University of La Verne, La Verne, California 91750
Model organisms have become the transformative tools for biological discovery of the cellular and molecular processes that underlie human disease pathogenesis. Here, we discuss the use and translational value of rodent models, and highlight their strengths and caveats in the context of human psychiatric illnesses such as depression, anxiety, and posttraumatic stress disorder. Human genetic association studies and epidemiological analyses cannot detect causative biological mechanisms that control behavior; however, we can use nonhuman animal models to validate and evaluate the function, and potential contribution, of likely candidate genes that were previously tied to differences in disease-relevant endophenotypes. Although animal experimentation allows rigorous control of both genetic and environmental variables, all model organisms have limited biological validity and will never fully capture the broad diagnostic criteria for human psychiatric illness, arguably the most complex of all human disorders. With this in mind, we evaluate the utility and limits of translating rodent psychiatric illness-relevant behavioral assay (elevated-zero maze, forced-swim test, sucrose preference test, and tail suspension test) data to humans. Shortcomings also may include deficiencies in development of models, poor experimental design, inadequate methodologies, physiological differences between species, and problems with the interpretation of results. Research on animals will continue despite these limitations, and innovative translational approaches to neuropsychiatric disorders such as the automation of behavioral assays, neural imaging in awake animals, and epigenetic profiling will elucidate the neurocircuitry of behavioral dysregulation. Optimizing the translational value of model organisms could contribute to an improved understanding and treatment of mental illness.