From Screening to Treatment: Rethinking Suicide Risk with Elizabeth Ballard, PhD

Journal of Clinical Psychiatry

Publisher of peer-reviewed research discussed in this episode.

Ask Suicide-Screening Questions (ASQ) Toolkit – NIMH

https://www.nimh.nih.gov/research/research-conducted-at-nimh/asq-toolkit-materials

Free NIMH toolkit for the screening instrument Dr. Ballard helped develop, discussed at length in this episode.

Dr. Elizabeth Ballard – LinkedIn

https://www.linkedin.com/in/elizabeth-ballard-943245350/

Elizabeth Ballard, PhD, is Director of Psychology and Behavioral Research and Director of Pre-Doctoral Training at NIMH’s Experimental Therapeutics and Pathophysiology Branch, where she has spent more than a decade studying the neurobiology of suicide. She helped develop the Ask Suicide Screening Questionnaire (ASQ), now used in emergency departments nationwide, and was first co-author on the individual patient data meta-analysis establishing ketamine’s rapid antisuicidal effect. In 2024, she received the NIH Director’s Award for this work.

Ben Everett, PhD, is the creator and host of The JCP Podcast, a series that brings together leading voices in psychiatry to explore the latest research and its clinical implications. Everett earned his PhD in Biochemistry with an emphasis in Neuroscience from the University of Tennessee Health Science Center. Over a two-decade career spanning academia, publishing, and the pharmaceutical industry, he has helped launch more than a dozen new treatments across psychiatry, neurology, and cardiometabolic medicine. His current work focuses on translating complex scientific advances into accessible, evidence-based insights that inform clinical practice and foster meaningful dialogue among mental health professionals.

00:00 – Introduction: Dr. Elizabeth Ballard’s Path to Suicide Research

Dr. Ben Everett: Hello and welcome to the “JCP” podcast. I’m your host, Dr. Ben Everett. In each episode, we sit down with leading clinicians, researchers, and educators to explore the science shaping mental health care today, with a focus on the insights that matter most in clinical practice. Suicide risk is something every mental health professional assesses in some form in nearly every patient encounter, and yet the tools we use to do it and the evidence behind our treatments are still very much a work in progress. researchers have done more over the last decade to sharpen both sides of that equation than my guest today. listeners will remember our conversation earlier this year with Dr. Brett Jones. Today’s episode continues that series, widening the lens from acute inpatient care of suicidality to the full arc of suicide risk assessment and treatment, from screening the emergency department to the latest evidence on rapid-acting interventions.

My guest today is Dr. Elizabeth Ballard. Dr. Ballard is Director of Psychology and Behavioral Research and Director of Pre-Doctoral Training at the National Institute of Mental Health’s Experimental Therapeutics and Pathophysiology Branch, where she has spent more than a decade working alongside Dr. Carlos Zarate on the neurobiology of suicide. She was part of the team led by Dr. Lisa Horowitz that developed the Ask Suicide Screening Questionnaire or ASQ instrument, which is Joint Commission approved for use in patients of all ages and is now used in emergency departments and medical settings across the country. was first co-author on the individual patient data meta-analysis establishing ketamine’s rapid effect on suicidal ideation, published in the American Journal of Psychiatry. Her more recent work has pushed into biomarkers of suicide risk, sleep, electrophysiology, implicit cognition, and into hopelessness itself as a treatment target. In 2024, that body of work earned her the NIH Director’s Award, cited specifically for advances in identifying and treating individuals at highest risk for suicide. Dr. Ballard, welcome to the JCP podcast. This is a topic where I think a lot of practicing psychiatrists feel like they’re operating more on instinct than evidence, so I’m glad to have you on today. You’ve spent your career really trying to refine these assessment tools and treatment strategies.

Dr. Elizabeth Ballard: Very excited and honored to be here. Thanks so much.

Dr. Ben Everett: All right. Well, look, let’s get into it. So your earlier publications or really earliest in your career were actually in pediatric, uh, psychosomatic medicine, advanced care planning documents for adolescents with cancer, , antidepressant use in pediatric oncology. Very different starting point from where really you, you’ve dialed in to the, uh, last decade of your career. What was the actual thread that took you from end-of-life planning in a pediatric oncology setting to now becoming one of the country’s leading researchers on suicide?

Dr. Elizabeth Ballard: Um, what a great question. So I think a lot of times research careers are understood backwards. Um, but I think especially thinking about pediatric palliative care in general, it’s a, it’s a topic that incites a lot of anxiety in clinicians. It’s something that people don’t wanna talk about, really don’t wanna think about.

And so I think the similarities… So what I was involved with was the adapt- adaptation of, um, fi- Five Wishes, an end-of-life palliative care document for children and adolescents. And, um, what that involved was sitting down with very, very ill youth and talking to them about their end-of-life wishes. And so that’s similar in suicide that you’re sitting with a very difficult topic, and you just have to sit there and listen, and I think that oftentimes clinicians want to help but lack the words.

You really… They need the guidance. They need the framework. And so how I think about talking about death with kids as compared to sitting down and talking about suicide with a psychiatric patient is there’s a lot of similarities in the sense that you need the guidance. You need the words. You need to have the support to know that it’s important to do this.

You’re not gonna cause harm by bringing up these topics. Um, and it also just speaks to the wealth of opportunities available at NIH. That’s where I did the bulk of my training. And, um, NIH on the medical side sees very, very ill rare cases. And so it was possible to do this really innovative work related to pediatric consultation liaison psychiatry and even talk to kids at the end of their lives, um, after a long struggle with medical illness.

But I think there’s really important, um, sort of things that we can learn from palliative care discussions, um, as compared to suicide risk discussions, and a lot of that is sitting with somebody, listening to somebody, and having a c- a certain sense of curiosity about what they’re experiencing and feeling.

Dr. Ben Everett: Yeah. That’s, that’s nice. I like how you frame that about like research careers being understood better, uh, backwards. But yeah, I think it, it really is true that you’re really sitting with mortality, uh, in both settings. But it, but it’s a very different, I think, discussion and, and the way that we think about these things.

