Posted 4 October 2009

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Attendees/Participants

Jean Addington, University of Calgary, Canada
Andrea Auther, Zucker Hillside Hospital, New York
William Carpenter, Maryland Psychiatric Research
Cam Carter, University of California at Davis
Cheryl Corcoran, Columbia University Medical Center
Barbara Cornblatt, Zucker Hillside Hospital, New York
Camilo de la Fuente-Sandoval, Mexico City Prodromal Research Program
Angela Epshtein, Schizophrenia Research Forum
Paul French, Manchester University, United Kingdom
Howard Goldman, University of Maryland
Hakon Heimer, Schizophrenia Research Forum
Todd Lencz, Zucker Hillside Hospital, New York
Maureen Martin, Washington University School of Medicine
Thomas McGlashan, Yale University School of Medicine
Margaret Migliorati, EARLY Program (EDIPPP) New Mexico
Michael O’Sullivan
Andrea Pelletier, University of North Carolina
John Saksa, Yale University School of Medicine
Tamara Sale, Early Assessment and Support Team, Oregon
Amresh Shrivastava, University of Western Ontario
Magenta Simmons, Orygen Youth Health Research Centre, Melbourne
Helen Stain, University of Newcastle, Australia
Renate Thienel, University of Newcastle, Australia
Andrew Thompson, Orygen Yough Health, Melbourne
Joseph Ventura, University of California at Los Angeles
Scott Woods, Yale University PRIME Research Clinic
Qing Xu, Cornell University
Alison Yung, PACE Clinic, Melbourne

Note: Transcript has been edited for clarity and accuracy.

Angela Epshtein
I think we can start with the preliminaries. Let's start off by having everybody in the "room" introduce themselves: Please type your name and affiliation or institution. I'm Angela Epshtein, managing editor of Schizophrenia Research Forum.

Hakon Heimer
Hakon Heimer, editor of Schizophrenia Research Forum.

Margaret Migliorati
Margaret Migliorati, therapist, EARLY Program (EDIPPP) New Mexico.

Scott Woods
Yale University PRIME Research Clinic.

John Saksa
John Saksa, Yale University School of Medicine.

William Carpenter
Will Carpenter, Maryland Psychiatric Research Center, University of Maryland School of Medicine.

Cheryl Corcoran
Cheryl Corcoran, COPE, Department of Psychiatry, Columbia University Medical Center.

Magenta Simmons
Magenta Simmons, CAARMS Coordinator, Orygen Youth Health Research Centre, Melbourne, Australia.

Amresh Shrivastava
Amresh Shrivastava, University of Western Ontario, Canada.

Camilo de la Fuente-Sandoval
Camilo de la Fuente-Sandoval, Mexico City Prodromal Research Program, Mexico.

Alison Yung
Alison Yung, PACE Clinic, Melbourne, Australia.

Tamara Sale
Tamara Sale, coordinator of the Early Assessment and Support Team, Oregon.

Andrea Pelletier
Andrea Pelletier, University of North Carolina.

Howard Goldman
Howard Goldman, University of Maryland.

Renate Thienel
Renate Thienel, University of Newcastle, Australia.

Helen Stain
Helen Stain, Centre for Rural and Remote Mental Health, University of Newcastle, Australia.

Barbara Cornblatt
Barbara Cornblatt, RAP program, Zucker Hillside Hospital, New York.

Paul French
Paul French, Manchester University, United Kingdom.

Andrea Auther
Andrea Auther, RAP program, Zucker Hillside Hospital, New York.

Jean Addington
University of Calgary, Canada.

Thomas McGlashan
Yale University School of Medicine.

Qing Xu
Cornell University.

Maureen Martin
Washington University School of Medicine.

Joseph Ventura
University of California at Los Angeles.

Cam Carter
Cameron Carter, University of California at Davis.

Todd Lencz
Zucker Hillside Hospital, New York.

Andrew Thompson
Orygen Youth Health, Melbourne, Australia.

Angela Epshtein
All, in the interest in time, I will begin as folks introduce themselves. If you haven't chatted before, you'll see that many things can happen at once in the chatroom. So, while the rest of you introduce yourselves, I would like to introduce and thank our chat leader, William Carpenter. In our usual informal spirit, I won't list his lengthy achievements, but just say that Will is a professor of psychiatry and pharmacology at the University of Maryland School of Medicine, director of the Maryland Psychiatric Research Center, and chair of the DSM-V psychosis work group.

Amresh Shrivastava
All, thanks, we all know Will; it’s great to have him here tonight.

William Carpenter
All, our discussion, in conjunction with the preliminary comments that have been posted, will be important feedback for the DSM-V work group on schizophrenia and related psychoses. Identifying individuals as being at increased risk for a psychotic disorder is feasible and valid. This part is simple. The fact that stigma, excessive treatment, and false positive ascertainments will complicate any approach to defining this clinical syndrome makes the task complex. A final judgment on including or excluding this category from the DSM-V will have to be made, and this judgment will be difficult. In the chatroom tonight (or morning or afternoon, depending on where you live), we hope comments and responses will move beyond the obvious. For example, we all know that there is the danger of stigma. We need to know how severe is the danger, how to weigh it against advantages of early therapeutic intervention, and what can be done to minimize adverse effects. We will shape the discussion into four roughly 15-minute segments. 1. Criteria and validity for identifying individuals at risk—who are the false positives? 2. Should the risk syndrome be for schizophrenia, or psychosis, or mood and/or psychotic disorders? How broad should the risk syndrome category be? 3. The downsides to creating the “at risk for psychosis” category, namely, stigma and excessive treatment. 4. Finally, considering all the data, how ought a judgment be reached regarding the inclusion of an at-risk category for psychosis in the DSM-V? Note that material posted on the Schizophrenia Research Forum Live Discussion page will remain available. Recent postings include the proposed criteria set being considered by the DSM-V work group. Also, we have posted an editorial on this issue by me that will appear in the September 2009 issue of Schizophrenia Bulletin titled, “Anticipating DSM-V: Should Psychosis Risk Become a Diagnostic Class?” Also in the September issue will be an article by Scott Woods et al. titled, “Validity of the Prodromal Risk Syndrome for First Psychosis: Findings From the North American Prodrome Longitudinal Study.”

