So, I am thrilled to be here and talk with all of you because talking with all of you even on a Saturday late afternoon is a lot better than Zoom. And we're going to spend, come on, let's have a little fun. We're going to spend a little while talking about what I think, honestly, is one of the biggest issues in brain injury care, and that's behavior. And the incidents and the problems that we're going to use a case-based approach. Our colleague, Dr. Ginger Polish, who is with us at Spalding and Harvard Medical School and Mass General Brigham, was unable to be with us tonight. She is on family leave, but she was kind enough to record an outstanding lecture where she will go over depression and anxiety. And Ginger has spent a lot of time focusing in on these issues with our colleagues in behavioral health and understanding some of the biologics as well as the therapeutics. And then Dr. Icarino, who really is the medical director of the home-based program at Mass General Brigham and Mass General Hospital, will focus in on post-traumatic stress disorder. So those are the three behavioral issues that we're going to spend the time on. We're not going to spend time getting into more abstracture. Perhaps next year or another year we'll do that. But that's the big three. So I'll ask my friend to start the counter, if he would be so kind. And we will start. These are my disclosures. Some are related to the book that we have that I give the proceeds to our residency program and the others are I'm on an unpaid SAB for a couple of companies. So we're going to talk about, is injury truly related to behavioral health? And we hope to show you data from one of our studies that we think epidemiologically is quite stunning and would compel all of you to really think, and almost all of your patients, about screening. I would argue to you that well over 80, 90% of the people in the TRACK study are milder injury people. They should not be susceptible, right? They should go on and be fine. That's what everyone in my era was taught. Perhaps not so much. How is injury or severity of injury and markers of injury associated with risk? Is a more severe injury worse? And what contributes to what I refer to in one of our other much larger studies as the maladaptive phenotype? What causes somebody to not do so good? It's complicated. So what happens to people? Because that's what we really care about. I'm not going to do the biologics today, right? That's what we care about. The vast majority of people here are clinical practitioners. And this is a study from Raquel Gardner that was with our cohort, the COBRAT study. And what Raquel did is she looked at everyone who had a similar cohort of injury. In other words, similar characteristics. She threw them up in the air and used mathematical latent class modeling. How do I find out how these people behave and what their unique characteristics really are? And, you know, I would have predicted, silly me, that there are one or two groups. There are eight groups. There are eight paths. And that tells us what we don't know about phenotyping in this group of people. This is a slide from our book that David Arsenagis and John Silver did in which I've used multiple different times that really talks about the fact that people are unique. There are pre-injury characteristics. There's an injury or perhaps multiple injuries. There are post-injury factors. These interact to cause cognitive disturbances, emotional behavioral issues, physical disturbances that I would argue in this lovely cartoon interact, right? If you have a lot more pain, you're more anxious. If you're more anxious, you're more likely to experience pain. And that many of these things go to person-based concerns, headaches, cognitive dysfunction, your mood, how you interact with your family, even your sleep, and, as I said, pain. Pain is an incredibly common thing after brain injury. All the way back to Debbie Malampally's article in JAMA, which was a lovely review years ago talking about the penetrance of this. And we're a part of a large study really trying to characterize that phenotype. And risk for even people with mild injury may be complex. This is Tom McMillan's old study from the north of Scotland. It's old, right? And what Tom McMillan did is he looked at 767 patients coming into the north of Scotland and noted that there was a crazy rate of mortality. Even people attending emergency department for the next 13 years. These are mild injury patients. What the heck is going on with this? We know from the TBI model systems that there is a nine-year decrement in lifespan. So yeah, could neurodegenerative disease be playing a role? Sure. But there's got to be more to it. We're trying to characterize this more to it in a very different cohort of people who actually were once ultra-elite athletes. So there are critical factors to think about when we think about these issues in so-called psychobiology. And that is injury pathology itself. So I would argue genetics are a misunderstood but strongly penetrant issue, education, what treatment people have gotten or lack thereof, what education they've gotten, support systems, bias against them and social disparities of health, expectations, and their acute issues. There's a lot here. This is a characteristic slide to look at, in some ways, what things improve or decrease resilience to events and decline after an injury. All of you are remarkably resilient. You're here on a Friday afternoon. But I would say that brain injury, midlife obesity, and we have data that suggests in another group of these elite athletes who decline, early life obesity does that. Midlife hypertension, current smoking, diabetes, depression, sleep disturbances, hyperlipidemia. And then if we think about resilience, well, years of education, your diet, physical activity. There's questions about alcohol consumption and social engagement. Social engagement, as we all learned during COVID, is critically important. Remember, data from our good friend Marcia Fava at Mass General Hospital suggests that between those 18 to 24, during the middle of COVID, the depression rate may have been over 60%. That is stunning. It's spellbinding and shows you what social isolation does. So is there a pre-existing risk to the behavioral maladaptive phenotype, right? So this is a very cool paper from Murray Steen from the TRAX-TBI group. This is a study that we are a small part of. Joe Giacino and my group is an even larger part of, in which people who come to the ED can require a CT scan, receive biomarkers, MRIs, and are followed up in an extensive fashion, really trying to understand the different complications here. And it really begins to look at this idea of the brain reserve hypotheses. How much you got and your unique characteristics may put you at risk for other things. Did you start off as a higher risk population? Remember the Seabury article from the TRAX group. Only 50% of the people who go to an ED and require a CT and further evaluation ever get further care. And most of those are one visit. We could never deal with all of it. The issue is, who's at risk? And how do we define that? And then see those people and mitigate some elements of that risk. This is a very cool paper and what they showed, what they showed was that if you have a smaller hippocampal volume to start with, you're at further risk for PTSD. This concept relates to other risk factors for PTSD that were done by Roger Pittman at Mass General related to a twin cohort study, where the susceptible twin were people with smaller hippocampal volume. So I believe in this wholeheartedly. If you have bad stuff going on early in your life, it's bad for you later. It is one of the most underappreciated things about how we treat each other. Let's look. This is a very cool study we published with Andrea Roberts, in which we looked at a series of ultra-elite players who had a number of ACEs. ACEs are Adverse Childhood Experiences. This is purely and simplistically on here. Number of ACEs are on your y-axis. This is your risk ratio. The further right you go in the slide, the higher your chances of this phenomenologic. So if you have four ACEs, these are early life experiences that are negative. They could be parents fighting, they could be food insecurity, they could be all the noxious things we do to each other, what do we see? Crazy rates of anxiety, pain scores, poor cognition, depression, and pain interference. So understanding who people are as we intake them is extraordinarily physiatric. But I would argue, and I think Monica might shoot me for putting this slide up, that it's not only brain injury. This is a recent paper in JAMA Psychiatry from Wang and others, in which they looked at premorbid distress, depression, and anxiety-based factors. Those people with those premorbid factors had a much larger chance of having long COVID and long COVID-related issues. That doesn't mean Ross is saying long COVID is psychogenic. It is, in my opinion, biologic. But that interaction term may be quite noxious for people and underappreciated. Oops, I'm