Genetic findings blur not only psychiatric disease boundaries but also the boundaries between disease state and normal variation. One recent study suggests that polygenic risk for BPD and SCZ contributes to creativity (49). Unaffected individuals within families harboring major psychiatric illness often harbor quantitative traits shared with affected individuals, but below the diagnostic threshold, so-called intermediate phenotypes or endophenotypes (50). Yet despite many attempts to break psychiatric diseases into simpler intermediate components, the use of quantitative or qualitative endophenotypes in genetic studies has had mixed success (51–53). Severity or age of onset may be useful for risk stratification in some cases (22, 54) but not in others. Additionally, many potential endophenotypes, ranging from cognitive, to behavioral, to anatomical, although highly heritable, appear nearly as genetically complex as the disorders with which they are associated, as is the case for structural neuroimaging phenotypes (55). Still, as risk genes are identified, studying genotype-intermediate phenotype relationships should greatly inform our understanding of disease mechanisms (48).