And I, I think you’re also just spot on about, you know, just because it’s a difficult conversation doesn’t mean it’s not an important conversation, and sometimes they are the most important conversations that we could be having. So thanks for that. All right. Well, look, I want to start now with something that really touches nearly every, clinician, mental health professional in every day of, of their clinic, whether it’s the emergency department or an outpatient, you know, psychotherapy clinic. Whether they think of themselves as a suicide reach-researcher or not, they really kind of are. And, and they’re screening patients every single encounter, or really, they should be. You were part of the team that was led by Lisa, uh, Horowitz, who developed the ASQ. So can you talk about what actually went into building an instrument like that?

05:30 – Building and Calibrating the ASQ Screening Tool

Dr. Elizabeth Ballard: Yeah. Um, that was a fantastic experience, um, early in my graduate career, and Dr. Horowitz had been involved with, um, instrument development mostly for psychiatric patients. And the impetus of this was specifically related to children coming in for medical reasons, not necessarily psychiatric reasons, and sort of what could we do for them?

And specifically, this was always targeted at nursing. And so I remember early conversations, we, you know, would go onto- into the ED, ask the nurses, “Okay, how do you ask your kid- the kids that come in about suicide risk?” And there was such a range. There was such a range of ways that they were doing it. One of them just said, “Oh, are you safe?”

Not even mentioning suicidal thoughts or behaviors at all. And so there was a real need to, again, to provide concrete language for these nurses, yes or no questions. And so the development of this task involved approaching a lot of families that were in the emergency room and asking if we could talk to their kids about suicide risk.

So if you imagine as a parent, you know, you have a kid with a broken arm in the emergency department, and here I come, and I say, “Hi, I know you’re not here for a psychiatric reason, but can I talk to your kid about suicide for this research study?” And it was really stunning, um, sort of the willingness of, um, these families and these kids to participate.

And a lot of times the kids would even say, “Okay, I’m not suicidal, but I have friends that worry about this, and if this is going to help somebody, then, um, then I’m willing to contribute.” And it really was an amazing experience. And so from that initial data collection, we were able to develop the task. It was always meant to be brief, and like I said, for, for a nursing environment and initially for medical patients, um, that could really easily be incorporated into existing healthcare systems.

And I think, um, I’m gonna bring this up just I think it’s critical to think about what’s a screening instrument versus a risk assessment instrument. As psychiatrists and psychologists, we’re well-versed in a suicide risk assessment and a history and trying to sort of think about what’s gonna happen to this person in the future.

And the ASQ is really a screening instrument, just like, okay, we’re gonna ask some basic questions and see who needs further evaluation. It’s not meant to be be all, end all. It’s not like these four questions predict who’s gonna die like ten years from now. It’s really for the healthcare system, how do we identify the patients at most need?

Dr. Ben Everett: Yeah, that’s really a, I think an important distinction. And so in developing a questionnaire like this that’s, you know, intended to be used in a busy, you know, pediatric emergency department, you’re trying to be brief. Do you feel like you, you had to give up anything in the design in, in doing something that’s trying to be rapid?

Or do you feel like you really, you know, got exactly what y’all were trying to get out of it?

Dr. Elizabeth Ballard: I think it’s been remarkable to watch how Dr. Horowitz has sort of kept on evaluating this tool over time. And for the most part, it’s remarkable that these four questions seem to hold up, because then she did go on and evaluate this in, um, across different pediatric settings and then adult settings. Oh, we’re gonna have different questions.

But overall, I mean, there’s slight modifications that you do when you’re working with adults, specifically as related to history of suicide attempt. But for the most part, the questions, they seem to work, and I think that really speaks to the rigor of the study design that we had a candidate list of like 14 or 15 questions and then narrowed it down rather than, um, sort of coming up with sort of what, you know, from the beginning what our questions would be.

We really let the science guide us.

Dr. Ben Everett: Yeah, that’s great. And what I think is really, uh, you know, an, an evidence of, of how effective these, uh, tools have been is that now, universal screening, not just in psychiatric settings, but in general medical settings, has become effectively policy, right? And, you know, first through hospital adoption, then through accreditation requirements as someone who– Well, and I’ll just back up and say I actually saw my GP yesterday, and of course, they’ve got a new portal, and I had to re- you know, go in and re- you know, check all the boxes. But I, I was asked, you know, some, some general questions about suicidality, you know, anxiety, depression, and things that, you know, they’re so easy to do and, and that gives, uh, you know, the GP an idea of, of where I am going into that appointment the next morning. So I think it’s, it’s great to see these adopted and, and pushed out. So as, as someone who helped build, you know, one of these instruments, how do you think about, you know, the trade-off between a tool that’s sensitive enough to, to catch the real risk and one that’s specific enough not to overwhelm the system with false positives? And, you know, as a resource generator, I, I think that’s probably an important thing, something you have to bake in at the front end.

How do you think about doing that?

Dr. Elizabeth Ballard: Um, especially for screening, there’s always the trade-off between sensitivity and specificity. Y- this is literally a life or death situation, and so you don’t want people slipping through the cracks that aren’t getting identified. But addit- additionally, all of those individuals can’t have the highest levels of resources or y- you’d basically become frozen.

And so I think a lot of it, yes, there’s the study design and sort of thinking about, um, sensitivity and specificity. It also matters what environment you’re in. If you’re in a psychiatric setting, you know, these people hopefully will be d- assessed by their therapist, by their psychiatrist eventually as compared to something like a medical setting where this might be one of the only chances somebody does get to get these sort of mental health questions.

And then there’s the critical aspect of what happens next. And so, um, you know, in terms of follow-up because if, you know, you were asked by your GP these questions and then what if you did say that you were suicidal and then nothing happened, um, that’s gonna, you know, be concerning and what about risk?

But then also that’s very demoralizing that what if this was something that you really hadn’t disclosed to anybody, you finally were brave enough to talk about it, and then nobody does anything. And so, um, it really has to be on the same side that individuals think about screening and then what are we going to do with the positives and sort of what kind of response, what sort of resources.

Not everybody needs a one-to-one, um, observation status because they attempted suicide five years ago. That’s inappropriate. But at the same time, um, you don’t want somebody again to disclose, “Oh yes, I’ve been, you know, thinking about suicide every day for the last few weeks,” and somebody say, “Okay.

Well, call me if it gets worse,” or something like that. Like we have to take that seriously.