Hakon Heimer
Will, whew! Now that's an intro! You type fast, Will.

Amresh Shrivastava
All, the presenters have provided us with excellent educational material; we have much to discuss.

William Carpenter
Thomas McGlashan, would you lead off by stating the main criticisms that you have heard on the proposal to place a risk syndrome in DSM-V?

Scott Woods
Will, maybe we can dedicate some time for discussing the benefits of a risk syndrome, too?

Amresh Shrivastava
Will, can we begin by hearing more about what will be achieved by having an ARS category in the DSM-V?

Thomas McGlashan
All, the main criticisms regarding the inclusion of a risk syndrome in the DSM-V appear to focus on the risks for the false positives, stigma, and excessive treatment.

Cam Carter
All, it would also help to understand whether the risk category is to be defined as a heterogeneous risk syndrome (as in mild cognitive impairment) or a disorder. Based on what we know, it seems implausible that it will be defined as a disorder. Namely, low positive predictive value and heterogeneous outcomes requiring markedly different evidence-based interventions make it difficult to consider the risk syndrome a disorder.

Thomas McGlashan
Cam, the syndrome is not an established disorder, and adding to the DSM-V would constitute adding unnecessary categories into the DSM-V.

William Carpenter
Cam, the DSM-V work group’s conceptualization of the risk syndrome parallels the characterization of hypercholesterolemia and hypertension.

Alison Yung
Cam, I think the danger of including the risk syndrome in the DSM-V is that it will be perceived as a disorder and treated as such.

Helen Stain
Cam, I agree with your comment, namely, the characterization of the risk category as a heterogeneous risk syndrome rather than a disorder.

William Carpenter
Amresh, the inclusion of an at-risk category in the DSM-V would be based on whether or not it is scientifically valid as a clinical entity. Further, inclusion would encourage attention to the clinical problem, development of interventions, perhaps alter the course of psychotic illness, and provide clinicians with a method to diagnose and receive reimbursement. Secondary prevention would be a primary hope.

Amresh Shrivastava
Will, thanks, but if it is not a disorder/disease, only a risk condition, should we not have a category for subclinical states?

Cheryl Corcoran
Will, it seems all but reimbursement to clinicians could be accomplished by including the risk syndrome in the appendix of the DSM-V.

Helen Stain
Will, while inclusion of the risk syndrome would help those who will develop psychosis, there remains the danger of overtreatment (especially with regard to medication) in the case of false positives. This could also lead to a lifetime trajectory of a “mental illness” identity or self-perception.

William Carpenter
Helen, we can address your point during the third part of the discussion.

Barbara Cornblatt
Will, my view of treating the risk syndrome as a clinical entity is that the diagnostic categories have not yet been validated, especially in the community setting.

Amresh Shrivastava
All, as many have pointed out, the fundamental question is whether or not the risk syndrome is a mental disorder. Scott, what do you think?

Scott Woods
Amresh, part of the benefit of the risk syndrome category is that it will support future intervention research. Right now we are in a Catch-22: the diagnosis may be premature partly because we do not have enough treatment research, but treatment research can be viewed as premature because we don't have an accepted diagnosis.

Cheryl Corcoran
Scott, this could be accomplished by placing the syndrome in the appendix of the DSM-V.

Amresh Shrivastava
Scott, then why not have a phase-specific condition or a coding on severity? Alternatively, why not have a class for sub-threshold symptoms?

Alison Yung
Will, perhaps it would be useful to the non-U.S. citizens for someone to explain how individuals gain access to psychiatric treatment in the U.S. Do they need a DSM diagnosis?

Howard Goldman
Alison, practitioners are required to assign a diagnosis in order to be paid for treatment in the US. But, if the condition is considered a risk syndrome analogous to hypertension or hypercholesterolemia, then it might be possible to get paid for treatment of this condition/risk category and avoid considering it a mental disorder.

Thomas McGlashan
Alison, for private insurance, which represents the majority of insurance coverage in the U.S., individuals must have a DSM diagnosis.

Alison Yung
Tom, thanks. Most individuals that meet ultra high-risk (UHR) criteria also meet criteria for a non-psychotic disorder such as depression.

Cheryl Corcoran
Tom, but the comorbidity is so high among prodromal patients that many have some sort of DSM diagnosis.

Scott Woods
Cheryl, yes they do have comorbid diagnoses, but we have no treatment research to show whether treating those comorbid diagnoses helps their primary problems.

Barbara Cornblatt
Cheryl, do you think that putting the definitions in the appendix will stop typical clinicians from viewing the prodrome as a clinical entity to be treated?

Cheryl Corcoran
Barbara, I don't know. I can research that question to find out what has happened with other provisional diagnoses in the appendix.

Scott Woods
Cheryl, the high comorbidity among prodromal patients would help, but funders of treatment research would be more enthusiastic if we had a diagnosis.

Cheryl Corcoran
Scott, I agree, it is an empirical question whether treating comorbid depression might prevent psychosis. Barbara published data that suggest that it might (Cornblatt et al., 2007).

Helen Stain
Barbara and Cheryl, yes, listing the syndrome in the appendix of the DSM-V will still lead clinicians toward interpreting the syndrome as a clear diagnosis.

