title: Reimagining psychoses: an agnostic approach to diagnosis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Beth Israel Deaconess Hospital, Harvard Medical School, Boston, MA, United States. keshavanms@gmail.com
authors.forename: Matcheri S
authors.initials: MS
authors.lastname: Keshavan
authors.forename: Brett A
authors.initials: BA
authors.lastname: Clementz
authors.forename: Godfrey D
authors.initials: GD
authors.lastname: Pearlson
authors.forename: John A
authors.initials: JA
authors.lastname: Sweeney
authors.forename: Carol A
authors.initials: CA
authors.lastname: Tamminga
mesh_terms: D039721:Diagnostic and Statistical Manual of Mental Disorders; D058068:Endophenotypes; D006801:Humans; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000145:classification* / Q000175:diagnosis / Q000523:psychology*; D015203:Reproducibility of Results