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NIMH Research Domain Criteria (RDoC) Initiative


>> WEBINAR OPERATOR: Good day, everyone, and welcome to today's webinar, titled, "NIMH Research Domain Criteria (RDoC) Initiative." At this time, all participants are in a listen-only mode. If you'd like to submit a topic or technical-related question, you may do so at any time via the Q&A pod located at the bottom of your screen. Also, we will be taking questions verbally at the end of today's presentation, and if you'd like to register, please press the star and 1 on your touch-tone phone. Please note, this webinar is being recorded. I'll be standing by if you should need any assistance. It is now my pleasure to turn the conference over to Makeda Williams.

>> MAKEDA WILLIAMS: Thank you for the webinar logistics overview, Wendy. My name is Dr. Makeda Williams. I'm from the National Institute of Mental Health, and I'm pleased to welcome you today to this webinar titled "NIMH Research Domain Criteria Initiative." This is the final webinar in a series of four webinars for the 2017 Global Mental Health webinar series. This series has been issued by NIMH Office for Research on Disparities and Global Mental Health. Please note that this webinar is being recorded and will be posted on our website.

Now it gives me great pleasure to introduce you to our speakers for today. Our first speaker is Dr. Sarah Morris. She is the Chief of the Adult Psychopathology and Psychosocial Treatment Development Branch in the Division of Translational Research in the NIMH Extramural Program. After graduating from the doctoral program in clinical psychology at the University of California, Los Angeles, in 2001, she conducted psychophysiology research on self-monitoring processes in schizophrenia at the Baltimore VA Medical Center and joined the faculty at the University of Maryland School of Medicine. In 2010, she moved to NIMH, where she manages a portfolio of research grants focused on translational research in adult psychopathology, serves as a science officer for the North American Prodrome Longitudinal Study, and the International Harmony Consortium of Psychosis Research Studies, and serves as the Associate Head for the Research Domain Criteria Unit, which mission is to promote research that takes a dimensional, integrative approach to conceptualizing mental disorders.

Our second speaker is Dr. Ishmael Amarreh. Dr. Amarreh is the Chief of Research Scientist Development and a Program Officer for Global Mental Health for the Office for Research on Disparities and Global Mental Health at NIMH. Dr. Amarreh is responsible for the initiation, planning, execution, assessment, coordination, and promotion of the international research and scientist development activities within ORDGMH, and in conjunction with other NIMH Institutes and Centers, and governmental and international organizations, as needed. In addition, he is responsible for supporting the Research in Global Mental Health Program for ORDGMH. In this capacity, he works very closely with the Chief for Global Mental Health Research and advises on policies, goals, and objectives for global mental health research. Dr. Amarreh's unique and highly specific expertise in … a Ph.D. with neuroscience, a master's of international public affairs, and a bachelor's degree in microbiology.

I'm delighted to welcome both of our speakers today for their talk on the NIMH research domain criteria, and now I'll be turning it over to Dr. Sarah Morris.

>> SARAH MORRIS: Hi. Good morning, everybody. And thank you, Makeda for including RDoC in your webinar series. We're very happy to be heard today. So, I'm going to give a talk about 40–45 minutes, with an overview of RDoC, and a few comments about its relationship to global mental health. But we've left plenty of time for questions at the end. Hopefully, we can clear up some misconceptions about RDoC and provide some guidance for future grant applications to NIMH or other projects.

RDoC is all about classification and diagnosis, so I think it's helpful to look at the past, present, and future of diagnosis. This slide shows admission records from West Virginia's Hospital for the Insane back in the mid- to late 1800s, and I know it's a little bit hard to read, but it does provide a snapshot of how people thought about psychiatric diagnosis back then. It includes some things related to alcohol abuse, such as "bad whiskey," and "snuff eating for 2 years." A little bit of neuroscience -- there's a diagnosis of "spinal irritation." A lot of interesting and outdated ideas about sex differences and women's health, so one of the diagnoses is "woman trouble," and "excessive masturbation," I believe, is on there. So it's a real hodgepodge of behavioral and psychological problems.

Fortunately, we've moved beyond that. And just to briefly give a snapshot of our current diagnostic practices, mainly focused on the DSM. and the ICD, as published by the American Psychiatric Association and the World Health Organization, respectively. These continued to be the state of the practice in psychiatry for diagnosis, and although RDoC encourages new ideas about classification, we fully acknowledge that these systems are in place and functioning for the purposes of medical records, and for insurance billing, and that's not likely to change anytime in the near future.

