Neuroinflammatory Hypotheses of Depression

good afternoon and welcome to the brain and behavior research foundations meet the scientists monthly webinar series I'm dr. Jeff Borenstein president and CEO of the foundation and your host and moderator for today's webinar today dr. Annette chalene will present neuro inflammatory hypotheses of depression the brain and behavior Research Foundation is committed to alleviating the suffering caused by mental illness by awarding grants that will lead to advances and breakthroughs in scientific research the foundation is the largest private funder of mental health research grants since 1987 the foundation has awarded more than 360 million dollars to fund more than 5,000 grants to more than 4,000 scientists around the world 100% of all donor contributions for research are invested in our grants to scientists who are working to find breakthroughs and disorders such as ADHD anxiety autism bipolar disorder borderline personality disorder depression OCD post-traumatic stress addiction and schizophrenia I'm delighted to introduce dr. Yvette Selene dr. Selene is the McClure professor of psychiatry and behavioral research in the department of psychiatry at the University of Pennsylvania Perelman School of Medicine she is a member of the brain and behavior Research Foundation scientific Council and has received several Foundation grants including a Young Investigator grant and two independent investigator grants today's webinar will begin with dr. Celine's presentation this will be followed by a question and answer period to submit your questions please use the questions tab on the control panel on your screen please feel free to submit your questions throughout the presentation following the presentation I will present your questions to dr. chalene and we will discuss as many as possible in the time allotted now I'm very pleased to introduce dr. Evette chalene that the floor is yours great thank you Jeff I'm just getting my my slides up and going here yes perfect right can you see them yes okay good so I'm going to be talking today about neuro inflammation and depression let's see I can make it advance just click on the slide I did click on the oh ok there we go so I'm going to talk about this in several different sections first we're going to have how inflammation got changed and altered over the course of evolution so that it became a negative instead of a positive thing we'll talk about inflammation pathways to get to that negative outcome inflammation factors and inflammatory cell types the brain effects of inflammation inflammation affects multiple disease processes factors that decrease inflammation and then finally antidepressant treatment effects so we'll start with a definition of neuro inflammation which has been defined as the interplay of the immune system and the central nervous system involving pro-inflammatory cytokines and related molecular processes that lead to microglial activation and after gliosis this is referred to as neuro inflammation so by the end of this lecture I hope you'll know a little bit more about pro-inflammatory cytokines what I mean by that and what are the molecular processes and what are microglia all of those are important in understanding inflammation so we know that inflammation causes depression we know that for instance people who receive interferon treatment had a subsequent oppression in about 30 to 40 percent of all the people who received that treatment even if they had never received even if they had never had depression before so commonly interferon was used for conditions like hepatitis C and so it was completely unrelated to depression further when people with treatment resistant depression are examined when their spinal fluid or their blood is examined a much greater percentage of those than in the general population have elevated inflammatory factors so as you can see the it's a two-way street depression causes no inflammation and inflammation can cause depression so is inflammation necessarily a bad thing so not under the right circumstances at at low levels it can protect against infection we need inflammation to be able to stay alive without the ability to fight off infections we wouldn't survive and in fact there are congenital conditions like that and those infants don't survive at high levels though inflammation mediates depression and mediates other illnesses as well and we'll talk about that a bit besides depression so from the evolutionary perspective back in in the early days of the evolution of mankind I you can see here that basically there are a lot of things the body had to be wary of predators pathogens you had to be wary about other people who might be trying to attack you so in that hunter-gatherer phase inflammation was a necessary and important part of life and so you could say there was a pro-inflammatory bias so here the alarm avoidance wound healing and fighting infection and then as we moved into modern times we have much less in the way of germs around so we have much more sterile environment we also have many more environmental and psychosocial stresses and a lot of and because we live longer a lot of medical illness so in this environment inflammation becomes actually a negative factor it's it's not something that in general helps us other than when we have a severe infection so we'll talk next about the inflammation pathways to that negative outcome and this is a sort of synthetic perspective you can see that there