sorry. So allostatic load. So allostatic load is also an important risk factor for it. This is McEwen's concept, for those of you who don't remember, and it goes back to this idea of early life experiences. These are emotional stressors, behavioral responses, physiologic responses, maybe trauma abuse. If you've had six allostatic load experiences early in life, your odds of depression, anxiety after another challenge are crazy. but it also means that you're probably going to lose a decade of life. Huge, underappreciated impact on behavioral health, stress, and other factors. So what could be a uniting biologic theme in all of this? What I would say that all of these things produce some form of redox, of oxidative stress, pre-radicals, cellular stress, early cellular aging or cellular senescence, inflammatory response, altered autonomics, and sympathetic ratios. Think about all of you and how the elderly, like me, once had a very different experience. When I grew up as a kid, Sunday afternoon, we might spend it calm with my grandparents. We might have dinner. Many groups of people went to some form of religious service. There was some parasympathetic time, whatever one thought of it. How many people here spend a lot of parasympathetic time every week? It's gone. You have almost unopposed sympathetic input, perhaps in a cohort of people who are more vulnerable. A big issue for us, and Ginger wrote a brilliant article about this in which she was first author in Journal of Neurotrauma, about the nocebo effect. Nocebo effect is a real thing. It is this conceptual that if you are introduced to a possibility of a negative response, you're going to accept that. It's a real biologic, not a psychologic effect. Nocebo effects are actually mediated by cholecystokinin, opiates. It's really only blockage of this with RACLA that you can actually produce an abrogation of this. It's an actual biologic effect. I would tell you that there appears to be data that suggests that the nocebo effect also has a genomic predilection. I want to show you quickly this idea of social infection. I believe it comes into depression or feeling bad, or even maladaptive phenotypes. This is a very cool article years ago from Ben Attendee, who was in Italy. What they did is they took a group of medical students. They told them they were going up to 3,000 meters. In a group of those folks, they told them, please come back to us and make sure that you get preventative treatment for headache because you're likely to get a headache. We want to take care of you. Those folks infected other people in the group. He's since extended this much larger to this original study. What do you think the headache rate was in the people who heard about this headache phenomena versus the other? Astronomically higher. What we tell our patients is critically important. Sorry about that. This is another study from the TRACS group that I'm a part of, this study. What we looked at here was emotional resilience. They really divided this primitively into distressed and not distressed, or distressed and resilient patients. They looked at 172-mile brain injury patients. Here what they saw was greater compromise of the white matter microstructural phenomena in the distressed patients. They did that by measuring global axial diffusivity. Maybe it is biologic. Maybe it is all injury pattern, but not so fast. This is Fred Corley's study in Lancet, again with the Lancet Neurology, with the TRACS group. What Fred did here in that study is they brought biomarkers to people immediately when they come to the ED. What they did was there are two major biomarkers, although I would argue that there are a series of them that will be putatively important shortly. One is GFAP, which is an astroglial marker, and the other is UCHL1. Those are also the only markers approved to discriminate who may need or may not need a CT. The markers were very good at predicting death, unfavorable outcome on the Glasgow outcome scale extended. They weren't at all good for saying someone was incompletely recovered, suggesting there's more going on than just astroglial and neuronal injury. There's some interaction term. This is even more so. This is also at a Fred's group in TRACS. I think Joe Giacino in our group was on the first part of this paper. I was an add-on author at the back, and Jacqueline was the first author. What they did is they looked at day of injury GFAP and high sensitivity C-reactive protein, an inflammatory marker. You would think their hypothesis was, hey, there's a link to PTSD, right? The worse your injury, the exact opposite. The lower your GFAP, the higher your risk for PTSD. What could be the reason? More extensive glial injury probably interferes with encoding. You don't remember. You don't get PTSD. That's kind of simplistic, and it's linked with a shorter duration of PTA. Makes some sense, right? So it's actually the reverse. Does it really happen in mild brain injury? So what's the evidence? So this is the TRACS study again, Lindsey Nelson. What Lindsey saw here was that we were all taught years ago that everybody with a mild injury gets better. Everybody gets better, not so much. What Lindsey found is that there were a lot of folks, I mean a lot, reporting functional limitations at 12 months, 53%, half. And it made sense. Those people with positive CTs had a higher risk. The vast majority of that problem, though, was behavioral. This is the follow-up study, or actually the a priori study from Murray Steen in the same group. And what he did is they looked at what were the issues at six and 12 months for this group's of people, and the major issues were PTSD and major depressive disorder. Risk factors, less education, psychiatric history, minority status, and assault or violence as a causative. This is another large group that used an administrative claims data set, Wilder et al., published recently in the American Journal of PM&R. And what they found was 48.64% of people who had had a brain injury, and this is administrative data set, was a mild brain injury, rather, were diagnosed with a mental illness within three years, 48%. There is almost nothing with a risk factor like that. So does brain trauma lead to behavioral comorbidities? So this is a paper that we published with Safe Izzy as the first author, and I'm the senior author. We had 29,000 people. We split them into two 9,000-person cohorts, and what we did was matching. We looked at these people over a decade, and we looked for the following. You cannot have had any comorbidity before you started with us. So we just tracked you for a decade. And I want you to look at these hazards ratios, depression, threefold, bipolar disorder, threefold in essence, anxiety disorder, 2.8, enormous. But this is probably displayed better this way. Y-axis is hazards ratio, X-axis is the disorder, the gradation here is 0 to 15. Can't you look at some of these? They're just stunning. And it penetrates all age groups. It's not just old people like me. It's even those folks who are younger wind up with these penetrant behavioral issues than others. And here we have a time-to-event analysis, Y-axis and X. And it doesn't occur at year eight. This split off of depression happens very, very early on. Look at this. The dark line is the brain injury group, sleep disorder, anxiety. I will tell you that those splits hold when you even do orthopedic trauma controls, let alone just plain controls. They hold with trauma controls. So there is something native to the group or the biological process that makes this a challenge. We also did encounter bias analyses. So what we did with the encounter bias analysis is we made sure that because you came to see us more times, that wasn't the cause. You see people more, physicians more times. What do physicians do? They make diagnoses. No, that wasn't the issue. Can we look at the moderate and severe patients? Everybody in the room says, I'm a physiatrist, I only see moderate and severe patients. Well, okay, here you go. Y-axis, X. The bottom is psychiatric disorder. But I would turn your eyes here in a later paper that we've done and other things that are coming out. This is cardiovascular disease, too, guys. This is psychiatric disorders. This range is 0 to 15, oh, I'm sorry, 0 to 20 here. And look at the elevations in anxiety, depression, psychosis, alcoholism. And yet we don't sub-follow this group of people. So near the end, we'll make an argument. The argument is that the instance is so high in this group, the tie is so strong, the problems are so real, that physiatrists have to be familiar with screening, understanding the pathology, knowing when to refer out, and early management. And here's my early management side. This is, again, from my good friend, Dr. Fava. This is the national shortage for behavioral health providers in the U.S. The U.S. is basically 16,000 short psychiatrists and 27,000 short mental health counselors and 60,000 short psychologists before the pandemic. Thus, there are a lot of things we can impact. Early identification, avoiding