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Modeling psychiatric disorders for developing effective treatments

Abstract

Recent advances in identifying risk-associated genes have provided unprecedented opportunities for developing animal models for psychiatric disease research with the goal of attaining translational utility to ultimately develop novel treatments. However, at this early stage, successful translation has yet to be achieved. Here we review recent advances in modeling psychiatric disease, discuss the utility and limitations of animal models, and emphasize the importance of shifting from behavioral analysis to identifying neurophysiological abnormalities, which are likely to be more conserved across species and thus may increase translatability. Looking forward, we envision that preclinical research will align with clinical research to build a common framework of comparable neurobiological abnormalities and to help form subgroups of patients on the basis of similar pathophysiology. Experimental neuroscience can then use animal models to discover mechanisms underlying distinct abnormalities and develop strategies for effective treatments.

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Figure 1: Clinical approval of CNS-drugs.
Figure 2: The change in cortical fields and medial frontal cortex architecture since the last common ancestor of rodents and humans.
Figure 3: The path forward: convergence of clinical and preclinical research.

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Acknowledgements

We thank J. Hawrot, P. Monteiro and C. Jennings for their contributions through valuable discussion and critical reading of the manuscript. T.K. is supported by the Henry E. Singleton fellowship. G.F. is supported by the US National Institute of Mental Health (5R01MH097104), the Poitras Center for Affective Disorders Research at the Massachusetts Institute of Technology (MIT), the Stanley Center for Psychiatric Research at Broad Institute of MIT and Harvard, the Nancy Lurie Marks Family Foundation, the Simons Foundation Autism Research Initiative (SFARI) and the Simons Center for the Social Brain at MIT.

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Kaiser, T., Feng, G. Modeling psychiatric disorders for developing effective treatments. Nat Med 21, 979–988 (2015). https://doi.org/10.1038/nm.3935

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