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Live Discussion Transcript


Posted 14 April 2010

E-mail discussion
Printable version

Live Discussion: Do We Need Schizoaffective Disorder?

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Attendees/Participants

Carla Canuso, Ortho-McNeil Janssen Scientific Affairs
William Carpenter, University of Maryland
Nick Craddock, Cardiff University, Wales
Angela Epshtein, Schizophrenia Research Forum
Pamela DeRosse, NSLIJHS Zucker Hillside Hospital
Stephan Heckers, Vanderbilt University
Hakon Heimer, Schizophrenia Research Forum
J. Kando
Dara Manoach, Massachusetts General Hospital
Andrey Potapov, Moscow Research Institute of Psychiatry
Eugenia Radulescu, Bucharest
Abraham Rudnick, University of Western Ontario
Maristela Schaufelberger, University of S„o Paulo
Amresh Srivastava, University of Western Ontario
Rajiv Tandon, Florida Department of Children and Families
Norris Turner, Ortho-McNeil Janssen Scientific Affairs
Neil Woodward, Vanderbilt University

Note: Transcript has been edited for clarity and accuracy.


Angela Epshtein
I would like to introduce and thank our chat leaders: Rajiv Tandon, who is currently chief of psychiatry at the Florida Department of Children and Families and professor at the University of Florida, and Stephan Heckers, who is chair of psychiatry and professor of radiology at Vanderbilt University. Both Rajiv and Stephan are involved in the DSM-V work group on psychotic disorders.

Stephan Heckers
Hi; thank you for joining us today. This is a roundtable discussion on the topic of schizoaffective disorder (SAD).

We hope that this session is interesting and informative for all participants. Our discussion, in conjunction with the preliminary comments that have been posted, will be important feedback for the DSM-V Psychotic Disorders Work Group as well as the Mood Disorders Work Group. We will shape the discussion into roughly three 20-minute segments:

1. Given the history of the SAD diagnostic category, has it been a useful construct for clinicians and researchers? In what ways?

2. Will a longitudinal versus an episodic approach to SAD diagnosis help us address the reliability and validity issues of the diagnosis?

3. Finally, weíll review the options for the diagnosis of schizoaffective disorder.

Question to all: How useful is the diagnosis of SAD?

Pamela DeRosse
Stephan, I believe it serves as a bridge between the affective and psychotic dimensions, so in terms of identifying the molecular substrates of symptoms, I would argue it is very useful.

Nick Craddock
One benefit is that it identifies cases with a specific set of symptoms, which can get lost if subsumed under either schizophrenia or bipolar disorder.

Eugenia Radulescu
Itís still a compromise. Itís difficult to give up SAD for the moment.

Amresh Srivastava
It has been neither useful to clinicians, researchers, nor patients. It would be a bold decision to give up SAD.

Pamela DeRosse
Amresh, clinically, diagnosis doesn't change treatment.

Amresh Srivastava
Pamela, it is for the time being that diagnosis does not change treatment. That may be history soon.

Stephan Heckers
If the diagnosis of SAD is not useful, why is it being used so often?

Nick Craddock
Stephan, it describes a lot of patients! Perhaps it is actually the "typical" psychosis.

Stephan Heckers
Nick, SAD describes a lot of patients only if it is vaguely defined. A more stringent diagnosis makes it much less prevalent than schizophrenia.

Nick Craddock
Stephan, yes, quite correct. Current DSM usage of SAD is exceptionally narrow—hence, the poor reliability. However, the "essence" captured (i.e., mood and schizophrenia-like psychosis) is very common.

Amresh Srivastava
Mood symptoms have always been part of schizophrenia.

Pamela DeRosse
Amresh, I think the most relevant issue is the severity and pervasiveness of the mood syndrome.

Amresh Srivastava
Pamela, quantitative measure need not decide diagnosis; it needs to be qualitative difference.

Rajiv Tandon
We considered difficulties with the category: poor validity, low reliability, limited diagnostic stability. But it is widely used. Why?

Amresh Srivastava
Itís used mainly by clinicians in a rush for a shortcut diagnosis.

William Carpenter
For your information, SAD and psychosis not otherwise specified are by far the most common diagnoses in the psychosis chapter of DSM-IV.

Pamela DeRosse
Will, it depends on how the diagnosis is given.