are predisposing factors that predispose to inflammation such as being overweight or having a history of major depression having early life life stress and a genetic predisposition and then you also have the interplay with the month the gut microbiome all the organisms that the now estimated to be billions of organisms that live inside of us and so these factors then lead to increases in inflammation and when that inflammatory response becomes prolong we get what are called sickness behaviors and those are things like loss of pleasure fatigue all the kinds of things that you feel like when you're sick and that has negative health outcome so you get you can get in the presence of an exaggerated inflammatory response you can get persistent inflammation which then can lead on into a long lasting set of depressive symptoms and then it can sort of set up a vicious cycle so what are those inflammation factors and inflammatory cell types oops this one isn't a very sorry about this what we have here and I'm apologizing looks quite blurry on my screen um it's trying to show so what's going on here in this brain of this depressed person which is that you have microglial activation that is a cell type glia usually are resting they're resting quietly but when they have these immune factors like il-1 beta i'll 6 tnf-alpha that that activate them they go into an activated state and and become attackers so and this goes on all of these things go on in the brain you also have excitatory neurotransmitters such as glutamate that that accelerate this process so you've got neurotransmitter involvement cell type involvement in these floating humoral factors floating in our blood and in our cerebral spinal fluid that all make up what this inflammatory process is and the consequence of that one of the most distressing things is that people who have depression and especially various other kinds of inflammatory processes will tell you that it's hard to feel excited about anything they've lost their sense of pleasure so the nucleus accumbens is the brain area that's implicated in reward signaling and you can see here that it's getting signals the nucleus accumbens is this tiny little region way deep in the brain but it gets signals from medial prefrontal cortex from the cingulate cortex that feed in and signal to this reward pathway from other brain regions and this occurs by dopamine signaling dopamine is a neurotransmitter that's very involved in the ability to have and receive rewards in in the brain it's a brain chemical that makes us feel like we've been rewarded it's also overactive in some disorders such as pathological gambling such as addiction and so forth but it's underactive in depression and disorders that are involved in inflammation so what do the cell types look like that are involved in depression well on on the left here this is a typical resting monocyte which becomes a microglial cell and it's it's a so-called ramified or branching form you can see all these nice little branches and it's just kind of reaching out with its arms embracing the environment looking for signals from other cells and then as we move to the right you see that it becomes progressively less branchy and more amoeboid and so all the way at the right look at this this is just a big fat amoeba sitting here with no branches and that's a fully activated microglial cell that that you might see in a disorder such as multiple sclerosis the kinds of microglial cells activated microglia that are seen in depression typically are these more intermediate forms that are not quite so extreme as the ones that we see all the way on the left but there have been neuro paths on studies showing that people who've died with depression have more of these activated microglial in in the brain so um let's see here now I'm going to talk a little bit about the brain effects of inflammation and here what we see is the bone marrow which is where the monocytes are made out here in the periphery and in the context of psychosocial stress catecholamines such as noradrenaline you can see here are released by act activated sympathetic service system fibers to stimulate bone marrow production and release these monocytes and these enter the periphery where they then encounter in the presence of stress they encounter stress induced damage molecular patterns that's a mouthful those are called damps and also bacteria potentially so these are all things they can encounter that will accelerate this process bacteria and other associated patterns that have leaked from the gut here so if you have if you have an infection it produces this leaky gut and then the inflammatory signaling pathways such as here you can see NF Kappa beta lead to the production of mature interleukin 1 il-1 beta and il-6 and these then produce the release of other pro-inflammatory cytokines and together these can access the brain through two different ways one is a nervous route so in through nerves like the vagus nerve and the other is a is a humoral route so in here they they get in through the bloodstream and then finally there's a cellular route to where sometimes stress produces leakiness in the blood-brain barrier and so the the monocytes can enter directly where they then get transformed into macrophages so these are then active inflammatory cells and once in the brain the activated macrophages perpetuate this central inflammatory response and so you've got this vicious cycle now you've got more inflammation and it starts