Editor's Note: Over the next weeks, we will be bringing you reports from the International Congress on Schizophrenia Research (ICOSR), 28 March to 1 April 2007, and the satellite Mt. Sinai Conference on Cognition in Schizophrenia, 27-28 March, in Colorado Springs, Colorado. In the case of the ICOSR, we are very grateful to organizers Carol Tamminga and Charles Schulz, who helped us recruit some roving reporters from among the Young Investigator awardees. A special thanks also to Laura Rowland and Scott Sponheim, who directed the Young Investigator program. Our first news story is a real treat—Jenny Barnett of the University of Cambridge attended two workshops about the future of schizophrenia/psychosis diagnosis and reports on the often contentious discussions. Read on....
2 April 2007. For better or worse, when the American Psychiatric Association speaks, via its Diagnostic and Statistical Manual of Mental Disorders (DSM), the world of mental health research and treatment has to take notice. The manual is due for a new edition...in 2012, and discussion has already begun on the shape it will take. Two workshops on the topic were organized at the 2007 ICOSR.
Should DSM-V Be a Schizophrenia-free Zone?
This question was the subject of a lively debate, chaired by Shôn Lewis of the University of Manchester, United Kingdom, on the Thursday evening of the ICOSR conference at Colorado Springs.
The discussion was kicked off by Jim Van Os, Maastricht University, Netherlands, in proposition of the motion. Van Os argued that "disorders are names for theories, not things" (Wing, 1978). What we call schizophrenia, he argued, is neither a rare nor distinct entity. Moreover, the diagnosis meets none of the criteria for construct validity: there are no specific symptoms, causes, outcomes, or treatments for schizophrenia.
He backed up his argument with two recent studies. The first, an 8,000-person population screening survey from Finland (Perala et al., 2007; see SRF related news story) has shown that psychotic disorders are not especially rare, with a lifetime prevalence of 3.5 percent in the general population. The second (Cuesta et al., 2007) is the first taxometric analysis ever to be applied to schizophrenia. The authors included positive, negative, and disorganization symptoms from 660 in-patients with acute psychosis. Surprisingly, the analysis showed no evidence of any taxa within psychotic disorders, suggesting that dimensional concepts may be more appropriate.
Van Os concluded by suggesting that both categorical and dimensional descriptions are useful and both contribute to understanding the needs and outcomes of patients with psychotic disorders. He argued that, since treatment needs are common to all psychotic patients, we should err on the side of “lumping” rather than “splitting” in the number of categories we use. His suggestion for DSM-V was the inclusion of two Axis I categories, General Affective Syndrome and General Psychotic Syndrome, plus four Axis II dimensions, describing positive, negative, depressed, and manic symptoms.
Next up, and arguing against the proposition, Assen Jablensky, University of Western Australia, Perth, gave a scholarly account of the diagnosis of schizophrenia. He reminded us that what caused Kraepelin to identify schizophrenia as a unitary syndrome was his insight that while hebephrenia, paranoid dementia, and catatonia presented quite differently, over time they showed similarities, all gravitating towards “dementia praecox.”
Modern research, Jablensky argued, has borne out Kraepelin’s insight that schizophrenia is a clinical syndrome, though not a disease entity. Epidemiological studies have shown that the pattern of course and outcome in schizophrenia are generally predictable, and the genetic evidence demonstrates that if schizophrenia is a myth, "it is a myth with high genetic loading" (Wing, 1988). There are sufficient consistencies in the cognitive, imaging and neurophysiological evidence for us to believe in the clinical syndrome of schizophrenia. He argued that the heterogeneity that undoubtedly exists within this syndrome explains our sometimes inconsistent findings. While schizophrenia is not a valid disease entity, neither are most psychiatric disorders. Crucially, using the diagnosis of schizophrenia allows us to generate testable hypotheses, thereby enabling us to improve our understanding of what schizophrenia actually is.
Back on the case for removing the diagnosis of schizophrenia from DSM-V, the next proponent was Robin Murray of the Institute of Psychiatry in London. Always entertaining, Murray put forward two main objections to the current diagnosis of schizophrenia. His first objection, to the idea that there is a binary distinction between schizophrenia and normality, built on Van Os’s argument that psychotic symptoms are remarkably common. He cited data from the Dunedin study showing that at age 26, individual psychotic-like symptoms are endorsed by up to 10 percent of the general population. He argued that this dimensional view of psychosis is not incompatible with a medical model, and is already accepted for disorders such as obesity and hypertension. In schizophrenia, as in these disorders, we impose a cut-off simply to provide guidance as to where on the continuum it may be useful to start treatment.
Murray’s second argument for rejecting schizophrenia centered on the distinction between schizophrenia and bipolar disorder. Even excellent clinicians cannot make this distinction, he argued, hence the existence in DSM-IV of schizoaffective disorder. Schizophrenia and bipolar disorder show overlap in symptoms and genetic risk, both respond to dopamine D2 receptor blockade, and both arise typically in early adulthood, showing a more severe course and/or early onset in men than women. He argued that while there are some obvious differences in patients at the two ends of the schizophrenia-bipolar spectrum, our insistence that the two are separate entities exposes psychiatry to ridicule.