Cheryl Corcoran
Helen, I am not sure. I don't know if there are data to support this.

Tamara Sale
Scott and Will, could the DSM-V work group expand the description of schizophrenia to include an overview of the research around onset and common progression without adding a separate risk category?

Paul French
Tom, I agree with Cheryl. Everyone we see in our trials would be able to get some form of DSM-based diagnosis without recourse to a special at-risk status.

Cheryl Corcoran
Scott, you may be right. Funders of treatment research would be more enthusiastic if the risk syndrome was not in the DSM-V appendix. But I see this counterbalanced by the problem of overtreatment by community clinicians (possibly) if the syndrome is listed in the main text of the DSM-V vs. the appendix.

Helen Stain
All, are we talking about access to antipsychotics in light of a diagnosis?

Cheryl Corcoran
Helen, I can' t imagine that community-based clinicians will not prescribe antipsychotics for psychosis risk.

Amresh Shrivastava
Will, what about “do no harm”? That’s the most important aspect of this process.

Barbara Cornblatt
Scott, I think Cheryl's point, or at least my point, is that all of our patients that have been with us for 10+ years have always been covered by insurance for comorbid conditions regardless of what we are actually treating them for.

Thomas McGlashan
Barbara, I guess the question is, Should they be treated with whatever diagnosis in order to get paid as a clinician?

Angela Epshtein
Everyone, I'm going to invite Will to transition into the second topic. I realize we have an active discussion going about topic 1, and that can continue as well.

Scott Woods
To all, I thought Pat McGorry’s suggestion (see commentary) that any DSM diagnosis text explicitly state that the diagnosis is not equated with the need for antipsychotic medication, is an excellent idea. We have never recommended that type of language be inserted into the DSM.

Amresh Shrivastava
Scott, yes, but if you give a diagnosis to an individual, treatment and intervention become a natural option for many clinicians.

William Carpenter
All, we are nearing the halfway mark. Have we addressed the issue of how broad the risk syndrome should be? Pat McGorry advocates maybe combining the risk syndrome with mood disorder risk.

Cheryl Corcoran
Will, combining risk syndrome with mood disorder risk? Will there be any adolescents left?!

Helen Stain
Will, mood disorder should be included/addressed.

Cheryl Corcoran
Helen, Hafner has retrospectively documented how prevalent depression is in the prodrome. A number of other groups, namely, PRIME, RAP, COPE, and CAPPS have shown the extent to which depression is comorbid in our risk syndrome samples (Häfner et al., 2008; Rosen et al., 2006; Meyer et al., 2005).

Alison Yung
Cheryl, Scott, and Helen, I think the issue of antipsychotics is a crucial one. If someone meeting risk syndrome criteria also has depression and anxiety (the majority do), could they not be treated with psychological therapies such as cognitive behavioral therapy (CBT)? This has been shown to be effective in the EDIE trial (published in BJP, 2004). So why the need for a specific risk syndrome diagnosis? Is the agenda really to use antipsychotics?

William Carpenter
All, the excess treatment discussion is included in part 3 of our discussion.

Helen Stain
Alison, yes, my concern is the overuse of antipsychotics for the risk syndrome group.

Scott Woods
Alison, we need more and better psychotherapy studies, too. A rising tide floats all boats.

Tamara Sale
All, if there is a risk category, regardless of how broad it may be, there should also be some consensus on how inclusion in the category guides treatment.

Cheryl Corcoran
Will, please state what we should be discussing now.

Thomas McGlashan
The risk syndrome is specific for psychosis, not for other disorders by and large, which is one reason why it has good validity.

Amresh Shrivastava
All, how many individuals in most parts of the world have access to CBT for early intervention?

Cheryl Corcoran
Amresh, access to CBT is limited, reimbursement less so.

Paul French
Amresh, we have a high availability of CBT in the U.K.

Tamara Sale
Amresh, in the U.S. almost no one has access to CBT for early intervention. It’s hard to even get training specific to psychotic illness. Also, there is still debate about its relevance here in the U.S.

Amresh Shrivastava
Yes, but the scene in two-thirds of the world is different than North America and the developed world.

Barbara Cornblatt
All, I agree with Tamara; availability of appropriate treatment should be a major guiding factor.

Alison Yung
Scott, yes, sure we need more treatment studies (i.e., psychotherapies, neuroprotective agents). But, my question was, Why the need to reify the diagnosis if the agenda is to access treatment, since the majority (as Barbara indicated) can access treatment anyway?

Cheryl Corcoran
Amresh, forgive my parochialism; I was referring to access to CBT in the U.S.

Magenta Simmons
Scott, can we call the at-risk mental state the primary problem? The primary problems of many ultra high-risk (UHR) consumers have nothing to do with attenuated psychosis. Also, given that the majority will not go on to develop psychosis, their primary problems are often mood disorders and/or functioning issues.

William Carpenter
All, let's close on the validity and broadness issue and address the downsides of inclusion of the risk syndrome in the DSM-V: stigma, excessive treatment, harm to false positives, etc.

Cam Carter
Will, that clarification is helpful. Given the heterogeneous outcomes, including positive cases without intervention, the question is whether the analogy to hypertension is a valid one. It seems that we need more research to refine our ability to predict who is at risk for a major mental disorder and who is not (the false positive problem). I’d like to reiterate Alison’s point, namely, recent evidence suggests that we are not very good at predicting risk and that the end states for those at risk are quite diverse and will require a range of divergent interventions.

Scott Woods
Will, as Pat mentioned in his commentary, risk syndromes for non-psychotic affective disorders haven't been combined in any research yet, so it seems even more premature.

