A Hundred-Year Challenge

For several years, Brian Kirkpatrick directed the research fellowship program at the Maryland Psychiatric Research Center (MPRC). He started the tradition of having each visiting scientist meet with the fellows and give a brief talk, always titled, “How I Won the War. ” The editor of the Journal has asked me to write a brief essay rather along the same line. I apologize if the following is a little excessive. The “I” is, of course, a “we,” with work shared with many distinguished colleagues. We did tackle an important problem, and accomplished a paradigm shift in the schizophrenia concept. Throughout the last century, the reigning paradigm for the schizophrenia construct was the disease entity model. The influence of the paradigm is evident. Investigations begin with the class membership (e.g., “all subjects meet criteria for schizophrenia”), and most end there. When more specific attributes are the focus of an investigation, they are usually conceptualized as a schizophrenia class phenomena, with individual patients varying on a severity scale. For example, studies relating negative symptoms to neuroimaging data usually take schizophrenia as the independent variable and presume that individual cases have negative symptom pathology with between-individual variability in severity. To date, drug treatments are approved for schizophrenia, not for specific components of the disease. Paradigms such as neurodevelopmental accept schizophrenia as a class and draw attention to a hypothetical model for integrating data about the class pathology. Genetic studies continue to treat schizophrenia as the disease phenotype despite many references to heterogeneity. In this essay, I briefly note the origin of the disease entity paradigm and review our research, which suggests two alternative paradigms. In the latter part of the 19th century, the disease entity approach was a powerful paradigm leading to important distinctions between disease classes, especially in infectious disease. Syphilitic insanity was a disease entity incorporating diverse illness manifestations caused by the same etiologic agent. Identifying this form of insanity, and separating these patients from other severely mentally ill persons, enabled Kraepelin (1893/1971) to observe similarities between seemingly discreet entities (i.e., hebephrenia, catatonia, paranoia). He incorporated them into a single disease class, dementia praecox, which he distinguished from manic-depressive psychosis. Although avolitional and dissociative pathologies were described as distinctive manifestations of dementia praecox, they were viewed as arising from the same disease process. Bleuler (1911/1950) referred to the group of schizophrenias, but he observed dissociative pathology as fundamental to all cases. There were subtypes that varied in their characteristic features, but dissociative pathology held them together in a single disease entity framework. Years later, contributions from Langfeldt (1937, 1939) and Schneider (1959) defined the symptoms that were critical in diagnosing “true” schizophrenia, and the concept of nuclear schizophrenia was established. The symptoms postulated to be most robust in identifying cases of schizophrenia (e.g., Schneiderian first-rank symptoms) can be viewed as ego boundary disturbances. This was the beginning of a subtle, but important, shift in the definition of schizophrenia from dissociative pathology to reality distortion symptoms.