But our hope, as I talk about RDoC and as we learn a little bit more about it, is that it will be clear that the research agenda doesn't need to abide by what's been published in these diagnostic criteria. They have advanced the science of psychiatry by providing reliable methods, reliable criteria for diagnosing mental disorders, so that a researcher in one city can be pretty sure that a patient diagnosed with schizophrenia, for example, in that city has some similar characteristics to one who's diagnosed in a different city by a different clinician, although that reliability has, one could argue, come at the expense of validity.

So the validity of our diagnoses -- the more we study them using modern methods, the diagnoses are not terribly predictive of medication response, for example, of illness course, of heritability. And so, all those ways that we would validate diagnoses are coming up short using existing diagnostic methods. There's no reliable biomarkers for any of the DSM diagnoses and no definitive disease mechanisms, no diagnostic tests. And they are characterized -- because they are made up of syndromes of symptoms -- characterized by excessive heterogeneity and co-occurrence of disorders. So, I think this paper by Isaac Galatzer-Levy captures the problem perfectly. If you take all of the different symptoms of PTSD and the various ways to combine them to meet criteria for the diagnosis, there's over 630,000 ways to meet those criteria. And so the idea that we would group those patients together as if that's a meaningful entity, and then study differences between PTSD and healthy subjects, or PTSD and other disorders, and expect to find meaningful differences -- it's an uphill climb, to say the least.

Just a glimpse at a possible future of diagnosis: I don't know how many people are aware of the big genetic finding in schizophrenia about Complement Component 4 Syndrome. This is the collection of alleles that pops up in that big Manhattan plot when you look at the big GWAS study of schizophrenia, it's CC4. So in the future we might find that different numbers of risk alleles within that gene might have meaning for treatment decisions and for heritability and disease course, and so on. But my argument today is that we can't get from the present to the future if we continue to only support research that focuses on existing diagnostic criteria and fail to test out other classification methods.

And that's the whole rationale behind RDoC. Back in 2010, our Institute Director at the time, Tom Insel, introduced ... I'm sorry, this is in 2011 … introduced RDoC by saying that we need to begin collecting the genetic, imaging, physiologic, and cognitive data to see how all the data, not just symptoms, cluster, and how they relate to treatment response. And so, we were, at that time, reorienting away from DSM categories. And so, the emphasis has always been on improving treatment response, and RDoC is a research initiative to begin to develop a better system for classifying patients. It's not, in and of itself, a system for classifying patients right now, so nobody can go to their doctor and get an RDoC diagnosis, but it's a way of stimulating the field to look at classification differently and see if we might do better than our existing diagnoses, some of which have been around for hundreds of years and precede modern behavioral neuroscience.

This is just a rationale about RDoC. It is again, NIMH-led to change how patients, as well as non-patients, are identified and classified for research purposes. So instead of grouping patients into heterogeneous diagnostic groups, RDoC provides a framework for classifying patients on the basis of these different constructs that we have defined. Again, to stimulate research, to understand the heterogeneity of psychopathology, improve our classification, and hopefully lead to better use of existing treatments, as well as identification of new treatment targets.

And as far as how this links to global mental health, I've copied here the Global Mental Health Grand Challenge goals, published in 2011, that I'm sure many of you are familiar with. And to my eyes, goals A, B, and C are the ones that are most amenable to an RDoC approach. So, goal A, to identify root causes, risk and protective factors; goal B, to advance prevention and implementation of early interventions; and goal C, to improve treatments -- are all things that could be approached in an RDoC way, by improving diagnoses.

And this isn't just a mental health problem; it's an issue that many areas of medicine are grappling with. I've shown here an example from diabetes. And they're making the point that diabetes is itself a heterogeneous disease, and that the traditional classification into type 1 and type 2 is insufficient to explain the wide variety of clinical manifestations of this disease. So I hope you can see how that problem is parallel to the problem that we're trying to address in mental health.