all over again so here's the psychosocial stressor here which then produces more and noradrenaline and around and around we go oh I meant to do this - sorry so these are they the the big summary points that stress hormones stimulate bone marrow to cells are released encounter bacteria and damage associated patterns activate signal pathways for inflammation these these soluble factors access the brain and then the activated monocytes and microglia perpetuate this central inflammation so what does what does that do to the brain well when people with depression have been examined there are many different brain regions that are involved in inflammation so we have not only cognitive areas such as the dorsolateral prefrontal cortex here and the dorsal anterior cingulate but also regions like the amygdala that and the orbital frontal cortex that are very involved with emotion and when you look in these regions you can see this has been done some with some PET scanning you can see increased inflammation in those brain regions the problem with doing those kinds of studies is so far we don't really have very good pet binding strategies so we're still awaiting better technology to be able to really examine this carefully but what we do have is the downstream effects of that so we have less good signaling in response to rewarding tasks for example and let's see here we also in addition to having the overall effects on brain regions where we might see smaller volumes or or less of a functional effect we have neurotransmitter effects as well excuse me and what we see and this is a sort of complicated slide I'll try to describe it in a way that's as simple as possible there are sort of three different ways in which inflammation affects brain neurotransmitters brain neurotransmitters are the the chemicals that perpetuate the electrical signal that is responsible for all of the sinking and feeling and everything that all the brain work that we do so the pro-inflammatory cytokines decrease the availability of what we call mono amines and that would be things like serotonin and dopamine and noradrenalin and they do that by decreasing the availability because they have an increase they increase the uptake so it goes back into the presynaptic terminal so that's one way that it's done they also decrease the availability of mono amines by activating the enzyme indole to three dioxygenase i dough which is I will I'll show you that on another slide as well but what it does is it shunts the precursor to serotonin which is tryptophane into a different pathway that actually makes excitotoxin so instead of having a good effect and making serotonin instead it shunts it into a different pathway where you get excitatory damage from glutamate excess glutamate and also an excitotoxin see that results in decreased brain derived neurotrophic factor so you can see here brain derived neurotrophic factor goes down and neurogenesis goes down so you have loss at the presynaptic terminal less synthesis of of transmitters that you need such as serotonin and dopamine and then you also actually have toxicity from the products that are made here is showing the effect of BDNF stimulating these neural stem cells which are the ones that regenerate new brain cells in the hippocampus so all of these are effects that will exacerbate depression you can see that by having less of the important neurotransmitters that would lead to a state in which we have less of an opportunity to rebalance the brain and this is just explaining a little bit more about the one particular pathway I told you about that is it increases the expression of I dough which converts tryptophane into kinder rain which is kind of down the wrong path way like I was saying and it's metabolized to quinol in ik acid and it's it's an NMDA agonist so that helps the transmitter glutamate which can be excited toxic and it interferes with brain-derived neurotropic factor and with neurogenesis finally on the conversion of tryptophane diverts it from the pathway of serotonin synthesis and thus there's less there tonin available for mood regulations pathways and this is just showing you schematically what I was saying that here tryptophane goes into this pathway down to quinol in ik acid which is an excited tox in' rather than into a pathway that would take it in this direction where it would make serotonin so besides affecting depression there are other disease processes that inflammation effects it's not just depression and as you can see here that kind of makes sense because when you think about and illnesses they have they have some common predisposing factors such as obesity early life adversity for example people who have early life adversity early life abuse or neglect or other kinds of stressors continue to have an elevated risk of a variety of different diseases such as cardiovascular disease such as even diabetes throughout life it is something that never changes in have in being disproportionately represented similarly there are genetic predispositions that are shared by many diseases and so then in the presence of inflammation whatever these diseases are with these predisposing factors you have an exacerbation of that of that negative outcome with further exaggerated stress responses cycling back to exacerbating the illness so these are some of the most common diseases but there it's certainly not an exhaustive list so some of the ones where inflammation really is a significant mediator include mild cognitive