a very powerful
• 41:38
  Speaker 2: antidepressant treatment. So we know that these three notes ranging
• 41:42
  Speaker 2: from the cortex to subcortical areas to the brain stem,
• 41:47
  Speaker 2: that there's the whole network that's being aligned that's functional,
• 41:51
  Speaker 2: has some functionality in the bet officienology of depression, and
• 41:55
  Speaker 2: indeed therefore mediates a heart rate heart friability heart with
• 42:00
  Speaker 2: friability levels. But also there's a big cross start between
• 42:03
  Speaker 2: cardiovascular disease and depression. People that experienced cardi vascular accidents
• 42:09
  Speaker 2: are more likely to develop a depression and people with
• 42:12
  Speaker 2: depression are more likely to develop cardiovascular accidents. So there's
• 42:16
  Speaker 2: a lot of overlap between those two networks. And that's
• 42:20
  Speaker 2: basically the network that we utilize. So imagine that the TMS.
• 42:24
  Speaker 2: We always thought that the TMS we're only stimulating local
• 42:27
  Speaker 2: focal areas. Not true. We're stimulating a prefont area and
• 42:32
  Speaker 2: the stimulation pattern that we apply on your prefonted cortex
• 42:37
  Speaker 2: is a pattern that your vaguel nerve is responding to
• 42:40
  Speaker 2: with an identical stimulation pattern that we can read out
• 42:44
  Speaker 2: on your heart rate, So we can even tell by
• 42:47
  Speaker 2: using one protocol or the other. I can tell by
• 42:50
  Speaker 2: looking at your heart rate. Only I can tell which
• 42:53
  Speaker 2: producol you're stimulated with if you hit the right area.
• 42:56
  Speaker 2: And we've tested this because many colleagues share data with us,
• 42:59
  Speaker 2: heard great data, and we did not know who we
• 43:02
  Speaker 2: were dealing with. But by simply looking at the heart rate,
• 43:05
  Speaker 2: we could unblind clinical trials within ninety percent accuracy, so
• 43:10
  Speaker 2: we could tell like, this is real, this is faced
• 43:13
  Speaker 2: and by just looking at heart rates, So that's how
• 43:16
  Speaker 2: profound these effects are as well. We're not looking at
• 43:18
  Speaker 2: a small correlation. We're looking about something that you can
• 43:22
  Speaker 2: individually apply and tell on an individual level as well.
• 43:27
  Speaker 3: Is there I mean that that is just unbelievable. Is
• 43:30
  Speaker 3: there Is there anybody looking at or is there any
• 43:33
  Speaker 3: intention to then look at whether the gut microbiome is
• 43:37
  Speaker 3: being affected as well? Because the vegus nerve stimulates the
• 43:43
  Speaker 3: gut and I know it has an impact on the
• 43:45
  Speaker 3: gut microbiom. I mean, anybody who has had had arable
• 43:49
  Speaker 3: bowel syndrome from stress knows that body brain and connection.
• 43:54
  Speaker 3: And we know that eating a shit do and changing
• 43:57
  Speaker 3: your microbiome can influence your brain function and drive depression
• 44:01
  Speaker 3: as well. So is there anybody looking at that or
• 44:04
  Speaker 3: is there any plans to look at the whether the
• 44:07
  Speaker 3: gut microbound was playing a role?
• 44:09
  Speaker 2: Well, very spot on. I mean two aspects there. I
• 44:12
  Speaker 2: think looking at the heart, brain, gut access. Some of
• 44:18
  Speaker 2: our colleagues in at Burn University in Switzerland are currently
• 44:21
  Speaker 2: running a study where they look at that, where they
• 44:24
  Speaker 2: look at TMS applied to the cortex, look at hardware changes,
• 44:27
  Speaker 2: but also looking at the electro gastrogram, which is like
• 44:31
  Speaker 2: the measuring the very slow electrical activity of the gut.
