The Art of Manliness - #585： Inflammation, Saunas, and the New Science of Depression

00:00:00.000 brett mckay here and welcome to another edition of the art of manliness podcast i've dealt with

00:00:11.440 depression in my life my body temperature also seems to run hot in fact my wife kate has nicknamed

00:00:16.340 me the baked potato my guest today says there may be a connection between those two things

00:00:20.840 name is charles razan he's a psychiatrist professor of psychiatry and the co-author of

00:00:24.660 the new mind body science of depression we begin our conversation with why charles thinks it's

00:00:28.520 important to ask the question does major depression even exist and what we do and don't

00:00:32.340 know about what causes depression we then turn to the emerging theory that physical inflammation may

00:00:36.560 play a role in depression charles describes what inflammation is and why the body may become

00:00:40.620 inflamed and physically hotter not only in response to physical illness but psychological stress as

00:00:44.980 well we then discuss the paradoxical finding that short-term exposure to inflammation in the form of

00:00:49.340 exercise or sitting in a sauna can reduce long-term inflammation and how hot you probably have to get

00:00:53.700 in a sauna for to have antidepressant effects we also talk about how intermittent fasting may have

00:00:58.300 a beneficial effect on inflammation before turning to whether taking anti-inflammatory drugs could

00:01:02.520 also help and why you might want to get a blood test to see if your body's inflamed we enter

00:01:06.100 conversation with charles thoughts on how to figure out the right treatment for depression for each

00:01:09.680 individual after the show's over check out the show notes at aom.is slash inflammation depression

00:01:14.320 all right dr charles razan welcome to the show

00:01:27.720 thank you for having me so you're a psychiatrist you're at the university of wisconsin and you got

00:01:33.100 this book out called the new mind body science of depression i really enjoyed it it's basically

00:01:38.500 having like all the latest research about depression in like one place but tell us about your background

00:01:43.740 and like what's the approach you take at looking at depression and treating depression

00:01:48.320 yeah so i am a psychiatrist and i started life actually as a full-time clinician back in the 90s

00:01:56.380 and i got more and more interested in doing research and was very interested always sort of interested in

00:02:01.580 mind body stuff and questions around you know consciousness and conscious experience things that

00:02:07.720 are sort of very au courant right now that were a little bit more on the fringe i think when i was

00:02:12.880 interested in these things but i actually became a researcher to try to understand how bodily

00:02:18.580 processes might be harnessed to enhance mental states i was really interested in certain very

00:02:25.000 advanced tibetan buddhist meditation practices so i became a researcher and and spent a number of

00:02:30.660 years looking at how inflammation produces depression and how inflammatory processes how they alter the

00:02:37.700 brain and i was always kind of a depression guy but one of the implications of this was that you know

00:02:44.340 if inflammation can cause depression maybe if we use one of these really powerful anti-inflammatory

00:02:49.860 cytokine blockers that are out now for treating things like psoriasis and such that maybe if we did

00:02:54.620 that we would discover a brand new antidepressant and as it turned out that wasn't true there's an

00:02:59.760 interesting story there but that got me into the the sort of business of of trying to discover new

00:03:05.820 treatments for depression in general and especially old new treatments so a lot of the work i do these

00:03:11.200 days is is not just inflammation but looking at things i call ancient practices things that humans

00:03:16.680 discovered repeatedly across history often used for spiritual purposes or healing purposes that i'm

00:03:22.720 trying to retrofit and look at as antidepressant strategies so we've done work with with heat with

00:03:28.140 hyperthermia and i'm much involved in this movement currently to see if psychedelic medicines might have

00:03:33.840 promised for the treatment of depression so long answer to a short question but that that's pretty

00:03:38.800 much who i am yeah that's the way i discovered you is your research about the connection between

00:03:43.300 inflammation and depression we'll get in that to the bit because that's it's novel it's different a

00:03:47.040 lot of people don't connect inflammation and depression so we'll get that here in a bit but let's start

00:03:51.460 off with this question in the beginning of your book the new mind body science of depression you

00:03:56.380 start the book off with your co-author with this provocative question

00:03:59.400 does major depression even exist and i'm sure there's people who are listening to this episode

00:04:04.760 who have experienced major depression or know someone who has so they're probably thinking well

00:04:09.140 this is a really silly question of course it does but why do you think it's important as a depression

00:04:13.860 researcher that you ask that basic question yeah it's a key question and i've been depressed myself

00:04:18.860 so i'm right with them so you know my co-author vlad malatek he's also very eloquent about this

00:04:24.540 and there's a couple of ways in which depression doesn't exist it doesn't exist as a single thing

00:04:32.660 that's for sure right so we know in fact in the largest antidepressant study ever done they went

00:04:38.140 back and looked at sort of the different patterns of symptoms people could have they had like 4 000

00:04:43.520 people in the study and they had like 2 000 different presentations so in a 4 000 person group there

00:04:49.120 like 2 000 sort of different depressions and if you look at how you know there's this thing called

00:04:54.760 the dsm which is the guidebook for mental health and it lays out the criteria for depression you got

00:04:59.860 to have five out of nine symptoms well that means actually that you could two people could be depressed

00:05:05.180 and share one symptom in common and have everything else different so that's the first thing is that

00:05:10.260 it doesn't exist as a single thing the second thing is that there have been a lot of studies that

00:05:16.280 that suggest i think rightly that on average depression tends to be associated with certain

00:05:22.640 changes in the way the brain and the body function but there's no one thing that causes depression

00:05:29.040 right so for instance you know if you got type 1 diabetes the reason you got type 1 diabetes is

00:05:34.280 because there's these cells in your pancreas that make insulin called you know beta cells and they get

00:05:39.020 wiped out right and if you wipe out the beta cells you got type 1 diabetes that's what it is

00:05:43.960 there's nothing like that for depression right there's no single abnormality that all depressed

00:05:48.640 people have to have or is there an abnormality that that causes depression in all people so

00:05:54.060 it's not a disease state that way it may be a thousand different disease states each one very specific and we

00:06:02.180 just can't find them or it may be that there's a thousand little contributors and on average to any

00:06:08.100 given person's depression biological contributors so you know if you say well so what is depression

00:06:13.720 well i like the question because it's also not true that it just flat out doesn't exist it does

00:06:21.240 exist it kind of exists the way buddhists think the world exists which is sort of conventionally and

00:06:26.320 provisionally depression is a is a set of symptoms and it's a disorder that's characterized by people

00:06:34.160 demonstrating or reporting a series of symptoms you know much the way most 19th century diseases

00:06:39.520 were right so you look at things like pleurisy and lumbago and things like this they were symptom

00:06:44.540 based diseases and that that's what depression is so you know for instance people often want to try

00:06:50.720 to find a biomarker for depression you know some kind of blood test but you know even a little bit

00:06:55.980 of thought shows that that's kind of a fool's errand because you know if if the biomarker was

00:07:01.440 absolutely positive but you felt great no doctor would say you're horribly depressed you just don't

00:07:06.260 know it and conversely if the biomarker was normal but you're suicidal and depressed nobody would say

00:07:11.000 well you can't be depressed the biomarker's off right depression is a phenomenological condition

00:07:16.620 it it it is as it does and as it says now having said that i said it's not nothing either it is a