impairment it is on the pathway to Alzheimer's disease cardiovascular disease diabetes hypertension a number of different irritable bowel syndrome and obesity of course and all of them have as a common mediator the influence of neuro inflammation and this this is kind of breaking it down into showing that it's not just the it's not just the the inflammatory cytokines but also the sympathetic and parasympathetic nervous system the loss of feedback of the stress hormones so so called resistance glucocorticoid resistance where the brain no longer has the appropriate regulation of cortisol and so what you end up getting is this vicious circle where you know you have inflammation leading to depression leading to medical illness and and actually the arrows go this way too so medical illness leading to depression leading to inflammation leading to stress if you can go around and around the clock this way or you can go around and around the other direction but it just shows you that once you have enough of these factors it gets very hard to to interrupt this cycle and this is one illustration of those relationships so taking cardiovascular disease it's showing that when you have a a predisposition to cardiac disease such as myocardial ischemia ventricular arrhythmias you have a diseased heart um you and you have stressors so a hyperactive hypothalamic-pituitary-adrenal axis and sympathetic nervous system these feed back onto the immune cells which then as we talked about earlier go into the brain result in activated macrophages and further exacerbate this stress cycle we also have the effect of catecholamines activating platelets which then helped form the atherosclerosis a so you have the blood vessels getting clogged because of the the influence of the immune cells and of catecholamines and of cortisol finally you have just as you have in inflammation you have the effects on the autonomic nervous system which further feeds into this into this cycle and we could we could have used a different example we could have used gastrointestinal illness and looked at some of the same factors of inflammation or we could have looked at the fact that mild cognitive impairment has increases in inflammation that have been seen in the time period leading up to the beginning of the mild and cognitive impairment and then progressing on to Alzheimer's disease that those inflammatory factors also play a role there so so I don't want to pretend that it's just cardiovascular disease or it's just depression this is a kind of general medical factor so what can we do about that what could we do to interrupt this vicious cycle so some of the things that we know we can do that are protective are exercise there's very good evidence that people who receive an adequate amount of exercise have lower circulating inflammatory factors diet so whether it's just maintaining a good healthy diet or actually there's now been some studies of intermittent fasting such as people do for religious [Music] reasons or for health reasons but in any case having an intermittent fasting cycle does appear to pretty significantly reduce inflammatory factors getting adequate sleep they've done a lot of studies showing that people who are chronically sleep-deprived have higher levels of inflammation well this is one that's hard to arrange in modern life but if if people can simply figure out a way to decrease the stress that they're under of course that also leads to decreases in inflammation and and you know finding a way for those people who have depression to get the depression treated sufficiently is is a final way in which we can definitely decrease the amount of inflammation so I it's kind of a checkerboard maybe people can't do all of those but the more they can do the more they can protect themselves against inflammation so finally what about antidepressant treatment effects there is one thing we can do to I clearly if possible interrupt a cycle and that's to treat depression and get people who have depression better so they aren't kind of going around and around this cycle the other thing that we can do is we can actually treat the inflammation so so there's now evidence for both of those things as well of course as medical illness and stress but there is some data that treating with anti-inflammatory medication can augment the antidepressant response so if you are trying to treat depression and you're not getting a good response with a traditional course of antidepressants so in some studies there's an augmentive effect of adding in anti-inflammatory medication and we're here at Penn we're currently conducting a treatment trial in people over 60 to test that that hypothesis we think that people who have a less complete response to antidepressants may have higher levels of inflammatory factors which can be lowered by antidepressants partially but may do better with a combination of anti-inflammatory agents and antidepressants so what we're doing is actually looking in the cerebrospinal fluid of people in other words conducting spinal taps before and after treatment with depression to see if it is these higher levels of inflammatory factors that are getting in the way of treatment response and then for the people who have persistently elevated levels of inflammation and who don't get better from traditional antidepressant treatment we can then add in an anti-inflammatory agent to to see if that directly helps them get better from their depression so like I said decreasing