12:30 – The 2018 AJP Ketamine Meta-Analysis: Pooling Individual Patient Data

Dr. Ben Everett: Yeah, it’s really, really good. So let, let’s move now from, from screening on to treatment, and I think one of the most exciting things in suicide treatment in, in recent years has been the, the advance of, of ketamine research. But one of the issues I’ve noticed just from an outsider trying to keep up with the literature is when you’ve got an agent like ketamine that’s been approved since 1970, it’s pretty easy for anyone with a DEA license to prescribe.

So not every study design is exactly the same, and sometimes we’ve got a lot of small studies, and it’s, it’s how do you compare and how do you try and, know, make sense of, of the literature. And, you know, to your credit, you and, uh, Samuel Wilkinson took a crack at, at, at trying to, to solve this issue. And y’all were shared first co-authors on a 2018 American Journal of Psychiatry meta-analysis where you looked at pooled data, uh, it was one hundred and sixty-seven patients across ten separate studies, and you have the individual patient-level data in here, and I think that’s really what, what, what makes this study so robust in its design. And you compare IV ketamine, so it’s not lozenges, it’s not, you know, Spravato, this is literally IV ketamine, uh, to saline or midazolam as controls, so you do have a control arm in patients with suicidal ideation. You know, what prompted this, uh, in the first place?

Dr. Elizabeth Ballard: Yeah. Well, I think, um, ketamine is such an interesting example because in graduate school, what I was sort of taught as the model is you develop an intervention and then you spend, I think it’s like 14 years basically begging people to implement your intervention. Like it, it takes a while for systems to adopt it.

And ketamine, it’s a bit of the reverse that very quickly because as you say, this is a known compound and anesthesiologists are very comfortable with using it, that the implementation and the development of ketamine clinics rapidly outpaced the research literature. And so there were these open questions about suicide, and that’s what brought me to the field.

I was so fascinated by, um, the potential for rapid, um, changes in suicidal thoughts. Um, but then there were so few patients that had actually gone through a clinical trial. And so at the time that we were doing this, 2017, we really could get all of those researchers on one paper and somehow sort of get all of their data together to look at the individual level to try to understand really what’s going on here.

Um, and I think it was, you know, a great service to the field to do that at that time. And of course, it’s exploded even more after that, and it’d be much harder to do that sort of individual level analysis now just because there’s so many countries are doing the studies and like you said, in so many different ways and in so many different formulations.

But it was nice at that point, um, in the research literature to sort of bring together the research evidence, um, for ketamine as specifically as related to suicide.

Dr. Ben Everett: Yeah. And actually, you know, I mentioned the, the conversation we had with Brett Jones. That was actually exactly what his paper found, was of all the interventions that they had looked at, that IV ketamine was by far the most effective. Um, I think it’s great that now we have a, a tool, um, to use in the– you know, in this setting that seems to be working very well.

It’s rapid. Um, and that’s really what’s important about it, I think. Um, so, you know, we talked about this type of analysis, but typically, I think when I think of a meta-analysis anyway, you’re thinking like huge patient datasets, you know, fifty thousand patients maybe looking at an EHR, EMR database or something like that. Do you think maybe y’all get into that next, or is there no need, or I’m just curious?

Dr. Elizabeth Ballard: Oh, cer- certainly. I don’t know if I, I’m gonna be the one that spearheads it, but I think the field should certainly go into that. I guess for that moment, you know, there was a real need to sort of look across the research literature, and like I said, you have a much more power when you can collapse, um, with the individual level characteristics.

And we’ve done a s- a series of, um, follow-up studies looking on functional unblinding and placebo effects sort of with that data set. It’s a very, um, helpful resource. Um, but right now, because again, the uptake in the field has been so rapid and widespread, at a certain point, yes, we do need to move to EHR and sort of big picture, big data across healthcare systems, um, across VAs, and sort of see what, what is going on in the community there.

Um, but it, it, it’s hard. There’s no requirements that you have to track these outcomes. Everybody uses slightly different outcomes, so, um, my hat’s off to whoever ends up doing that, ’cause that’s gonna be quite the undertaking.

Dr. Ben Everett: I agree. Sometimes I read those studies and I’m just like, man, I– it’s, I

Dr. Elizabeth Ballard: Yeah.

Dr. Ben Everett: Yeah, I wouldn’t know how to begin. I think you’ve got to have like an epidemiologist or a public health kind of a training to think about how to do that. I certainly don’t know how. I probably should have gotten to this one before, before that one.

17:30 – Disentangling Ketamine’s Effect on Suicidality from Depression

Dr. Ben Everett: But, you know, in, in terms of going back to the findings of the paper, you know, ketamine is, or at least S-ketamine indicated now to treat, um, depression as well as, uh, you know, suicidal ideation or action in, in MDD patients. So in, in looking at your analysis, did y’all try and tease out the impact on suicidality versus the impact on depression? Or does it not matter if it works?

Dr. Elizabeth Ballard: I think that this, um, throughline of, uh, psychopathology but specific depression versus suicide is, it just comes up in any research area I’m involved with. With screening, there’s sort of a sense of, “Couldn’t we just use a depression screening and then do suicide risk from there?” And the answer is no, you really do need to ask about suicide.

And then the question for treatment is, “Well, can’t you just treat the depression, and won’t those suicidal thoughts, um, go away?” And I think if you look at the uptick in suicidal thoughts and behaviors over the last 20 years, it doesn’t, it doesn’t seem that, oh, we just need to treat depression better, ’cause we have had these advances in depression treatment, and we really have not seen commensurate, uh, reductions in suicidal behavior.

So that’s always a key finding for me is, okay, is this something that could be better accounted for by depression, by other forms of psychopathology? Because why, why reinvent the wheel if there’s something that we know that it works? Um, and so that was always my first question, especially as a psychologist coming into this literature, was, “Okay, but is this, is this just depression, or is there something distinct for suicide?”

And I, I do believe there’s something distinct for suicide. Especially as the ketamine literature has expanded, we’ve seen it’s im- you know, people have evaluated it with PTSD, with OCD, with, um, actually substance use disorder. So it’s really being used across diagnoses. Um, and for me, you know, to a certain extent, if you’re a doc treating a suicidal patient, you just wanna know that it works.

