A critical overview of animal models of psychiatric disorders: challenges and perspectives.

Animal models of psychiatric disorders are a challenging but highly relevant issue. Most psychiatric disorders are very heterogeneous syndromes, resulting from multiple and varied causal factors and characterized by symptoms that can only be inferred with significant limitations in non-human models. As constructing a model that reproduces a whole psychiatric syndrome seems virtually impossible, researchers have tried to focus on endophenotypes, i.e., discrete traits that are more proximal to predisposing genes than the whole syndrome. These can be explored in a wide range of approaches, such as in pharmacological, lesion, and environmental models. Another challenge is to understand how genes interact with environmental factors over time to result in the syndromic phenotype. A better understanding of the subcellular mechanisms that enhance or allow brain resistance to environmental influences is required, as is a global thesis compatible with the diversity of diseases sharing similar behavioral and biological traits. With an experimental inventory of the possible causes of minor developmental failures, we may systematically explore their consequences in the adult animal and be able to decide if this will enlighten the understanding of one or another psychiatric disease.