Rajiv Tandon
We considered giving up the diagnosis. But there are many patients with an admixture of mood and psychotic symptoms (concurrently and over time) that cannot easily be categorized into schizophrenia or major mood disorders. We hence decided that we needed to retain this diagnosis either dimensionally or categorically, or both.

Stephan Heckers
Few people are left who are in favor of SAD as a diagnostic class, but even fewer want to change the status quo. It seems that we have not tested alternative diagnoses well enough.

Amresh Srivastava
Nick, can the three—major mood disorders, schizophrenia, and SAD—be distinct entities?

Rajiv Tandon
That was the challenge, Amresh. Mood symptoms occur in schizophrenia. Schizophrenic symptoms occur in major mood disorders. Where are the boundaries, and does schizoaffective disorder serve a useful purpose? The boundaries of the condition have varied over time, but it is widely used, suggesting the need to redefine it but retain it in some way.

Nick Craddock
Amresh, the problem with the current schizophrenia concept is that the mood symptoms get "lost" or "forgotten" in the diagnosis. Also, the balance of mood to psychosis at any time determines whether someone gets put in one of three categories (schizophrenia, SAD, bipolar disorder). That seems pretty unhelpful.

Stephan Heckers
If our primary interest is to capture mood symptoms in a person with a primary psychotic disorder, then we can do this with specifiers added to a psychotic disorder. This does not require the diagnosis of SAD.

Amresh Srivastava
I agree with Stephan.

Rajiv Tandon
In DSM-III, SAD was virtually abolished and has slowly been brought back. The reality is that there are patients not easily categorized in the two other categories.

Hakon Heimer
Ragiv et al., on why SAD is still used, Ray DePaulo told me this past week that at his institution, they train their residents not to use it, the implication being that some training programs are not as rigorous (he alluded to this in his comment). If it is a grab bag for clinicians who are not up to deciding among disorders, is it worth keeping?

Stephan Heckers
Hakon, the effect of training site is significant. Itís not too different from what we saw in the 1970s, when bipolar disorder became more "prevalent" after the introduction of lithium as a major mood stabilizer.

Rajiv Tandon
Let's step back. Question #1: Should we retain some concept of schizoaffective disorder at the ill-defined boundary of schizophrenia and major mood disorder? If the answer is ďyes, but not as at present,Ē then we could get to the next issues of how best to do this.

William Carpenter
To all, should SAD be a diagnosis for overall course of illness, or just an episode designator? If an episode, why would it not be better to have a depression dimension, a manic dimension, and a psychosis dimension?

Pamela DeRosse
Will, I think as a course of illness it is more appropriate.

Amresh Srivastava
Will, thatís a better perspective, throughout the course of illness.

Stephan Heckers
Will, that is a key question. DSM-III-R looked at lifetime illness; DSM-IV switched to episode (with the goal to increase reliability). We are now poised to go back to DSM-III-R.

Amresh Srivastava
Stephan, what you are saying has been historically the position with SAD, and we are revolving back into it.

Nick Craddock
All, dimensions are a good way to go, particularly for research (Craddock and Owen, 2007). However, we do not yet know exactly what to do. It is important not to make major changes for which there is no clear evidence. Retaining SAD makes sense because it is used—and there are genetic studies that support the possibility of some specificity (Craddock et al., 2010).

Neil Woodward
Nick, and poor reliability of diagnosis.

Pamela DeRosse
Nick, isn't it possible at the biological level that SAD is an admixture of both psychotic and affective illness?

Nick Craddock
Pamela, yes, it is possible. But we don't yet know, so why make major changes on the basis of personal hunches?

Pamela DeRosse
Nick, I absolutely agree.

Stephan Heckers
Rajiv Tandon, it seems to me that geneticists and those who have done family studies are the primary advocates for keeping SAD in the DSM. There is less enthusiasm from other camps.

Rajiv Tandon
If we agree that we need to retain some kind of boundary condition between schizophrenia and major mood disorder, then we can get to the questions of how: 1) dimensionally, 2) categorically with better definitions, or 3) both.

Amresh Srivastava
Dimensionally, of course.

Stephan Heckers
Rajiv, we do not need categories, but there is no proven alternative.

Rajiv Tandon
Also, if we agree about the need for such a condition, should it be an episode diagnosis (better reliability but poorer validity) or lifelong diagnosis (better validity and utility)?

Amresh Srivastava
It can even be a domain.

Nick Craddock
Rajiv, I think the most useful/valid is longitudinal.

Amresh Srivastava
Clinical reality is perhaps episodic.