But I think, you know, particularly thinking about precision medicine and matching the right treatment to the right patient, we really need to know how and why and what symptoms that it works for. So I think that was, uh, a critically important question, and we were, you know, happy to learn that there was this distinct effect on suicidal thoughts, and that seems to have been borne out with, um, subsequent studies.

Dr. Ben Everett: I think it’s really important also, but, you know, I’m a scientist, not a clinician, but these are the things that I really, yeah, well, I nerd out on, is trying to figure out these differences. And as we move to precision medicine, I think it’s really important to understand these distinctions and get these distinctions out so that people kinda understand, not that it matters here with ketamine, but in other areas where you might have multiple agents you can choose from for a certain patient, it’s trying to match, you know, the best medication for the patient in front of you at that time.

20:30 – Ketamine’s Response Trajectory and IV vs. Esketamine Comparison

Dr. Ben Everett: Look, let’s move on to a companion paper that you authored, and I really like this because it gets into the time effect. And we know that the ketamine works rapidly, but at least in depression setting, you know, it’s– it doesn’t have the durability of some of the other, uh, agents that are in the psychedelic umbrella, um, like, you know, and what Compass, uh, is doing with their three-sixty studies.

So y’all looked at this in the Journal of Affective Disorders, and you specifically characterized the course of suicidal ideation response to ketamine over a three-day interval rather than just looking at it as a single endpoint. And I think it’s a really elegant way that you did this. In terms of your analysis, what’d you actually find in terms of the trajectory over this three-day period? And, you know, what does that tell us about dosing intervals?

Dr. Elizabeth Ballard: Yeah. So this was, um, a great study analysis I did with one of our brilliant, uh, statisticians, and we were able to model what it looks like exactly what you said over the three days, and specifically identifying what did the non-responders look like. And then we found non, um, non-responders, responders, and then remitters, the people that just their suicidal thoughts went away and, and stayed down, and that was the most sort of dramatic group.

Um, and sort of going back to our previous theme, we found that changes in depression did not map on to those groups, that it wasn’t purely explained by that. And so I think that is important because, um, clinicians do wanna know, okay, you know, like, is it gonna take a couple of doses to get this happening?

Like, what’s gonna happen sort of within the first dose? And we’re not able to quite answer the multiple doses question, but we do wanna know g- in general, what can it look like for a patient to explain what can happen to them. And so in terms of the results, and it’s really hard, um, to really find predictors of response to any intervention, much less ketamine, we did find that the individuals that were more characterized by more what I would say sort of chronic suicide risk, sort of self-injury, which would, um, include non-suicidal self-injury, sort of more severity of suicide, were much more likely to be in this non-responder group.

And we’ve seen that, um, sort of over the years in terms of other ketamine trials that, um, I do think sort of more for the more chronic suicidal ideation and then maybe characteristics potentially as related to personality disorders or other sort of more chronic factors, we don’t see as rapid of a response, especially on the suicide angle, um, to ketamine.

Again, suggesting maybe for these individuals they need something else maybe in addition to ketamine or instead of ketamine.

Dr. Ben Everett: Yeah, yeah. That’s– I think that’s an important distinction there. So let me ask you when, you know, we’ve mostly been talking about IV ketamine, but I’ve mentioned, you know, esketamine, Spravato. It, uh, it does also have, um, this indication or really is the only one because the IV ketamine, of course, is, is again, just kind of operating this interesting place, uh, just because it was approved so long ago. Um, you have very different trial designs in, in how Spravato went about getting their indication. You know, in terms of kind of this precision medicine we were talking about a minute ago, how do you think people should approach, you know, hey, what’s right for this patient, IV ketamine versus esketamine?

And some of it might frankly just be institutionally what, what, what you have access to. But let’s say it’s a perfect world, you’ve got access to both of them. How do you think about finding which one of these is better?

Dr. Elizabeth Ballard: Yeah. So this is tricky because as you said, there’s a lot of differences. The IV ketamine research field is mostly academia and government because we’re part of the government, and then the, um, Spravato esketamine is mostly by industry. The trials are very different. The instruments themselves that are used were quite different as well.

And so it’s been, uh, difficult to piece apart because the findings, because you do see a bit of a more consistent statistical effect of IV ketamine on suicidal thoughts that you don’t necessarily see with, um, esketamine. And so, um, I think if clinicians are deciding, they, they sort of have to weigh that data.

But again, it’s not apples and apples. Those trials are quite different. But, um, with a focus on suicide, I do think that, um, there are more, um, positive findings as related to IV ketamine. But again, um, you really sort of have to think about sort of what’s in the best interest of the patient, and especially there’s not insignificant costs associated with both things.

There’s potentially different side effect profiles, um, clinical monitoring that you have to do. So it’s one variable to consider amongst many when you’re thinking about which one to choose.

Dr. Ben Everett: It makes these things difficult sometimes with that head-to-head research and, and I don’t know if we’ll ever see a head-to-head trial here. But, you know, I, I think it’s, it’s good when we can have more options, um, for patients and, you know, when you have more tools at your disposal, you know, I think the, the chances for a positive outcome, you know, for the patient are better.

25:30 – Nocturnal Wakefulness as a Warning Sign for Suicidal Ideation

Dr. Ben Everett: Um, all right. So we, we’ve kinda– we’ve talked about assessment, we’ve talked a little bit about treatment. So let’s look now towards like objective markers and the limits of, of self-reporting. So screening tools, even, you know, most clinical trial endpoints for suicidal ideation, you said, you know, they’re very different endpoints that can be used, still rely almost entirely on patients telling us how they feel.

So there’s a lot of s-you know, subjective and, and potential bias in, in patients doing that. A lot of your more recent work has been trying to find something underneath self-reporting, kinda moving towards, you know, objective markers, potentially biomarkers. You have a twenty sixteen paper in Journal of Clinical Psychiatry.

We always love journal– you know, papers that get, uh, Journal of, uh, Clinical Psychiatry. found that nocturnal wakefulness predicted next day suicidal ideation in major depression and bipolar disorder. So why sleep specifically as a place to look for a, as a, as a warning sign?

Dr. Elizabeth Ballard: Um, I, uh, love sleep as a potential warning sign for a number of reasons. In first, because oftentimes with suicide risk, there’s a push and pull, there’s a little of a power struggle. The patient has a number of reasons to minimize the suicidal thoughts. They might be worried about hospitalization, they might be worried about stigma.