00:07:24.480 tendency it's like a cloud it's like a quantum cloud right that so you know if you get really depressed

00:07:30.800 if your mood gets really down you're very likely to pull in the other symptoms of depression that

00:07:37.040 that's how they came to form the disorder so almost always when humans get catastrophically depressed

00:07:42.620 they get changes in their sleep they get changes in their appetite they start having trouble thinking

00:07:47.200 they often are exhausted they they begin to think about suicide all over the world even in like

00:07:52.440 hunter-gatherer tribes this is the case right so what i sometimes say is you know if people want my

00:07:57.620 opinion so what is depression i like to say that it is the most standard most common way that human

00:08:06.600 beings break down under adversity and that is why you see depression in every culture that's why

00:08:13.500 depression tracks both with personal adversity and and societal adversity and why it tends to have the

00:08:20.440 same symptoms all over the world because it it it is you know we have a genetic heritage that that all

00:08:28.020 of us to one degree or other uh makes us susceptible to developing this syndrome when uh when bad things

00:08:34.580 happen to us let's talk about the causes of depression at least the the common explanations that are put out

00:08:39.840 there for the causes of depression what are those well you know so it's really interesting the the official

00:08:45.900 line in the field is that we we don't know what causes depression because we don't know what causes

00:08:50.780 any psychiatric illness right but you know that's actually not true and and this is something i make

00:08:56.180 we make much of in the book you know like other illnesses like other psychiatric illnesses actually

00:09:01.940 like a lot of other medical illnesses depression seems to arise usually from a an interaction between a

00:09:07.940 genetic vulnerability and an environmental circumstance and so that being the case you know you know there's

00:09:15.060 this idea that depression is just sort of a brain disorder or it's a you know neurotransmitter deficiency

00:09:20.800 or something well those sorts of ideas suggest that you know there should be a gene and if we know what the

00:09:25.820 gene was then you have the answer and we really have not been able to find genes very well it wasn't until

00:09:32.080 a couple years ago maybe a year ago that we actually finally had a study with enough people in it

00:09:37.080 to find reliably a risk factor gene for depression i mean there have been a lot of studies looking at

00:09:43.960 genes for depression but they were all very flawed so we don't really know very much genetically about

00:09:49.520 what causes depression but on the other hand we know exactly what causes depression environmentally

00:09:54.480 and this just it fascinates me and it has to do with what we were talking about a minute ago and that

00:09:59.180 is adversity right so the things so so if if depression is a genetic environmental interaction

00:10:06.300 it suggests that there's some people that may be so genetically protected that that there isn't an

00:10:11.400 environment in the world that make them depressed and other people are so genetically vulnerable

00:10:15.860 whatever those genes are that they're you know that the world is definitely going to make them

00:10:19.940 depressed because the world's a hard place right but when it comes to environmental causes of

00:10:24.060 depression it's really adversity it's it's psychosocial adversity and you know the thing that we've

00:10:29.500 studied a lot it's actually immunologic adversity right so one of the things i often say is that

00:10:35.460 at the end of the day depression really seems to be about managing relationships it certainly it

00:10:41.060 certainly is about relationships it it is the it is disturbances and threats in our relationships of

00:10:47.460 all kinds that most reliably produce depression so you know in this in the human realm things that

00:10:54.440 that are powerful depressogenic factors are losing somebody upon whom your self-esteem yourself

00:11:00.160 self-vision requires it's being shamed it's losing it's losing in encounters when you're up against

00:11:06.680 somebody what they call agonistic encounters if you're in a competition and you lose

00:11:10.040 all these things that essentially at the end of the day anything that tells a person and they believe it

00:11:16.140 that they're a failure that they're a loser that they're not as good as other people

00:11:19.580 that they're alone that they they're not they're inadequate to life all anything in the environment that does

00:11:26.320 that really reliably increases the risk for depression and then there's this thing called

00:11:31.320 entrapment and entrapment is this sense that you're powerless to uh to change your circumstances right

00:11:38.380 and so you know if you're in a situation say where you have an abusive spouse and you're getting beaten

00:11:44.880 up you're very very likely to be depressed because interpersonal conflict is a very powerful depressive

00:11:49.840 driver if you feel that you could never escape the relationship you will be depressed right

00:11:54.260 so that's the sort of other element so so those factors are very very powerful depressogens in our

00:12:01.420 human human interactions but you know we are just a small part of the interdependent world in which we

00:12:08.040 live and we have such a powerful and intimate relationship with the microbial world because it's very small we

00:12:15.760 often miss it but but our relationship with the bugs with bacteria parasites viruses is as powerful

00:12:23.440 a factor in our emotional mental well-being as our relationships with other people you know because

00:12:29.480 of course how we handle those microbial agents really you know sort of dictates whether we're going to live

00:12:36.220 or die especially across human evolution where death from infection was by far the number one cause of

00:12:42.460 you know sort of failing to survive and reproduce so because of that of course you know any genes that

00:12:48.280 evolved that that that mutated to provide us with sort of an enhanced ability to fight dying of

00:12:54.740 infection especially early in life were selected and it turns out just one of the things we've argued

00:12:59.580 that those those genes or those behaviors actually appear to have some benefit in in fighting infection

00:13:05.960 so you know and then of course the other aspect of the microbial world has to do with the good bacteria

00:13:11.440 if i can put it that way right so you know we are largely composed of bacteria and we have one of

00:13:18.640 the one of the causes that some of us speculate may be driving the increased depression in the modern world

00:13:24.700 is the fact that we've so disrupted our our sort of co-evolved relationships with this huge microbial

00:13:32.240 world upon which we depended for a number of things that those disruptions even though we don't

00:13:37.140 necessarily recognize them consciously may also be contributing to the the what seems to be a

00:13:42.340 something of an epidemic of depression in the modern world all right so there's a lot to unpack

00:13:46.500 there so i think there's you raise an interesting point the way you sound like the approach you take

00:13:51.140 it's against this mind body approach you're unifying mind and body because i think typically

00:13:56.020 the way most people think about depression it's like that cartesian split like there's the there's the

00:14:01.800 mind there's the mind and then there's the body so the sort of the people in the body camp would say

00:14:06.800 well depression is just a biological thing you've got something a genetic makes you have a propensity

00:14:11.860 towards depression you just have a chemical imbalance in your brain here take this prozac it'll

00:14:16.340 make you feel better and then on the mind side uh they say well no depression is just a matter of

00:14:21.840 cognition you've got faulty thinking if you go to therapy you can fix your thinking and fix your

00:14:26.740 depression sounds like what you're saying is that it's both like both things are going on yeah i was

00:14:31.580 going to say they're both they're both right uh they're both right and both perspectives are huge

00:14:37.540 have have significant clinical potential and and somehow neither one by itself is fully enough

00:14:43.900 i mean that's the crisis we're at in mental health care is that you know trying to find ways

00:14:49.160 to marry those two things together to leverage the strength of each perspective or each you know

00:14:54.960 each system of causality if i can put it that way trying to find ways to marry these things

00:15:00.300 together is is something that a number of us working in the field are really really interested

00:15:04.400 in so because here's it was kind of walk through an example of the mind affecting the body and the

00:15:08.760 body affecting the mind so the mind affecting the body you have examples of social stressors you

