Although this will necessarily include studies with humans, modeling similar phenomena in animals provides a potentially advantageous complement to investigations that attempt to model complex human behaviors like symptoms of disorder (e.g., anxiety, drug self-administration) and offers an avenue for studying processes related to clinical phenotypes that are without obvious animal analogs (e.g., psychosis). In addition to the fact that animal studies offer control over confounds that complicate human research, and thus may simplify the task of identifying relevant brain systems, they also facilitate study of gene function related to these systems (e.g., Rosen et al., 2015). Animal research that yields a gene finding for an analog endophenotype that involves a genetic homolog in humans has obvious merit: It can be used to generate a human candidate gene study that adopts a hypothesis backed by high biological plausibility. However, there are many candidate gene studies of clinical phenotypes in humans backed by this type of biological plausibility, and these studies have not yielded verified genetic variants. Thus, it remains to be seen whether endophenotypes would fare any better when following this approach.