depression dampens down the inflammatory response indirectly and stops the vicious cycle antidepressant may have a direct effect so there's some evidence that antidepressants have a direct effect on the inflammation factors themselves and then antidepressants in addition to affecting the inflammation factors they they increase compliance with treatment regimens for medical illnesses that can get in the way such as hypertension diabetes and cardiac disease so that's the end of this talk just to summarize we talked about an evolutionary perspective why it is that people now have this increased inflammation that gets in the way of feeling better what the inflammation pathways to a negative outcome are what influence what specifically the inflammation factors are and what the inflammatory cell types namely microglia are that perpetuate the response the brain effects of inflammation the fact that inflammation affects multiple disease processes some evidence that there are factors that decrease inflammation factors that we can actually control thank goodness and finally antidepressant treatment response treatment effects and some of the newer data suggesting that in fact by augmenting with anti-inflammatory agents we may get a better antidepressant treatment effect so I'll stop there and take questions great that thank you very much you are able to take some very complicated information and put it into a context that I think is they were useful to people who are listening and one of the questions that we received a few times has to do with the anti-inflammatory agents that you're using in your studies could you tell us a little bit about which agents you think might be most effective for these purposes uh-huh sure so in our study what we're doing is we're first you know when we do antidepressant treatment trials our first hypothesis is that people may not have been treated adequately or with sufficient doses were for sufficient time so the first thing we do is we put them into a standard SSRI treatment trial and just see and you'd be surprised there are quite a few people who get better just from that but then for people who don't in our study we're using an experimental protocol where we add in a cox-2 inhibitor that is is available on the market so you could get this yourself and it comes with a variety of different generic names but basically celecoxib is one of them and i you know we we feel that the evidence is not there yet to go out and recommend that people do that does have some some risk factors but if we can show in our treatment trial that people get a better antidepressant response with adding in celecoxib then then we'll be happy great excellent I just want to emphasize an important point you made at the beginning of your response which is that there are people who might have appeared not to respond to treatment but may not have had the full maximum dose or the full amount of time that it sometimes athlete to be effective and that's important for people to keep in mind to make sure that they are receiving the full dose and not giving enough time for that dose to work could you say a little bit about your experience with that because I'm sure there are people who are so happy I've been doing antidepressant treatment trials for a long long time I'm always impressed by I used to think um that there were just a fair number of bad doctors out there and then I realized well it's kind of a combination because people are so desperate to get better of course they are I mean they're feeling miserable they want to feel better and so they're telling their doctor I you know I got to do something do something else do something more and so then these changes start to get made and then it ends up seeming as if nothing has worked but you may have only had somebody beyond a few weeks of this and then a few weeks of that and so the net effect is that they haven't had a full treatment trial of an antidepressant and that's why I think it's so important to or they or a lot of times I see people who will change doctors like one doctor than another doctor than another doctor and so nobody's really managing um the treatment and I think I think those situations really are unfortunate because then you don't know if the person has had an adequate treatment trial so you really want to be sure that the simple things work first before you move on to other things so the if somebody is taking a medicine but not yet at the full dose of the medicine and as a general rule of thumb and there's always exceptions to that it makes sense to build up to that full dose as long as they're able to tolerate that without side effects etc to see if that medicine would work right exactly and to be on it for long enough to give it a chance right the one of the questions somebody asks is is there a way for a person to know if they are having inflammation in the context of their depression can somebody on be able to tell that they are a person with inflammation you know you really wouldn't know that there's no there's no symptom in your body or anything simple that would tell you that I mean the only way to know is to actually have pretty fancy tests done for these inflammation factors and then the other complicating thing is even if you have those tests it's not yet there's no standard level that is like this is clearly inflammation this is too much inflammation and that isn't so that's what's being worked out right now is I mean what I'd love would be in the future