clinical heterogeneity of Schizophrenia
The clinical heterogeneity of schizophrenia has been a subject of debate since the earliest modern descriptions. Kraepelin’s seminal distinction between Dementia Praecox and Manic-Depressive Illness was accompanied by his subsuming several heterogeneous conditions under the rubric of Dementia Praecox. These included catatonia, paranoia, hebephrenia, etc. However, it is sometimes forgotten that Kraepelin himself described up to 10 subtypes of Dementia Praecox in his influential textbook. Bleuler, working simultaneously with Kraepelin, posited that the psychotic disorders were a “Group of Schizophrenias.”25 Furthermore, his distinction between fundamental and accessory symptoms gave primacy to negative symptom–like clinical features as being more specific to schizophrenia. Much of the debate about the classification of schizophrenia since then has been a footnote to these 2 viewpoints. Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-3) carried over previous concepts about more distinct psychotic syndromes into the paranoid, catatonic, disorganized, and residual subtypes. Several decades of work have resulted in little empirical support for the validity, reliability, or longitudinal stability of these constructs, and there has been decreased usage of them in the research literature.26 This has led to their elimination in DSM-5.27 Meanwhile, clinicians and researchers have continued to document and attempt to explain the clinical heterogeneity of schizophrenia, with the development of numerous symptom rating scales and factor analytic and other studies attempting to validate symptom dimensions.28 While such studies have presented numerous models of psychopathology, the general distinctness of positive and negative symptoms has been generally upheld, while disorganization has variably been conceptualized as independent or subsumed into the negative factor.28 More recently, the cognitive deficits prominently observed in the illness29 have been emphasized as contributing to psychosocial dysfunction30 and while associated with negative symptoms, might be a partially etiologically distinct feature of the illness.31
Molecular genetic studies of clinical variation among schizophrenia cases have built on family studies, which have