00:15:13.840 experience some sort of defeat and you you know you think about it all the time everyone's had that

00:15:17.440 moment where they've had some sort of defeat in their life they lost a job they got rejected by

00:15:22.140 somebody and you just feel bad and you just think about it all the time and that's going to affect

00:15:26.480 your body correct right is that what you're saying yes okay and then the body parts like the body can

00:15:31.800 affect the mind by you get sick with some sort of something bacteria and it causes you to feel sad

00:15:38.880 and down in the dumps yes absolutely that's exactly right all right well let's talk about so let's i

00:15:44.960 want to this is this is really uh it's going to be hard to suss out because this is really interesting

00:15:49.600 because all this stuff it's it's happening all at the same time possibly right so it's not like yes and

00:15:54.180 in a loop right yeah in a loop right things go right so you know the mind affects the body the

00:15:58.560 body affects the mind which then affects the body you know and see you can get these circles going and

00:16:03.220 and and that's part of what we think probably happens in depression where people there's a lot of

00:16:07.500 evidence when you look at sort of patterns of brain functioning that that on average depression you

00:16:13.140 know kind of biologically one of its characteristics is that people have this sort of locked in pattern of

00:16:17.860 over activation in in areas that that are sort of fixated on danger fixated on the self and then

00:16:25.340 you you know you kind of ruminate you just same negative thoughts over and over and over again so

00:16:29.500 this this being trapped in circles is one of the characteristics of clinical depression okay so let's

00:16:36.640 let's talk about this talk about this let's get to your idea of cause of depression not the only cause

00:16:41.380 but a cause and that's inflammation so i think first we got to talk about what inflammation is i think

00:16:45.820 people have a sort of kind of basic understanding if you cut yourself the wound becomes inflamed it gets

00:16:51.460 red around there so let's let's dig a little deeper like what happens when your body becomes

00:16:57.660 inflamed yeah okay so right when i went to med school in the 80s you know and the immune system

00:17:02.580 was really just beginning to be figured out we thought inflammation was you know what you say hot

00:17:07.140 red painful rubor dolor calor it's kind of localized phenomena what what sort of you know it's sort of

00:17:13.820 street how it how it's seen just in popular culture but i think a better way to think about

00:17:19.140 inflammation step back and think about what happens when you get sick so think about you know here you

00:17:25.180 are and you've now just picked up an invading microorganism that the immune system thinks is

00:17:32.060 really a threat the hot red and painful finger when you got a splinter in it is because it's trying

00:17:37.200 to kill that invading thing right there at the source right but then you know let's say that

00:17:43.680 fails and now it's in your body so what are you going to do well it turns out the mammalian immune

00:17:49.280 systems especially human immune systems have two branches they have a branch called the innate

00:17:53.760 immune system and a branch called the acquired or adaptive immune system and they serve different

00:18:00.180 functions the innate immune system is what what gets fired off first so you you know your body sees

00:18:07.940 this dangerous thing and there's a part of your immune system that that recognizes it very

00:18:12.180 generally it just doesn't like foreigners basically right and seeing that the foreigner is there it

00:18:17.220 thinks the forest the foreigner is dangerous enough it pulls out a shotgun and starts firing

00:18:21.240 and what it fires are these very hot angry destructive chemicals called inflammatory cytokines

00:18:27.560 and they're pretty good at killing dangerous foreign things but they have a lot of collateral damage and

00:18:33.680 this is why inflammation over time is associated with things like heart attacks and strokes is

00:18:38.880 because it tears up the tissues of the body also it also makes you prone to diabetes and things like

00:18:44.480 that but you need this innate immune system it's it's it's sloppy it's imprecise but it's very fast

00:18:51.560 and there are unfortunate children born without functioning innate systems and they're dead within a

00:18:56.380 week or two so you got to have it because otherwise you're not fast enough off the draw to fight

00:19:00.980 these dangerous pathogens but we've also evolved this other immune system is acquired or adaptive immune

00:19:06.780 system and this is what people usually mean when they talk about the immune system which is that

00:19:10.480 antibodies and t-cells and things like that and and this is a really an amazing thing and what it

00:19:16.480 basically what it is is that your body produces you know billions billions of immune cells b-cells

00:19:23.740 and t-cells each one of them just randomly has a slightly different pattern on its surface

00:19:28.160 and that pattern just randomly may or may not recognize a pattern on a bacteria or a virus

00:19:34.180 but you know these cells kind of float around in your body and when they see that virus or bacteria if

00:19:41.040 it's the right cell it activates and this the the shotgun immune system the innate immune system

00:19:46.200 plays a key role in presenting the the dangerous bacteria cells to those antibody cells and those t-cells

00:19:54.880 so when those guys get activated they um they produce a ton of killer modalities that is they're like

00:20:02.300 snipers they be they only fire at cells that have that mark on them and that mark generally is not

00:20:09.760 on human cells it's generally on the only on that virus only on that bacteria that's invaded your body

00:20:15.800 so it's able to completely kill the bacteria or the virus and not cause you any trouble now every once in a

00:20:21.560 while there's a screw-up and the t-cells or the b-cells mistake something in your body for a bacteria

00:20:26.680 or a virus and when that happens you get an autoimmune condition like type 1 diabetes or

00:20:31.540 multiple sclerosis or something like that it's you know that's why that happens but when things

00:20:35.600 function well what happens you get this early shotgun immunity that is that is fast and sloppy and just

00:20:42.740 shoots at everything but it activates this sniper-like immune system that takes four to five days to

00:20:49.080 operate to come up to steam and but once that system's activated the inflammation should die down

00:20:54.480 and these very specific sniper cells should take out the the pathogen and then when they're done

00:20:59.960 doing that instead of all vanishing once your body has seen a particular virus or bacteria the the

00:21:05.660 specific cells that multiplied by the millions and billions they don't all die a little army of them

00:21:11.440 stays in the body they're called memory t-cells and those cells patrol around and if they ever see

00:21:16.520 that invading organism again they can immediately ramp up like a million times faster that's how vaccines

00:21:22.160 work right they leave you with this little army of memory t-cells for hopefully the flu or for you

00:21:26.800 know measles or whatever so when we say inflammation you can have inflammation from either arm of the

00:21:32.660 immune system but generally what we find in something like depression is hyperactivity of that shotgun

00:21:38.100 immunity right so let's think about you getting the flu right so what's the first thing that happens

00:21:42.960 you know you start feeling weird you start feeling freezing you you huddle up you start getting a fever

00:21:48.580 you know maybe you throw up you you feel exhausted you got body aches you want to sleep you don't want

00:21:54.680 to do things it's hard to think about complicated stuff some people start feeling down emotionally so

00:22:00.640 you know how does that happen you know it does the flu virus you know does it go up to your head and

00:22:04.660 sort of sit in a driver's seat and start kicking on your brain no it doesn't do that what it does

00:22:08.620 is it activates these inflammatory cytokines these hot inflammatory molecules when when that innate

00:22:15.580 shotgun immune system recognizes the danger of the flu virus it starts pumping out these inflammatory

00:22:21.640 cytokines they can make your finger hot and red but they also go to the brain and when they get to

00:22:26.760 the brain and this is for some work we did with andy miller years ago when they get to the brain they