The goals of RDoC are to develop a framework for studying psychopathology based on observable behavior and neurobiological measures, to posit the fundamental components that might span multiple disorders, and find out what is the full range of variation from normal to abnormal, instead of ... A lot of the research that NIMH funds operates under the assumption that, or are under a methodology where you group all the patients together, and all the controls together, and then do between-group comparisons. And RDoC would say it would be more informative to -- instead of excluding the people who don't quite meet diagnostic criteria, and maybe have sub-threshold symptoms -- that it would be better and more reflective of the natural world to study everybody in between, instead of focusing on very healthy, non-representative controls and those at the extreme ends of symptomatology.

Another goal is to be integrative of different methods -- genetic, neurobiological, behavioral, environmental, and experiential. And then finally, to develop reliable and valid measures of those components.

This next slide -- and I'll describe it for any of our visually impaired attendees this morning -- shows a landscape that's consistent with RDoC. It was published by Gottesman and Gould back in 2003. And I guess to make two points: that we're not the only ones or the first ones to be thinking along these lines; these ideas have been out in the field of psychiatry for many, many years. One of the challenges has been, though, from the funding perspective, that it was difficult to get grants funded unless they identified what diagnostic class they were focusing on. And so RDoC is a way to solve a very practical review problem, to get the message out that NIMH is okay with alternative classification systems. So this figure shows a set of hierarchical systems, starting with gene clusters, going to endophenotypes, and then a larger landscape of psychopathology, showing schizophrenia peaking in the landscape with schizophreniform … schizophrenia spectrum disorders at a lower level. And so I would argue that the goal of RDoC is to really understand that whole landscape, and that there will be peaks that we would identify, that might be what we call schizophrenia now but could be identified more clearly if we knew the whole lay of the land. And to understand all the peaks and valleys, and everything in between, rather than focusing just on the, I guess, the peaks that we would identify with existing diagnoses.

The RDoC framework itself can be viewed in detail at the RDoC website on the NIMH webpage. But considered in the context of neurodevelopmental processes that begin prenatally and continue into older adulthood, the RDoC framework sits on top of that, with a set of constructs and domain … sorry … domains that can then be measured at different units of analysis. And all of this also in the context of environmental influences.

We get a lot of questions about, is my proposed project RDoC-y? And it's a little hard to specify exactly what makes an RDoC project. It's one of those things you know it when you see it. So I've tried to articulate here the general principles that make a study RDoC-y versus not. And first off, it's a change of mindset. Again, instead of starting with what's in the DSM and then trying to explain it and understand it and treat it -- instead, take a step back and start with everything we know about normal neurobehavioral processes, and then figure out how those go wrong to cause the symptoms or impairment in functioning.

Secondly, to focus on specific clinical problems instead of heterogeneous diagnoses, because we know that so many of the symptoms do span diagnostic classes. To assume dimensionality among disorders and between illness and health. And that self-support of symptoms does not need to be the "gold standard." On the previous slides, those units of analysis, the ways of measuring things, were parallel with each other instead of hierarchical. And that's to capture … that's deliberate: It's to capture the idea that they each inform each other, rather than one being thought to be more fundamental, or basic, or important. So it may be that, although symptoms are important, there may be signs and signals in other systems -- physiological or other systems -- that are detectable earlier, before a symptom is available for self-support, that might lead to better early detection.

And then finally, to assume … just as the brain is densely interconnected and dynamic with itself, we assume interactions among constructs. So, in that table and in the matrix, if you look it up on the website, we don't want to replace one set of boxes, our existing set of boxes, with a new set of boxes. It is a framework and meant to be dynamic and interactive. [I'm getting a message that my audio is lost. Oh, okay. Never mind, it's back. Okay, I will keep going.] Just from a practical point of view now, moving through an update about RDoC and where we're at this time, we've issued a series of five RFAs focused on RDoC projects, and funded 36 RO1s over the last several years.

We have currently an RO3 announcement out to encourage applications to look at secondary data analysis. So, with the idea that there is a lot of data out there sitting on shelves and sitting on hard drives that were collected using a more traditional patient-versus-control approach, that could possibly be reanalyzed in a more dimensional way, looking at sub-threshold symptoms, or looking at specific symptoms across patient groups, for example. We had, a few years back, an RFA focused on eating disorders. And then finally, more recently, we had a couple announcements focused on understanding psychosis. So at this point, the only active funding announcement from RDoC is the one on secondary analyses. So most of the grants that are funded now that implement RDoC are investigator initiated and don't come in under a specific NIMH funding announcement.