• 44:35
  Speaker 2: So that's one group that's the first kind of research
• 44:38
  Speaker 2: to see if that type of top down stimulation is
• 44:42
  Speaker 2: also arriving in the gut as the first first step,
• 44:45
  Speaker 2: but I think also a second step is that there's
• 44:47
  Speaker 2: a lot of overlap between the vegel system and vegel
• 44:50
  Speaker 2: integrity on one hand in immune function, and we know
• 44:54
  Speaker 2: inflammatory marks also highly elevated in subgroups of the PRESS
• 44:58
  Speaker 2: patients and to get with another group in Germany, they
• 45:02
  Speaker 2: are also looking at using hardware and coupling to tease
• 45:06
  Speaker 2: out how that relates to possible anti inflammatory effects or
• 45:10
  Speaker 2: inflammation in general. So yes, for sure this technique is
• 45:15
  Speaker 2: getting more widely available. It's very easy to do obviously,
• 45:18
  Speaker 2: but as multiple people currently diving into.
• 45:21
  Speaker 3: This much deeper and Martin, so just to clarify for
• 45:26
  Speaker 3: our listeners who may have miss missed that the immune system.
• 45:31
  Speaker 3: The reason why this is important is that about the
• 45:34
  Speaker 3: eighty percent of your immune system resides in the gut
• 45:37
  Speaker 3: because basically that barrier between the micoso barrier is the
• 45:45
  Speaker 3: last barrier between the outside world and the inside world
• 45:48
  Speaker 3: essentially and is a very easy way for pathogens to
• 45:52
  Speaker 3: get into our system. Hence, if people have an irritable
• 45:56
  Speaker 3: bile they can develop or they have leaky got they
• 45:59
  Speaker 3: can develop.
• 46:00
  Speaker 1: All sorts of autoimmune disorders.
• 46:01
  Speaker 3: So not only do so, these magnets then are applied
• 46:07
  Speaker 3: to the head, stimulating brilliant tissue and pathways that then
• 46:12
  Speaker 3: through the activate the nervous system, have an impact on
• 46:16
  Speaker 3: the heart also then can impact on the gut and
• 46:19
  Speaker 3: potentially modulate the immune system just from placing magnets on
• 46:24
  Speaker 3: the head.
• 46:25
  Speaker 1: Who would have known not fifty years ago. It's crazy exactly.
• 46:29
  Speaker 2: But this is also a very very new information. And
• 46:31
  Speaker 2: also I think it testifies to the fact that brain stimulation,
• 46:36
  Speaker 2: where we saw that was very focal and only one effect.
• 46:38
  Speaker 2: We now see this a multitudes of potential mechanisms that
• 46:43
  Speaker 2: might impact and therefore treats various subgroups of people as well,
• 46:47
  Speaker 2: maybe people with an inflammatory subtype or people with a
• 46:51
  Speaker 2: brain connectivity issue that can And that's why I stated
• 46:55
  Speaker 2: before trying to already jump the gun and start thinking
• 46:59
  Speaker 2: about war working mechanism or what is affecting what is
• 47:02
  Speaker 2: the final common pathway like BD and F in my
• 47:05
  Speaker 2: view of jumping again, we first need to split understand
• 47:08
  Speaker 2: the subgroups much better before we can really talk about
• 47:12
  Speaker 2: a final common pathway or a working mechanism, et cetera.
• 47:16
  Speaker 2: Because here, again we had one treatment where we thought
• 47:18
  Speaker 2: we only had one effect, but we've also already isolated
• 47:21
  Speaker 2: here a couple of potential mechanisms in how the press
• 47:26
  Speaker 2: of symptoms could be mediated, whether anti inflammatory, whether from
• 47:30
  Speaker 2: brain connectivity, et cetera.
• 47:32
  Speaker 3: Wow, that is just astounding. Let's not jump and talk
• 47:37
  Speaker 3: to ADHD. I have often said to people that if
• 47:45
  Speaker 3: your diet is shit, and you don't sleep well, and
• 47:49
  Speaker 3: you don't exercise well, and you will probably feel an
• 47:55
  Speaker 3: IDIOHD example. And what's your view on the lifestyle factors
• 48:02
  Speaker 3: playing into ADHD and this explosion that we are seeing
• 48:08
  Speaker 3: in ADHD diagnosis? And I'm not going to ask you
• 48:13
  Speaker 3: to put a figure on it, but is at least
• 48:17
  Speaker 3: some of that mediated by poor lifestyle?