00:22:31.900 basically cause every change in the brain that has been associated with depression and that is why you

00:22:38.020 get sick the reason you get sick is because it's not because you know the virus wants you to get sick

00:22:44.140 contrary it's the opposite you you get sick to fight the virus because those cytokines when they

00:22:49.780 activate sickness behavior which is sort of the classic expression of inflammatory activation when

00:22:55.420 it's intense almost everything about sickness behavior has an antibiotic strategy so the reason

00:23:00.680 you get a fever when you get sick is not because it feels bad it's because higher temperatures kill

00:23:05.240 viruses and bacteria and higher body temperatures sort of drive your immune system when you get sick

00:23:10.840 your body starts getting rid of all of its iron it starts to try to hide away its iron so you get

00:23:15.820 anemic if it goes on long enough so why would you get anemic well the answer is because a number of

00:23:20.740 bacterias they need the the iron so badly that if you can deprive them of iron they'll starve and die

00:23:26.960 in your body right so there's a list of things like that that all happen when people get sick and by the

00:23:33.460 way you know when you get the flu you know you feel crappy for three or four or five days that's your in

00:23:37.660 that's inflammation making you feel like that and then you know one morning you wake up you start

00:23:42.420 feeling better and the reason you're feeling better is because that that sniper like adaptive

00:23:46.640 immunity has come online and it's uh it's killing the uh it's killing the virus without doing anything

00:23:52.160 to you which is why you start feeling better right so the the the realization that inflammation

00:23:59.520 maybe had something to do with depression really um it came from a couple of sources but a primary source

00:24:04.620 was this realization that inflammation produces sickness and in animal studies when you when you

00:24:11.140 inflame a little animal when you inject it with one of these inflammatory cytokines in its body

00:24:15.280 it starts acting exactly the same way as if you'd put it in a terrible psychological stressor

00:24:20.560 so then people started looking around and they made a couple of interesting discoveries they found out that

00:24:26.100 as a group people with depression tend to have higher levels of inflammation than people that are

00:24:32.000 similar but otherwise but not depressed so it looked like there was this signal within the medically

00:24:36.680 healthy people that they had elevated inflammation and this sort of realization that oh my goodness you

00:24:42.880 know sickness looks a lot like depression or depression looks a lot like sickness and and it's very

00:24:48.440 interesting ways so for instance you know no surprise that when you get really sick you get a fever

00:24:54.260 not so well known that people with depression also have an elevated body temperature

00:24:59.180 they they they're hyperthermic at least and and you treat them and their body temperature returns to

00:25:05.140 normal they tend to have the same iron deficiencies that you see in sickness so we and others have

00:25:10.200 actually argued that that maybe depression evolved out of sickness as a way to help protect us from

00:25:15.600 from pathogens so but so anyway this was it was this sort of line of reasoning that made many of us

00:25:21.640 realize that you know wow if you inject people with inflammation they get depressed if you look at

00:25:27.120 depressed people they seem to as a group have increased inflammation and then the coup de gras

00:25:31.860 on this thing was well okay you know makes sense if you're sick you get inflamed if you get inflamed

00:25:36.920 you get depressed so that's probably partly why medical illness is such a risk factor for depression

00:25:41.980 but what about you know what about stress you know especially younger people they usually get depressed

00:25:46.540 because of a psychological stressor so starting in the kind of the early mid-2000s people would take

00:25:52.000 normal humans and stick them in a laboratory and give them a psychological stressor we did hundreds

00:25:56.920 of these back in the day and you can show very clearly and absolutely reliably that all i have to do

00:26:02.480 is take take you put you in a psychologically stressful situation and i can show that it activates

00:26:07.900 your inflammation you know within an hour your inflammation shooting up and and if you're somebody

00:26:12.520 who was neglected or abused or you know sort of traumatized as a kid your inflammation is going to shoot up

00:26:19.740 even higher way higher in fact because that early adverse experiences primed your body to respond

00:26:25.920 to danger with increased inflammation so these pathways came together and you know voila that's

00:26:31.960 why it has now become this sort of widely thought about idea that that that depression and inflammation

00:26:38.300 have something to do with each other okay so let's talk i want to track backtrack about this idea that

00:26:43.300 these uh cytokines cytokines cytokines so you say they get to the brain and they cause all the things

00:26:50.460 that we see in depressives so we're talking does like it disrupt neurotransmitter stuff does it change

00:26:56.360 the structure of the brains is that what's going on yeah yeah they they they the inflammation wipes out a

00:27:02.680 necessary cofactor for neurotransmitter production uh and does it change like structures of the brain so

00:27:08.600 you've heard those things people who are depressed have a sensitive sensitive amygdala

00:27:12.540 the almond shape thing does inflammation affect that yep yep it it absolutely does it also induces

00:27:19.240 brain changes similar to those seen in depression absolutely does it change the structure of the brain

00:27:25.980 that's a good question i've uh you know it's like everything where you know there's such a huge field

00:27:33.400 now i've never seen a study that it actually changes you know like the size of the brain um or something

00:27:39.860 like that we but but but the activity of the brain absolutely and and my old mentor andy miller at

00:27:46.200 emory who's really i think the king of this field in so many ways has shown that if you take just a

00:27:51.980 big group of normal medically healthy depressed people and you measure their inflammation the people

00:27:56.720 that are depressed and have high inflammation have very different patterns of brain function

00:28:00.560 than the people that are depressed without inflammation we're gonna take a quick break

00:28:04.420 for your word from our sponsors

00:28:05.500 and now back to the show so how why does our body when we experience psychological stress

00:28:16.080 why does it create inflammation because i think people when they think of stress they think of cortisol

00:28:21.280 uh but i don't think oh my body's gonna act like it's sick and send out inflammation signals

00:28:26.780 yeah it's it's really interesting isn't it i mean you'd think right that when the going gets tough the

00:28:32.800 tough would get going and you know sometimes when i give lectures i i will spend the whole beginning

00:28:38.800 sort of trying to get people to marvel at this remarkable fact that we have this weird inflammatory

00:28:45.140 bias you know we think of inflammation making us tired and sick and maybe not think straight you

00:28:50.920 you know if you're being chased by the saber-toothed cat for god's sakes why would you want that

00:28:55.280 but i i think the answer is and and a number of us sort of hit upon this it's sort of the same time

00:29:01.640 the the evolutionary answer we believe is that if you think about what stress has meant across

00:29:09.260 mammalian evolution um and even before the mammals but we just stick to our our ourselves here you

00:29:15.280 know stress reliably meant usually one of three things right either

00:29:20.560 either you're about to be eaten or you are chasing down somebody to eat and that thing has got horns

00:29:27.780 and hoofs or you know you're wanting to make a baby and you're having to fight with the other guy with

00:29:34.340 horns and hoofs and so you know in all of those situations because other than that you know most

00:29:40.320 animals tend to like kind of hang out right they sleep or they hang out and and so so stress the

00:29:48.460 argument goes that stress was so reliably associated with the risk of wounding over evolutionary history

00:29:55.360 that genes that evolved to to prepotently and and and sort of jump the gun activate inflammation

00:30:03.720 in response to stress were selected because you know if you directly die from the stressful encounter

00:30:10.860 from the wounding well whatever you're dead but many many times organisms would survive and then