Cheryl Corcoran
To all, are there any empirical data about stigma among patients who are "prodromal"? Thomas McGlashan and I published on this issue with regard to family members.

Amresh Shrivastava
Cheryl, no stigma work has addressed the issue of the prodrome. Most of the work has been done in chronic patients, which is less relevant to the discussion at hand.

Scott Woods
All, to what extent can stigma be mitigated by education of clinicians? Ultra high-risk (UHR) research clinics work hard to mitigate stigma of research subjects.

Howard Goldman
All, I ally myself with Cam's comments and concerns. Specifically, given the heterogeneous outcomes, including positive cases without intervention, the question is whether the analogy to hypertension is a valid one. It seems that we need more research to refine our ability to predict who is at risk for a major mental disorder and who is not (the false positive problem).

Cheryl Corcoran
Howard, it seems by that you mean that without validity, the stigma issue is less relevant, which I think makes sense.

Howard Goldman
Cheryl, I think that there is a potential stigma issue with or without the validity of the diagnosis. My concern is really about the intervention and its benefits and costs, monetized and otherwise.

Cheryl Corcoran
Howard, I agree.

Magenta Simmons
All, but it's not the “prodrome” for most people; our language alone is a powerful instigator of stigma.

Tamara Sale
Magenta, I could not agree with you more on the inappropriateness of the term “prodrome” as a diagnosis. Cam, I agree with you; the current syndrome definitions are too broad. Perhaps some description of the more refined NAPLS findings could be helpful since it suggests a higher predictive validity for a subgroup.

Amresh Shrivastava
All, people are willing to accept and deal with stigma if help is available. One of our studies in Mumbai indicated that 85 percent of our subjects believed that the best way to deal with stigma is to make treatment available. ("Stigma and Discrimination: the Mumbai Experience." The Fourth International Stigma Conference 2009, London, U.K, Jan. 2009. Available at: http://works.bepress.com/amreshsrivastava/44.)

Cam Carter
Will, can you also clarify the purpose of DSM-V? It seems that we want to revise the nosology to provide a more scientifically based classification system. I worry about having other agendas, i.e., promoting research or facilitating billing. Most of these kids do have a parity diagnosis. Our lack of certainty in this area is our best argument for needing more research.

Magenta Simmons
Cam, I agree. Also, if the primary aim is to prevent the onset of a psychotic disorder, then we have two diluting factors: 1) not everybody will go on to develop psychosis, and 2) for those who do go on to develop psychosis, we still don't have effective treatments to prevent all cases. Therefore, the proportion of people initially “diagnosed” with the risk syndrome who are actually helped (in terms of preventing psychosis) will be few.

Tamara Sale
Magenta, our program is less interested in preventing psychosis than in preventing disability. We are very interested in the cognitive and environmental changes prior to acute psychosis and how to modify the course.

Alison Yung
Will, I'm sorry, we are closing on the validity issue. I don’t think we really addressed it. I have concerns about the validity. The risk syndrome is a heterogeneous group with variable outcomes. I don't think it's sufficiently validated yet.

Cheryl Corcoran
All, I agree with Cam.

Helen Stain
All, I agree with Alison.

Alison Yung
All, yes I agree with Cam, too. He is Australian after all.

Thomas McGlashan
All, I agree with Cam.

Barbara Cornblatt
A downside I'd like to mention: Recently I was contacted about the use of the prodromal risk as a justification for someone's parole. Legal implications have to be considered here as well.

Tamara Sale
Barbara, egads!

Alison Yung
Barbara and all, absolutely; there are a number of social consequences of receiving a diagnosis (see my slidecast).

William Carpenter
All, in our DSM-V work group, we hope to diminish stigma by naming a risk syndrome, making clear it is not schizophrenia but rather psychosis, and locating the category in a new section on risk syndromes along with maybe mild cognitive impairment. We anticipate that more will be developed over the years and that the DSM-V will be dynamic and open to changes in advance of DSM-VI.

Amresh Shrivastava
Will, so can the DSM-V be a gateway for changing the name of schizophrenia?

Cheryl Corcoran
Will, that is a good plan, but I believe stigma remains a risk nonetheless. Most "prodromal" researchers do schizophrenia research, and our patients Google us. Cam, what are your thoughts about having the risk syndrome in the appendix?

Scott Woods
To all, DSM-V will be used for patients who come to doctors with an explicit request for diagnosis. Doesn't this address some of the stigma concern? No one is suggesting forcing diagnoses on people.

Tamara Sale
All, we’ve had a number of conversations with communities that are thinking about starting early psychosis programs, and the distinction between schizophrenia and the prodrome is lost to them.

Helen Stain
Scott, if the risk syndrome sits as a diagnosis in the DSM-V, then people will diagnose themselves.

Cam Carter
All, I think a risk category that is identified as needing further research would be a way of earmarking the progress that has happened in the field and prepare us for further progress on risk prediction and interventions over the next few years.

Tamara Sale
Scott, given that community education and proactive identification are a part of most programs, we can't assume people are actively seeking a diagnosis.

Alison Yung
Will, I think, unfortunately, "psychosis" is becoming a stigmatizing label. We have all heard terms like "psychotic axe murderer" in movies. Plus, the temptation for the average clinician will be to treat some “at risk for psychosis” patients with an antipsychotic agent.

William Carpenter
Howard, how do you conceptualize the cost and the public health benefit/risk of calling official attention to the risk syndrome by including it in the DSM-V?

Amresh Shrivastava
Will, I don’t think an economic argument for this issue is a good one. The risk syndrome requires merit for inclusion as a “diagnosis” regardless of the economic implications.

Scott Woods
Will, what about the excessive treatment issue?