• 48:22
  Speaker 2: Very good question. Well, lifestyle for sure, although I cannot
• 48:26
  Speaker 2: cover all aspects of lifestyle. I think there's one important one.
• 48:29
  Speaker 2: I was trained as in sleep medicine for a while
• 48:34
  Speaker 2: as well during my studies, and I've always found sleep
• 48:37
  Speaker 2: very fascinating. And we spent about thirty percent of our
• 48:40
  Speaker 2: whole life in this state called sleep, so that must
• 48:44
  Speaker 2: have ripercussions in our daily function, especially I think in
• 48:48
  Speaker 2: psychiatry where Unfortunately, psychiatry and sleep medicine are to completely
• 48:53
  Speaker 2: isolated fields and they don't really talk to one another,
• 48:56
  Speaker 2: whereas in my field. In my view, is very important
• 48:59
  Speaker 2: because the symptom checklist for depression and for ADHD, there
• 49:03
  Speaker 2: is questions relating to sleep, asking about it but not
• 49:06
  Speaker 2: acknowledging it could be an ethological factor in causing such symptoms.
• 49:12
  Speaker 2: In depression, the most powerful treatment we have is sleep
• 49:16
  Speaker 2: deprivation treatment. You keep someone up all minds the depression
• 49:19
  Speaker 2: has gone next morning. Unfortunately, unfortunately, when they fall asleep again,
• 49:25
  Speaker 2: their depression pops back up. There's a way to mitigate it,
• 49:28
  Speaker 2: but that's a whole different discussion. So sleep plays a
• 49:32
  Speaker 2: very very crucial role in my views in psychiatry. So
• 49:36
  Speaker 2: with ADHD we stumbled on this quite accidentally. We have
• 49:40
  Speaker 2: been involved in a field called neurofeedback for quite a
• 49:43
  Speaker 2: long while I will not dwell on it too long.
• 49:45
  Speaker 2: There has a lot of pros and cons about that field,
• 49:47
  Speaker 2: and know myself as well, but one of the things
• 49:50
  Speaker 2: we observed at that time was that when we did
• 49:52
  Speaker 2: a specific protocol called sensory motorator neuro feedback, which can
• 49:56
  Speaker 2: also be used in sleep, people sleep problems. That's the
• 49:59
  Speaker 2: most free wequ report. A side effect people reported was
• 50:03
  Speaker 2: improving sleep, and we were treating a lot of people
• 50:05
  Speaker 2: with ADHD, and after a while we started using actigraphy
• 50:11
  Speaker 2: similar to Apple watches and all the devices we have
• 50:14
  Speaker 2: to quantify sleep these days, and we started actually putting
• 50:18
  Speaker 2: a magnifying glass and did saying like, well, what's happening
• 50:20
  Speaker 2: with sleep? And when we started doing it, we found
• 50:23
  Speaker 2: that many people with ADHD actually were presenting with what
• 50:28
  Speaker 2: we call sleep onset insomnia, having difficulty falling asleep or
• 50:33
  Speaker 2: falling asleep at a time way too late for someone's
• 50:37
  Speaker 2: age group bedtime, so to say, but also disrupted sleep
• 50:41
  Speaker 2: in very short sleep in the second half of night. Well,
• 50:44
  Speaker 2: to cut a long story short, there's actually quite a
• 50:46
  Speaker 2: lot of research available right now, also out of Australia,
• 50:51
  Speaker 2: there's some some groups looking at it. But I think
• 50:54
  Speaker 2: what we now know is that when you look at
• 50:56
  Speaker 2: the population of ADHD, about seventy to eighty percent eight
• 51:00
  Speaker 2: zero of people with ADHD suffer from something called sleep
• 51:04
  Speaker 2: onset insomnia, which means that they take longer to fall asleep.
