Psychiatric diagnoses and inconsistent results of association studies in behavioral genetics.

Case-control association studies investigating polymorphisms of candidate genes in behavioral disorders have produced a lot of positive and negative findings with few consistent replications. The inconsistent results of association studies in behavioral genetics are usually explained by the fact that significant-appearing relationships may be found as an artifact of genetic differences between the cases and controls because population stratification (or admixture) due to ethnic variation or other confounding factors can generate considerable population differences in marker allele frequencies. The author suggests that a major problem of association studies in psychiatric genetics is that psychiatric diagnoses are not biologically real disease entities: syndromal psychiatric diagnostic categories such as depression or schizophrenia include etiologically, pathologically, and prognostically heterogenous disorders. The author further suggests that extensive clinical research and observations are necessary to classify heterogeneous diagnostic categories into more scientific and more homogenous disease entities.