In a recent heuristic, paper Flint and Munafo85 performed several meta-analyses aimed at examining the basic assumption that effect sizes of genetic loci contributing to endophenotypes are larger than those contributing to disease susceptibility. By investigating several neuropsychological measures, catechol-O-methyl transferase (COMT) genotypes and schizophrenia, the authors concluded that the genetic basis for potential (cognitive) endophenotypes might be as genetically complex as the related psychiatric disease. This idea is close to the concept of fractality or scale invariance, in which the shapes remain complex irrespective of the scale.88 However, faced with psychiatric disorders, including SB, characterized by a high level of complexity, the endophenotypic strategy currently represents a valuable approach to enhance our understanding of the link between genes and neurobiological processes. This may ultimately provide trait markers of susceptibility to disease, models of the disease process, improvements in classification and diagnosis, elucidation of new therapeutic targets, and improvements in the development of animal disease models. However, although it was an original aim of this strategy, the endophenotype approach may not be most appropriate to robustly enhance our ability to