00:30:17.080 they die of infection because skin is the greatest of all immunologic organs and and one of the absolute

00:30:23.200 number one best ways to die before there were antidepressants was to get your skin opened up

00:30:27.460 and of course now we know with the failure of antibiotics this is becoming more and more of a risk

00:30:31.960 again right it's terrifying so so the reason that inflammation the stress activates inflammation is

00:30:37.960 stress has been a reliable signal that you're in danger of having your skin opened up if your skin

00:30:43.720 gets opened up you're very likely to get an infection that puts you at risk for dying so rather than sitting

00:30:48.760 around and waiting for it to happen we are going to jump the gun it's called smoke alarm principle

00:30:53.380 right and and we're going to turn on inflammation to be ahead of the game and to be ready for the

00:30:58.680 the immunologic damage or the the pathogen exposure we think is going to happen right and of course you

00:31:05.120 know if you do false alarms a thousand times yeah you may you may incur some tissue cost from the

00:31:11.540 inflammatory chemicals but you know all you got to do is not respond once and you're dead and so it's

00:31:17.040 like this thing called the smoke alarm principle so what we're looking at here of course is an

00:31:21.920 evolutionary mismatch in the modern world which is that for many of us especially in first world

00:31:27.500 countries stress does not very often anymore mean that you're at risk for being wounded you know

00:31:33.560 humans tend to make things that are concrete abstract that's one of the great things our brain does

00:31:38.320 and so you know now all these psychological stressors that are no longer associated with

00:31:43.940 wounding still activate those ancient pathways they still activate those ancient reactions

00:31:48.640 and produce inflammation even though the inflammation is of no value as far as we can tell

00:31:54.480 and is actually detrimental so that's it's a good case of an environmental mismatch that we are the

00:32:00.840 inheritors of because the the world has changed so fast in in modern times evolution hasn't been able

00:32:07.360 to catch up all right so there's psychological stress but there's also other kinds of stress too

00:32:12.040 like physical stress from exercise that creates inflammation in the body as well

00:32:16.140 but it also makes you feel good so what's going on the dynamic there

00:32:19.960 so this has been my little you know uh it's funny how we all have our little sort of areas that are

00:32:26.180 fascinomas for us that is true that is a very fascinating observation so we know that exercise

00:32:31.840 acutely activates inflammation you know early on when you asked me what i who i was and what i did i said

00:32:37.820 i kind of studied ancient practices and one of the other antidepressant things we've studied is

00:32:43.120 hyperthermia heat and we have shown and now it's been replicated by others that in fact if you expose humans

00:32:49.080 to kind of a to a really heat stressor for a time limited period it produces an antidepressant effect

00:32:54.580 i mean that's why people go to saunas right steam rooms and stuff so we measured inflammation before

00:32:59.500 and after taking depressed people and sticking them in this this hyperthermia machine and lo and behold

00:33:05.100 it didn't activate the whole inflammatory cascade it activated something that looked a lot like what

00:33:10.160 exercise does and there was a signal in there that the more that inflammation got activated the better

00:33:15.180 people felt the less undepressed the more undepressed they were a week later so there's a little bit of

00:33:21.400 a mystery here and and some of us including me think that the answer actually can be seen in exercise

00:33:27.220 that you know if you look what does exercise do it acutely it raises inflammation what does it do

00:33:33.360 chronically it lowers inflammation and so i think for many of these systems what happens is you can

00:33:40.020 actually um strengthen them or toughen them or in some cases down regulate them by certain types of

00:33:46.460 acute repeated exposure right so so there may be cases in which brief exposure to stimuli that induce

00:33:55.540 inflammation may actually have benefits for depression years ago back in 95 or 96 there was a small study

00:34:02.680 out of germany published in biological psychiatry where they they took a very small study only took seven

00:34:08.340 people but these were really really depressed in patients they were in a psychiatric hospital and they

00:34:13.160 they did something really cool they they shot them up with a bunch of inflammation into their veins

00:34:18.640 and basically made the people sick and every single one of them had a powerful antidepressant response it

00:34:25.180 it didn't last in most of them but in several of them they actually continue to feel better for days and days

00:34:31.120 afterwards so you know what we can say is that when you're chronically inflamed it's a pretty powerful

00:34:39.060 risk factor for depression there may be some instances for reasons we don't fully understand where an acute

00:34:45.360 inflammatory stimuli might actually have mood protective effects it's like the hair of the dog sort of like

00:34:53.480 the hair of the dog well said yeah that's right so this the sauna research is it have you guys figured out

00:34:59.720 like how long you need to stay in a sauna for to have that effect is it like five minutes

00:35:04.820 no no no no well so so the the the short answer is no we have not figured that out my colleague ashley

00:35:11.360 mason at university of california san francisco is gearing up to do studies now that will that will really

00:35:16.140 begin to try to look at that we we got into this it was sort of interesting i i had two young colleagues

00:35:22.040 who were graduate students of mine in austria of all places i used to teach there episodically and

00:35:26.640 they uh they worked at a a sort of non-traditional psychiatric hospital that did mind body treatments

00:35:32.300 and one of them was an engineer he found an old hyperthermia machine in a basement rebuilt it and we

00:35:38.400 decided to stick depressed people in it and we did we we cooked them up and we saw this really you know

00:35:44.400 striking antidepressant response that was you could see it five six seven days after treatment so we we i

00:35:51.280 brought one of the guys to the united states and we we got another fancy machine and we did it really

00:35:56.220 well with a control condition and all this stuff and we saw exactly the same thing now the thing was

00:36:01.600 though we we in in in switzerland we had treated people to uh to basically a core body temperature of

00:36:09.020 101.3 38.5 centigrade it worked and since it worked there we did the same thing in the united states

00:36:17.480 but we never we never did a dose response study so we never looked to see you know well what if we

00:36:23.360 cooked you up more would it would it would it work even better 38.5 core body temperature 101.3 is the

00:36:30.840 upper end of what's classified as mild hyperthermia you get people much hotter than that and you start

00:36:37.080 the health risks begin to sort of increase significantly so we think that that's a good marker for

00:36:44.860 uh a a temperature a core body temperature that we you know really seems to have an antidepressant

00:36:50.000 response we did that with a study we did in arizona was kind of cool because we had this nice nice

00:36:55.040 comparative condition where we we put people into the same machine and we had fake lights and and but

00:37:00.420 we gave them a little bit of heat there were some coils at the bottom of the box and we wanted to fool

00:37:05.000 them and we did we fooled the majority of them but it actually warmed them up too and so you know

00:37:11.060 that people's body temperature the the placebo condition wasn't really a full placebo they

00:37:15.940 actually warmed up a little bit but they didn't have nearly as big an antidepressant response so

00:37:20.860 i think we can say based on that that the data at this point suggests that that if you wanted to do

00:37:25.900 it you should you know you should you should get yourself a rectal thermometer and and see if you

00:37:30.340 actually people that's usually the end of the discussion but you know see if you can get yourself

00:37:34.080 up to like 101.3 and the way we did in study was we just we got people up to 38.5 and and we we the

00:37:41.020 temperature was assessed with a rectal probe every i think 30 seconds and when they had two or three

00:37:46.140 38.5 we turned the machine off and then we just sort of let them sit there for an hour because the body

