Genes and environment: nosology and psychiatry

Psychiatric syndromal nosology is defined in terms of prototypical symptoms and course. Diagnosis does not depend on knowledge of etiology, pathophysiology or objective tests. Of what use is such a nosology? As formulated by Sydenham, and demonstrated by Kraepelin, certain concatenations of signs and symptoms afford improved prognostic ability. This is highly desirable, especially when treatment is ineffective. More recently, syndromes have provided some guidance for therapeutic choice. However, a syndrome has no claim for etiological homogeneity. Therefore, linkage studies are plagued by phenocopies that amount to false positives. An attempt to deal with the phenocopy problem in the area of depression is presented.