Abstract
Animal models of psychiatric disorders are usually discussed with regard to three criteria first elaborated by Willner; face, predictive and construct validity. Here, we draw the history of these concepts and then try to redraw and refine these criteria, using the framework of the diathesis model of depression that has been proposed by several authors. We thus propose a set of five major criteria (with sub-categories for some of them); homological validity (including species validity and strain validity), pathogenic validity (including ontopathogenic validity and triggering validity), mechanistic validity, face validity (including ethological and biomarker validity) and predictive validity (including induction and remission validity). Homological validity requires that an adequate species and strain be chosen: considering species validity, primates will be considered to have a higher score than drosophila, and considering strains, a high stress reactivity in a strain scores higher than a low stress reactivity in another strain. Pathological validity corresponds to the fact that, in order to shape pathological characteristics, the organism has been manipulated both during the developmental period (for example, maternal separation: ontopathogenic validity) and during adulthood (for example, stress: triggering validity). Mechanistic validity corresponds to the fact that the cognitive (for example, cognitive bias) or biological mechanisms (such as dysfunction of the hormonal stress axis regulation) underlying the disorder are identical in both humans and animals. Face validity corresponds to the observable behavioral (ethological validity) or biological (biomarker validity) outcomes: for example anhedonic behavior (ethological validity) or elevated corticosterone (biomarker validity). Finally, predictive validity corresponds to the identity of the relationship between the triggering factor and the outcome (induction validity) and between the effects of the treatments on the two organisms (remission validity). The relevance of this framework is then discussed regarding various animal models of depression.
Highlights
In recent years, the translational approach, which aims at bridging the gaps between basic animal research and medical practice, has gained much popularity
What we have proposed is a general framework to assess the validity of animal models of psychiatric disorders, focusing on anxiety disorders and depression
It consists of five general criteria: homological validity, pathogenic validity, mechanistic validity, face validity and predictive validity
Summary
The translational approach, which aims at bridging the gaps between basic animal research and medical practice, has gained much popularity. Internal validity addresses the consistency of the experimental design: reproducibility, inter-observer reliability, randomization, multicentric design, design (test-control), blind experimentation, and so on These questions are not specific to animal studies, but are widely shared across all fields of experimental science [11]. External validity concerns the general question of the applicability of the results of a study on a sample to the target population: it obviously raises supplemental concern in the case of animal models because of the necessity to resort to analogical arguments It is these concerns that led to the need for specific criteria for ensuring the external validity of animal studies. This author proposed eight criteria to decide whether a procedure was relevant or not:
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