Amresh Shrivastava
Scott, I think that’s a huge possibility and irrational pharmacotherapy will be rampant.

Scott Woods
Amresh, it's already a problem. Maybe the problem is that we haven't educated our community about these issues. DSM-V would give criteria for who does not have a risk syndrome.

Amresh Shrivastava
Scott, I agree; we need to focus on inclusion and exclusion criteria.

Cam Carter
All, I agree that validity has to be the issue and it is poor at this time for this construct. Many people have recently been pointing out how the DSM has high reliability and low validity, and adding the risk syndrome to the list of the disorders will lower it even further.

Alison Yung
All, we speak of preventing "psychosis," but the threshold for "psychosis," especially diagnosed prospectively, has not been adequately validated. We see people who have crossed the arbitrary "psychosis threshold" only to revert to a less symptomatic picture and good functioning.

Michael O’Sullivan
Will and Howard, thinking about it from a public health/epidemiology perspective is important. Can we actually identify something to diagnose? In my mind, not yet. If we are able to, can we treat it? No. Therefore, we should not place it in the DSM yet, and we ought to collaborate to ensure scientific rigor.

William Carpenter
Michael, only persons seeking help and manifesting distress and/or disability would meet criteria. Clinicians must attend to them. The question is whether more specific attention to the issue helps more than it hurts.

Helen Stain
Will, but the question remains, Is this the right criteria/category for them?

Magenta Simmons
Tamara, I think this might be why we find that basic case management is beneficial for ultra high-risk (UHR) consumers. It addresses the concerns that they have and need help with in their lives.

Thomas McGlashan
DSM is an important document for many reasons. Having a risk syndrome can help bring psychiatry abreast of medicine in anticipating disorders.

Tamara Sale
Scott, I don't think psychosocial or lifestyle issues are problematic, but given blood sugar/obesity/lipid levels, antipsychotics are still a concern.

Cheryl Corcoran
Tom, the DSM is primarily a diagnostic manual for clinicians to help them with establishing diagnosis.

Howard Goldman
Will, from a public health and public policy perspective, I like to think in terms of the potential benefit from preventing the downstream consequences of schizophrenia. In order to achieve that goal we need to demonstrate that the upfront costs and risks (medical and social) of specific interventions are justified by the benefits and savings. Achieving that goal entails valid criteria, and that is where the DSM revision comes in. There are many other issues related to adding or changing the diagnostic nomenclature (that was the topic of my slidecast), but for a risk syndrome, it is all about prevention.

Magenta Simmons
Howard, should this work be done in the arena of research rather than clinical diagnosis?

Howard Goldman
Magenta, I think the research needs to come first. We are getting very concerned about comparative effectiveness of interventions driving policy decisions regarding the financing of services.

William Carpenter
All, we are about to go to the fourth and last segment. It seems evident that there is a clinical issue and that formally addressing it in the DSM-V has potential benefits and harms. How is a wise and scientifically justified decision to be reached? How do you weigh all the considerations and make a judgment?

Barbara Cornblatt
I know that the discussion has now shifted again; however, I think that this all relates back to the question of whether our definition of risk, either for schizophrenia or psychosis, has been adequately validated—a point raised earlier by Alison.

Cheryl Corcoran
Barbara, your point has been expanded upon by Cam. I agree this is a concern.

Amresh Shrivastava
All, no, I think it is about defining a “disease” that can be classified as a mental illness.

Helen Stain
Will, I think many participants in our discussion are saying that we need more research to determine the criteria for being at risk for psychosis and to determine effective treatment, especially psychotherapies.

Cheryl Corcoran
Helen, I agree.

Amresh Shrivastava
Helen, that’s correct.

Magenta Simmons
Helen, I agree, too!

Barbara Cornblatt
Helen, agreed.

Camilo de la Fuente-Sandoval
All, I agree.

Michael O’Sullivan
All, agreed.

Alison Yung
Will, how is a wise decision to be made? I think there are concerns about validity, especially predictive validity, and this relates to potentially stigmatizing and unjustified treatment for some individuals as well as all the negative social effects of diagnosis. I think including the risk syndrome in the DSM-V is premature.

Barbara Cornblatt
Alison, also agreed.

Thomas McGlashan
Will, how is the psychotic disorders committee proceeding? Are they pursuing field trials?

Amresh Shrivastava
All, is there enough to suggest a separate class for subclinical diagnosis in the DSM-V?

William Carpenter
Helen, I do not think classification in the DSM depends on effective treatment. That has not been a criterion in medicine.

Cheryl Corcoran
All, I don't think we fully addressed the risk that thousands of adolescents will be placed on antipsychotics indefinitely and many will develop metabolic syndrome. As Amresh said, “Do no harm.”

Magenta Simmons
Tom, like Barbara (I think it was) said at the start, we don’t know the transition rate in the general population. Should this be a starting point? I think it will just confirm that these criteria are useful for specialist services but not for general screening purposes.

Helen Stain
Cheryl, yes, I have grave concerns about the overuse of antipsychotics in vulnerable youth.

Cheryl Corcoran
Will, that may be different for a risk syndrome in terms of whether any strategies exist for prevention. There is possible harm in telling someone he or she is at risk for something but that you have nothing to offer.

Magenta Simmons
Will, but it does depend on valid and reliable criteria and we don't have that for the general population.

Scott Woods
Cheryl, I see many patients on antipsychotics who do not meet the risk syndrome criteria. DSM-V might reduce their numbers.

Cheryl Corcoran
Scott, I know, and the epidemiological data support that (e.g., Mark Olfson’s work).

Hakon Heimer
All, there are some research diagnostic criteria (RDC) for schizophrenia used in genetics research. Are the criteria for research on the prodrome used in different countries/research centers fully compatible and useful for any research that needs to be done? If not, is there an effort to get uniformity?

