Additionally, there is an inherent tension between the study of individual genes and the emerging genetic architecture of psychiatric illness, which implicates potentially thousands of genes in each disorder. If psychiatric disorders are a collection of rare conditions, then detailed individual investigation is the most direct route forward. The evidence supports this hypothesis at least in part for ASD and other childhood-onset disorders, in which we now know that the effects of different rare major–effect-size alleles account for some of the phenotypic complexity. Yet there is remarkably little evidence that this is true for SCZ, BPD, major depression, substance abuse, and the anxiety disorders. The apparent specificity of drug action in some of these conditions might be interpreted to imply shared mechanisms among responders. Yet one would not assume shared etiologies among patients with infectious or rheumatologic diseases, whose fevers symptomatically respond to aspirin. The existence of only a few central switches that determine vulnerability to illness is challenged by the extreme polygenicity and apparent genetic heterogeneity in these disorders. We need to understand in an unbiased manner whether there is a convergence of these multiple complex genetic factors on a relatively constrained set of biochemical pathways (62).