• 51:08
  Speaker 2: And we also know that's pretty much related to melatonin
• 51:11
  Speaker 2: because Melatonin is a sleep hormone that starts slowly to
• 51:15
  Speaker 2: be released in your brain to make you fall asleep
• 51:19
  Speaker 2: more likely to fall asleep, and that rhythm is often
• 51:22
  Speaker 2: delayed in ADHD. So not only do we have the
• 51:25
  Speaker 2: behavioral symptom of difficulty falling asleep, we also know that
• 51:29
  Speaker 2: the sleep hormone is significantly delayed for a couple of
• 51:32
  Speaker 2: hours in people with ADHD. So what we're seeing is
• 51:36
  Speaker 2: that these many people with ADHD. Basically, especially if we
• 51:42
  Speaker 2: focus on children, school times are the same for everyone,
• 51:45
  Speaker 2: but if you fall asleep two hours later, you are
• 51:48
  Speaker 2: chronically missing out on two hours of sleep per night.
• 51:52
  Speaker 2: So how can we link that to behavior? Well, that's
• 51:55
  Speaker 2: very simple. A lot of research has been done in
• 51:57
  Speaker 2: the United States, for example, with very simple question, if
• 52:00
  Speaker 2: we send our people out to a war zone, can
• 52:03
  Speaker 2: they do well with less sleep? And so they've done
• 52:06
  Speaker 2: a lot of sleep restrictions, that is, chronically sleep restricting
• 52:10
  Speaker 2: completely healthy people and measuring the consequences. Well, the very
• 52:13
  Speaker 2: simple answer is no, they cannot do with less sleep.
• 52:16
  Speaker 2: So they've taken healthy people and if you measure something
• 52:19
  Speaker 2: called the PVT lapses, which is like a neuside test,
• 52:23
  Speaker 2: you then observe how often they have lapse of attention.
• 52:27
  Speaker 2: Then people were submitted to sleeping eight hours for two weeks,
• 52:31
  Speaker 2: six hours or four hours, and there was also a
• 52:34
  Speaker 2: group of people that were not allowed to sleep at
• 52:36
  Speaker 2: all for two nights because you can't extend that much longer.
• 52:40
  Speaker 2: So after two weeks of sleep restricting people to let's
• 52:44
  Speaker 2: take the six hour example, and I think many people
• 52:47
  Speaker 2: listening to your show will say like, well, that's me.
• 52:50
  Speaker 2: Some people are proud of it. Personally, I would not
• 52:52
  Speaker 2: be too proud of it. And basically after two weeks,
• 52:55
  Speaker 2: their concentration would be as that after two weeks as
• 53:02
  Speaker 2: the people that did not sleep at all for two nights,
• 53:05
  Speaker 2: with the very big difference. If you ask them like,
• 53:08
  Speaker 2: how are you performing? How are you functioning, they would
• 53:10
  Speaker 2: say I'm doing fine. So sleep restriction is really a
• 53:15
  Speaker 2: silent killer because without you being aware of it, without
• 53:19
  Speaker 2: you knowing it, your cognitive performance, your working memory, your
• 53:23
  Speaker 2: concentration will significantly deteriorate after two weeks to a level
• 53:30
  Speaker 2: quite similar to someone being sleep deprived for two nights
• 53:34
  Speaker 2: you are not aware of it, and also recovering from
• 53:37
  Speaker 2: sleep debts, you can go to a bank and borrow money.
• 53:40
  Speaker 2: But your body is even worse than a bank. If
• 53:43
  Speaker 2: you build up a sleep debt, you need to pay
• 53:46
  Speaker 2: back your sleep debt. If you don't pay it back
• 53:48
  Speaker 2: in time, you will be suffering in terms of cognition,
• 53:52
  Speaker 2: et cetera. So the sleep debt that has been gradually
• 53:56
  Speaker 2: building up over two weeks, you need to pay it off,
• 53:58
  Speaker 2: and it takes often the same amount of time before
• 54:02
  Speaker 2: you have paid back the sleep debt. So it's not
• 54:04
  Speaker 2: true that sleeping in on the weekend for one or
• 54:06
  Speaker 2: two nights, which really is not like the same quality
• 54:09
  Speaker 2: of sleep that you've been lacking off. But that's not enough.
