he problem of pathophysiological diagnosis inpsychiatry is unmet, with the possible exception ofAlzheimer’s disease. Diagnostic efforts includingInternational Classification of Diseases (ICD)1andDiagnostic and Statistical Manual of Mental Disorders(DSM),2are descriptive in nature and based on phenom-enology.Virtually all of the phenomenological “markers”can be arrived at through different gene–environmentinteractions and via totally different pathways.The resultis a diagnosis based on phenomenological similarity anda diagnostic category that is heterogeneous and unclearregarding etiopathogenesis. The individuals so labeledmay resemble each other at a given moment in time, butthey are not classified on the basis of etiopathogenesis.For the last 100 years, diagnosis in medicine has movedaway from phenomenology and toward etiopathogenesis.It is that movement that has made for a truly scientificmedicine. Psychiatry must follow this path.The quest forpathophysiological markers goes back to Emil Kraepelinand continued for many years thereafter.With the adventof psychodynamic thinking, the search for pathophysiol-ogy diminished and was replaced by the search for inter-nalized conflicts. Part of the reason for the failure of thatpathophysiological quest included limitations in the sci-entific methods available to investigators. The develop-ment of imaging technology has brought a dramaticchange in the power available to investigators.DiscriminatesIn an article published in Science,3 it was demonstratedthat data derived from quantitative electroencephalog-raphy (EEG) were strongly correlated with DSM diag-noses. The data were age-corrected and Z-transformed,so as to make it possible to use appropriately powerfulstatistical techniques (“neurometric analysis”) (Figure 1).Discriminate equations could then be written, which, onKeywords: subtyping; psychiatric disorder; drug development; attention-deficitdisorder; obsessive-compulsive disorder; schizophreniaAuthor affiliations: Department of Psychiatry, New York University School ofMedicine, New York, USA (Robert Cancro; E. Roy John; Robert Chabot; LesliePrichep); Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NewYork, USA (Robert Cancro; E. Roy John; Leslie Prichep)Address for correspondence: Robert Cancro, MD, MedDSc, New YorkUniversity School of Medicine, Room MLH-HN 323, 550 First Avenue, NewYork, NY 10016, USA(e-mail: robert.cancro@med.nyu.edu)C l i n i c a l r e s e a r c h3 2 9Subtyping of psychiatric disorders:implications for drug developmentRobert Cancro, MD, MedDSc; E. Roy John, PhD;Robert Chabot, PhD; Leslie Prichep, PhDTPsychiatric diagnosis suffers from being based on phe-nomenology and not on pathophysiology. Data are pre-sented showing that psychiatric patients reveal consistentquantitative electroencephalographic abnormalities, suchthat they can be separated from normals and from eachother. Clustering these pathophysiological groupingsreveals an underlying variability, which permits useful sub-typing. Data are presented relating subtyping to phar-macological treatment.Dialogues Clin Neurosci. 2002;4:329-335.
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