00:37:50.940 temperature remained elevated you're not going to get to 101.3 by five minutes in the sauna with this

00:37:57.640 machine it took people on average about 90 minutes so more than an hour the machine is it was designed

00:38:03.940 to be more comfortable so you know it wasn't like you know something a hellish sauna where your face

00:38:09.240 is on fire and you're dying you know so we don't know you know ashley my colleague out in in california

00:38:16.540 has been working with infrared saunas and but it takes you got to stay there for a while man it is

00:38:21.420 you're gonna commit an hour to it probably at least to try to get up to that temperature

00:38:24.920 and so you mentioned you've been exploring other sort of ancient practices that humans have used that

00:38:29.920 might have antidepressive benefits to it so there's there's saunas people have been doing that

00:38:34.400 for a long time exercise is one any other practices that you found that may have an anti-inflammatory

00:38:39.840 anti-depressive benefit well yes and and so there's one that i am personally fascinated by and i just don't

00:38:47.560 have the bandwidth uh to to study it you know it's interesting and that is intermittent fasting and i bet

00:38:53.040 you've talked about that a lot on your your program probably we have yeah yeah because it's one of

00:38:57.940 these things that's sort of hip right now but there's some really interesting data i'm thinking

00:39:02.040 of one study in particular where they took a bunch of kind of normal dudes and fasted them and measured

00:39:05.960 the activity of this thing called the inflammasome which is sort of the initiating biological mechanism

00:39:12.060 within cells that turns on inflammation and you fast them and man the activity i think drops drops

00:39:17.220 drops and then they fed them and it up up up right which makes sense right you think about you know

00:39:22.040 inflammation like the brain is charged with this large task of trying to figure out you know

00:39:27.620 what is the self and what are its boundaries and and and how do i maintain the integrity of the self

00:39:35.240 especially when that integrity requires that i let foreign things in right so you know food is a massive

00:39:43.100 danger and you know still to this day there's a bunch of people that die every year from food poisoning

00:39:48.220 at restaurants in the united states you know i mean food is a foreign object it is it it's often

00:39:54.300 you know carries you know back you know organisms that can be dangerous so of course it makes sense

00:39:59.840 that when you eat you are putting an inflammatory stressor on your body you're also putting a thermal

00:40:05.220 stressor on your body so every time you eat you kind of run a little fever you have to you you have

00:40:10.060 to it's called diet induced thermogenesis you kind of kind of burn it off so yeah i mean you know

00:40:15.400 it is probably the case that fasting has anti-inflammatory properties i i know from my

00:40:21.720 buddy rob knight who's one of the kings of the microbiome that that fasting is also probably the

00:40:26.500 fastest way to alter your microbiome in ways that we think of as being positive and so it's interesting

00:40:32.360 you know there's a couple of small studies now suggesting that fasting intermittent fasting

00:40:35.960 has antidepressant properties and there's there's a larger database where they they fasted people and

00:40:41.160 sometimes you know much more than this sort of you know 18 hours or 12 hours without eating you know

00:40:46.020 people go for a couple days in some of these studies but man it pretty pretty reliably people's mood

00:40:51.840 really increases you know you know the first day kind of stinks you're you know there's there's a

00:40:57.040 hump but when people get over the hump they often develop this this sort of really elevated mood

00:41:02.020 well so you've been researching these ancient practices but someone might be listening okay

00:41:06.200 depression inflammation's involved can i just pop like an anti like an advil

00:41:10.640 or get a steroid shot and reduce inflammation and reduce my depression

00:41:15.280 yeah that's such a great question and and i'm so glad you asked it because there's really something

00:41:21.500 important to say about that based on the literature we've seen so far that is this well okay so we

00:41:27.840 back up so we did a study where we we decided we were going to really test whether depression was an

00:41:32.760 inflammatory condition we were going to give depressed people a really powerful anti-inflammatory agent

00:41:37.680 not like advil or a steroid shot but i mean one of these things it used to be marketed as remicade

00:41:43.460 it's called infliximab it it has no other effects other than completely wiping out one of the two

00:41:49.400 primary pro-inflammatory cytokines it just it kills inflammation which is why these drugs are so good

00:41:54.360 for crohn's disease and rheumatoid arthritis psoriasis and stuff like that so we took 60 depressed people

00:41:59.740 we gave half of them three infusions of this infliximab to block their their inflammatory cytokine

00:42:06.400 we gave the other half three infusions of salt water and and nobody knew who was getting what

00:42:11.720 and then we followed them for 12 weeks and and and you know the results were quite striking the salt

00:42:17.820 water worked a little better than the anti-inflammatory agent it wasn't significant but the salt water

00:42:23.420 had a very powerful antidepressant effect you talk about the power of placebo because these were people

00:42:27.360 that had failed other antidepressants but we saw something really interesting this is the important

00:42:32.280 point the placebo and and the anti-inflammatory cytokine blocker if you looked at the two groups

00:42:39.960 their their effect on depression was almost identical but it wasn't because they were the same they were

00:42:45.720 actually opposite and so before we gave people the first shot we measured their inflammation

00:42:50.360 and we found that if you were depressed and had high inflammation the the infliximab the cytokine

00:42:57.640 antagonist worked you know significantly better than the placebo but if you were just as depressed and

00:43:04.560 had lower inflammation and this was two-thirds of this study population you did so much better with

00:43:10.580 salt water than infliximab that the only conclusion we could draw is that you know if you're really

00:43:17.420 depressed but your inflammation is not elevated blocking it further is doing something bad for

00:43:22.440 you it it it it's it's at the very least it's making you not able to respond to placebo so it's

00:43:28.080 interfering with your ability to hope and to trust and to whatever placebo response is and there have

00:43:33.900 been a number of studies several studies after this that that sort of shown the same thing one in

00:43:39.900 particular from mark rapidport who's the chair down at emory he did the what will forever be probably the

00:43:45.320 world's largest study of omega-3 fatty acids um just as a single treatment for depression you know

00:43:50.660 no antidepressants just placebo or omega-3 fatty acids and the fatty acids didn't work for squat

00:43:57.220 they don't they don't have general antidepressant effects but but he took a page from our lesson book and

00:44:03.260 and looked at their inflammation levels before they started the omega-3s he saw exactly the same thing

00:44:09.100 that if you are depressed with elevated inflammation the omega-3s worked better than placebo but

00:44:14.500 if you were just as depressed and had lower inflammation you you want a placebo you don't

00:44:19.520 want to be taking omega-3 fatty acids so you know if if those are true results you know omega-3 fatty

00:44:25.580 acids may help your heart but if you're really depressed and you're one of at least half or maybe

00:44:30.440 two-thirds of people that do not have elevated inflammation you know taking omega-3 fatty acid you're

00:44:35.440 probably not doing yourself any favors so no we me i do not suggest that people routinely

00:44:41.780 try anti-inflammatories for depression at this point caveat there is a a good study from a guy

00:44:48.720 named jonathan savitz at the laureate brain institute where he looked at low dose aspirin

00:44:52.660 versus something called minocyclin which is an antibiotic which is an anti-inflammatory versus

00:44:57.100 placebo the minocyclin only worked in people with elevated inflammation just what you'd predict

00:45:02.100 but the aspirin worked in everybody and it's not because it's an anti-inflammatory at that low dose