if we you know if you know your glucose is supposed to be 100 and not higher not lower well what should your inflammation levels be and then we could could really direct people into one treatment or another but um so what's being done right now is above a certain amount of inflammation and and those levels change depending on who's doing the study it's thought to be like this is clearly increased inflammation and that you know by working with a doctor you could figure out like yeah I really do have increased inflammation levels then I somebody who had you know quite high inflammation levels could be treated with an anti-inflammatory if it was just a little high is that good enough reason to be on an anti-inflammatory in addition to an antidepressant we don't know that's that's exactly what the study I'm doing right now is taking a look at so kind of really high or really low we could say like no you really don't have any inflammation or yeah you really do have inflammation but in the middle of where maybe you've got a little do we have evidence that adding in an anti-inflammatory to an antidepressant will improve you jury's out you you spoke about diet and good healthy eating habits and perhaps intermittent fasting are there any types of foods that people should be thinking about to avoid or to have more of that may be useful in terms of the inflammation issue well there's a huge nutrition literature on the inflammatory effects of animal meat I happen to have in my family a rabid nutritionist my brother who's a family doctors who is a rabid vegan and he could I don't have these articles but he could point you to and I do believe he's correct that especially red meat but also any kind of um animal meat has increased inflammatory factors that may be promoting inflammation in all of us so the kinds of things you want to eat are the green leafy vegetables fruits I mean every kind of fruit and vegetable is going to be anti-inflammatory and grains so plenty of grains and also not in too high a quantity because that we know that obesity is is inflammation promoting so keeping on the lean side and eating plenty of fruits and vegetables and grains fish IIIi think the jury's out of fish I don't think I don't know of anything bad about fish okay so things that people again it is that general healthy diet and that's Rania's dying goes like yeah right it um I want to ask you to a little bit explain just in the broadest of terms about inflammation but some of the people in our audience who are so we're not scientists but are very interested in this are asking questions just a better understanding of the information process in the body and can you say just a little bit about that in the most basic level for that some of the people can better understand that okay so I gave lots of to pick enzymes and and factors and so forth it boils down to this your body is primed to respond against factors that it perceives as foreign and that so in but it can even be from your own gut right and also things that prime it to do that our stressors so if you're stressed then your body is going to produce these either circulating hormones and circulating factors like cytokines or it's going to Goose up these monocytes that become activated microglia so it becomes a sort of vicious cycle where you activate certain kinds of inflammation cells and you activate certain inflammation factors that then enter the brain and that process of of having things over activated is what we call inflammation good tension thank you - a good basic [Music] definition if somebody's listening now and they or a loved one I've been getting receiving treatment for depression and it's not working we've already given the advice to make sure that they are maximizing the course with particular medicine if that doesn't work what should they do next mm-hmm well so inflammation is not the only problem so certainly doing all the things to help somebody not have inflammation is one thing but there are some people who just have more severe depression so that even if like let's take a case where hypothetically you had treated with antidepressants and you also had done all the things that were going to contain in maybe you would even been on an anti-inflammatory agent but still the person with persisting and having a really severe case of depression then I then there are centers doctors who specialize in treating particularly refractory depression and so I think you know in consultation with with a doctor it might be time if they have this severe kind of depression to get kind of the most help you can get from things that are stronger and those could be things like electro convulsive therapy it could be for some people transcranial magnetic stimulation which is really in a developing phase where we're starting to understand more about it and see what the specific effects are some people have had remarkable success with vagus nerve stimulation or at the extreme deep brain stimulation I mean these are all extremes except for ECT which is the most underutilized treatment we have and you know when somebody has severe depression god forbid that we don't get them the treatment because the worst thing that can happen is that they just give up and and commit suicide which is you know so preventable so so preventable so for anybody listening who has somebody where they are really worried about that person then absolutely getting them maximal help is is what needs to happen it's a very important point