How the Diagnosis of Schizophrenia Impeded the Advance of Knowledge (and What to Do About It)
- PMID: 33886224
- Bookshelf ID: NBK569652
How the Diagnosis of Schizophrenia Impeded the Advance of Knowledge (and What to Do About It)
Excerpt
Schizophrenia is sometimes conceptualized as a disease entity where all patients share the same fundamental causal mechanism and core brain pathophysiology. Alternatively, it is viewed as a clinical syndrome comprising several different causal mechanisms and pathophysiologies. In the latter concept, differences between individuals may be substantial and this heterogeneity reduces the power of most study designs. Currently schizophrenia is viewed as a mental disorder with implications of a clinical syndrome and without compelling evidence of a homogeneous disease. Most investigations over the past century, however, have been designed without addressing heterogeneity. Acquisition of knowledge has thus been impeded.
Recent paradigm shifts in the schizophrenia construct are intended to provide more valid and more robust approaches to new knowledge. These include:
Identifying patient subgroups to enrich study cohort homogeneity on causal pathway and pathophysiology.
Deconstructing schizophrenia from the top down by identifying key domains of psychopathology using each domain as the pathology of interest.
Approaching the deconstruction from the level of the neural circuit or behavioral construct to investigate molecules, genes, and pathways related to known neural circuits and behavioral constructs which, in turn, are related to psychopathology domains.
Using stages of vulnerability development prior to fully manifest schizophrenia as study targets, to conceptualize causal pathways to early vulnerability that are not specific to schizophrenia as well as later stages associated with pathological variables which have greater disorder-outcome specificity.
The first paradigm shift can be informative for a form of schizophrenia that may not generalize to all forms of the disorder. The last three provide for more specific study targets but address pathologies that will cut across current disorder boundaries. The fourth paradigm, in particular, calls attention to preventive and resiliency factors as well as causal factors.
© Massachusetts Institute of Technology and the Frankfurt Institute for Advanced Studies.
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