It's a little bit difficult to quantify how much of our portfolio is RDoC versus not, because some projects might incorporate some elements of RDoC, and to a greater or lesser extent. It's not like we have one pool of grants or money that we use for RDoC and a separate pool that we use for other kinds of projects. In my division -- I'm based in the division of translational research -- we get the majority of RDoC-related grants, and I would say about 50% of our portfolio at this time I would classify as RDoC. So I say that just to, I guess, correct or address the misunderstanding that NIMH only funds RDoC projects, because it's not the case. And anybody can go to NIMH RePORTer and look up what we're funding, and you'll see a mix of things. While we encourage investigators to consider RDoC principles, and to consider how diagnostic heterogeneity might affect their findings or inform their hypotheses, we don't have a firm requirement that we only fund RDoC work.

And some other thoughts about how RDoC relates to global mental health research: I mean, I think everything that I've said about RDoC can be applied to global mental health research to the extent that it makes sense for the science. Ultimately, the goal is to free applications and free investigators from the confines of the current diagnostic system. So, at its core, if you wanted to put it on a bumper sticker, the RDoC Initiative means that NIMH is not the national institute of the DSM. We're free to explore other ways of classifying mental illness. And so that would apply as well to global mental health research. Scientifically, global mental health researchers may have access to a broader set of environmental, genetic, and epigenetic factors, such as migration, poverty, and violence, that could be relevant to RDoC hypothesis.

Regarding the use of integrative methods: again, I talked already about not relying on self-support as a gold standard, that might be helpful with illness detection in cultures where expression of negative affect is discouraged. And then finally, sometimes we get the question from global researchers, as well as U.S. based, whether neuroimaging is required for RDoC projects, and it's definitely not. So, although the conceptualization of RDoC starts with what do we know about the brain and how does it go wrong, that doesn't mean that every single study has to measure brain activity. We can start from that place but test hypotheses that are informed by it, without always needing to do FMRI, or EEG, or some of those more expensive methods that aren't going to be available in under-resourced settings.

I included here two examples of RDoC studies. And you can go to the RDoC website, under research, our research funding tab, and there is towards the bottom of the page (it's kind of hard to describe) a link to a list of all of the grants that have been funded under those funding announcements I listed on the other page. So if you're curious about how people are implementing these principles, take a look at that. You can see summaries of the studies, and I've summarized those summaries here for just two of the studies.

The first one is out of the University of Michigan. Christopher Monk is the principal investigator, and he's looking at the effects of poverty on affective development, testing the hypotheses that being in poverty increases different kinds of stressors, which leads to disruption of the HPA axis, changes in amygdala activation, and changes in regulatory connections. So this is a very circuit-based application. And then, looking at the extended effects of poverty exposure and the changes in the developmental trajectories of the HPA axis. So he's looking at low-income families in Chicago, Detroit, and Toledo, and doing repeated measures over time.

A second example, this time out of Harvard/McLean, Diego Pizzagalli is the PI, studying multilevel analysis of positive valence systems, which is an RDoC domain, across mood disorders. So again, transdiagnostically. Looking at patients with mood disorders, they'll use stratified recruitment to enroll treatment-seeking individuals. Agnostic with regard to diagnosis, but trying to get a range of performance on a reward learning task. And then, looking at different mechanisms of reward learning, testing the hypothesis that a composite score for reward learning will have better predictive power for symptoms than DSM diagnosis.

And finally, beginning to wrap up here, I have just a couple updates about our communications and how you can learn more about RDoC on an ongoing basis. We have a few webinars that are archived on our website, including one on facts and myths, another on data analytic approaches, and so on. We welcome your suggestions about webinars that would be useful. We have a Twitter feed, so we're always happy to get new followers on our Twitter feed -- it's @NIMH_RDoC. And we also have open office hours, so an opportunity for anybody to dial in and talk with members of the RDoC workgroup about RDoC -- any questions you might have. It's just a very informal setting and it's a lot of fun. It's on the second Friday of the month, from one o'clock until two o'clock. So if you look at the RDoC webpage, we send out announcements about that, or if you follow us on Twitter, you'll get the update and the link.

And then we also have, in the last couple of years, initiated a data repository for RDoC-related data. So many of you who have gotten grants to do clinical research in the last few years might be familiar with this. But it's growing and growing and growing -- thousands and thousands of subjects, with many different kinds of data. So it's a terrific resource for doing analyses that might be preliminary tests of hypotheses, or hypothesis generating, analysis without all of the costs and time of collecting new data. So I encourage everybody to check that out.