If they’re in a hospital setting, they might wanna get out, they wanna be discharged. So there’s a lot of factors leading patients to minimize. And so sleep is not… I think that most people could say, “Yeah, I’d li- I’d love to sleep better.” Um, it’s not as stigmatizing. It’s something that’s more commonly talked about.

Um, and there are treatments that work for sleep, um, you know, both pharmacologically and psychotherapeutically. And then as, um, a near-term risk factor, I think it is particularly interesting. There were these, uh, findings around the time in 2016 that suggested that when you adjust for time awake, uh, being awake overnight is substantially associated with suicide risk, that, you know, it’s a high-risk time for suicide death.

And if you think about what’s happening overnight, is that for the most part, us as clinicians, we’re not available to our patients and clients overnight. Usually, you call your clinician, and you get the voicemail response, um, “I’m not here. Please go to the emergency room.” Also, other social supports are not usually available, uh, at night.

Additionally, um, sort of we’re supposed to be asleep at night. Your brain does not make its best decisions at three o’clock in the morning, regardless if you’re depressed or not, you know, in terms of impulse control, emotion regulation. W- With… Sleep is a biologically important, um, state to be in. And there’s the propensity that individuals might be coming off of the effects of drugs or alcohol, which are also associated with suicide risk.

So there’s a confluence of factors that make it so that if somebody is awake during the night, that especially sort of with outlying risk factors, that’s a particularly high-risk time. And so that’s what, uh, really brought me to this research and continues to fascinate me about this, is that it does seem to have real-world applications, um, for some patients, not all, that, um, it could be this particularly important, um, risk factor.

And so the study that we had showed that potentially being awake, and so we did these sleep studies, sleep EEG moment by moment, and were able to show that being awake later in the night, particularly at the 4:00 a.m. hour, was associated with suicidal thoughts the next day. And so we’ve been expanding on this and trying to understand really what does that mean, what’s going on there, um, more, but, um, does speak to, uh, one potential near-term warning sign or modifiable risk factor for suicide.

Dr. Ben Everett: Yeah. And, and so where the research is right now, do you think it’s, it’s, you know, worthwhile for a clinician to, to talk about sleep quality as part of a same-day risk conversation? Or do you think it’s still more research, maybe not ready for prime time?

Dr. Elizabeth Ballard: I think that sleep is a known risk factor for suicide, so I don’t think that’s a new, new finding for anybody. So yes, certainly that can be part of the conversation. I think where, um, what we haven’t figured out yet is how to adequately treat that. You know, if it was… there have been the trials that pharmacologically or with CBT for insomnia have looked at, um, you know, do you treat the sleep and then does the suicide risk get better?

And it’s a little more nuanced than that. Like, again, from a precision approach, I think it’s probably gonna be a subset of individuals whose suicidal thoughts are driven by sleep that are going to most benefit, and so that’s what we don’t know. But certainly, if you’re doing a risk assessment and you ask about sleep and it turns out this individual before their suicide attempt, you know, had a lot of trouble sleeping, then that should be a warning sign that the clinician discusses with the patient.

“Okay, let’s plan around that. Let’s think about that. Like, how can we treat that?” And again, if you get into this period again where you aren’t sleeping, like, how are you gonna let somebody know, um, that you’re in this high-risk time? So that as a risk factor, I think we’re clearly there, um, but thinking about exactly how that leads to treatment, I think there’s a really important research that still needs to be done.

Dr. Ben Everett: Yeah. And, uh, uh, I don’t think it’s, uh… Patients will typically tell you if they’re having problems sleeping, you know, ’cause

Dr. Elizabeth Ballard: Yes.

Dr. Ben Everett: help with that.

Dr. Elizabeth Ballard: Exactly.

31:00 – MEG and Electrophysiological Signatures of Suicide Risk

Dr. Ben Everett: um, so yeah, it might be low-hanging fruit, but, uh, yeah, I’ll be interested to see, you know, how the literature continues to develop here. Um, all right. You know, that’s one set of sort of data, um, you know, that we can objectively talk to patients about. Looking at the brain itself, you’ve moved into magnetoencephalography or MEG, uh, including you had a ’22 paper– a 2022 paper on the relationship between alpha and beta power and next day suicidal ideation. More recent work, uh, you’ve looked at electrophysiological, uh, correlates of hopelessness itself, which we kind of talked about in the, in the intro a little bit. So what is this MEG or MEG letting you see that sleep and behavioral measures, you know, can’t?

Dr. Elizabeth Ballard: Um, so as a point of clarification, the alpha and beta power was actually done with sleep EEG. So it’s electro– It’s, it’s under the same umbrella as MEG, um, but sort of both, um, slightly different metrics ’cause one’s done at nighttime and one’s during the day. And so from a sleep perspective, as I was alluding to before, um, there is this question of, okay, if we are gonna intervene at the sleep level, we really need to understand sort of what’s the dysfunction.

‘Cause it is possible that what’s happening is that somebody is awake in the night and is ruminating and just thinking a lot about suicide, and that’s what’s driving the next day suicidal thoughts, or there could be some sort of biological process at, uh, at play. And so a lot of the sort of diving deep into the dynamic oscillations of alpha and beta power has been to really isolate sort of what’s going on in the brain, um, during sleep that’s leading to next day suicidal thoughts.

Like, is there a direct connection? And then, um, more broadly for, um, MEG and other forms of electrophysiology, again, um, moving beyond a sort of more typical depression or psychopathological measures, sort of what can we isolate as related to, um, neurobiological signatures of, uh, suicide? And so that’s a lot of the work, and we can talk more about the hopelessness.

It’s an area I’m really excited about. Um, but really understanding how… Is there a distinct circuit, or is there a distinct construct that we can think about and target? And a lot of my work is thinking about this in the context of treatment. I think that it’s great to think about, um, you know, neurobiology in the context of prediction over the long term, but I think we all know there’s no way, especially for something like MEG, that, you know, you’re gonna have a patient and then pop them in a scanner and then read the results and have that be useful in real time.

But, you know, if we do the scanning, if we do this neuroscience, um, sort of as part of research and understand more, especially about how our treatments work, that can provide us with critical information that we can then pass along to the clinicians that can help, um, with their clinical decision-making.