isolation, going into a cocoon is bad, minimizing nocebo effect. Alexis and Ginger will talk about some concepts and even treatments. Support structures and activities. And lastly, brain health is not a bad thing. So this is a study of people with preclinical and early clinical Alzheimer's who were recruited into this study. What they did with them is they gave them appropriate antidepressant meds, cognitive training, exercise, nutrition, and sleep. And they took even the people who were clinical Alzheimer's or pre-Alzheimer's and pushed out their disease. So there is something about this brain resilience training and compensating for all these things that we've known for years, but it's starting to be proven has a large effect. So I want to thank all of you. Just say that brain health issues are complex. Injury itself may intertwine with a lot of risk factors. And these are common issues after brain injury and things we should be a part of the early treatment thereof. Thank you, sir. And we'll have you go on to click into Dr. Polish's presentation. Thank you, guys. Thank you. along with a variety of behavioral symptoms. So, depression and anxiety can... and use that to create a diagnostic formulation and a rational treatment plan for anxiety and depression when there's a lot of comorbidity. So case number one, 49-year-old male tuna boat fisherman with extreme severe TBI brought in by his mother who reports that her son is depressed. So the patient was involved in a motor vehicle collision versus tree about a year ago. He was driving under the influence and veered off the road. He had PTA for about four weeks. Early agitation in the hospital required helicare and all for a while. Eventually discharged home to his mother. The mother does most of the talking in the clinic. She describes her son as unmotivated, having a difficult time completing tasks, rarely leaving the home, and having poor hygiene. The patient himself offers little. He appears flat and demonstrates minimal verbal output. When asked how he's feeling or what exactly is going on, he says, I don't feel anything. I feel sad. He doesn't feel happy. He doesn't feel joy in anything he used to. He generally feels empty. He said he has few spontaneous thoughts and does repeatedly think that he is, quote unquote, a loser. Agrees that he has difficulty with initiation, so he just doesn't care enough. When his friends or family try to take him out, he will. He'll go along to the coffee store or just get out of the house, though he really still doesn't feel like doing it. He'll just kind of follow along. Sleeping a little more than usual, low energy. Cognition is down. Food intake depends on what's in the fridge and he denies any SI. He does say, though, that he's feeling like a lost cause and doubting that things will ever change. He has no psychiatric history. He does have a history of ADHD diagnosed in middle school. He identifies as a risk taker. Gets easily bored. He had a single history of depressive episodes in his 20s, which responded well to SSRIs. That he was on for only several months. Social history, the divorced father worked in tech and then three years ago used all his money to buy a tuna boat and did quite well up until the time of this accident. His PCP started in a month's telepram a few months ago. He doesn't think it helped his mood and wonders if he's flat or sensitive. He uses marijuana daily. And for metrics, PHQ-9 is 14 and prior neuropsych testing showed mild deficits in attention, processing speed, and executive function, which were believed to be probably a bit worse since this accident. So here's his imaging. This is an MRI axial view of the GRE sequence. You can see grade 2 DAI along with a large intracranial hemorrhage right there. Medial temporal basal ganglia. Semi-intensible campyl formation. Alright, so if we were to kind of think diagnostically here, we'll think about depressive symptoms, apathy symptoms, and then cognitive symptoms. So he's got his history of depression, current depressive symptoms. Proactively, we'll consider a few things. Is this a feature of his depression versus something that's standing alone and how might medications or substances contribute? And then cognitively, right? His history of ADHD and a little bit worse, his executive profile. So a pheromone has been written with regards to depression after TBI and generally the ASM criteria is applied, right? So two or more weeks of depressed mood, sadness, tearfulness, and or anhedonia. Loss of interest or pleasure along with five or more in the following. I think most people are pretty familiar with this criteria. The challenge in TBI is that there are a number of symptoms that are neurovegetative that can exist outside of depression or could exist because of depression. Generally speaking, though, experts recommend following an inclusive diagnosis, meaning just treat the symptoms on the same note no matter what you think it might be from. So if you're trying to assess for depression or score on a metric, whether or not you think it's actually related to depression or not, just take the symptoms as are. So that being said, there are a few symptoms that are not neurovegetative. So sadness, tearfulness, along with this feeling of worthlessness or guilt or hopelessness and any type of SI. Those might help give one a little more confidence in thinking that depression is the correct diagnosis. For those who like metrics, the PHQ-9 has been designated as the most helpful for ruling in and out depression after TBI. So in this case, the patient's PHQ-9 is 14, which would be a moderate level of depression if we were to apply the inclusive diagnosis. And he has anhedonia along with thoughts like, I'm a loser and this will never get better. So that all kind of, again, it raises our confidence. So then what about the patient's flatness or lack of motivation? Is this anhedonia alone or is this something more? So here we introduce the concept of apathy, quantitative reduction of self-generated voluntary or purposeful behaviors. And there was a case series recently published from a neuropsychiatric clinic of consecutive TBI referrals. And the authors looked at who had depression, who had apathy, and who had the overlap. And 60% had overlap depression anxiety, 10% had only depression, 10% had only apathy, which would suggest this overlap phenomenon is quite common. So here's a little bit more detail here if we were to kind of sort in piece and parcel of the following. So our patient under depression was hopeless and pessimistic under the overlap. He had low social engagement, decreased enthusiasm, and anhedonia. But then under apathy, he also had this major reduction in initiative, interest in the environment, and a blunted emotional response. So he really kind of fit this overlapping category. So for apathy, we can categorize this in a number of different ways. A DSM way to categorize it is medical personality change due to a medical condition. A medical condition being filled with TBI or stroke or tumor, etc. And again, this is a personality change that would suggest in the chronic stage something more pervasive that is more consistent. As opposed to a mood disorder like depression, which can be quite episodic and might change when the patient is treated or the episode resolves. Collateral can be very helpful in assessing for these personality changes. And subtypes in the DSM are apathetic, labile, disinhibited, depressive, and paranoid. And these are all terms we commonly use and apply to the TBI population. So then why even consider using this medical personality change? For people who like using kind of more formalized rubrics, this can be useful. It potentially could also be useful in speaking to patients and families. Just saying, like, this is a thing that happens. And using this jargon, like a medical personality change, could potentially be helpful. All right. So can neuroimaging help in this case? So there's a recent systematic review on neuroimaging correlates of depression after TBI. And the authors of this systematic review concluded that, well, a number of studies suggest that prefrontal cortex anterior cingulate might be involved. By and large, this is not replicable, and all the data is not converging on these areas. So for more research to be done, we do not have a neural signature for depression after TBI. For apathy, however, in TBI and for other conditions, there seems to be a little bit more of a neural endotopic signature involving the medial prefrontal cortex, meaning the dorsal anterior cingulate and the normal frontal cortex, as well as subcortical regions, like the medial thalamus and lobe glute, hippocampus, ventral striatum, et cetera. All right. So our patient—oh, one more thing about the apathy circuits. So also these subcortical loops tend to involve high density of dopaminergic and, to a lesser extent, neuroadrenergic neurons. So our patient suffered grade II DAI with the primary endoparenchymal hemorrhage and the right medial temporal lobe, basal pancrea, and hippocampal formation. So that