And finally, I want to acknowledge the workgroup and unit members. We have representation from almost all of the NIMH division … divisions, including the intramural program, and then I've listed the past members here who were formative in the development of RDoC.

And that's our website. So let me say thank you very much for listening, and I guess we're going to open it up for questions right now. I'll remind you that Ish Amarreh is on the line, and we're both happy to take your questions.

>> WEBINAR OPERATOR: Thank you. At this time, if you would like to register to ask a question, please press the star and 1 on your touch-tone phone. You may withdraw your question at any time by pressing the pound key. You may also submit a question via the Web by using the Q&A pod located at the bottom of your screen. And we will take a few moments to allow questions to queue. And once again, to ask a question, please press the star and 1 on your touch-tone phone, or you may submit a question using the Q&A pod at the bottom of your screen. And we do not have any questions via phone at this time.

>> SARAH MORRIS: So I'm seeing a question here in the Q&A box -- thank you, Sam. The question is, "Are families or family caregivers linked in any way to RDoC work?" So I'm taking that to mean … I guess I'm not clear. So that could mean, are they related to RDoC research? Or might they be a source of information to test RDoC-related hypotheses? It could also mean, are they involved in the process here at NIMH for developing the framework? I would say, interpreting it the first way, we do acknowledge the importance of the environment in all of these processes that are part of the RDoC framework. To the extent that family members and family caregivers are part of that environment, and might interact in a way to affect mental health–related processes, I would say, sure. Now, RDoC is mainly a way of understanding an individual‘s behavior, so it doesn't go really beyond the things that you can measure at an individual level, but if an investigator wanted to incorporate those elements, I think that could be fine. It would depend really on what's the hypotheses, and does it make sense to study it in that way, incorporating the role of family and family caregivers?

Sam, if that didn't answer your question, please follow up.

>> ISHMAEL AMARREH: We have a second question. This is Ish Amarreh. I think the question disappeared, I don't know. Why did it disappear? And basically, I think what the question said was, "Are there any good examples of currently funded global mental health research studies that are using RDoC? And if there are any specific funding initiatives currently active that are for global mental health and from RDoC." So I'll let Sarah answer the second one, but the first one -- we don't have global mental health currently, and that came in specifically to use the RDoC and framework, but that's what we're hoping that we will be able to do moving forward, and this webinar is one of our efforts to get the global mental health community to start thinking about RDoC framework, and how they could incorporate it into their global mental health research.

Sarah, are there any RDoC initiatives that are open to global mental health research currently?

>> SARAH MORRIS: Well, right now, the only active RDoC funding announcement is the one related to secondary data analysis, so it's not specifically geared toward global mental health, but certainly, if there were existing data that were collected in a global setting, that would be perfectly appropriate. We try to work with our other divisions that write and publish funding announcements, to incorporate RDoC-related language and guidance for investigators. So, for example, in our NIMH clinical trials RFAs, there is some language in there about RDoC -- again, it's guidance to potential applicants. In many of the RFAs that are published, you'll kind of see that incorporation of dimensional perspective.

>> ISHMAEL AMARREH: I think some of our global mental health researchers would like to know if those FOAs are open to foreign institutions.

>> SARAH MORRIS: Which one? If they're not trying to --

>> ISHMAEL AMARREH: The one's that active, the one that's currently active. Can foreign institutions that are doing secondary data analysis apply to it? Or is it only open for U.S. institutions?

>> SARAH MORRIS: I am pretty sure that foreign applications are allowed, but I'm going to look it up right now, and I will answer that in a moment. Ish, maybe you can move to a different question?

>> ISHMAEL AMARREH: Yes, sure. And we have a question from Jacob Meyer, and his question is, "Given that clinicians will still be using DSM and ICD for diagnosis, and likely for determining treatment paths, is NIMH still interested in treatment based on traditional diagnosis? More specifically, should treatment development focus on RDoC domain, or on diagnosis that patients will receive from their clinician?" So, I'll try to answer it, and Sarah could jump in whenever you want to jump in. NIMH still funds research that's based on the DSM. We don't say that we're only funding RDoC-based studies. So that answers the first part of the question. The second one is, should treatments develop focus on RDoC domain? Or on diagnoses that the patients would receive from their clinician? The hope is that moving forward, people would use the RDoC framework to develop the treatments, but that doesn't mean that treatments, currently, that are part of the clinical care shouldn't be used in those studies.