34:00 – Concordance Across Suicide Risk Assessment Scales

Dr. Ben Everett: Love that you’re thinking about treatment, like when you’re doing this, because I think so often in neuroscience and neurobiology, we’re just trying to understand things, and then we figure out, well, maybe down the road we’ll find something that could be a druggable target, and we can figure out how to make it work. But thinking about it now, I think is a much more efficient way, and hopefully we can get to treatments a lot quicker that way. Um, all right, so you know, talking about scales now, and you are a co-author on a very large– So we talked about your small meta-analysis. This is a

Dr. Elizabeth Ballard: Yes.

Dr. Ben Everett: meta-analysis, a 2023, uh, meta-analysis published in Neuropsychology, looking at concurrent validity and reliability of 20 different suicide risk assessment instruments across 27 international cohorts.

So without asking you to specific, you know, like single out any specific scale or anything like that, what did that analysis really suggest about, you know, is there agreement here? Do we find these tools are pretty concurrent? there discordance? And, and how good are they really in, in terms of routine clinical practice?

Dr. Elizabeth Ballard: Yeah, I think the overall result is especially for the most commonly used, more comprehensive scales, that there’s overall good concordance. And that, I guess, if you think about it, that makes sense. We’re trying to get at suicidal thoughts. Is there that many w- you know, are there 40 ways to ask about suicidal thoughts versus 20 ways?

Like, there’s probably a certain number, you know. You have to do it a certain number of ways to capture the, um, experience that somebody’s having. And so, um, going to the literature and sort of finding these key tools, it is heartening to see that they relate. But I think, um, getting back to the earlier screening discussion, it really though matters sort of what you’re then using it for because, um, I think suicide is unique in that we have screening tools, we have the risk assessment tools, and then, um, as related to the work that I do, you have these ra- tools that are trying to capture rapid changes, which are going to be different than a risk assessment tool.

Um, somebody’s family history of suicidal behavior is not going to change day to day, and so that’s not something that you should repeatedly assess as compared to their suicidal thoughts and their intent. And so it’s really… I think we’re at the point that, yes, overall our, um, general suicide risks tools are in general agreement, but then how do we do these more fine gl- grained analysis across these rapid interventions with ecological momentary assessment, with sort of the smartphone assessment?

That’s, I think, sort of where the field is wrestling with now, sort of how do we do that, and then how do we make sure that we’re not just sort of copy-pasting, um, sort of previous tools and expecting them to work in a totally new setting in a totally new way?

Dr. Ben Everett: Yeah. I’m curious how, you know, ’cause you’re over pre-doctoral training, you know, how do you think about this in, in– when, when you’re teaching and, and answering questions from students?

Dr. Elizabeth Ballard: Yeah, I think, um, having them think about, like, what is the goal of, of sort of what are you trying to, um, get, like, achieve in this situation? Sort of what is the clinical decision that you’re trying to answer, um, is not, is not usually where their head’s at, is sort of what they’re thinking about, you know.

Like, they’re thinking about, “Well, I have to use a standardized tool because that’s what I’ve been told to do.” And a lot of what I think good training is trying to have them understand what is the impetus, what is the system trying to do, and what are you trying to do as the clinician, and what’s in the best interest of the patient?

And so sort of I … Sometimes, um, instrument development, psychometrics can be a bit dry, but there really are, especially in this realm, like real, real world, and again, life-and-death implications. And sort of having them think through that, um, is, is gratifying when they get it.

Dr. Ben Everett: So I love that. I was a high school teacher for a couple of years, and kinda when, when you see the light bulb

Dr. Elizabeth Ballard: Yes.

Dr. Ben Everett: It’s so great. And I also like how you approach that because it’s not just like use this tool, it’s getting to the why, right?

Dr. Elizabeth Ballard: Mm-hmm.

Dr. Ben Everett: why do you wanna use this tool? And it’s really understanding it in a more complete and thorough manner. And I think that’s how we really train, you know, people to be, to be really good at their jobs and be really good

Dr. Elizabeth Ballard: Yeah.

38:00 – Hopelessness as a Distinct, Modifiable Treatment Target

Dr. Ben Everett: so. all right, so we’ve talked about hopelessness a couple of times.

It’s, it’s come up, now we can really lean into it, and I know you’ve got– you know, you’re, you’re pretty passionate about this area. You know, you’ve been in this direction more and more, and this idea that, you know, hopelessness, that hopelessness itself, not just suicidal ideation, is a symptom might be worth treating directly. And so you have a 2022 paper in Journal of Affective Disorders where you look prospectively at this. You looked at psychological pain and hopelessness uh, as it related to suicidal thoughts. So what made you wanna isolate hopelessness here and, and as opposed to just, you know, treating it as, as an item that might be embedded in a depression, uh, scale?

Dr. Elizabeth Ballard: Yeah. So I think as, um, most psychiatrists and psychologists know, you know, suicide risk is multifactorial. There’s so many factors that lead somebody in a moment of crisis to think about ending their lives. And as I alluded to before, you can’t treat all of them at the same time. That’s just not possible.

That’s not feasible. You’re not going to resolve somebody’s long-standing childhood history of trauma, um, in two days. Let’s just– It’s just not possible. And so, um, as related as, you know, to the sleep discussion, finding factors that are, um, modifiable and are a little more straightforward. If I tried to, for example, computationally model suicide, there’s just so many different factors, so many different things going in there.

And I like hopelessness because it does track with suicide risk, um, but is a bit more streamlined as a concept. Like, you can study– you can sort of isolate it and, and study it in a laboratory environment a little more straightforward. And in my work, I’m thinking about what, what are the levers that we can push to treat a suicidal individual?

And I think hopelessness and future perception might be one of these key levers. I think that’s something that we can think about treating directly and, um, seeing if that overall reduces suicide risk. And so, um, I’ve been thinking about it clinically, sort of moving into what’s going on neurobiologically, and then, um, the hope is, as we understand that a bit more, sort of what can we do to help hopelessness and the ideas that could potentially change, um, overall suicide risk.

But of course, that’s a, that’s a big conceptual leap, and we– I have to sort of start making the case for it now.

