Cross-species anxiety tests in psychiatry: pitfalls and promises

Behavioural anxiety tests in non-human animals are used for anxiolytic drug discovery, and to investigate the neurobiology of threat avoidance. Over the past decade, several of them were translated to humans with three clinically relevant goals: to assess potential efficacy of candidate treatments in healthy humans; to develop diagnostic tests or biomarkers; and to elucidate the pathophysiology of anxiety disorders. In this review, we scrutinise these promises and compare seven anxiety tests that are validated across species: five approach-avoidance conflict tests, unpredictable shock anticipation, and the social intrusion test in children. Regarding the first goal, three tests appear suitable for anxiolytic drug screening in humans. However, they have not become part of the drug development pipeline and achieving this may require independent confirmation of predictive validity and cost-effectiveness. Secondly, two tests have shown potential to measure clinically relevant individual differences, but their psychometric properties, predictive value, and clinical applicability need to be clarified. Finally, cross-species research has not yet revealed new evidence that the physiology of healthy human behaviour in anxiety tests relates to the physiology of anxiety symptoms in patients. To summarise, cross-species anxiety tests could be rendered useful for drug screening and for development of diagnostic instruments. Using these tests for aetiology research in healthy humans or animals needs to be queried and may turn out to be unrealistic.

Automated summary

Behavioral anxiety tests in non-human animals are used for anxiolytic drug discovery and to investigate the neurobiology of threat avoidance. Some of these tests have been translated to humans with the goal of assessing potential efficacy of candidate treatments, developing diagnostic tests or biomarkers, and elucidating the pathophysiology of anxiety disorders. Certain tests show promise for anxiolytic drug screening and measuring clinically relevant individual differences, but further research is needed to validate their predictive validity, cost-effectiveness, and clinical applicability. Additionally, there is currently no evidence from cross-species research linking the physiology of behavior in anxiety tests to symptoms of anxiety disorders in patients.