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Review
. 2019 Sep;21(3):249-259.
doi: 10.31887/DCNS.2019.21.3/mrossner.

Assessing behavior and cognition in rodents, nonhuman primates, and humans: where are the limits of translation?

Marius Stephan  1 , Paul Volkmann  2 , Moritz J Rossner  2
Affiliations
Review

Assessing behavior and cognition in rodents, nonhuman primates, and humans: where are the limits of translation?

Marius Stephan et al. Dialogues Clin Neurosci. 2019 Sep.

Abstract
in English, Spanish, French

New psychopharmacological treatments are needed for affective and nonaffective psychoses, especially for the associated negative and cognitive symptoms. Earlier developments mostly failed, probably partly because of limitations in behavioral models used for validation. Now, deeper understanding of the genetics underlying disease pathogenesis and progress in genetic engineering will generate many rodent models with increased construct validity. To improve these models' translational value, we need complementary data from nonhuman primates. We also have to improve and streamline behavioral test systems to cope with increased demand. Here, we propose a comprehensive neurocognitive test battery that should overcome the disadvantages of single tests and yield cognitive/behavioral profiles for modeling subsets of patient symptoms. Further, we delineate a concept for classifying disease-relevant cognitive endophenotypes to balance between face and construct validity and clinical diagnostics. In summary, this review discusses new concepts and the limitations and future potential of translational research on cognition in psychiatry. .

Se requiere de nuevos tratamientos psicofarmacológicos para las psicosis afectivas y no afectivas, especialmente para los síntomas negativos y cognitivos asociados. La mayoría de los desarrollos anteriores fallaron; en parte debido, probablemente, a las limitaciones en los modelos conductuales empleados para la validación. Ahora, una comprensión más profunda de la genética subyacente a la patogénesis de la enfermedad y el progreso en la ingeniería genética generará muchos modelos de roedores con una mayor validez de constructo. Para mejorar el valor de estos modelos translacionales se requiere de datos complementarios de primates no humanos. También hay que mejorar y racionalizar los sistemas de pruebas conductuales para hacer frente a una mayor demanda. En este artículo se propone una batería completa de pruebas neurocognitivas que debería superar las desventajas de las pruebas individuales y generar perfiles cognitivo-conductuales para modelar subconjuntos de síntomas del paciente. Además, se plantea un concepto para clasificar los endofenotipos cognitivos relevantes para la enfermedad a fin de equilibrar la validez aparente y de constructo con el diagnóstico clínico. En resumen, esta revisión analiza nuevos conceptos, y las limitaciones y el potencial futuro de la investigación translacional sobre la cognición en psiquiatría.

De nouveaux traitements psychopharmacologiques sont nécessaires pour les psychoses dysthymiques ou non, surtout pour les symptômes associés négatifs et cognitifs. Par le passé, la plupart des développements ont échoué, probablement en partie en raison des limites des modèles comportementaux utilisés pour la validation. Aujourd’hui, une meilleure compréhension de la génétique de la pathogenèse de la maladie et les progrès du génie génétique vont produire de nombreux modèles de rongeurs mieux construits. Des données supplémentaires issues de primates non humains sont nécessaires pour améliorer la valeur traductive de ces modèles. Afin de satisfaire une demande croissante, nous devons aussi améliorer et rationaliser les systèmes de tests comportementaux. Nous proposons ici une batterie complète de tests neurocognitifs susceptible de palier les inconvénients des tests isolés et de fournir des profils cognitifs/comportementaux pour des sous-groupes de modélisation des symptômes des patients. En outre, nous définissons un concept pour classer les endophénotypes cognitifs pertinents pour la maladie afin de trouver un équilibre entre une validité de façade et de construit et les diagnostics cliniques. En résumé, cet article analyse de nouveaux concepts ainsi que les limites et les futures possibilités de la recherche translationnelle sur la cognition en psychiatrie.

Keywords: affective and nonaffective psychosis; animal model; behavioral profiling; cognition; neurocognitive test
battery; nonhuman primate.

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Figures

Figure 1.
Figure 1.. Translational behavioral and cognitive tests for major neurodevelopmental mental disorders. The figure lists the names of tests that can be applied in rodents, nonhuman primates, and humans to assess behaviors in the social, cognitive, and vigilance/sleep subdomains and in the negative and positive clinical symptom spectrum, as described in the main text. 
The need for an arrayed set of tests covering these behavioral subdomains is indicated by the shaded and colored bar graphs at the top of the figure, which shows the graded association with major depressive disorder (MDD), bipolar disorder (BPD), and schizophrenia (SZ). For detailed descriptions of the behavioral tests and references, see main text.
See this image and copyright information in PMC

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