Vol 8, No 1 Diagnosis and Management of Schizophrenic Disorders
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7 I n  t h i s  i s s u e . . . Schizophrenia research: a new hope Investigators conducting research in schizophrenia have been among the first to apply new tools and technologies that are then subsequently adapted to the study of other mental illnesses. While this work has led to significant improvements in the treatment of schizophrenia, much remains to be done. Articles in this issue suggest that promising new directions are now being explored that represent more than “new technologies,” and that are more cognizant of the complexities of schizophrenia research. They are characterized by new conceptualiza- tions and approaches. These include redefining the clini- cal targets for treatment, designing studies with an inter- disciplinary and translational emphasis, and employing collaborative strategies in research designs. Research in schizophrenia has typically been at the van- guard of modern research in mental illness. It led the way in genetics with the pioneering work of Seymour Kety, Irv- ing Gottesman, Eliot Slater, and others. It led the way in creating a plausible neurochemical explanation for schiz- ophrenia through the dopamine hypothesis, as articulat- ed by Arvid Carlsson and others. The first effective psy- choactive drug, chlorpromazine, was a treatment for schizophrenia, and many creative synthetic chemists such as Paul Janssen were intrigued by the challenge of improv- ing pharmacological treatments and further elucidating their mechanisms of action. Schizophrenia researchers created new methods in phenomenology and epidemiol- ogy, such as structured interviews and diagnostic criteria, though the work of John Wing and the International Pilot Study of Schizophrenia. When powerful new imaging tools such as computed tomography (CT) and magnetic resonance (MR) imaging became available, they were first applied to the study of schizophrenia by Tim Crow, Daniel Weinberger, and myself. A desire to apply the most cutting-edge technologies to schizophrenia first among mental illnesses is not surpris- ing. Not only does schizophrenia rank ninth as a cause of disability throughout the world, as described in a World Health Organization study of “the global burden of dis- ease,” but also those of us who work on the front lines with patients and their families have a first-hand empath- ic understanding of the pain and suffering that this dis- ease inflicts. Like a stone thrown onto the smooth surface of a peaceful pond, schizophrenia disrupts lives in ever- expanding concentric circles, so that many lives and many people suffer the pain that arises from a single case. In short, schizophrenia is one of the most important public health problems in the world today. Consequently, many talented researchers (as evidenced in this issue) have cho- sen to use their skills to try to ameliorate the suffering caused by schizophrenia. Despite the pioneering efforts of many dedicated individ- uals, as recently as a decade ago most honest schizo- phrenia researchers would shake their heads negatively, if asked whether “a breakthrough is around the corner.” Schizophrenia is the prototype of a “complex medical dis- order.” It appears to be heterogeneous at many levels— phenotypically, genetically, genomically, developmentally, anatomically, cognitively. Findings are difficult to replicate. Most interesting findings to date reflect between-group differences  (eg,  anatomic  MR  differences  between patients and controls), but not differences between indi- viduals within those groups. Distributions have significant overlaps between patients and controls. Diagnostic mark- ers have been sought for, but rarely (if ever) found. Per- haps the most consistent finding is that a group of indi- viduals with schizophrenia, studied by almost any measure of almost any variable, will have a larger standard devia- tion than healthy normal volunteers. The heterogeneity of schizophrenia presents a host of challenges to researchers. Can one isolate more homogeneous subgroups? By using what definition? To whom would the findings generalize? How can one collect sufficiently large samples to cope with this heterogeneity? Although many of these frustrations persist in 2006, the articles in this issue (originally presented at the XVth Col- loque de Rouffach) suggest that the tide may be turning and that there may be a new hope for schizophrenia research. Many investigators have been doing an agoniz- ing reappraisal of what must be done to improve our work. At the Colloque, and in this issue, some promising new  themes  emerged.  (Or  if  not  new,  now  widely embraced by a majority of the scientists in the schizo- phrenia community.) There is currently a strong concurrence that our current treatments, while better than nothing, are far from ade- quate. A search for better treatments on all levels—from neurochemical to cellular to neuroanatomical to clinical— has become a top priority. One theme examined in this context is the clinical target at which treatments must be aimed. For nearly 50 years psychotic symptoms have been conceptualized as the primary target. Although a few of us have been pointing out the folly of this approach for