00:45:06.700 it's doing something else we don't know what you know so there's a little bit of evidence if you're

00:45:10.760 going to do something you know off the grid that taking low dose aspirin may have some antidepressant

00:45:16.360 benefit so then of course the next question everybody asks is well okay well shoot you know

00:45:20.900 should i go get my inflammation measured and my answer these days is well maybe five years ago i'd say

00:45:27.940 no it's too preliminary but you know there's a thing called c-reactive protein or crp you can get it

00:45:33.040 easily done it's a standard lab test is standardized and it'll give you pretty good readout on your

00:45:38.980 inflammation you know if it's elevated you're more likely to die of a heart attack and a stroke you're

00:45:43.580 more likely to get diabetes and depression and dementia and it tends to be elevated and depressed

00:45:49.060 people another reason why it's an interesting inflammatory biomarker is there's now a couple of

00:45:54.720 studies including some work that i've done showing that it can predict whether you're going to respond

00:45:59.860 to prozac or not right and so there are now a couple of studies one of them fairly large actually

00:46:05.800 suggesting that if you just get to simple inflammatory measure c-reactive protein or crp

00:46:11.400 if it's elevated elevated here is like a level greater than one one milligram per liter you don't

00:46:17.400 tend to respond to ssris you know the serotonin antidepressants like prozac paxel zoloft lexapro

00:46:22.920 selexa those are the brand names but if you're if your crp is elevated you're more likely to respond

00:46:30.280 to something that has dopamine properties something like for instance wellbutrin which is the generic

00:46:36.020 of that is bupropion or in one study was nortriptyline which is more of a norepinephrine

00:46:40.640 drug but it's a complicated but it fits the pattern right but i think the key here is that

00:46:46.380 you know almost all of us get depressed get stuck on a drug where the primary mechanism of action is

00:46:51.260 blocking the serotonin reuptake site and there is now this gathering data to suggest that you know

00:46:56.840 if your inflammation is elevated you're not you're not as likely to respond to those and then we've

00:47:01.440 shown recently working with actually a large pharmaceutical company that crp can predict people

00:47:07.300 who do and don't respond to a very different kind of drug that's used to treat bipolar disorder when

00:47:13.420 people are depressed there's it's a drug called lorazodone it's marketed as latuda it's an atypical

00:47:18.840 antipsychotic it's a dopamine modulating agent and we measured crp before before people started

00:47:25.640 treatment with it versus placebo and uh man you know if your crp is low the uh the the antipsychotic

00:47:32.700 latuda was no better than placebo but if your crp was high it worked like gangbusters as an

00:47:39.300 antidepressant and we we've replicated that not perfectly but but we about three quarters of the

00:47:44.860 way replicated in another large population of children with bipolar depression so so this is

00:47:50.820 sort of interesting right that that it's not quite ready for prime time but it's ready enough and you

00:47:56.760 know that the only risk is a blood stick that that i now often say yeah you know i think this is actually

00:48:01.580 something worth doing is you know look at the crp levels if you're trying to decide what antidepressant

00:48:05.820 to use you know we need larger studies a lot of caveats but you're going to pick one eenie

00:48:11.280 mini mayo any you know just randomly anyway yeah take a look you know if your if your inflammation is

00:48:17.080 elevated elevated reach for something other than an ssri in general i'm not hugely overwhelmed with

00:48:24.620 anti-inflammatory agents as antidepressants even in our big study yeah be placebo but it was not a

00:48:32.320 miracle cure you know inflammation is a widespread ancient process and it sets in motion a lot of

00:48:40.800 downstream changes and almost certainly those downstream changes are going to be more directly

00:48:46.240 involved in the production of depression and those pathways probably probably make better targets

00:48:51.860 than inflammation itself well i think it's an important point to make that you to bring out

00:48:58.160 as you were talking about those studies about the the effectiveness of antidepressants based on your

00:49:02.860 crp levels is that you can be depressed but not inflamed or inflamed and not depressed right

00:49:09.000 absolutely both are very true because i think people could hear this like oh inflammation

00:49:13.280 depression i just go to my doctor hey doctor i'm inflamed i'm gonna do sit in the sauna that's

00:49:17.960 gonna cure but that might not be you might not be inflamed but still can be depressed absolutely

00:49:22.340 most most depressed people are not inflamed so why is that why why do some people get inflamed

00:49:27.560 when they're depressed and some people get depressed but not inflamed don't know so this conversation

00:49:32.820 with this research shows is that okay again there's no single cause for depression right but it's all

00:49:37.300 these different things working together so as a doctor or maybe someone who's got depression like

00:49:43.600 how do you figure out the best approach to help a patient like i think at the end of the book you

00:49:48.140 gave some case studies which is really interesting walking through but is it just a matter of trying

00:49:52.340 different things to see what sticks or have you kind of figured out a systematic way where you can

00:49:56.960 find the the thing or things that will help no no unfortunately so my opinion uh but i know the

00:50:05.760 feel pretty well whenever you hear anybody talking in depression that they're going to treat you with

00:50:09.880 a brain scan or they're going to do a brain scan and tell you what to take or that they've got an

00:50:13.860 algorithm that gets guaranteed to work no that's bs now it works sometimes because it induces a great

00:50:20.580 deal of hope and trust and optimism and and and those are very powerful effects but the the biology of it

00:50:29.480 is always just really shaky so you know the the truth of the matter still is that we don't know

00:50:36.800 ahead of time really who's going to respond to what you know the little crp is a little caveat there if

00:50:41.740 it really gets replicated it would be ironic that our first reliable predictive biomarker is not a brain

00:50:47.220 thing but an immune system thing but no you know the real question these days for me is whether you start

00:50:55.020 somebody on an antidepressant and send them down that path because i think that the continental divide

00:51:01.120 in the treatment of depression really is around this issue of do you do something that sort of helps

00:51:08.540 people build up resiliency within their own mind body brain complex it's not dependent on a constant

00:51:15.340 presence of an external substance or do you go the other route where you fortify people with a

00:51:20.560 drug that is kind of always on the brain and always there these are things i never would have thought

00:51:26.600 of 15 20 years ago 20 years ago i thought antidepressants were like brain food i thought

00:51:30.160 they were like you know fertilizer for the brain unfortunately we now know that that that when

00:51:36.720 antidepressants really help people which they do no doubt about it and they're lifesavers no doubt

00:51:41.840 about that but in our time and place many many people once they've kind of gone down the

00:51:47.860 antidepressant path find that they don't do very well if they go off the antidepressants

00:51:52.480 that they they're they're really convincing data that starting an antidepressant and stopping it

00:51:58.680 is more likely to make you depressed in the future than having never started in the first place

00:52:03.260 oddly placebo responses are more durable than antidepressant responses when you take away the

00:52:09.920 placebo or the antidepressant psychotherapy responses while not perfect are also more durable

00:52:16.020 one of my huge interests in psychedelics is not just the fact that they have a different mechanism

00:52:21.060 of action in terms of inducing psychedelic states but you know they they seem to one treatment last

00:52:27.600 six seven eight hours and then in certain populations especially now there's a study out

00:52:31.880 from nyu you know people report being undepressed three four years later it's it's like it was a reset