41:00 – Neurofeedback and Episodic Future Thinking at Neu Hope

Dr. Ben Everett: Well, I like that you’re looking at it because it certainly makes sense that that would, you know, that would be a, a core, um, driver of, of suicidal risk in, in this patient population. Talking about hope and now, you know, neuromodulating hope, you’re a consultant at Neu Hope, and that’s N-E-U Neu Hope. You’re studying neurofeedback targeting ventromedial prefrontal cortex activation during episodic future thinking in people with suicidal thoughts and behaviors. So walk us through that logic o-of this intervention and why episodic future thinking, like why that particular brain region?

Dr. Elizabeth Ballard: So as I said before, you know, modeling all of suicidal thoughts and risk is very difficult, but there are… Like, when you sort of isolate on future thinking, there are ways, um, to think about that. And so one task that has been used in the literature is episodic future thinking. Basically, first you sit down with a patient, and you ask them to think about some things that could happen to you maybe in the next week or two, and then you ask them, you know, what would…

Good things, bad things, positive and negative. Um, and then you have them sort of generate that list for you. And in this, um, particular, uh, study, what they then did, they did that sort of at one to two weeks and then five to 10 years, and then asked and took a few of those events and asked them to think about it in the scanner.

So again, these are sp- you’re not telling them to think about a future event that you’ve decided. You’re having the participant and the patient generate a future event with meaning to them and have them think about this in the scanner. And again, they saw these differences in the ventromedial prefrontal cortex, um, between individuals at suicide risk and, um, who had, uh, individuals with depression, um, without suicidal thoughts and behaviors.

And so first of all, that was just fascinating to see because, um, again, same probe, same thing, but differences. And then, um, really very small sample, only I think six people did the neurofeedback intervention, but then thinking through this, like could this potentially be a target doing neurofeedback during, um, sort of while thinking about this future event?

And again, it’s… I like it for a number of reasons. Um, it’s, it’s, it’s just scientifically new, innovative, different, cool. Um, but then it’s also very streamlined, as was said before, and non-stigmatizing. And what if you could do something like that, like have somebody practice thinking about the future? Again, um, less of a power struggle, a sort of something that somebody could sort of easily grasp onto and do, and what if just sort of over time that could help with their suicide risk?

So I think it’s a really exciting and very new and different way of thinking about treatment for suicide risk. But again, this is based on pilot feasibility, like can we do this? And then, um, they just received a funding, and I’m a consultant on it to study it, um, sort of in a prospectively in a larger sample.

And so of course, we just… We have to see what works. But I do think even if this trial doesn’t work, this approach, you know, could suggest other forms of neuromodulation, psychotherapy, um, that could be helpful for our patients.

Dr. Ben Everett: I’m curious, are y’all capturing any data on like what patients or do patients even tell you what future that they’re thinking about? And i- is there, is there anything in the data there? thinking

Dr. Elizabeth Ballard: So I, I, I know they capture it. Um, we do the behavioral task ourselves, um, in our research before and after ketamine, um, but we haven’t looked at that data yet. And, um, I, you know, wanna go through and code because, you know, anecdotally you will see individuals, you know, will say like, “Okay, what’s a future event?

Well, I’m just gonna go back home and still be depressed as usual,” as compared to, you know, if they’re feeling better, maybe they have a future event that’s like, “Oh, I’m looking forward to seeing my mom for lunch,” or something like that. And so like, how do we go through and code that? I think that’s gonna be really fascinating to see,

Dr. Ben Everett: Yeah, that’s

Dr. Elizabeth Ballard: how we categorize that.

But yes. But I do think there’s a lot that we can study from the brain, but then even sort of what people are thinking and articulating, I think there’s really a lot of value in, in studying that as well.

45:00 – Ethically Including Suicidal Patients in Clinical Research

Dr. Ben Everett: All right. So in, in moving this close, I, I want to really, you know, talk about something that I think it sits underneath everything that we’ve discussed today, and that’s whether you can actually study suicidal patients, like safely, rigorously enough to generate the evidence that we’ve been talking about.

I, I can only imagine trying to get IRB approval for some of these things. in, in, in thinking about that, you know, you actually wrote a letter, uh, in, in JCP, and we’re, we’re proud to have, um, that really directly addressed this idea that including suicidal individuals in clinical trials is inherently, you know, too risky, unethical. What does the actual evidence show about whether suicidal patients can, can safely be enrolled in research? And then what happens to the evidence base if we just say, “Oh, we-we’re gonna exclude everybody that’s, ha-having issues of suicidality”?

Dr. Elizabeth Ballard: Yes. Uh, short answer, yes, I do believe that it can be done. I think we are in that situation, that individuals are being excluded. If anything, I think that it’s more likely, um, for patients to be excluded from trials just because there is this concerns about adverse events.

Um, and so w- from my read of the literature, um, especially depression pharma trials are more likely to exclude individuals with suicidal thoughts and behaviors. And what happens therefore is that we have these treatments that aren’t generalizable to sort of the highest risk patients that, you know, just because there’s no trials from it doesn’t mean that people won’t still come to their psychiatrist and psychologist with suicidal thoughts.

It’s still there, whether we study it or not. And then, um, an outgrowth of that is that I think that, um, as you alluded to at the beginning of this, is that then clinicians don’t have research evidence to rely on, and so then they l- rely on clinical lore, or as you say, instinct, rather, um, than the research base.

So it is possible to do this research. We have been doing this research, but, um, in full disclosure, it was, like you said, a lot of work. Um, and especially at the outset, and als- a lot of educating of IRBs, educating of the entire hospital system. And I think this gets back to a lot of root cause, uh, stigma as related to mental health as compared to physical health.

I think that, um, you know, NIH hospitals across the country understand that people will die from cancer, but we still have to study it and still have to treat it. And sometimes it doesn’t seem that they think about mental health and suicide particular in the same way. And so, um, thinking through, okay, but th- this is potentially going to happen.

We might have individuals, you know, attempt suicide during this trial, and how are we going to account for this? Um, I think it’s a really important question to hap- happen before you do the trial itself, and ideally talk about it with the healthcare system, talk about it with the IRB, and, um, what are the safeguards going to be rather than getting the trial in and then just hoping nothing goes wrong.