kind of fits a little bit, at least, with this reported apathy circuit. So we might hypothesize that his dopamine and norepinephrine circuits might be impacted. So another consideration in this patient's case is the contribution of substances and medication. So I won't go into cannabis, but most people, I think, would agree that high usage for chronic, long periods of time has been associated with an amotivational syndrome. So it may be a consideration. But medications also, in this patient's case, is something to think about. So there's this phenomenon called SSRI and use indifference, where you push an SSRI to a high dose and it actually leads to apathy and emotional blunting. And what happens here pharmacologically is as serotonergic activity increases, it can actually have an inhibitory effect. Membrane dopamine release that projects to the prefrontal cortex. And this can lead to a low dopamine or norepinephrine state and this emotional blunting apathy. So treatment here would just be to change the medication. I would recommend switching out an SSRI for an SNRI. Or, if you're really thinking depression apathy overlapped from the beginning, you might want to choose an SNRI. Or a different antidepressant agent as opposed to an SSRI to avoid all the weeks to months that it might take to potentially have the SSRI not work. Alright, so then let's think kind of in summary here. If we were to consider only depression in this patient's case, we treat just depression, the typical psychotherapy in meds. But we're thinking about these apathy and cognition symptoms too. So for apathy, we're saying this is not simply anhedonia. It seems to be more of a pervasive personality change in medications and substances. It should be considered. And then cognition. We're not going to go into it. But again, ADHD, this executive syndrome. So here's what we did for this patient. So we divided this into lifestyle, pharmacologic, and psychosocial efforts. So this took place well over a year. And every weeks to months, this patient was seen. And things were titrated and adjusted and we tried many things. So here's kind of what we did over time. So recommended decreasing marijuana. Patient declined. So then we ended up trying taking the patient off the teleprime. And it helped us out. It would be a tiny bit, not hugely tiny bit. Psychosocially recommended psychotherapy. The patient didn't want to participate. So that did not work. Continued to recommend getting off marijuana. Patient continued to say no thank you. Tried venlafaxine, so try that SNRI. Didn't really help with mood. And neither really helped with apathy. Though that wouldn't be a treatment for apathy. We were just trying to treat it there, but no impact. Eventually the patient stopped marijuana. He actually got a lot of money. And that was a new interest for reducing the usage. In this setting, we agreed to trial methylphenidate. To see if that could help everything or anything. It did improve his cognitive processing. It helped him move mildly. And definitely helped with apathy. And methylphenidate is a common treatment for apathy. So things started moving in a better direction at this point. We got him to group psychotherapy. He was not interested. Did not like it. So that ended quickly. Because his mood symptoms persisted. We then tried bupropion. Because this has more dopaminergic and more reactivity. And this resulted in a little bit more food improvement. Though his apathy wasn't really helped beyond what was helped by the methylphenidate here. So then we tried, as opposed to individual or group psychotherapy. We tried getting a patient a TBI buddy. So this was someone paid for by the state. That would meet with the patient. Take him out. Do tasks. This is almost like an external compensatory human-like strategy. And that seemed to help the patient more. So a few years at this point passed. The injury. He's definitely doing better. Does he feel great? No. But he's doing a lot more. He feels less down. And his initiative is better. So he will probably live with these impairments chronically. But he's certainly better than he was. All right. So that is patient number one. Next. Social anxiety case. All right. So this is case two. 37-year-old male Catholic priest with a remote history of TBI. Comes in saying, I may lose my job due to anxiety. So he sustained a severe TBI 15 years prior. He was intoxicated in college. And fell off a bridge, quote, unquote, directly onto his head. He says he was in the hospital for weeks. We talked to his family and the patient. Both were pretty helpful in kind of giving some information. So his family reports, we're going back a long time here. So the family reports that after the accident, he became much more rigid and short with others. Less warm and understanding and less social. He also became a lot more interested in Orthodox religion. His family had been Catholic, but only minimally affiliated with the church. So he became much more interested in the Orthodoxy afterward. And did some just kind of surprising things here and there. Becoming more conservative in certain aspects of his life. At one point for Christmas, he bought his teenage sister a loose-fitting, long-sleeved, full-length dress. Implicating that she should dress more modestly. This was something that would be very uncharacteristic in his family. And everyone found it very unusual, except for the patient himself. So moving forward, that was his accident. After his accident, he worked in business for about a decade. And three years ago, left to train to become a Catholic priest. He found the training very difficult, but was ultimately ordained. Struggled, however, with his first three assignments. The first he would let go of because he was delivering sermons in Latin, rather than English, despite being asked to use English. Because that's what the church goers preferred. Parishers complained of the harshness of his responses. For example, one asked the patient at one point, whether or not the patient thought her sister would go to heaven because she doesn't believe in God. And the patient responded, currently, if your sister doesn't believe in God, she'll go to hell. And many examples of this were coming out from this priest. So the patient reported feeling very internally uncomfortable when others tried to relax religion custom. He felt confused and frustrated by the negative feedback from church members. And over time, felt his confidence was being eroded. And started really worrying about the negative feedback. He was worried about his job. And became much more anxious in social situations when seeing others. He denied any frank avoidance. He had no panic attacks, no agoraphobia. For psychiatric history, he was a bit shy as a child of teen, but not functional. He was well-related. No concerns for autism spectrum disorder growing up. Neuropsych testing. We've had this done previously. And it showed intact, for the most part, cognitive functioning. A little bit of variability in processing, attention, and working memory tasks. And here's his imaging. This is a sagittal view on brain MRI. And you'll see on the right side, there's going to be substantial tissue loss in the frontal. And middle femoral gyrus. And a little bit of deferral or radiata. So, diagnostic considerations, so here, how anxious is this patient? You can see, again, on the spectrum, some symptoms here and there of anxiety, you can see you have an adjustment disorder, it's a meeting criteria for focal DSM, social anxiety disorder, and then the other consideration is cognition, right? You've got this executive syndrome model, but also something that hasn't been raised, and the phrasing is whether he has some social cognition impairments. So, with regards to anxiety, so for social anxiety disorder, the patient would have to have persistent, intense fear about a social situation and belief that he'll be negatively judged, embarrassed, or humiliated, have avoidance of those scenarios. This should cause clinically significant distress or functional limitations and be out of proportion. So, we ultimately decided he has certainly some features of this, but no slam dunk by any means, and his anxiety was not meeting the full criteria for a focal DSM diagnosis. Yet, social anxiety after TBI is fairly common, and this can happen at increased rates after brain injury due to changes in personal identity, especially with those with cognitive and attention and short-term memory issues. This can cause embarrassment and self-consciousness. Also, after TBI, people often have reduced social engagement and occupational pursuits, which lead to fewer opportunities to practice social skills, which can increase the risk of social anxiety disorder. So, social cognition for this patient, again, I think he had some degree of anxiety, but nothing severe. So, social cognition issues after TBI is common. Multiple beliefs can be impacted, including social perception. So, this means reading others' emotions, such as facial affect, tone of voice, body posture, theory of mind, which means