Stephan Heckers
Rajiv, lifetime diagnosis makes more sense, but we need better patient histories. Our clinicians are not encouraged to go the extra mile for this.

Amresh Srivastava
Stephan, you are right, and thatís the problem. Is there a common neurobiology between schizophrenia and mood disorder at all?

Rajiv Tandon
I agree, Stephan. The category is not working well, but the alternatives are not very good. As we explore what to do, can we agree that schizoaffective disorder is useful in some fashion?

Neil Woodward
Stephan and Nick, to what extent can premorbid personality, social functioning, and childhood diagnosis be used to inform diagnosis made in adulthood?

Nick Craddock
If diagnosis is about directing treatment and prognosis, we must be making lifetime diagnoses.

William Carpenter
Nick, if longitudinal (and I agree), we need to recognize that most often diagnosis will be made with little information about co-occurrence over the lifetime. Imagine the primary care doctor or emergency room when a psychotic patient with mood disturbance is seen, and you try to piece together the lifetime course of the two dimensions.

Nick Craddock
Will, it is an aspect of psychiatry that it may take a period of observation (perhaps long) to be sure of diagnosis. There is nothing new here.

Pamela DeRosse
Stephan, do you think the differential between schizophrenia and SAD alters the way a clinician treats the patient?

Stephan Heckers
Pamela, yes, definitely. It has a huge effect on the patient. Most prefer SAD over schizophrenia.

Amresh Srivastava
Thatís an impact of stigma.

Stephan Heckers
Amresh, agreed.

Rajiv Tandon
I think the diagnosis of schizophrenia (with or without mood symptoms) versus mood disorder (with or without psychotic symptoms) and schizoaffective disorders do come with different treatment and prognostic implications (not easily or logically separated or distinguished, but still different).

Carla Canuso
I do think differential diagnosis does result in different treatment. While patients with schizophrenia and SAD are equally likely to receive antipsychotic medication and antidepressants, patients with SAD are much more likely to receive mood stabilizers or mood stabilizers and antidepressants in addition to antipsychotics.

Abraham Rudnick
What do people think of viewing schizophrenia and major mood disorders as possibly comorbid?

Stephan Heckers
Abraham, I see little value in comorbidity of two diagnostic classes.

Nick Craddock
Abraham, I dislike the idea of "comorbidity" because it reifies the components.

William Carpenter
Nick, we have to write the DSM-V for all the usual clinical situations, not for the research application.

Pamela DeRosse
Will, but shouldn't the DSM-V also function to specify the diagnostic groups that we are studying?

Nick Craddock
Will, I agree DSM is not primarily a research instrument, but we have to remember that it has a pretty big impact on the way people think.

Amresh Srivastava
Nick, I agree; a well-defined diagnosis needs to have a definite origin point.

Rajiv Tandon
Can we move to a discussion of whether this should be an episode or lifelong construct?

Stephan Heckers
To all, a major question for the DSM-V work group on psychosis is, Should SAD be diagnosed based on the episode (as it is currently in DSM-IV-TR)? It seems there is little support to keep it linked to the episode, correct?

Rajiv Tandon
I agree, Stephan. It should be a lifelong (not episode) construct; that would be more meaningful from both clinical and research perspectives.

Pamela DeRosse
Stephan, I think there are too few data on the question, but longitudinally seems to make more sense.

Nick Craddock
Stephan, I think linking to episode is not helpful (of course, an episode might be described as "mood/psychosis" or "schizoaffective," but the concept should be longitudinally based).

Stephan Heckers
To all, why do we hold on to a diagnosis that has low (<0.4) reliability ratings? What would we do if MDD or schizophrenia had similar reliability scores? The poor reliability of SAD is primarily due to our inability to capture mood symptoms accurately over time.

Pamela DeRosse
Stephan, I think it also has to do with the poor reliability of patient reporting.

William Carpenter
Pamela, our work group is assigned all of the schizophrenia and related disorders group of psychoses as the starting point and will be very close to that at the end. Problems are within each class. Here it is: Should we be focusing on the current episode, as in DSM-IV, or over the course of illness, as in DSM-III? I think that only the overall course is conceptually coherent, but that approach has the big problem of needing detailed history. If only episode, I would favor capturing with dimensions.

Rajiv Tandon
I completely agree with Will's view: If only episode diagnosis, we do not need a category but could address with dimensional assessments. But longitudinally, there is value to having a schizoaffective category still instead of artificially assigning some patients to schizophrenia and others to mood disorders.