We should return, he argued, to what we know about the proximal cause of psychosis. If we accept that dopamine acts as the “wind of psychotic fire” and that dopamine dysregulation is the common mediator of psychosis, then we should introduce the non-derogatory term “dopamine dysregulation disorder” as our DSM-V diagnosis. Patients could then be described in terms of three dimensions, namely positive symptoms, affective symptoms, and developmental impairment.
The final speaker, William Carpenter of the Maryland Psychiatric Research Center in Baltimore started from Jablensky’s earlier point that schizophrenia is not a disease entity but a clinical syndrome. He argued that rather than arguing about which label to use, we need instead to deal with the heterogeneity that is present in schizophrenia and deconstruct the syndrome into meaningful sub-syndromes. This may allow us to better determine the multiple etiologies that clearly underpin the syndrome of schizophrenia, as has occurred in dementia, for example. He reminded us that, just because psychosis is the only aspect of schizophrenia which we can effectively treat, it is not the defining feature of schizophrenia.
In summary, he argued, while we all accept that both categorical and dimensional descriptions can be useful, we have to use names. What benefit would there be in simply changing the name “schizophrenia”?
The audience had a few suggestions of their own as to possible name changes, including Kraepelin-Bleuler syndrome, hypolateralization syndrome, and Psychosis Purposefully Not Specified. Most comments from the floor centered around the question of whether simply dropping the term schizophrenia would be useful in reducing stigma and public misconceptions about what schizophrenia is. Chairman Shon Lewis’s summary suggested there are really three options: to keep both the construct and the term schizophrenia, to keep the construct but jettison the name, or to lose both the construct and the name. The final audience vote suggested opinions are closely tied on the matter: 62 in favor of the motion that DSM-V should be schizophrenia-free, and 61 against.
The Bigger Picture
The debate was followed on the Friday night by a session, chaired by Will Carpenter, discussing in greater depth the possible formulations of schizophrenia in DSM-V.
Darrel Regier of the American Psychiatric Association, and vice chair of the DSM-V task force, gave an overview of the DSM-V planning process, which started back in 1999 and will result in the publication of DSM-V in 2012. The current phase is centered around workgroups which are each tasked with a specific disorder. In addition, there are cross-cutting themes being considered by all workgroups. These include a lifespan diagnostic approach, diagnostic specificity, the interface between psychiatric and general medicine, and gender and cross-cultural issues. An emphasis on dimensional concepts is also present across all disorders.
Carol Tamminga of the University of Texas, Southwestern, in Dallas, described the work of the panel tasked with deconstructing psychosis, which she chaired. The panel discussed psychosis across all disorders, but with emphasis on schizophrenia and schizoaffective disorder, bipolar disorder, and psychotic depression. They discussed evidence from multiple domains including genetic, imaging, and postmortem in considering the similarities and differences among disorders. The group noted that while the experience of psychosis is similar across diagnoses, there is an important difference in illness course. With respect to treatment, they noted that antipsychotics target psychosis regardless of diagnosis, and that response to treatment is common across all disorders. There was consensus that there is a need for a dimensional description system. While some group members argued for an exclusively dimensional system, the majority want both categories and dimensions in DSM-V.
Reiterating a number of points from the previous night’s debate, Will Carpenter showed data from 1974 demonstrating that the symptoms which most discriminate schizophrenia from other diagnoses are not psychotic symptoms, but poor rapport, poor insight, and flat affect. He argued that we should therefore be using domains of psychopathology, such as psychosis, negative symptoms, or interpersonal function, as the dependent variable in research, rather than the diagnosis of schizophrenia. For DSM-V, he suggested, we should consider using three dimensions to describe patients: psychopathology (including negative and cognitive symptoms), therapeutic targets (such as depression, anxiety, and occupational function), and recovery goals (such as autonomy, functional outcome, and quality of life).
Again echoing the previous night’s discussion, Robin Murray pointed out that psychosis is a continuum, with between 9 and 20 percent of the general population admitting to a psychotic symptom. He argued that not only are these symptoms common, but that the factors which predict psychotic experiences in the general population are the same as those that predict schizophrenia. These include low IQ and education, cannabis use, migration, urbanicity, and neuroticism (Johns et al., 2004). The sixth version of DSM, he argued, should have entirely dimensional criteria. However since the insurance industry requires categorical diagnoses, DSM-V must represent a compromise between dimensions and categories. His preferred solution would be the inclusion of dimensional measures of positive, negative, and disorganized symptoms, depression, and mania. In addition, he argued, we should include a dimension of developmental impairment, which would help distinguish individuals on the schizophrenia-bipolar spectrum. Unfortunately, no such measure is currently available.