>> SARAH MORRIS: Yeah. I completely agree, and the answer really depends on the stage of treatment development and the setting in which the research is being done. So for very much later stages of treatment development and testing, where you're out in community clinics, it makes sense that the emphasis would be more on existing diagnostic classifications. But at the earlier stages, where new treatment targets are being explored, there's no reason to limit that to existing diagnoses. So something like fear learning, or anhedonia, and reward processing that we see impaired in depression, as well as in schizophrenia. If one is developing and testing a new treatment focused on something like that, there would be no reason to limit it to a single diagnostic class, and it might help get at the problem of variable treatment response within diagnostic groups.

>> ISHMAEL AMARREH: And we have a follow-up question from Sam Nichols, Sarah, and he says, "Expressed emotions might be an example of family-related impact on individual behavior? Relapse?"

>> SARAH MORRIS: Yeah, yeah. I see that. That helps a lot. So I think that could be conceptualized within the RDoC framework under the ... There is a construct related to expression and interpretation of emotions, so social communication, affiliation and attachment, production and reception of non-facial communication -- things like that. Language, under cognition, so at that interface of language, and affect, and social systems. Again, it gets very integrative, but I can imagine how that would fit in.

>> ISHMAEL AMARREH: We have another question, from Ann Vander Stoep, and her question is, "Are RDoC criteria being applied to substance use disorders? Basically, are other institutes like NIDA and NIAAA using the RDoC framework." Sarah?

>> SARAH MORRIS: I hate to speak for them because I will get it wrong, and I don't want them to come upstairs and knock on my door. So --

>> ISHMAEL AMARREH: That's why I gave that question to you, so ...

>> SARAH MORRIS: Yes, thank you, Ish. So we have had ongoing conversations with other Institutes who are grappling with this same issue, because it's certainly, like I made the point earlier, it's certainly not restricted to mental health, and certainly the close relationship between substance abuse disorders and the psychiatric disorders that NIMH focuses on can't be ignored. That would be un-RDoC-ian to ignore those relationships. So that's all I can say is that, we're in communication, they're struggling with the same ideas. At this point, RDoC is an NIMH initiative, but talk to your NIDA or NIAAA program officer and see what they say.

>> ISHMAEL AMARREH: And we have a question from Cheryl Corkin, and her question is, "I'm more of an RDoC researcher, and have little or no experience in global mental health but hope to pursue an RDoC application with investigators in South America. Can you provide guidance for non–global mental health researchers who want to get into this area?" Sarah, do you want to take a stab, or I could tell her ...

>> SARAH MORRIS: I think you should.

>> ISHMAEL AMARREH: Okay. So, at the beginning Sarah said that NIMH is not the Institute for the DSM, so you could apply to any investigator-initiated FOA and use an RDoC framework. You don't have to apply only to specific FOAs that say that they are RDoC related. So most of the FOAs that are issued by NIMH will accept research in the RDoC framework. And I'll suggest that you go to our website and look at the different divisions and see where within the Institute your research falls, and try to contact the specific person who is the person responsible for that portfolio. But we could also help you, and navigate you through that if you need that help.

And we have a question from Aqsa Masood, and the question is, "As the mental health research in low- and middle-income countries is more focused on task shifting of interventions which use transdiagnostic approach, how can RDoC be related to transdiagnostic approach?"

>> SARAH MORRIS: That all --


>> SARAH MORRIS: Yeah, sure. So, that's all very consistent with RDoC principles -- the idea that you don't necessarily need a certain treatment for schizophrenia that's distinct from a treatment for bipolar disorder. With some exceptions: Obviously, lithium is effective for a significant subgroup of people with bipolar disorder. So we wouldn't ignore that clinical reality, for example. So I think in response to your question, it all goes back to how you frame your research hypotheses. I'm not sure this answers your question, but it makes perfect sense in a clinical setting, that you're going to have people who walk in the door, and they may be diagnosed according to ICD or DSM, but for the purpose of testing a research hypothesis, you might group them all together. It's really about identifying the optimal population that's going to provide the strongest test of the research hypothesis, within the constraints of the setting in which you're working. But it kind of goes back to not making assumptions about diagnosis, not taking those as the gold standard and assuming that the diagnoses are valid for different purposes.