Amresh Srivastava
Is there any evidence that SAD retains its character in longitudinal course?

Pamela DeRosse
Amresh, only insofar as you look at outcome.

Amresh Srivastava
Pamela, that makes it difficult to accept as a diagnosis.

Stephan Heckers
Amresh, there is strong evidence that it does not. Please look at my slide set; it lists some recent studies on this topic.

Amresh Srivastava
Stephan, thatís what I am saying; where is the compulsion to retain this as diagnosis?

Nick Craddock
Stephan, the low reliability is because of the narrow definition. If the definition were more inclusive, it would have greater reliability (Craddock et al., 2009). Narrowing the concept of either schizophrenia or bipolar disorder would make them have low reliability!!

Stephan Heckers
Nick, very important. You are suggesting to make SAD broader, correct?

Nick Craddock
Stephan, yes.

Amresh Srivastava
Is this diagnosis different in different parts of the world?

Stephan Heckers
Amresh, I hope not.

Carla Canuso
ICD-10 (International Classification of Diseases, 10th Revision) is different from DSM, and more inclusive.

William Carpenter
Amresh, itís a different concept in ICD.

Amresh Srivastava
Is affective schizophrenia more common in a few places?

Stephan Heckers
Amresh, yes, ICD is broader. It does not require psychotic symptoms without mood symptoms for two weeks, as in DSM.

Amresh Srivastava
Will, we need to look at the entire dataset to decide this question. In reactive psychosis, it is more common, perhaps.

Stephan Heckers
Nick, do you use ICD or DSM criteria for your genetic studies?

Dara Manoach
In research practice, in essence, schizoaffective is divided up, with schizoaffective depression being included in the schizophrenia group, and schizoaffective bipolar not included.

Neil Woodward
Nick, would broadening the definition not decrease validity?

Stephan Heckers
Nick, how would you broaden the current criteria?

Nick Craddock
Stephan, currently SAD is pretty much written as a diagnosis of last resort after not being able to opt for bipolar disorder or schizophrenia because of the very fine "balance." That is narrow. If the wording allowed greater overlap—but clearly specified—that would be more reliable, because people would not easily change category according to small changes in available information, longitudinal history, or the opinion of the doctors.

Rajiv Tandon
Nick and Stephan, you make an interesting suggestion—broaden the concept of schizoaffective disorder—but that would be at the expense of schizophrenia with varying amounts of mood symptoms and major mood disorders with psychotic symptoms. Would that really make things better?

Amresh Srivastava
Rajiv, maybe it will.

Pamela DeRosse
Rajiv, I would argue not. There are different types of affective episodes that show up superimposed on schizophrenia.

Amresh Srivastava
Pamela, but it still remains predominantly schizophrenia.

Rajiv Tandon
The division of schizoaffective disorder into bipolar type (with major mood disorders) and depressive type (with schizophrenia) is based on a 1987 Andreasen study (Andreasen et al., 1987). It has not been replicated.

Stephan Heckers
Rajiv, a broader concept of SAD might increase reliability. That is Nick's point.

Nick Craddock
Rajiv, if a diagnosis of SAD flags up both mood and schizophrenia-like problems, that seems to me to serve a clinically useful function. It will also make it easier to research this very common overlap.

William Carpenter
A big problem with DSM-IV is that the mood disturbance is required to meet full criteria for a mood disorder. It is absurd to think that clinicians can adhere to this requirement over the life course of illness. I suppose it is based on the impression that mood is disturbed much of the time rather than considering whether someone meets full criteria in the past three episodes.

Hakon Heimer
Will, Rajiv, Stephan, if SAD is in the purview of the psychosis group, and mood disorder specialists are not part of this group, does that weaken your efforts to come to grips with the diagnosis? (Was that a provocative question or just naive?)

Amresh Srivastava
Perhaps itís not a question for mood disorder researchers.

Angela Epshtein
Hakon, we have a comment from Jan Fawcett, who is the mood disorder work group leader.

William Carpenter
Hakon, Ray DePaulo is liaison with us, Bill Coryell has been in conference with us, and it is discussed more generally with the mood disorders group.

Stephan Heckers
Hakon, I would not worry too much about buy-in from different groups. Nobody has the perfect alternative, but the mood disorder group is more content with the status quo.