about the issue of suicide and suicide prevention and that people shouldn't give up that just because it hasn't worked up till now there are other alternatives and I I would say often a good approach would be if there is an academic institution too far away from home they often would be able to have the resources to help with some of these options that you just described exactly they'll have a concentration of people who specialize in the more severe forms of illness I mean be that depression or be it it's a free me or be at whatever that's going to be probably a good option for people you bring up other illnesses is there information that you could share with us about the issue of inflammation and some of the other illnesses such as schizophrenia or bipolar disorder so um particularly so bipolar disorder absolutely the same things I've been saying about major depression would be absolutely generalizable to bipolar disorder in schizophrenia there's some really interesting evidence about kind of early early inflammation that may have triggered things I think there's less evidence that this is an ongoing problem in schizophrenia then in say bipolar illness or depression but but certainly it can be a factor there as well and in the when talking about bipolar it is it for both a manic phase and the depressed periods or is it more just in the depression periods it's more in the depression period because like I was saying what it really what inflammation really interferes with is the synthesis of the neurotransmitter serotonin and dopamine and so those are more involved in in mood regulation and inflammation itself produces I may not have said this clearly enough that when you have something like say interferon alpha which is an incredibly strong treatment that's used in hepatitis C people feel just miserably sick they feel fatigued and they feel complete loss of motivation or and loss of pleasure so the kind of precursors or that what we used to call vegetative symptoms of depression um and as those go on then it morphs into a full-blown depression but the first thing is really just what what inflammation does which is to make you feel sick and some people from an evolutionary sense have-have hypothesized that well when you're sick you stay out of the way of other people so you're not going to get stabbed to death by your caveman peers and you're not going to get eaten by a lion because you're just kind of hunkering down and feeling sick so the point of having inflammation is to make you be stationary and and not go out into the world so it is more of a sort of thing that goes along with depression okay you know and I think you're pointed about the the sickness behaviors such as fatigue loss of pleasure really fit in very nicely with what people who have depression experience availing so yes back up and how about anxiety does it fit into people who have anxiety it illnesses with anxiety or anxiety in and of itself that's a hard one because um it's so hard to tell anxiety and depression apart um you know they really go hand in glove and so um if I if you told me that it made people with anxiety feel better I would be wondering well were they really people with depression who had a very anxious sort of depression so we're actually going to be looking at that in our latest grant where we're looking across what the NIH calls negative valence syndromes and we're looking across depression and anxiety and PTSD and all the things with that kind of negative slant to them to see if we can tease apart the brain variables and the in the symptom variables that cut across the disorder the so we and the other one that I was you know asking you just mentioned post-traumatic stress is another one that potentially which has you know a lot of depressed symptoms as well as anxiety is another one that may be affected by this exactly exactly and is there any anything that you could say out for people who have tragically died as a result of suicide is there evidence that people who passed away well even people have serious suicide attempts that there is a greater degree of inflammation absolutely when I yeah when I when I showed you those slides of activated microglia that's where the evidence came from showing that it was the activated microglia that were more common in people with depression like I was saying it's not all the way to the extreme forms because for instance in multiple sclerosis is just a huge whopping inflammation response that you get so it's not to that degree but certainly at having not stationary not the nice little quiet microglia but the ones that are activated those are seen in a higher number in people who have passed away from suicide the I want to say a little bit more about the relationship between some of the medical conditions inflammation and depression and you focus on cardiovascular and we know that people who have a heart attack have a higher risk of depression after having a heart attack and in fact untreated depression after a heart attack is a risk factor for for a bad medical outcome exactly I know I forget what the mortality is but it's some really quite increased mortality if you have depression with your heart attack and you don't get it treated yeah I've seen reports that say untreated depression after a heart attack is even worse than untreated hypertension which door untreated high cholesterol that the untreated depression is the worst thing you could you can you can do and therefore the most important thing