Um, because I think that’s really where people get in trouble is when they haven’t done the prep work and something goes awry. Um, and then that’s when you worry about like whole programs being shut down.

Dr. Ben Everett: Yeah, I think it’s really important. I’m glad you’re doing this work. And, you know, as someone who’s spent a lot of their career, you know, educating on new treatments when they come to clinic, it’s always, um, there’s a balance, right? Because if you’re a sponsor of a new treatment, you know, you’re trying to get it approved, and so you kind of want the cleanest research you can.

But then, you know, you have clinicians saying, “Yeah, but, like, I really don’t think it really works in most of these patients because XYZ.” It’s like you excluded all the patients that are really the bread and butter, like hard to treat patients. So I’m not sure it really works in hard to treat patients, you know, that type of thing. And I’ve seen this across all sorts of different therapeutic areas, whether it’s in lipids or hypertension or mental health. It’s a big problem. Um, and, you know, I think there are ways that we can go about doing this, uh, better. So since you’ve done this work and you’ve thought about this, you’ve written about this, you know, in your mind, what does go into making a robust but, you know, ethical and safe enough, you know, program?

Uh, what is it you’re putting into these to help convince an IRB that, yeah, not only can we do this appropriately, but it’s really important that we do this appropriately?

Dr. Elizabeth Ballard: Um, I think reaching out to other people who have done this before is critical, sort of having a network of individuals that, um, have dealt with this with their IRB. We, um, did a lot of pre-work and education, and we actually did, um, a bioethics consultation, um, sort of sitting down and looked at this intellectually with our bioethics department before studying this.

Of course, you don’t need to do that. Um, but again, it’s a lot of developing the safeguards of, you know, making sure the informed consent process has time to really go through these issues and checks. We do a quiz with our participants to make sure that they really understand sort of what treatments they are and are not, um, receiving.

We do more intensive monitoring, which you have to do, um, and are very clear about sort of what, you know, what will happen if you report this level of suicidal thoughts and behaviors. And so there’s, um, aspects of the physical environment. We do a lot of biological research which involves scans or sleep studies, and those settings aren’t usually thinking about suicide risk in the way a locked inpatient unit will be.

And so thinking through, okay, what would happen and sort of what materials are around if you were trying to scan or do a sleep study with an acutely suicidal patient. And so it’s a lot of vigilance, um, and it’s a lot of planning ahead, and it’s certainly a lot of communication and, um, sort of making sure, you know, um, we haven’t done this in a while, but, you know, when we would have acutely suicidal patients, we would let, we would let s- you know, the, the scanning staff all know that this patient was coming down.

‘Cause people wanna help, but you, but you, you have to let them know how to help, um, and also sort of what’s coming so that they can sort of be extra vigilant and on their guard.

Dr. Ben Everett: Well, I, I tell you, I’m really happy that you’re doing this work and that you’re, you’re being as thoughtful and deliberate, uh, about it as you are. It’s very important. We’ve got a big problem with suicide in our country right now across multiple different kind of cohorts of, of, of patients, the way we think about PTSD, veterans, uh, adolescents.

I hear it every once in a while, like in the lay press, but I don’t think it’s getting the attention it, it should be getting. And so I’m really– um, I’m very happy to have you on. I’m very happy that you’re, that you’re doing the work and, uh, really look forward to, to what comes out of this next.

52:00 – Closing Clinical Takeaway: Asking with Curiosity

Dr. Ben Everett: So last question, and I try and end on something that can be like, like what can– you know, what can be clinically relevant today. So if anybody listens to this, if there could be maybe one change or m- if they’re already doing it, great. But if there’s like one thing that you could say, “Hey, you’re not doing this right now in terms of suicide, uh, risk, uh, you know, assessment,” there’s something they could do at their next patient encounter that they’re not doing right now, what would you want it to be?

Dr. Elizabeth Ballard: Well, I assume that considering the audience that everybody is asking about suicidal thoughts, but usually my go-to when in doubt, ask. There’s no harm in asking. But, um, I think that one powerful thing that could happen now is to ask, especially in a clinical setting, with the spirit of curiosity, um, rather than, like I said, trying to get, um, into a power struggle.

I think so much, unfortunately, of suicide risk assessment, um, there’s the over… there’s the cloud of, um, sort of legal ramifications or concerns about documentation, and sometimes that does drive the bus. Um, and our patients can, and can feel that and sense that, and they know when somebody really wants to know why they’re suicidal as compared to when somebody’s just documenting something.

And so I think, um, coming with the spirit of curiosity, everybody, as was alluded to before, has different drivers. Some are gonna be motivated by sleep, some of them are motivated by hopelessness, some of them motivated by trauma. You’re not… It’s, it’s not one size fits all. And I think people understand that for risk, but, um, we’re still trying to piece apart what that means for treatment.

And so I think coming to these interactions with a spirit of curiosity when I work with a patient, and it’s clear that I’m not gonna try to shame them or tell them they shouldn’t be suicidal or threaten them, sometimes you just see them, see them relax that somebody’s actually sort of asking what this experience is like for them, and I think that can be really powerful.

Um, the spirit of curiosity, I think, um, can be a really important clinical tool.

Dr. Ben Everett: Well, Dr. Ballard, thanks for this wonderful conversation today. It’s a very important conversation. I’m glad you’re doing this work. I said that already, but I’ll say it again. And thanks for coming on and, you know, talking as candidly a-about this, you know, limits of our screening tools, our trial data, strengths. This kind of honesty is really what this topic needs. , I think one of the things that I’ve taken away from this, a-an encouraging theme from today’s discussion, is that, you know, suicide risk assessment and treatment continue to evolve.

As the evidence grows, as the tools get more robust, rely on becoming more refined and important advances are really being made in both treatment and screening, and I think it’s really important. I’ll also make a plug to two previous podcasts. If you’re new, um, I invite you to go back and listen to the conversation with Dr.

Brett Jones, where he talked about inpatient treatment of suicidality. And then we had a, a board-certified, uh, sleep professional on, Dr. Avi Bhar, and we talked about just sleep and how sleep is just a major driver for just about everything we think about in mental health. And so, you know, if you got a little bit of extra time, you hadn’t heard those, I’d invite you to go back and listen to those. With that, this has been the JCP podcast. Insightful, evidence-based, human-centered.