Rajiv Tandon
Hakon, a very good question. We did try working with the mood disorders group, and we had different sets of concerns and boundary issues. Initially, we were hoping to be able to eliminate SAD as a category and address it only dimensionally. But the mood disorders group was opposed to the idea, in part because it would have necessitated the same set of dimensional assessments for both major mood disorders and the psychotic disorders. Hence, we adopted our present set of recommendations.

Pamela DeRosse
Will, how do you think the loss of the depressive disorder and bipolar disorder not otherwise specified diagnoses being suggested by the affective disorders work group will affect the diagnosis of mood syndromes superimposed on schizophrenia?

William Carpenter
Pamela, I don't know. In general, DSM-V will try to decrease the use of ďnot otherwise specified,Ē and the assumption is that, in the mood disorders, it will force more specific mood disorder diagnosis. I doubt that it will push towards psychoses.

Pamela DeRosse
Will, perhaps it will force more people into the SAD category?

Stephan Heckers
To all, let's review the options for the diagnosis of schizoaffective disorder in DSM-V. We posted four options for DSM-V. It seems likely that we will end up with #2 (see SRF website).

Amresh Srivastava
Good luck.

Rajiv Tandon
Stephan, there are four criteria. The first defines severity and need for both psychotic (schizophrenia criterion A) and major mood symptoms; we are not proposing a change there. Criterion 2 tries to distinguish SAD from psychotic mood disorders; we propose a change to clarify here. Criterion 3 to help separate SAD from schizophrenia with mood symptoms; we propose a change to clarify here. Criterion 4 is the substance abuse and organicity exclusion—no changes proposed here.

Stephan Heckers
To all, can we remove Criterion B and get DSM and ICD closer together?

Carla Canuso
I don't think Criterion B is all that useful clinically, or in distinguishing SAD from a major mood disorder.

William Carpenter
Stephan, I like dropping the mood-comes-later-and-leaves-earlier criterion, since I think that is the reverse of natural history. That would be a good place to harmonize with ICD.

Rajiv Tandon
Will and Stephan, the problem with eliminating Criterion B is that the mood disorder group objects, as it wants a separation between SAD and psychotic mood disorder. It is somewhat artificial (based on the Coryell studies in the 1980s), but it is the best we have.

Pamela DeRosse
Stephan, I think that would make it harder for us to distinguish between a psychotic affective disorder (i.e., bipolar disorder with psychotic features) and SAD.

Stephan Heckers
Pamela, you are correct. But why are U.S. psychiatrists so concerned about it when the Europeans are not? Criterion B makes little sense (other than keeping psychotic mood disorder further away from SAD).

Rajiv Tandon
Absolutely Stephan, but as you know, the mood disorders group is adamant about this (with some good reason); we over-diagnosed schizophrenia in the U.S. prior to DSM-III.

Pamela DeRosse
Stephan, I don't agree. I think it functions to bridge the gap between the psychotic and affective disorders and is more consistent with the dimensional model that will likely emerge in later editions of the DSM.

Stephan Heckers
Pamela, thatís another way of looking at the same boundary.

William Carpenter
All, our big problem with dimensions is that we only think DSM-V can manage them as concurrent measures. Clinicians donít have enough time or informants for reliable life course dimensions. Therefore, dimensions can only solve the SAD problem if SAD is a current-episode diagnosis.

Rajiv Tandon
Maybe we need to change Criterion B, but we need some better separation between SAD and psychotic mood disorders. Perhaps we could look at our proposal to see if this might help.

Stephan Heckers
Rajiv, agreed.

Carla Canuso
Is the proposed language, ďdelusions and hallucinations for two or more weeks in the absence of psychopathologyĒ meeting criteria for a major mood episode?

Rajiv Tandon
Carla, yes, that is the proposal. I think it helps a clearer separation from psychotic disorders.

Carla Canuso
I agree.

Stephan Heckers
Nick, do geneticists in Europe use the ICD?

Nick Craddock
Stephan, it varies. DSM is very influential because of publishing (many U.S. journals...). In the Wellcome Trust Case Control Consortium genomewide association study (Wellcome Trust Case Control Consortium, 2007), I used RDC (Research Diagnostic Criteria)!! (Because it captures better the "mixed" cases.)

Stephan Heckers
Nick, does it make sense to compare the genetics of SAD based on either DSM or ICD or RDC?

Pamela DeRosse
Stephan, hasn't that been done at the family level by Kendler (e.g., Kendler et al., 1986; Kendler et al., 1997)?