• 54:14
  Speaker 2: You need to have a consistent amount of sleep, which
• 54:17
  Speaker 2: is really between seven to nine hours for the majority
• 54:20
  Speaker 2: of people. So with this model, we now understand that
• 54:24
  Speaker 2: if people are missing out in two, one or two
• 54:27
  Speaker 2: hours of sleep every night, their concentration in school will
• 54:31
  Speaker 2: be disadvantage will be at a lower level. We also
• 54:35
  Speaker 2: understand that if you and I would have that night
• 54:37
  Speaker 2: of bad sleep for multiple times we're driving a car,
• 54:40
  Speaker 2: we know the likelihood of an accident increase. So what
• 54:43
  Speaker 2: do we do. We take a red bull? So what
• 54:45
  Speaker 2: are we doing with the kids we're prescribing psycho stimulant
• 54:48
  Speaker 2: medication like metal vanidades, which we know will improve their
• 54:54
  Speaker 2: neuropsych function at that time, but it's not a cure
• 54:57
  Speaker 2: for their symptoms. The cure you will need to seek
• 55:00
  Speaker 2: into the sleep promote moting effects and sleep enhancement effects.
• 55:06
  Speaker 2: And this is really I think complementing the whole circle
• 55:09
  Speaker 2: in how we understand how one lifestyle effactor. Imagine if
• 55:13
  Speaker 2: we focus on all the other ones, but things like
• 55:15
  Speaker 2: sleep can explain the behavior. And also the high peractivity
• 55:20
  Speaker 2: is very easily explained as well because people you probably
• 55:23
  Speaker 2: have observed small children and when they need when they're
• 55:26
  Speaker 2: approaching that a bad time, they're running around like crazy,
• 55:29
  Speaker 2: which is a compensateory behavior to keep yourself awake, and
• 55:33
  Speaker 2: so it's an utter regulatory behavior. And therefore the whole
• 55:38
  Speaker 2: symptom domain of ADHD can be for a maturity of people,
• 55:42
  Speaker 2: not for everyone, but for many people can be explained
• 55:45
  Speaker 2: by not getting enough sleep. So remember then, a small
• 55:50
  Speaker 2: rewind we came from the biological clock, this melotone in
• 55:54
  Speaker 2: transcription being coming up too late, So how can we
• 55:59
  Speaker 2: understand that, Well, there's many environmental influences these days, like
• 56:03
  Speaker 2: blue lights, iPads, big screens very close to your eyes
• 56:09
  Speaker 2: that are emitting a lot of blue light, and we
• 56:12
  Speaker 2: know that this blue light can acutely suppressure melatonin. On
• 56:17
  Speaker 2: the other hand, the biggest source of blue light is sunlight,
• 56:22
  Speaker 2: and when you have a jet leg, the best way
• 56:24
  Speaker 2: to beat your jet leg is get out and get
• 56:27
  Speaker 2: enough sunlight so you resynchronize again. So we know that
• 56:30
  Speaker 2: there's like a balance between blue leg exposure in the
• 56:33
  Speaker 2: evening on one hand, but especially getting enough sunlight in
• 56:37
  Speaker 2: the morning that will resink your brain. So we've published
• 56:41
  Speaker 2: one study and I think there might be a couple
• 56:43
  Speaker 2: of graphs online about it, where we've looked at the
• 56:46
  Speaker 2: prevalence rate of ADHD in the United States and the
• 56:50
  Speaker 2: amount of sunlight you get throughout the US as so
• 56:54
  Speaker 2: basically a map where do I need to put my
• 56:56
  Speaker 2: solar panels. So we merit these two maps. Could find
• 57:00
  Speaker 2: that the amount of sunlight in California, for example, relative
• 57:04
  Speaker 2: to New York, would explain twenty five percent of the
• 57:08
  Speaker 2: prevalence rates in ADHD. So this is way more than
• 57:12
  Speaker 2: the current geogenetic influences we have found. And we've replicated
• 57:16
  Speaker 2: this now about three to four times, and it still
• 57:19
  Speaker 2: holds for mainland Europe in the US. It does not
• 57:24
  Speaker 2: hold for Nordic countries like Scandinavia. That's a whole different story.
• 57:28
  Speaker 2: Probably has to do with genetic differences in people being
• 57:32
  Speaker 2: more protected against low levels of sunlight because they're close
• 57:36
  Speaker 2: to the north.
• 57:38
  Speaker 1: They're adapted in some way.