understanding someone else's perspective, affective empathy, feeling in response to someone else's perceived situation, and social behavioral abnormalities, poor tact, lack of manners, and boundary infringements. So, we ended up having this patient undergo repeat neuropsych testing with a focus on social cognition. So, the neuropsychologist did some self-assessments, and they also did some tasks like the facial affect recognition task, where they played audio recordings of different verbal intonations, or showed a video where there's a social situation, and someone might be presenting something in their body language, but saying something that was a mismatch, and seeing if the patient could read between the lines. Overall, he did have a number of impairments. His intonation perception, in particular, was very poor, and he had a very difficult time understanding this. He could understand the meaning of verbal information, but again, reading between the lines, understanding jokes, understanding sarcasm, was all very difficult for him on testing. And so, this was believed to likely result in some nonverbal communication issues, and make it more difficult for him to be tactful in conversations. And this all could be exacerbated all the more by his underlying mis-executive profile. So, ultimately, again, this patient had some degree of anxiety, did also have some social communication and social cognition issues along with his mis-executive dysfunction. So, from a neuroimaging standpoint, nothing really matches too much of this blend up from anxiety or social cognition, but again, he had a superior and middle frontal gyri were implicated, and these regions are mostly functioning in attention regulation, executive function, or attention regulation, working memory, and inhibition. So, again, it doesn't really point us anywhere but the no-cognitive disorder. Alright, so then, thinking diagnostically again, if we were just focused on the anxiety, we would suggest some type of psychotherapy. Again, he didn't meet criteria enough to warrant medication, but if it was severe, maybe we could think of medications. But we're also thinking of his cognition and social cognition. So, with regards to that, there's a few more interventions that we might explore. Social cognition, in brief, is getting more and more intense in the brain injury world, and there's reports about different ways that this might be mediated, and there's different skills training, social skills training, social problem solving, that are being borrowed from other fields, such as those with Autism Spectrum Disorder, or Schizophrenia, or Nonverbal Learning Disorders, and applied to TBI with some success. So, we tried to integrate that into our treatment plan. So, here's our final treatment plan. So, we decided not to treat the patient's anxiety pharmacologically. We got him some individual psychotherapy to support his struggles and his work. He wanted to try level benedate for the processing speed attention issues, and we tried it with some mild benefit. He underwent speech therapy for caught rehab. We then had him return to speech therapy for an emphasis on social communication, and tried to work on some of the intonation issues. We also connected him with a local coach, who worked regularly with individuals with high functioning Autism Spectrum Disorder, who was really getting into the social problem solving with him, and helping teach social pragmatics, and this was useful because there wasn't a whole lot of individuals in the speech therapy realm who did a lot of work with social cognition, but this Autism Spectrum Disorder kind of coach had a ton of experience with this, and we felt like it was close enough to be a decent match, and it ultimately was. Finally, the patient also spoke to a supervisor who was going to change his parish location. He ended up working and starting to preach at a church that was very small for individuals who were Catholic priests who had substance use disorders, so he would preach to priests, and really enjoyed it, and was well received, and kind of his own special personality flare and style was just taken very favorably by this group. So again, kind of a bigger environmental change also really helped this individual move forward. So, long term, he's doing a little better, still has difficulties, and will also, like the first patient, likely have lifelong difficulties, but on a bit of a better path now than he has been before. Alright, so to summarize, typically TBI can result in a range of acquired cognitive and neurobehavioral symptoms, and these symptoms and impairments will overlap, leading to a greater challenge in building out a differential. So, if we apply the biopsychosocial model, take a careful history, consider all factors, get some good collateral, neuropsych testing, this can really help with creating a more nuanced diagnosis and treatment approach. Thank you. Hi, everyone. Thanks again for sticking around. Dr. Safant said we'd end on time, so to that I say, game on. I'm your last speaker. My name's Alexis Icarino. I work at Mass General. I see mostly concussion and mild TBI patients, and I have the privilege of overseeing our TBI and PTSD programs at the MGH home base for military service members. So, I was going to present to you two cases, but then I wrote up one, and it was complicated enough. So, we're going to talk about one complicated person and hit on some important topics related to PTSD. I don't have any relevant disclosures. I get some funding from the Wounded Warrior Project to do research, and the National Football League is a consultant. And these are the learning objectives that are printed, and we're going to focus on PTSD. And what I'm going to tell you about these people is they have a lot of layers, right? So, I'm on maternity leave right now, so I'm sort of in this baby space, and this one resonated with me, a lot of layers. And we'll try to peel those back slowly, but, you know, if this case happens to be your 430 patient on Friday afternoon, well, you're going to be late picking up your kids from daycare. Okay. So, this was a 52-year-old man, a newly retired military veteran, presenting to us in the TBI clinic for headaches and concentration difficulties. They were happening in multiple domains, at home, at work. They had reached a point where even somebody with tremendous pride and absolutely not wanting to come to medical care decided he would come to medical care. So, they had really reached a threshold for him and his functional abilities. And he had a 20-career service as an EOD tech, so Explosive Ordnance Device Tech, the guys who get near the stuff that goes boom all the time. And in his exit interview with the military, he had been given a diagnosis of mild traumatic brain injury that he previously did not know he had. But based on reporting loss-of-consciousness events around one of these explosions, he was given a diagnosis of mild TBI. So, this is a pretty common case for us. And notably, he had seven combat deployments, seven times. So, tremendous amount of exposure to highly stressful environments. Had, you know, seen colleagues die. Had felt his own life threatened multiple times. So, sir, tell me about your headaches. Okay. They are daily. They pound. They are moderate to severe in intensity. They are worse when I have to do stuff. Like, they go really bad at the grocery store when I have to go out. They are worse at work, particularly multiple people coming at me, large meetings. They get better when I get home in the quiet environment. And they weren't really tied to this MTBI event when I got, quote, blown up. It was really just started two years ago. It was insidious and onset and not really correlated to the TBI event. And sometimes over-the-counters help. And I have noise sensitivity and ringing in my ears when I get a headache. But I don't have prodrome or aura, nausea, vomiting, light sensitivity, some of those more migraines type features. And then I'm really struggling. Doc, I think I'm getting Alzheimer's. I knew a guy when I was deployed and I came back and I don't remember him anymore. I met him and he came up to me and he said, don't you remember we spent a year in Iraq together? But I couldn't remember him. I couldn't remember his name. I don't even remember meeting the guy. Total lapse for some memories while deployed. And unable to remember a grocery list and trouble focusing at work. So both concentration and concerns about his memory that he was really very startled by. And then, Zola, tell me a little bit more about you. So, well, I don't sleep well either. And I'm in a bad spot with my wife and my kids because I blow up. I get angry and I'm irritable and I can just go off the handle at any time. And nobody really knows what's going to make that happen. I'm having trouble going out and engaging with friends because of these behaviors. And then I've got also pain and I'm thinking about doing some testosterone therapy because my libido is low. And I can't exercise anymore and I've gained a lot of weight because