00:52:37.820 right and and that of course is what we should be looking for because you know any drug that you

00:52:45.180 take every day that operates on the brain seems to induce what's been called oppositional tolerance

00:52:51.660 which is the brain begins pushing back against the drug you know this is why you get withdrawal

00:52:55.900 reactions right you know if you if you take a valium every day for for you know if you take that for a

00:53:00.200 long period of time and you stop it suddenly you'll have a seizure because what's valium doing it's

00:53:04.560 it's constantly pushing on the brain to calm it down the brain begins to kind of fight back

00:53:09.200 it kind of gears up right and and so then you get this sort of compromise between the the pushing

00:53:14.880 down of the the valium and the pushing back the brain and then you take away the valium real

00:53:20.220 suddenly and the the pushing back of the brain is unopposed and it goes hyper excitable and you get

00:53:25.440 seizures stuff like that right antidepressants it's not as dramatic but lots of people have withdrawal

00:53:31.420 reactions and that's that what that tells you is that that the brain has sort of you could say it's

00:53:37.060 become dependent on it but i like better this idea that the brain has begun to come to some sort of

00:53:42.640 balance with the antidepressant that puts the brain in a place where it's trying to overcome the

00:53:46.940 antidepressant effects almost you take away the antidepressant and that that overcoming thing is

00:53:52.300 unopposed and you know um people have a very very high rate of crashing back into depression you know

00:53:58.080 one of the surest way to make people depressed if they're not depressed is to suddenly stop their

00:54:02.260 antidepressant so this is the thing you know i'm a i'm a i'm a pharmaceutical i'm a drug doctor i mean

00:54:08.280 the only the only real expertise i have clinically is you know writing writing prescriptions for

00:54:12.780 psychotropic agents and uh you know i've seen a lot of patients over the years and i can promise you

00:54:17.740 that god man damn some people these agents really work great for you know another problem is that they

00:54:23.120 they probably don't work optimally for at least 50 percent of people but you know they there's a lot of

00:54:28.700 people get a huge benefit but i worry increasingly about anything that the human side becomes utterly

00:54:35.720 depended on we tend to then tends to weaken the human element and then this is where you see this

00:54:41.500 increased risk of relapse and such so i've gotten more and more interested in in how we can begin to

00:54:47.820 find treatments for depression that instead of inducing some sort of state of dependency where the

00:54:52.180 human is now joined like almost like a cyborg to the technology say the antidepressant that what we've

00:54:57.540 done is found a technology that actually strengthens people stimulates them you know so that the this

00:55:03.660 intervention drops away but the person is now in a self-sustaining state of enhanced wellness

00:55:09.260 and it's promising you know this is it looks like there are ways of doing this i mean the hyperthermia

00:55:15.160 the heat showed a little bit of that signal people felt better for weeks afterwards so you know it's it

00:55:22.060 but again another very long answer to say that no we do not as a field have a magic formula if you

00:55:27.980 come to see me you're depressed i listen to you i think about what the situation is i wonder about

00:55:32.800 what to do but there's not a cookbook that gives me all the answers so but you're going to do things

00:55:38.760 like uh as you said like maybe maybe well you're going to ask more things about like are do you have

00:55:43.460 any sort of sickness like you might like that's something that doctors typically don't ask whenever they

00:55:47.420 a patient comes in saying i'm depressed they never ask about well are you are you inflamed have you

00:55:53.080 been sick that might be a thing they might start thinking about now no absolutely it might not be

00:55:57.880 the thing that determines it but it's another factor they'll they might want to consider well so i'll give

00:56:02.360 you a quick story one of my partner's closest friends has a mom who's had a history of very very

00:56:07.160 difficult bipolar disorder lots of depressions and manias she's older she's probably 78 she develops a

00:56:12.980 cataclysmic depression about two months ago i mean a woman becomes catatonic she's not eating she's

00:56:17.400 not talking she when she does talk she says you know please put the pillow over my head and kill

00:56:21.360 me i want to die they try antidepressants they were going to go for shock therapy but she'd fail that in

00:56:26.700 the past they started giving her ketamine you know this new treatment and then you know somebody gets

00:56:31.460 an x-ray and her lungs are riddled with cancer and she's dying right so there's a classic example of

00:56:39.000 that now you can't do anything about it particularly but it would have helped the family back in time

00:56:45.360 they could have spent been spared a month of this sort of like you know oh my god you know

00:56:49.880 our mom has such horrible depressions terrible should we let her die you know all this stuff

00:56:53.980 when you know it yes she had a horrible depression so she had a vulnerability and it was launched by

00:56:59.520 the fact that she was having massive inflammatory response to the cancer so i've literally just lived

00:57:06.680 through what you're talking about and so absolutely yes that's absolutely something they should ask about

00:57:10.600 the other thing that they should ask about but good luck because the doctor only has like four or five

00:57:16.080 minutes to see you just economically you know but they should also ask you like you know what's going

00:57:22.380 wrong in your life because you know depression can come out of the blue that definitely happens

00:57:27.540 but most of the time especially if people haven't been depressed a bunch of times before

00:57:32.060 there's a story there and people won't tell you the story right away you know i used to call it the

00:57:37.140 oh by the way phenomenon you know they bury the lead depression is often a narrative disorder

00:57:44.220 there's often a story that's driving it and and helping people with that can be profoundly powerful

00:57:51.860 as a treatment actually so it's the same thing of like you know ask about the sickness well

00:57:57.240 you ask there's immunologic adversity sickness and intersect social adversity and they both are the

00:58:03.560 powerful drivers of depression well charles this has been a great conversation is there some place

00:58:07.900 people can go to learn more about your work yes they can go i'll give me to give you a couple of just

00:58:14.180 names if people google this they can find it they can go to what's called the center for healthy minds

00:58:18.580 at the university of wisconsin madison they can go to the school of human ecology

00:58:24.160 at the university of wisconsin madison they can go to the center for the study of human health

00:58:31.860 at emory university in atlanta georgia and then if they're interested in the psychedelics they can

00:58:37.140 go to the website for usona that's us us o n a institute you can find out about me at all those

00:58:43.900 sites and and you know it's i if you just google me uh you'll find me pretty quickly i you'll i you

00:58:50.000 can listen to me ad nauseum say a lot of this you know but yeah i mean i'm pretty easy to find

00:58:54.920 well thanks well charles thanks for your time it's been a pleasure thanks brad i have great questions man

00:58:58.880 my guest today was dr charles rezon he is a psychiatrist and the co-author of the book

00:59:03.060 the new mind body science of depression it's available on amazon.com also just google his

00:59:07.160 name like he said we can find out more of the work that he does and the research he's done on

00:59:10.840 the topic of inflammation and depression also check out our show notes at aom.is

00:59:14.200 slash inflammation depression find links to resources ring delve deeper into this topic

00:59:18.660 well that wraps up another edition of the aom podcast check out our website at artofmanliness.com

00:59:29.940 where you find our podcast archives as well as thousands of articles we've written over the

00:59:33.260 years got a whole series about depression and men on the site so go check that out and if you

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01:00:02.720 reminding you not only listen to aom podcast but put what you've heard into action

01:00:14.840 you

The Art of Manliness - July 31, 2025

#585： Inflammation, Saunas, and the New Science of Depression

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