William Carpenter
Tom, field trials will be essential, but the question to be answered is whether ordinary clinicians can differentiate with reasonable reliability between the risk syndrome and other potential diagnoses or no diagnosis. So, criteria would be tested against maybe schizotypal personality, brief psychosis, mood disorder, no disorder, or something along those lines.

Amresh Shrivastava
All, how many people really take into account what the DSM says while prescribing in community settings?

Helen Stain
Scott, I don’t see that reverse argument working.

Magenta Simmons
Scott, if clinicians are prescribing to people who don't even meet a DSM criteria, then surely they will not be dissuaded by the risk syndrome being in the DSM? Sounds like they will do irresponsible prescribing anyway?

Scott Woods
Magenta, sometimes they think the symptom is ultra high-risk (UHR), but it's too stable or not frequent/severe enough, or clearly part of a comorbid problem like post-traumatic stress disorder (PTSD).

Cheryl Corcoran
Will, one of the prodromal programs in NAPLS used schizotypal personality as the basis for ascertainment.

Thomas McGlashan
All, the risk criteria are used for help-seeking populations, not as a screening instrument. The false positive rate is too high for screening populations.

Magenta Simmons
Tom, do you think this will be what actually happens in clinical practice? I agree with what Paul (I think it was) said earlier: that we need to add in help-seeking and distress to the criteria, but this is at risk of being a subjective call. We need a valid way to do this.

Howard Goldman
All, in the DSM IV, the standard for determining that a person has a mental disorder is the presence of distress or some level of dysfunction—the rest is about assigning a category to explain that distress and dysfunction. People with a risk syndrome can qualify for service without a new category. In my view, there needs to be a substantial body of research before identifying a specific disorder or at-risk category. I am more favorable toward the idea expressed earlier, namely, in attaching the considerations of risk and appropriateness of intervention under the general category of schizophrenia rather than taking a leap and creating a new category without more data.

Amresh Shrivastava
All, risk cannot be a disease; we need a different mechanism for our purpose.

Cheryl Corcoran
Tom, we don't know if community samples will be like those who seek help in academic centers or like individuals who are screened. It is an empirical question. Howard, well put.

Amresh Shrivastava
All, are there legal implications that might result from the risk syndrome being in the DSM-V?

Thomas McGlashan
Amresh, there are no legal implications that I know of.

Helen Stain
Howard, wise comments. Amresh, note Barbara's example regarding legal issues.

Cheryl Corcoran
Helen, that is a phone call Barbara just received!!

Scott Woods
All, Barbara got that call despite the fact that there is no risk syndrome category in the DSM-IV.

Alison Yung
Scott, it will be worse if it’s in DSM!

Cheryl Corcoran
Scott, a case report!

William Carpenter
Howard, the data are based on criteria which are "minor" forms of psychotic experience, and conversion rates are more often to psychoses than other disorders. But it is not specific to schizophrenia, and we are hesitant to make it broader than psychosis or as narrow as schizophrenia.

Alison Yung
All, we need to recognize that including the risk syndrome in the DSM-V may result in more people from less enriched samples being diagnosed. We saw this in Melbourne. Specifically, the greater publicity about ultra high-risk (UHR) status generated more referrals from general health settings, which would be expected to have a lower transition rate.

Amresh Shrivastava
All, no, it cannot be underplayed. Once the risk syndrome is classified as mental illness it will embrace all the problems that are present with such a diagnosis.

Howard Goldman
Will, how about considering the risk syndrome under a "psychosis not otherwise specified"?

Cheryl Corcoran
Howard, that will lead to antipsychotic treatment. Weren't you paying attention in Bethesda?

Thomas McGlashan
Howard, it's not yet a psychosis.

Helen Stain
Howard, but it’s not a psychosis.

Alison Yung
Howard, yes, I agree with Cheryl. This will not avert any problems we have been discussing.

Angela Epshtein
Will, Hakon asked an interesting question regarding the criteria for research on the prodrome: Are they uniform? If not, is there an effort to get uniformity?

William Carpenter
Howard, the criteria include not meeting criteria for a psychotic disorder including psychosis not otherwise specified (NOS). It is that thin (or not so thin) line between the criteria for risk and full psychosis.

Tamara Sale
Helen, there is a grey zone where insight is preserved and behavior is not as completely affected where people are considered high risk but would normally be diagnosed psychosis NOS in a first-episode clinic.

Thomas McGlashan
All, right now one set of criteria is being offered for the field trials.

Magenta Simmons
Angela and Hakon, good point. No, they are not uniform, and so all of the transition rates and treatment studies that we refer to use slightly (or quite) different criteria.

Scott Woods
All, back to the research. If we have large trials that show no benefit of antipsychotics, then that will stop it. If we have large trials that show a benefit then.... With no trials, we are flying blind.

Helen Stain
All, and there are those at risk who will not develop psychosis.

Cheryl Corcoran
Scott, but the DSM is for clinicians. Can't we get research support if the risk syndrome is in the appendix?

Thomas McGlashan
Cheryl, NIMH might be drafting research criteria.

Helen Stain
Scott, but that still leaves the issue of to whom we are applying these large trials of antipsychotics?

Cheryl Corcoran
All, I think if we are honest, prodromal research is a little bit like making sausage.

Tamara Sale
Cheryl, disturbingly apt.

Scott Woods
All, in the medication area, it will be hard to get large trials without an indication, and it will be hard to get an indication without a diagnosis.

Magenta Simmons
Scott, but that doesn't make the criteria valid....

Scott Woods
Magenta, that's right, but the validity data from NAPLS are pretty good. See the paper in Schizophrenia Bulletin published online.