of my pain. So these are very common comorbidities in this group. So he's got this mild TBI with what we also consider to be multiple close quarter detonations. So we're not going to go into detail about repetitive blast exposure and all these things. But the literature supports there's probably something to that, even if they're subclinical. He's got bilateral high frequency hearing loss. He's got some musculoskeletal problems. And despite all of this, he manages multiple teams at the DOD. So he's kind of a top dog at DOD. And he's doing some really cognitively challenging things in his work, even though he has these pretty profound cognitive complaints. He's got an MBA and he's using CBD for sleep and he's drinking about four drinks a night to get to sleep. And so he's using a little bit of alcohol. And then the other thing that's causing some family strife is that he has a concealed carry permit and he's carrying his gun everywhere. So he takes it to church. He takes it to the grocery store. He takes it to the mall. And his family feels like this is sort of inappropriate to be carrying all the time. This was his exam, neurologically unremarkable. He's got high blood pressure in the office. A lot of people do. His cognitive testing, which we just did parts of a mocha in the office, down and dirty, nothing extensive. He really begins to become very distressed at the cognitive testing to the point where he struggles to complete it. He has a lot of challenges on memory recall. He doesn't do well in digit spanning. He's getting very frustrated. And he has some areas, though, that are preserved. He does well on trail making and some visual spatial things. And he's got a lot of errors on impulse, just a quick go, no-go test in the office. But absolutely distressed trying to do these tasks. So we complete some measures on our patients. You can really pork up a visit with a lot of measures, but we try to keep it streamlined. So we do a HIT-6, which just gives us some self-report about headache severity. And this guy has headaches that would be characterized as impactful to his daily function. We get the NSI, which, if you're not familiar with it, looks at physical, cognitive, emotional, affective symptoms. And there's no cutoff scores in NSI, but people with TBI and with mental health conditions report high scores on the NSI. We did a depression inventory. He scored in the area for mild depression. We did the audit, which is very quick. And he had sufficient alcohol use to be considered alcohol misuse. And then we did the PCL, which we'll talk about a little in more depth, which is a self-report 20-item measure for PTSD. It's quick. You can do it in the office and get a provisional PTSD diagnosis. He scored in the moderate to severe range. He also screened positive for sleep apnea. And he screened positive for severe anxiety symptoms on the GAD. So this is a totally mixed bucket of things. And I think what it illustrates, no surprise, we're going to go on to diagnose this guy with PTSD, in case anybody was on the edge of their seat. But the point is that people with PTSD and mild TBI can present positive on a lot of these screening measures. And these screening measures have tremendous crossover, right? A lot of them ask the same thing. So it's not uncommon to get high scores in multiple areas. So how do we break this gentleman down? He's a middle-aged military veteran, multiple tour combats, chronic daily headaches not associated with head trauma, cognitive complaints with really incongruently poor performance on our testing, right? So for the work he does, he performed extremely poorly. So it's sort of out of proportion to what we would expect, given his high level of daily function. Very poor distress tolerance. And then concern for multiple mental health comorbidities and other physical comorbidities, including sleep apnea-type symptoms. Okay. So what are the next steps for this person? So given his history, his combat tours, and his scoring, we had concern that he could have post-traumatic stress disorder. And how do you go about diagnosing PTSD? So we're going to look a little more at the PCL in the next slide, but the gold standard diagnosis is going to be some sort of structured diagnostic interview. Now you heard that we are down mental health providers, right? Who's going to do, who am I going to refer to, right? The structured diagnostic interview. But ultimately it is important that you do get a patient some sort of structured psychiatric or psychological interview because of the mixed features and presentation and the symptoms that have tremendous overlap with multiple mental health diagnoses. And then if you do have a patient who has post-traumatic stress, there are a number of evidence-based trauma-focused therapies that they should be engaged in. So I point this out because I think, you know, lots of patients will say, oh yeah, I went to therapy, it didn't help. And the next question should always be what happened at therapy, right? Did you just talk to somebody about your day and your family and it didn't really get better? So evidence-based trauma-focused therapies are rigorous, rigid, structured therapies that are, that mental health providers are trained in specifically, right? So they'll have certification for things like cognitive processing therapy or exposure-based therapy, right? So this is a very specific type of psychotherapy. And there are lots of providers who are trained in it, but you need to ask your patient, particularly if they've already undergone some sort of psychological counseling, did you actually do something like this? Because this is actually what works in people who have PTSD. General talk therapy usually won't get you there. Then eye movement desensitization and reprocessing therapy is another form of therapy that involves eye motion that has been shown to have some benefit in moving the needle. Although, I'll tell you, we actually don't do a whole lot of EMDR in our clinics. We're mostly heavily based in CPT and PE. And then certainly our job, right, addressing TBI symptoms. But this is what you're looking for if you have concern for PTSD or you're asking patients, have you had treatment for PTSD? So what is PTSD exactly? So this is a delayed or protracted distress response. There is acute stress. And then if it goes on for a long time, months, we get into concerns for inset of post-traumatic stress disorder. And this distress response is to some extraordinary event. Now, the DSM originally said you had to have an index trauma. You had to have some specific event that caused you to believe your life was threatened or in danger or you were out of control of your situation. But now it's recognized, actually, that it doesn't have to be a single event. It could be an environment that you're in for a sustained period of time, such as being in an abusive setting or in a combat setting. So while most people have what is termed an index trauma, not everybody will. They may be sort of in an environment that's pervasive. And people have episodes of reliving and re-experiencing the event. There are triggers. But this all lays on a background of a flat, blunted person. So they're not always anxious. Actually, most of the time, they're quite withdrawn. And then they have episodes of reliving these traumatic experiences, whether it's in person or while awake or with nightmares or other type intrusive thoughts. And they're often quite avoidant. There's anhedonia. And then there's a component of sort of an autonomic hyperarousal, which I think has a lot of overlap when we think about TBI. There's hypervigilance. There's tachycardia. There's sweating, hypertension, this sort of poorly regulated flight or fight response. So we're not going to do structured interview. But we can use the PCL. And so it's pretty easy to do. So here's a copy of the PCL. And there's a couple of ways you can think about this if you use it in your office. The first is that roughly a cut off of 30 and you should start being worried about people. That's the down and dirty if you're in a busy clinic. If you get a little bit one layer deeper than that, patients have to have certain numbers of each type of PTSD symptom. So they have to have at least one intrusive symptom, like nightmares or re-experiencing, at least one avoidance type symptom, two sort of negative symptoms, and then two sort of hyperarousal or reactivity symptoms. But ultimately, I think for the non-mental health busy provider, if people are scoring over 30, you should be pretty concerned about that patient having PTSD. I'm just going to go back really quick. We used two gold standard clinical interview techniques at home base. One is called the CAPS, or the Clinically Administered PTSD Scale, from our mental health providers. And then the other is the Diamond. In case you ever see these in psychotherapy reports, the Diamond is another similar structured interview type. But these should be the sort of things that if you're seeing mental health reports for a patient, you're going to be looking for this