to make sure treatment occurs exact ROM I are you and your studies looking at that population as well or really more just this is great so what we're not we are not excluding them other than so they have to have a heart that's healthy enough to be treated with an antidepressant to be in our study and so if they're affecting their QRS their EKGs complex was too wide which would mean that their heart had was was somewhat unhealthy then we wouldn't be able to include them in the study but otherwise a history of heart attacks or even arrhythmias or anything like that we would we would include them because we want to understand about that right a couple of people asking about traumatic brain injury and how this relates to inflammatory factors etc I'm curious if you could say a little bit about that so now you're kind of getting further afield and I can really give you a definitive answer but but I would say TBI sets into motion a series of inflammatory pathways just because you've got this injury and anytime you've got injury you've got inflammation right so so yes it would it would definitely be present there and certainly lots of people with TBI have depression so I although I don't know the statistics and so forth I would say I I can't imagine that it wouldn't be a factor in TBI that both depression and inflammation would would be factors involved and then there's also the evidence I mean here's here's some indirect evidence people with TBI go on to a higher rate of mild cognitive impairment and Alzheimer's disease and one of the pathways is thought to be inflammation so even though I don't know whether people have looked at at TBI brains where people have passed away and found these inflammatory factors I would pretty strongly guess that the answer is yes although some future areas of endeavor in terms of research right now by you and others and how about the role of above me on medicine the role of talk therapy cognitive behavioral therapy other therapeutic interventions for depression has there been any studies about that absolutely actually I you're an audience plant Jeff we're just tending off a paper that looks at the brain effects of cognitive behavioral therapy and so we did studies where we gave this is your standard 12 week sessions where you meet with a cognitive behavioral therapist who does does the CBT buy the book in other words it's completely standardized so we can be sure that everybody got the same thing and what we found was after 12 weeks of therapy the brains you could see in the in the brain imaging that the cognitive control areas the prefrontal cortex had greater activity during a task that we were using to assess to assess how well the people did a task and then looked at the how much their brains lit up and people with depression have low levels of activity before treatment and higher afterwards significantly higher on likewise the connectivity you know the brain connections the functional connections between those areas and other parts of the brain improved with CBT so um you know CBT really does change the brain I can't I can't say myself anything about generalized talk therapy um I would I'm pretty sure it it does but it's much harder to show that because um I mean each therapist is different but when we do CBT we can make it be all the same like on day one we go through the strategies then you go home and you do your homework and you come back and you check in again and you do more homework so it's learning coping strategies for all the negative thoughts and and all the catastrophizing that people tend to do when they're depressed well this has been really a an outstanding presentation and great Q&A obviously based on the questions you see tremendous interests on the part of our audience and that I just want to thank you for the work that you've been doing and continue to do and certainly taking time to join us today to share this very important information so thank you very much my pleasure thank you yes also I want to thank the people who joined us today and all of the research that we fund is made possible through private donations and if you'd like to make a gift please visit our website DBR foundation.org or call our 800 number 1-800 eight to nine eight to eight nine this webinar has been recorded so if you've missed any portion of it or would like to share it with a family member or a friend please visit the webinar page on our website hope people will join us again next month when dr. fritz hen professor of psychiatry at the Icahn School of Medicine at Mount Sinai will present the webinar on bipolar disorder this will take place on Tuesday January 10th at 2:00 p.m. Eastern Time as this is our final webinar for 2016 I want to thank everybody for their participation and joining us for these webinars we're looking forward to having you join us in 2017 with again wonderful topics and a dynamic group of scientific presentations and I want to take this opportunity to wish everybody and their families very happy holidays and a happy healthy new year so once again thank you all very much you

Channel: Brain & Behavior Research Foundation

Views: 14,925

Keywords: schizophrenia, depression, bipolar disorder, anxiety, autism, post-traumatic stress disorder, ptsd, obsessive-compulsive disorder, ocd, adhd, brain research, narsad grants, symptoms, recovery, behavior research, warning signs, treatments, cure, diagnosis, hope

Id: XAAoooMVUk4

Length: 59min 53sec (3593 seconds)

Published: Wed Dec 14 2016