Amresh Shrivastava
All, so what is the consensus?

Cheryl Corcoran
All, at the very least, we are not all ascertaining exactly the same individuals.

Alison Yung
Amresh, I don’t think there is a consensus.

Cheryl Corcoran
All, I think many prodromal researchers use exclusion criteria that are not specifically articulated.

William Carpenter
All, this is terrific feedback, and our DSM-V work group will profit from a careful reading. Too much too fast for adequate digestion right now. As a personal view at this point, I think 1) criteria ought to include help-seeking and distress. Such individuals are likely to enter clinical care regardless, and the risk of stigma and excess medication is present regardless of the risk syndrome issue. The issue for DSM-V is whether we can do better. 2) There is rather a good deal of data that suggest high-risk individuals can be identified (maybe at 400 times the normal risk?). The question is, How good must the positive predictive power be to justify inclusion? The harm to false positives may be present without a risk syndrome (they still exist and get treated, including with antipsychotic medications), so do we make this better or worse?

Helen Stain
All, and it’s not just the current criteria and differences in criteria across sites but also the context of recruitment.

Amresh Shrivastava
All, this is an excellent opportunity and I wish that something very positive comes out of our discussion.

Alison Yung
Scott, regarding your paper, I think you have shown discriminate validity, but the predictive validity is still doubtful.

Magenta Simmons
Scott, I've seen your paper. Pretty good; is that good enough? Especially in terms of predictive validity.

Scott Woods
Magenta and Alison, predictive validity vs. those who do not meet risk syndrome criteria is very strong. Positive predictive value (PPV) is only 35 percent or so at 2.5 years.

Cheryl Corcoran
Will, 400 times is vs. the population rate, not in terms of vs. other disorders.

Howard Goldman
All, I realize that the criteria for the risk syndrome are for signs and symptoms that are below the threshold for psychosis. My comment was intended to suggest that the issue of risk be addressed within the context of another broad category in the DSM (in the chapter on psychotic disorders) in much the same way that we might discuss sub-syndromal depression in the chapter on mood disorders.

Amresh Shrivastava
Howard, that’s what I was indicating. It may be a good idea to have a class for sub-syndromal psychiatric illnesses.

William Carpenter
Howard, that may increase concerns through labeling individuals as psychotic and increasing the likelihood of antipsychotic use, and not addressing the fact that other disorders may be the outcome.

Tamara Sale
Will, it seems some description is helpful, but with the caveat that it is not predictive. In our ultra high-risk patients we're seeing high rates of suicidality and cognitive deficits that need attention, more so than the sub-threshold positive symptoms. If there is a category, it needs to be described accurately to recognize that the high-risk state can progress in a variety of directions.

Magenta Simmons
Tamara, that fits in with Pat McGorry’s comments regarding the staging model.

Alison Yung
All, I definitely think more research should be funded in this area!

Todd Lencz
Will, if the risk syndrome is added to DSM, the threshold for help-seeking behavior may be reduced such that the false positive rate is increased still further.

Cheryl Corcoran
To all, why not list the risk syndrome in the appendix?

Alison Yung
Todd, yes, that was the point I was making earlier. We risk changing the sampling.

Cheryl Corcoran
Magenta, it is a model in need of more data.

Magenta Simmons
Cheryl, but one worth pursuing....

Amresh Shrivastava
Cheryl, the DSM appendix is not equivalent to a category in the DSM.

Tamara Sale
Todd, but most who seek help do need it, in our experience. Maybe not for psychosis, though.

Helen Stain
Alison and Todd, yes, more people seek help, but do they get the right treatment?

William Carpenter
Tamara, DSM may have a suicide dimension cutting across all disorders. If we had efficacious treatment for cognitive impairment, that would come into play in many disorders and certainly in the risk syndrome. This is part of the future we are trying to anticipate and prepare for.

Scott Woods
All, no diagnosis is ever perfect. Half of DSM is being refined now. The risk syndrome could be refined over time, too.

Cheryl Corcoran
Helen, I think Alison and Todd are bringing this up as problematic in terms of predictive validity of the designation: that it is further watered down. Think what will happen in the community regarding psychiatrists without this specific expertise.

Alison Yung
Helen, more people seek help, but the risk is that instead of getting maybe supportive therapy, they get antipsychotics and they will be diagnosed with the risk syndrome.

Helen Stain
Alison, thanks; yes, I agree wholeheartedly.

Todd Lencz
Will, further to the point, we can do better. As I mentioned in my comment posted yesterday (see comment), there are numerous published studies as well as several ongoing studies that demonstrate that higher positive symptom thresholds and the addition of operationalized criteria for negative symptoms and/or functional disability can significantly increase positive predictive value.

Tamara Sale
Todd, good point. Unfortunately, no one in the community is trained in using the diagnostic tools.

Alison Yung
Todd, I agree, but I think a problem is that we risk losing sensitivity (missing true positives) in the quest to gain specificity. It is a conundrum and needs further research.

Thomas McGlashan
Alison, yes, it should be a focus of research, but why the idea that being in DSM will not foster that?

Howard Goldman
Tom, I agree, and having the risk syndrome in the DSM, even in the appendix or as a point of discussion, can further research. For example, the SOFAS was placed in the appendix of the DSM-IV as "not ready for primetime," but it has received some research attention since that time.

Cheryl Corcoran
Alison, if we gain specificity, we may be able to identify biomarkers that would improve the risk designation and inform treatment.

Magenta Simmons
Tom, because the DSM is the Diagnostic and Statistical Manual of Mental Disorders, not the DSM of good research ideas....

Tamara Sale
Magenta, funny!