sort of diagnostic assessment to know that this was actually done right. OK, PTSD and TBI. So Dr. Safant really took the literature apart in a much more thorough way. But just to remind you, physical injuries and TBI can be associated with the development of post-traumatic stress. And TBI likely incurs a higher rate of PTSD than other injuries. And certainly, in looking at mild TBI patients and orthopedic controls in the track data, that told us that pretty well. PTA may be protective. Although there is a study, which we have down here, which looked at loss of consciousness in mild TBI patients. And those with a loss of consciousness in just a mild TBI group were more likely to go on to develop post-traumatic stress. That was in a military cohort. And then more positive data in the moderate and severe TBI populations, perhaps because they're less likely to develop this phenomenon. PTSD is a well-known risk factor for prolonged and protracted mild TBI symptoms. You might ask yourself, chicken or the egg? And I think it's a good question. But these things often run together. And then from the track data, civilians with MTBI were greater risk of PTSD than orthopedic controls. Sleep disorders. PTSD is highly associated with sleep-related breathing disorders, of which obstructive sleep apnea is the most likely. We also know there's a lot of overlap between TBI and OSA. So in a person who's already presenting with two of these three things, it's not uncommon to get the third and have the trifecta, which is what happened in our patient. PTSD and other mental health conditions. So this is from Ron Kessler, who's at Harvard. This is old data, really old, 95. And this is a national database of mental health conditions. People who had PTSD were more likely to have another mental health condition, most likely anxiety or depression, and were much higher likelihood to have greater than three comorbid mental health conditions than someone without PTSD. So these folks are very likely to not just have post-traumatic stress, as our patient did, but also score highly in other areas of anxiety disorders, depression, and in our patient's case, alcohol use disorder. These patients are going to come to PM&R clinics. Why? Because if you have PTSD, you are more likely to utilize non-mental health medical services. So you're more likely to come to the doctor for other problems, most often pain, actually. So these people are more likely to utilize health care, although not in the mental health space. And so we are going to have these folks in our clinics. They have more medical visits. They have higher health care utilization, more missed days of work. And they're more likely, as Dr. Safant showed us, to have other physical comorbidities that put them at high risk for other diseases. So getting back to our patient, headache management. So for this patient, we had him do a headache diary. And what we quickly found out on follow-up visit was that many of his headaches were triggered around times of stress related to avoidance and intrusive thoughts around his PTSD. So we felt that these headaches were very much related to post-traumatic stress. And non-pharmacological treatments for these are very similar to what we might do in, say, a tension headache paradigm in our TBI population. So one is looking at stress reduction, understanding and identifying triggers, looking at sleep, which in this case, we also had to address obstructive sleep apnea, hydration, which in this case, we are dealing with an alcohol use disorder, exercise, and other sort of passive therapies. On the pharmacology side, this patient very clearly was needed regulation of autonomics. So he had high blood pressure in the office. Periods of stress were causing these high, throbbing headaches. And so in this group, I often go with propranolol as a starting point. And that's because I know I can sort of offset some of that autonomic tone. And it's second line for headaches in general for migraine. So we actually get a lot of bang for our buck with propranolol. And we get kind of less of the cognitive side effects that we might see with some of the other agents. So we started propranolol on this patient. Other things you might consider earlier on your trial chart than, say, with your general TBI patient or your general tension headache are things like SSRIs or SNRIs and perhaps gabapentin to help augment sleep. So there's no specific algorithm for the TBI PTSD combo patient. I think you take your TBI headache algorithm or your tension headache algorithm, and you start to think about those agents that might also offset some of the PTSD symptoms and work from there, which is what we did. You have to assess for comorbidities, which is where these patients can become really challenging and take up maybe a bit of your time. But just know that you don't have to do it all at once. You can do it over time, slowly. Over multiple visits, you build rapport and help patients start to parse out the various features. And then ultimately, on the cognitive front, neuropsychological assessments may be necessary, but they're hard to get. We have a two-year waiting list at MGH to get neuropsych testing. So you're going to have to go it alone for a while. And when you see that these cognitive complaints are so out of proportion to the patient's function, it leads me to think more about the impact of mental health factors on that patient than perhaps the development of some sort of degenerative neurocognitive process. And that was certainly true for this individual. And it's not uncommon for people with PTSD to have loss of memory during the time of tremendous stress, which is exactly what this gentleman had. Management of cognitive complaints. So cognitive rehabilitation has been shown to work for these folks. I'm going to show you a little bit of our data. Also, out of UCSD, they recently published a study on using combination of cognitive rehabilitation in the form of COGSMART with cognitive processing therapy, which is an evidence-based treatment for PTSD, found that patients who got both together did better than either group that got it alone. So there's something to be said for sort of double-dosing your therapeutic interventions in this group. So we conducted a two-week intensive treatment program for people with overwhelmingly mild to moderate TBI and comorbid post-traumatic stress using both cog rehab and evidence-based PTSD treatments along with, you can see here, a host of other therapies. Patients come for two weeks. They do eight hours a day of treatment. Compressed PTSD treatment in two-week period has been well-validated by some of our colleagues at Rush, Phil Held's group saw that if you do two weeks of intensive evidence-based therapy, it actually works as well as a 12-week outpatient course and has sustained benefit. These are our patients. We looked at the PCL and a number of other measures pre- and post-treatment. Again, these people also have comorbid TBI. And our group got quite a bit of benefit moving from pre-treatment having scores, again, above 30 and then coming down to sub-threshold PTSD post-two weeks of treatment. These are depression inventories. The depression symptoms get better. The neurobehavioral symptom inventory, the NSI neurobehavioral symptoms also get better. And then if you just look at the cognitive subscale of the NSI, since we are doing heavy cognitive rehab, we see a lot of movement there with high effect size. So we got good data that this sort of intervention works. Some of these people got medication. Some of them didn't. They all got a background of usual care as needed. So it's a little bit of mixed other therapies in the background. But these people can get a lot better. Their symptoms can get better. So back to our patient. We did assessment of sleep, pain, and mood. He ultimately did undergo neuropsych testing. And guess what? It was inconclusive. And I don't know how you guys feel about getting this back from your neuropsychologist. But he basically was too distressed to really engage in cognitive testing. And we see that a lot. And sometimes I think it gets mistaken for sort of malingering or other sort of things. But this is truly that one is so psychiatrically active that they actually can't put forth the appropriate effort to participate in neuropsychological testing. And so that's what happened to him. He had these additional diagnoses. And he did outpatient cognitive processing therapy followed by two weeks of intensive treatment. We put him on propranolol for headaches and prazosin, which is an alpha blocker for nightmares and to help sort of regulate autonomic function. And his headaches did start to get a little bit better. Very quickly, what should we actually expect for these people? This is a lot, a lot of layers. Back to slide one. Chronic PTSD is not uncommon. And so we can expect that these folks will get better, but not completely better often. So what are we setting the bar for? Well, we want people to have better function, right? This is a physiatric model, right? So we want them