• 57:41
  Speaker 2: So again the conclusion should not be takeaway all these iPads,
• 57:44
  Speaker 2: et cetera. Prohibition is something that I'm not a big
• 57:47
  Speaker 2: fan of as a Dutch Dutchman. But get people, get
• 57:51
  Speaker 2: people out in the sunlight. If you have your child
• 57:54
  Speaker 2: and you have a dog, well ask your child to
• 57:56
  Speaker 2: walk the dog in the morning. And you know the
• 57:59
  Speaker 2: story about where often they would say in classrooms like
• 58:02
  Speaker 2: well that hyperactificate kids, don't put it close to the
• 58:06
  Speaker 2: window because you will get distracted. Now we need to
• 58:09
  Speaker 2: invert it and say, well, yes, put that kid near
• 58:12
  Speaker 2: to the window, because they will get more sunlight catching
• 58:15
  Speaker 2: their eye and they will normalize. They're more lightly to
• 58:18
  Speaker 2: normalize their sleep in the morning. So more in the
• 58:20
  Speaker 2: early morning sunlight I think is a very important thing.
• 58:23
  Speaker 2: It's not going to cost the thing, it doesn't have
• 58:25
  Speaker 2: any side effect, it's not going to work for everyone,
• 58:27
  Speaker 2: but it might at least have some improvements. And if
• 58:30
  Speaker 2: at least twenty to forty percent of the people will
• 58:33
  Speaker 2: sink below the clinical threshold and not have a diagnose
• 58:36
  Speaker 2: of ADC, then I think we've won a lot already.
• 58:40
  Speaker 2: And also, I'm not advocating against medication. It's the most
• 58:44
  Speaker 2: powerful psychiatric treatment we have available, but I do think
• 58:50
  Speaker 2: that for many people we need to zoom in more
• 58:53
  Speaker 2: on sleep. Psychiatrists need to do their work better and
• 58:57
  Speaker 2: ask more questions about sleep, and maybe wearables use some
• 59:02
  Speaker 2: sleep red questionnaires to see if there's an other explanation
• 59:07
  Speaker 2: they can find for the symptoms, which is according to
• 59:09
  Speaker 2: the deism, they need to ask those questions. But most
• 59:13
  Speaker 2: people are simply too unfamiliar with sleep medicine to do
• 59:16
  Speaker 2: it an objective fashion.
• 59:18
  Speaker 3: That is unbelievable that it explains twenty five percent. And
• 59:22
  Speaker 3: to your point, you're not saying we shouldn't be medicating,
• 59:25
  Speaker 3: but if a chunk of these people don't actually need
• 59:29
  Speaker 3: to be on the medication, if we can prevent them
• 59:33
  Speaker 3: going into that, that is clearly the way ahead. And
• 59:38
  Speaker 3: you know, I'm sure nobody's done the study yet, but
• 59:41
  Speaker 3: I would be willing to bet my house, my business,
• 59:46
  Speaker 3: and pawn my children on the idea that if you
• 59:49
  Speaker 3: also improve people's diet and getting them exercising, especially outdoors,
• 59:55
  Speaker 3: we would see a significant drop in those symptoms, particularly
• 59:59
  Speaker 3: when we we see some of the data coming out
• 1:00:01
  Speaker 3: that American and Australian kids are spending ninety percent of
• 1:00:08
  Speaker 3: their time indoors, right. And you know, we have these
• 1:00:13
  Speaker 3: circadian rhythms for a reason, and most people don't realize, Martin,
• 1:00:16
  Speaker 3: lots of your hormones run off circadian biology as well.
• 1:00:20
  Speaker 3: So it's not just the sleep, it's the widespread effect
• 1:00:25
  Speaker 3: throughout that biological system that is the human being that
• 1:00:29
  Speaker 3: is hugely important. So this has been absolutely fascinating. I
• 1:00:34
  Speaker 3: could talk for hours about this, but before I do,
• 1:00:37
  Speaker 3: let you go. I know you're involved in a number
• 1:00:41
  Speaker 3: of spinoff ventures where you're actually taking this research technology
• 1:00:45
  Speaker 3: and applying it. Tell me about some of the stuff
• 1:00:49
  Speaker 3: that you're doing that you're finding quite exciting now for
• 1:00:52
  Speaker 3: the future.