>> ISHMAEL AMARREH: We have another question from Thahira. And the question is, "Is RDoC being used in Asia as well?" I am not aware of a study in Asia that's using the RDoC framework, but that doesn't mean that it shouldn't be applied or used in Asia, or anywhere in the world. We are hoping that RDoC will be a framework for all mental health research on the planet. But currently, I'm not aware of a study that is using the RDoC framework in Asia.

>> SARAH MORRIS: Yeah, the only one … well, two things: There's some work that I'm aware of, looking at psychosis risk, and they are focused on more dimensional outcomes instead of a dichotomous "converted to psychosis" versus "not converted to psychosis." Because we know that even people … people who are at risk for psychosis, even if they don't develop a diagnosable disorder, still many of them continue to have significant impairment and symptoms. So I'm aware of that one; it's kind of a cluster of studies being done in China. But actually we're having a visitor from Japan who has been tasked with learning more about RDoC and considering implementing something similar in the Japanese mental health research funding system. So we are engaged in international conversations but, of course, Asia is a big place.

>> ISHMAEL AMARREH: Thank you, Sarah. We have a question/comment from Ann, and the comment, I think, is, "For global health, if task shifting is being promoted, and teaching skills to lay people that can be applied to a broader part of the population of sufferers, then RDoC helps to promote population health." This kind of a statement -- is it a way to conceptualize the prior question? And I'm assuming your prior question was, "Are RDoC ..." (is that the question?) "Is RDoC being used in Asia?" -- is that the prior question, Anna? If it is, the prior question "Is RDoC being used in Asia?" Or the question that you proposed? The question that you asked previously, "Are RDoC criteria being applied to substance abuse?" And I think, I totally agree with your statement. I think, yes, RDoC may help in promoting population health, and it's a way of, yes, conceptualizing that prior question.

>> SARAH MORRIS: Yeah. So, I think it refers back to- --

>> ISHMAEL AMARREH: I think she --

>> SARAH MORRIS: Back to [crosstalk 00:51:41], back to the question. Yeah.

>> ISHMAEL AMARREH: Oh, about the task shifting. Yeah.

>> SARAH MORRIS: Right. I think you, Ann, the way you've articulated that makes a lot of sense. And, I don't know, there's, I guess, two ways to look at it. On one hand, if resources are limited, one wants to focus on delivering treatments that are likely to be beneficial for the individual, instead of an inefficient, shotgun approach. And I think RDoC can help with that, doing a better matching of treatment to patient, again, by addressing the heterogeneity problem. And then maybe related to that is the idea that not everybody who comes in and meets diagnostic criteria is going to have the same outcome. So how do you choose those who are maybe most in need of treatment? Or people who are at risk, in an earlier phase of illness, and might not meet diagnostic criteria but early intervention could be really beneficial? So, yeah, there's a lot of ways of thinking about that, and that applies here in the U.S. as well.

These are great questions, by the way.

>> WEBINAR OPERATOR: And at this time, I'd like to give one more reminder. For those of you on the phone, if you'd like to ask a question, please press the star and 1 on your touch-tone keypad. And to submit a question via the Web, please use to Q&A pod located at the bottom of your screen.

And we do have no further questions via phone.

>> SARAH MORRIS: Okay. Well, let's take another moment, if there are any more questions to come in via the text box. Of course, if you think of any questions later, you should join us at our office hours, second Friday of the month. Or tweet it to us. We do answer questions by Twitter. Okay, great. Makeda, I think we're ready to wrap up.

>> WEBINAR OPERATOR: Well, thanks to both of you. Thank you, Dr. Sarah Morris, and Ish Amarreh for a great presentation on the Research Domain Criteria. I think it was a great discussion and really good questions that were asked, and I appreciate your time. I would also like to thank NIMH, the Bizzell group, and One Source for their support of our webinar series and logistics. And finally, I'd like to thank all of the webinar attendees for their participation and support of our webinar series.
As I mentioned earlier, this is the final global mental health webinar of our four webinars for the 2017 global mental health webinar series. We will have all four of the global mental health webinars posted on the NIMH Office for Research on Disparities and Global Mental Health website.