to be able to do better at work, to be better with their family, to maintain those relationships, and to be able to engage socially. So we're not looking for a person who never has a headache again, who never has re-experiencing symptoms, or no nightmares ever again, or sleeps well every single night, right? We're looking to sort of bring them down a level. But I think it's unrealistic to expect, particularly early on, that you're going to get people 100% better. And I think everybody here, I hope you'd agree with me on that. You've probably seen these patients. And then lastly is avoiding what Dr. Safant so nicely explained, which is the nocebo, right? Which is the misattribution of symptoms to a particular condition, because you have a prior knowledge of it, right? So it's very common for people to not necessarily misattribute, but potentially over-attribute their symptoms, potentially to brain injury, when there may be an effect from a mental health condition, right? And so that's a tap dance, right, when you're with your patients, right? Because they're coming to you to treat these physical complaints. But you have to very carefully dance in that there may be a mental health component to this without alienating them, which I think is something I continue to work on as a provider, on how to best approach that with people, so that you get buy-in. You get appropriate attribution of symptoms. And you get people who are willing to engage in therapy. So patients with TBI and co-morbid mental health conditions are a complicated group. TBI is a risk factor for getting PTSD. PTSD has a lot of similar features to particularly mild TBI. You have to promptly recognize, diagnose, and treat these mental health conditions. And you can use both evidence-based psychotherapy strategies and medication. So thanks so much. 502. Failure. 502. All right. We'll take questions. We will take questions if anybody has any. Questions, comments, thoughts, frustrations. Opportunities to head to the bar. Yes. Hi. Good afternoon. Thank you for giving such a great talk and overview on the neuropsychiatric conditions following TBI. I was wondering, since the onset of these conditions can typically take up to a year to occur, are there evidence for, I guess, prophylactic treatments preventing that sequelae instead of just diagnosing and then treating, waiting for the best outcome? Is there evidence or any therapy that is out there that can be serving as prophylactics? Yeah, that's a great question. So in the PTSD literature, there is data to support early use of actually beta blockers in people who meet criteria for acute stress response. So this is really early symptoms of post-traumatic stress. We actually had the experience of doing this in our Boston Marathon bombing population because we had the ability to know those people very early after that traumatic event. The data is, there's not a lot of it. It's mixed. But I think, if it were me, I think I'd try it. I'm just going to say that. Yeah, the data supporting prophylactic treatment for depression isn't quite there yet, although there are some studies, right? The whole idea, you're asking a great question, is to define the subgroup of people who might be at ultimate risk, which is the point I was trying to bring out at the beginning, and then intervene ultra early in that group of people. Roger Pittman studied it from Mass General in PTSD with propranolol was negative, but some others have been positive. And so it's still believed that that might be an early adjuvant for people with extensive trauma and hyperreactivity. I was wondering if you can even track whether or not the prophylactic treatment is working through consistent brain imaging studies, like fMRI, because there are areas in the brain that will be altered for these depression patients, PTSD patients. I was wondering if those follow-up studies can use any biomarkers or imaging studies to sort of follow up on that progression. Yeah, the best stuff I know of is the TRACS group, the one we refer to. It's Jeff's study, Jeff Manley, and has multiple collaborators here. And then there's the European co-collaborative group. And really, they're seeing people with more significant injuries. So they're not including sport-related concussion, but they're following those people longitudinally and obtaining initial biomarkers and later biomarkers. Which as I showed you guys in the Quirley study in Fred's study was mixed, right? So the GFAP and UCHL, they didn't predict people's six-month outcome. But in the negative, GFAP predicted PTSD. In other words, the lower, the more likely. Yeah? I actually had a question about how you guys address the allostatic load and the Nocebo effect and specifically how this can relate to people who had traumatic brain injury and prophylactically kind of also keeping them up to a year or so of like preventing the Nocebo effect or the allostatic load, low-stress environments. Has there been any research as to how kind of being in a low-stress environment can help prevent PTSD development? I'm not aware of a good process study except for mindfulness-based stuff related to PTSD and prophylaxis as far as allostatic load. You know, that's a difficult thing to manage because some of it comes from our own communities, people experience early in life. Some of it, I'm just saying that we have to understand that in the interview process with people and that's kind of critical. Trying to manage it early on becomes both the interaction term between medicine and social society because some of it is socially driven. I would just add, I think on that sort of allostatic load front, I think there's particularly in the military space, which is where I do a lot of my work, there's I think a big push when I talk to my military colleagues about sort of upstream sort of CBT and cognitive processing and debriefing, thinking that, you know, military service members who are active duty would actually do very, that that might be a prophylactic approach for them. Embedded mental health in forward operating deployed units is a big thing now. So, you know, a psychologist, you know, just like you have a medic on the team, you've got a psychologist on the team, right? Because we've now seen how pervasive the mental health difficulties are. So, you know, can we address them sooner and be almost prophylactic about them? But I don't know of any data to support that work yet. Yeah, but the early intervention phenomenon is really incidentally positive. Yeah. And I think that, you know, sometimes we become so physically and anatomically worried that we forget, which I'm all for, that behavior probably pays a big role in a lot of things we treat and see, not only brain injury. I just had a question about interpreting neuropsychological testing where you have folks coming back and the neuropsychologist is saying they have a lot of variable responses, invalid responses, and they have a somatoform disorder. I pretty much get that on every Work.com patient. Yeah, I mean, yeah, yeah. I mean, I think, you know, we see it a lot, too, that the neuropsych testing is either normal or inconclusive. And I would say that my thoughts would be that I'm extraordinarily careful in how I interpret that data coming back because I do think that there are a lot of people, you know, who fail validity measures and really are just struggling to engage and are not necessarily looking to, yeah, looking to sort of circumvent the process. You know, our team, our neuropsychology team often adds on the MMPI, which is more of a personality index, which can be kind of helpful, I think. So you might talk to your neuropsychologist about that. MMPI is like, I don't know, it's like 150 or 200 questions. It's something like really long. It's on the computer. So it takes time to do, but it can sometimes be helpful because it looks for personality traits, which then might help back up sort of if you think that this person is like volitionally, you know, not doing well on validity testing or if it may be something less nefarious. So, but I think neuropsychological testing for me is helpful, but it's really not everything. But, you know, I think good relationship with your neuropsychologist to ask about those things helps. And we see people who do better on it, you know, after some treatment, too. So we don't routinely get it again. But I'm not quick to say, well, the neuropsych testing was invalid because you didn't make enough effort because you're trying to pull one over on us. I think the test results are one thing. The attribution is another. Yeah. So, I want to thank all of you for being here this late. I suggest that there are substances that will alter your awareness for this afternoon. You should go find them. You should go find them. Dr. Iaccarino has been kind enough to join us from her maternity leave, so big round.

behavioral issues

brain injuries

depression

anxiety

PTSD

case studies

treatment approaches

early identification

screening

traumatic brain injury

evidence-based therapies

individualized treatment plans