Reimagining psychoses: An agnostic approach to diagnosis

Beth Israel Deaconess Hospital, Harvard Medical School, Boston MA, United States. Electronic address: .
Schizophrenia Research (Impact Factor: 3.92). 03/2013; 146(1-3). DOI: 10.1016/j.schres.2013.02.022
Source: PubMed


Current approaches to defining and classifying psychotic disorders are compromised by substantive heterogeneity within, blurred boundaries between, as well as overlaps across the various disorders in outcome, treatment response, emerging evidence regarding pathophysiology and presumed etiology.

We herein review the evolution, current status and the constraints posed by classic symptom-based diagnostic approaches. We compare the continuing constructs that underlie the current classification of psychoses, and contrast those to evolving new thinking in other areas of medicine.

An important limitation in current psychiatric nosology may stem from the fact that symptom-based diagnoses do not "carve nature at its joints"; while symptom-based classifications have improved our reliability, they may lack validity. Next steps in developing a more valid scientific nosology for psychoses include a) agnostic deconstruction of disease dimensions, identifying disease markers and endophenotypes; b) mapping such markers across translational domains from behaviors to molecules, c) reclustering cross-cutting bio-behavioral data using modern phenotypic and biometric approaches, and finally d) validating such entities using etio-pathology, outcome and treatment-response measures.

The proposed steps of deconstruction and "bottom-up" disease definition, as elsewhere in medicine, may well provide a better foundation for developing a nosology for psychotic disorders that may have better utility in predicting outcome, treatment response and etiology, and identifying novel treatment approaches.

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Available from: John A Sweeney, Jan 20, 2015
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    • "As conceptual models of schizophrenia have developed during the last several decades, such fundamental alterations in consciousness have been deemphasized as core processes in favor of a focus on more discrete and observable symptoms and related neurocognitive and psychobiological processes (Keshavan et al., 2013; Nemeroff et al., 2013). One potential reason for the loss of interest in Bleuler's central observations is that it is difficult to measure the capacity to integrate and synthesize representations of self and others. "
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    • ") by distinguishing bipolar I disorder with psychosis (BDP) and schizophrenia (SZ) as categorical diseases despite substantial BDP-SZ overlap and nontrivial within-group heterogeneity on genetic disease risk (Craddock, O'Donovan, & Owen, 2009; Goes, Sanders, & Potash, 2008; Tamminga et al., 2013), clinical characteristics (Keshavan, Morris, et al., 2011; Tamminga et al., 2013), and biological profiles (Emsell & McDonald, 2009; Henry & Etain, 2010; Keshavan, Nasrallah, & Tandon, 2011; Nenadic, Gaser, & Sauer, 2012; Thaker, 2008). This distinction, therefore, may complicate understanding of etiology and disease processes underlying psychosis. "
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