• 1:00:54
  Speaker 2: Well, A Currently, we've had a couple of spin offlight like,
• 1:00:57
  Speaker 2: for example, the Whole Clinic where we by any it's
• 1:00:59
  Speaker 2: the TM since says what spun out as newer care group.
• 1:01:04
  Speaker 2: I think they also have clinics in Melbourne, Sydney, across
• 1:01:06
  Speaker 2: Europe and across the US as well, which I think
• 1:01:09
  Speaker 2: was quite exciting. Recently we also span out the EG
• 1:01:15
  Speaker 2: Prognostics department to Shineida where we do the stratification to
• 1:01:20
  Speaker 2: treatments using EG actually, so that also has basically, yeah,
• 1:01:25
  Speaker 2: given me a lot of time and then to think
• 1:01:28
  Speaker 2: about new things. I'm currently we see where the new
• 1:01:32
  Speaker 2: science is going to bring me some doing a sabbatical
• 1:01:34
  Speaker 2: currently at Stanford University on one end, wanting to learn
• 1:01:37
  Speaker 2: more about psychedelics, which I think is a really fascinating field,
• 1:01:41
  Speaker 2: and on the other hand, still pushing the research at
• 1:01:43
  Speaker 2: brain Clean's Foundation and collaboration with many partners on the
• 1:01:47
  Speaker 2: heart brain coupling. I think there's heart brain coupling to
• 1:01:50
  Speaker 2: form TMS is a very fascinating field. So that's mostly
• 1:01:54
  Speaker 2: the stuff that we're trying to focus on at this
• 1:01:56
  Speaker 2: point in time.
• 1:01:59
  Speaker 1: That is some very cool stuff right there. I'll tell
• 1:02:03
  Speaker 1: you what.
• 1:02:03
  Speaker 3: When I was a kid, I always admired explorers, and
• 1:02:08
  Speaker 3: there's not much exploration left to do in terms of
• 1:02:11
  Speaker 3: geographical exploration.
• 1:02:13
  Speaker 1: But oh my god, are you in an area where there's.
• 1:02:16
  Speaker 3: A lot of exploration to be done, and you're doing
• 1:02:19
  Speaker 3: some very very cool stuff. So so Martin, I tip
• 1:02:26
  Speaker 3: my hat to you, sir, and I love everything that
• 1:02:30
  Speaker 3: you've talked about here, the stuff that you're doing, it
• 1:02:32
  Speaker 3: is super exciting and hopefully that time in your sabbatical
• 1:02:37
  Speaker 3: spike some new neuronal connections and you'll be off onto
• 1:02:41
  Speaker 3: your next venture.
• 1:02:43
  Speaker 2: Looking forward to that.
• 1:02:45
  Speaker 3: And where can people find out more about you? If
• 1:02:47
  Speaker 3: they want to just look at your work words the
• 1:02:49
  Speaker 3: beggst place to send them.
• 1:02:58
  Speaker 2: The best place to look at this our website, which
• 1:03:01
  Speaker 2: is brain clinics dot com so brain Clinics plural. Also
• 1:03:06
  Speaker 2: on LinkedIn, you can find my profile and connect me
• 1:03:08
  Speaker 2: via LinkedIn or reach out via email whenever people prefer. Now,
• 1:03:13
  Speaker 2: for those of those people that have an interest in TMS,
• 1:03:15
  Speaker 2: we have an upcoming TMS masterclass end of September beginning
• 1:03:20
  Speaker 2: of October where we invited some of the world leading
• 1:03:23
  Speaker 2: experts with very new insights on TMS. Some people are
• 1:03:27
  Speaker 2: doing TMS in one day rather than spreading out across
• 1:03:31
  Speaker 2: multiple days. Many new innovations will be shared. So for
• 1:03:36
  Speaker 2: those interested to do real deep dive, we have this
• 1:03:39
  Speaker 2: master glass coming.
• 1:03:39
  Speaker 3: Up excellent Martin, thank you for your time. This has
• 1:03:43
  Speaker 3: been awesome.