Barbara Cornblatt
Will, it seems to me that most people still maintain the positions they joined with, and if you took a vote, it seems there would likely be more people opposed to inclusion than for it, based on the idea that it’s premature and should continue to be a focus of research.

Helen Stain
Barbara, yes, that’s my vote.

Tamara Sale
Barbara, I agree.

Camilo de la Fuente-Sandoval
I also agree with Barbara.

Howard Goldman
Will, I just don’t know where else you would address it in the DSM. The manifestations are signs and symptoms common to the other psychotic conditions, but with preservation of reality testing (correct?). It’s hard to know where else to put it in DSM, and, as you say, the issues of over-identification and overtreatment are associated with individuals already seeking help without creating a separate category for the risk syndrome. I don’t know if there would be additional harm if the risk syndrome were just discussed in the psychotic disorders chapter. Tough issues, for sure.

Magenta Simmons
Scott, but in the meantime, people's lives are directly affected by what is included in the DSM. I think an important question is, What is good enough? What transition rates are good enough? What treatment effects are good enough for inclusion? I don't want to propose an answer, but I feel we are not there yet.

Amresh Shrivastava
All, we need to realize that it is still non-specific and a kind of loose condition.

Alison Yung
Cheryl, yes, sure, I agree. We could then apply the biomarkers more broadly and assess their sensitivity and specificity. But we can do this without including the risk syndrome in the DSM-V!

Helen Stain
Cheryl, interesting point. Do we then add biomarkers to DSM?

Cheryl Corcoran
Helen, that is where the DSM is heading eventually—if not in this edition, in the next one. Alison, fully agreed.

William Carpenter
All, in the studies (e.g., Australia, Norway) where education has increased referral of high-risk individuals, does anyone think that most have been harmed more than helped? Or that benefit accrues only to those who convert to psychosis and harm accrues to those who don’t?

Helen Stain
Will, that depends on the treatment being offered.

Cheryl Corcoran
Will, with all due respect, I think there are problems with that analogy. In those studies, criteria were still evaluated rigorously, and there were not the pressures of reimbursement and pharmaceutical companies.

Amresh Shrivastava
All, individuals in crisis can develop several types of symptoms and clearly need help, but that does not mean that their condition warrants a DSM diagnosis.

Alison Yung
Will, good question. I think they have mostly been helped. But we are careful not to label them with a "psychosis" label (although we do convey that they are at increased risk). We also avoid antipsychotics and have a low-stigma health environment.

Thomas McGlashan
All, the risk syndrome needs a place in the DSM-V so that it can be studied on a large scale.

Howard Goldman
All, "goodbye" and "thanks for all the fish."

Angela Epshtein
Thank you, Howard!

William Carpenter
Alison, I agree; we have thought the risk syndrome rather than a psychosis label is most valid and least harmful.

Tamara Sale
Will, I think it depends very much on how it's presented and what happens post-diagnosis. Normalization of psychosis as highly prevalent and with a prodrome akin to other illness is destigmatizing. But there are many who feel the label is inherently damaging.

Cheryl Corcoran
Will, I would be careful about extrapolating from Scandinavia and Australia to the U.S. The DSM exists in a commercial context and this must be considered in terms of costs/benefits.

Magenta Simmons
All, I have to run now, too. Thanks, everyone; the sun is now shining in Melbourne! ( :

Tamara Sale
Magenta, say hi to Pat!

Angela Epshtein
Thank you, Magenta!

Alison Yung
All, Pat McGorry is in Ireland enjoying an extended sabbatical!

Cheryl Corcoran
All, Ah yes, finding his roots.

Amresh Shrivastava
All, I wish you good luck in developing consensus. Let’s see that this business is not risky. Goodbye.

Tamara Sale
Cheryl, our program is based on Australia, so I’m interested in your point.

Cheryl Corcoran
Tamara, the inclusion of a diagnosis in the DSM in the U.S. has enormous implications in terms of practice.

Alison Yung
All, unfortunately, I have to go and do some work; it's the middle of the day here.

Cheryl Corcoran
Bye, Alison!

William Carpenter
All, remember that the slidecasts, commentary, and articles will remain available on the live discussion section of Schizophrenia Research Forum. Also, the edited version of the chatroom will be available. Thanks to everyone. I'll log off as soon as the pizza arrives.

Cheryl Corcoran
All, say goodnight, Gracie.

Scott Woods
Great chatting, Alison!

Barbara Cornblatt
Bye, Alison, Tamara, everyone.

Alison Yung
Scott, yep, nice talking to you all.

Angela Epshtein
All, thank you for an interesting discussion. And thank you, Will, for your thoughtful leadership.

Tamara Sale
Cheryl, I do agree UHR is still research. Bye, Barbara and all the other illustrious folks online!

Helen Stain
Okay, sounds like goodbye, everyone. Thanks for a great discussion.

Cheryl Corcoran
Goodbye, everyone.

Angela Epshtein
Goodbye, Cheryl and Helen.

Tamara Sale
Barbara, you do owe me some slides. Bye, again.

Barbara Cornblatt
Tamara, oops.

Thomas McGlashan
Signing off from this Tower of Babel. Great chaos! The transcript should be remarkable.

Angela Epshtein
Bye, Tom!

Tamara Sale
Will, thanks for being so inclusive.

Todd Lencz
Goodbye, all. Thanks to Will for opening this forum, and to Hakon and SRF for hosting!

Angela Epshtein
You're very welcome, Todd.

Tamara Sale
Jean, come back and join us for another beach trip!

William Carpenter
All, winding down for sure. Thanks again. Wish us wisdom as we proceed.

Angela Epshtein
Goodnight (day), everyone. Signing off from SRF.

Scott Woods
Goodnight, all. Great discussion!