Gunvant Thakar of the Maryland Psychiatric Research Center in Baltimore then made the case for the inclusion of endophenotypes (see SRF Live Discussion led by Irving Gottesman) as diagnostic criteria for DSM-V. He argued that current clinical descriptions fail to distinguish between schizophrenia and bipolar disorder, as well as failing to distinguish subgroups within these disorders. There is therefore a clear need for biomarkers to help us do this. Such biomarkers should be heritable and stable; in fact, they should meet Gottesman and Gould’s (2003) endophenotype criteria. Thakar showed factor analyses demonstrating that putative endophenotypes such as impairments in cognitive function, prepulse inhibition, and P50 are largely independent. They therefore represent meaningful and independent groupings with which to describe and research patients with schizophrenia.
Taking the discussion of endophenotypes a step further, Phil Harvey of Mt. Sinai School of Medicine in New York City considered the utility of including cognitive function as a diagnostic element in DSM-V. He pointed out that 85-100 percent of individuals who meet current diagnostic criteria for schizophrenia show cognitive impairment, limiting its usefulness in discriminating between patients. Even when comparing cognitive function across psychotic diagnoses, there is a difference only in the level of impairment, and no cognitive deficit is specific to any diagnosis. Moreover, recent studies using identical diagnostic criteria and identical cognitive test batteries do not agree on how many cognitive factors exist in schizophrenia. Finally, he pointed out that the vast majority of clinicians would not routinely undertake neuropsychological testing in patients suspected of a diagnosis of schizophrenia. For this reason, including cognitive impairment in the diagnostic criteria would be futile.
The Floor Is Open for Debate
A lively debate then followed with many important points raised by the audience. Paul Hicks (San Antonio) pointed out that diagnostic criteria should, above all else, be useful. Diagnostic criteria have two purposes: to enable clinicians to decide how best to initiate treatment and to produce consensus for research purposes. Of these two, the first is the most important, so we should keep diagnostic criteria simple and measurable in the office.
In reply, the panel argued that we already treat dimensions/symptoms rather than diagnoses (Murray), and that plenty of precedents exist for diagnostic criteria that cannot be measured without specialist equipment, such as polysomnography in diagnosing sleep apnea (Regier).
Rich Keefe (Duke University, Durham, North Carolina) argued that DSM-V should not be limited by clinicians’ knowledge but instead should educate them. Cognitive dysfunction is a core impairment in schizophrenia that needs treating even if it does not help with diagnostic specificity. Including cognitive dysfunction as a dimensional diagnostic criteria will at least draw attention to its importance.
Shitij Kapur (University of Toronto) made the point that we already effectively have dimensional views of schizophrenia in DSM-IV: this is what the subtypes of schizophrenia describe. The reason that we do not differentially treat the subtypes is because it has not proved useful to do so.
Tania Lincoln (Philipps University, Marburg, Germany) suggested that as well as dimensional views of schizophrenia, we should think about dimensional views of single symptoms. So instead of rating the presence or absence of individual symptoms, we should consider a continuum of symptom severity. The experience of distress is the important difference between a person with schizophrenia and an otherwise healthy individual who has a delusional belief.
Steve Olsen (University of Minnesota) commented that with 500,000 SNP whole genome analyses now costing as little as $250 per person, genetic testing for diagnosis could become financially viable. DSM-V needs to be ready to take genetic advances into account.
Carpenter and Regier agreed: DSM-V needs to be forward-thinking and ready to "skate where the puck will be"; the system needs to be updateable to take new data into account.
On the subject of genetics, Carpenter pointed out that we should remember that no genes meet criteria for sensitivity or specificity. Tim Crow (Oxford University, London) agreed: whole genome scans and linkage studies have produced no consistent evidence, although the evidence for genetic overlap between schizophrenia and bipolar disorder is at least 30 years old. He also reported that a BBC Internet survey of 220,000 people has recently shown that laterality (as measured by ambidexterity) is associated with cognitive function. He suggested that laterality should be incorporated into DSM criteria. Murray pointed out that laterality is also relevant to bipolar disorder, where there is relatively little cognitive impairment.
Back on endophenotypes, William Sledge (Yale University, New Haven, Connecticut) pointed out that since 150 years of epidemiological and observational studies have not clarified the natural divisions of psychosis, endophenotypes may be the only possible innovation.
Mary Cannon (Royal College of Surgeons, Dublin, Ireland) disagreed. She pointed out that retaining categories is vital for epidemiological research. However, if we are to scrap categories, perhaps we should start again from first principles, investing more money in statistical analysis of the vast amount of phenomological data that we already have, such as independent and rigorous meta-analysis. Regier confirmed that both statisticians and epidemiologists are included on the DSM-V task forces, and are starting to collate databases. However, the existing data are themselves limited by the current categories.
In closing, Carpenter pointed out that clinicians learn to make diagnoses through a process of pattern recognition, for example, regarding timing and duration of symptoms and the nature of psychopathology. He suggested that if categories and dimensions are both meaningful and can be used simultaneously, then this will inevitably help our understanding of the disorder.—Jenny Barnett.