Stephan Heckers
Pamela, yes, but genetics does not equal family studies.

Pamela DeRosse
Stephan :) I guess it depends on whom you ask.

Nick Craddock
Stephan, we have a paper in Molecular Psychiatry (Craddock et al., 2010) showing a relatively specific association at the family of GABAA receptor genes and RDC SAD, bipolar disorder (and this is not present in bipolar disorder or schizophrenia cases). RDC schizoaffective disorder, bipolar type (SABP) is a broad definition!

Hakon Heimer
Nick, would there be any data or discussion from the psychiatric genomewide association study group (especially the cross-disorders group) that are germane to this discussion?

Nick Craddock
Hakon, not yet. I expect that over the next year or two there may be more understanding (Cross-Disorder Phenotype Group of the Psychiatric GWAS Consortium et al., 2009).

Rajiv Tandon
Could we consider our proposed change to Criterion C (that tries to better differentiate SAD from schizophrenia with some mood symptoms)?

Stephan Heckers
Rajiv, yes, please. Does an explicit threshold (say, 30 percent) make the task easier and more reliable?

Rajiv Tandon
Basically, our proposed changes to Criterion C have to do with making this a lifetime (not episode) diagnosis and suggesting 30 percent prevalence of mood symptoms as the separator of SAD from schizophrenia with some mood symptoms.

Pamela DeRosse
Stephan, 30 percent is certainly better than the current exclusion criteria of "relatively brief."

Carla Canuso
I think that objectifying "substantial proportion" helps, but doesn't get around the subjectivity that goes into making that assessment.

Stephan Heckers
Carla, I could not agree more.

Rajiv Tandon
It seems that Stephan, Carla, and Pam are all in agreement with Criterion C as proposed.

Stephan Heckers
Nick, we need to hear from you. Does a cut-off of 30 percent help?

William Carpenter
All, does anyone think meeting full criteria for mood disorder is either feasible or desirable? Is the concept of serious mood disturbance what clinicians must use, especially regarding the past?

Rajiv Tandon
Will, I think the requirement for a major mood symptom versus prominent mood symptom is helpful (more objective). Also, it helps better delineate SAD from schizophrenia with some mood symptoms.

Nick Craddock
All, I suspect that will still be somewhat difficult to use. Why not be radical and, for SABP, go with a clear-cut episode of mania?!

Stephan Heckers
Nick, even one episode will suffice?

Nick Craddock
Stephan, I think one episode could be appropriate for SABP. Mania is a pretty recognizable syndrome, and a person has an ongoing susceptibility to such disturbances. Of course, it might be more difficult thinking of doing this for depression.

Pamela DeRosse
Nick, I agree. Will, I think the full criteria for major mood episodes is feasible.

William Carpenter
Pamela, imagine a patient with a 10-year history and the doctor has 15 minutes to do everything. How does he/she figure out meeting full criteria over time?

Stephan Heckers
Will, that is the right question!

Pamela DeRosse
Will, clinically, that would be very difficult, so I see your point. However, the same holds true for the 30 percent criterion.

William Carpenter
Pamela, 30 percent is being offered as a magic bullet, and we don't dare look too closely.

Pamela DeRosse
Point taken.

Angela Epshtein
Everyone, we have just a few minutes left. Many of us will need to leave, though the chatroom will remain open. Does anyone have any last thoughts or comments to make before some of us leave?

Hakon Heimer
Stephan, all, what is needed in the next five to 10 years before DSM-VI? Dimensions? Genes?

Pamela DeRosse
Both!

Stephan Heckers
Dimensions.

Hakon Heimer
Stephan, is that happening?

Stephan Heckers
We are working on it.

Nick Craddock
Dimensions, but they need to be the right dimensions!! Genes, imaging, biology, and psychology will help.

Stephan Heckers
I agree with Nick. Dear all, thank you for joining us today. No revelations, but a good set of questions.

Rajiv Tandon
I think this has been a very valuable conversation. I hope we continue the process. We will incorporate suggestions proposed here into further revisions.

William Carpenter
Hakon and Angela, thanks for doing this, and Rajiv and Stephan.

Pamela DeRosse
Thanks for hosting!

Nick Craddock
Stephan, very interesting and worthwhile. Many thanks! Best wishes, Nick.

Angela Epshtein
Thank you, Rajiv and Stephan, for leading. Thanks to all for their comments.

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