The critical importance of basic animal research for neuropsychiatric disorders.

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The challenges and critical importance of keeping our thinking about neuropsychiatric disorders mechanisms and classifications up-to-date have prompted a dynamic discourse as to the value, appropriateness, and reliability of the animal models we use and the outcomes we measure. At a time when most major pharmaceutical companies are disbanding their research and development in neuroscience and mental health programs, academia is the remaining bastion for the identification and validation of novel drug targets and the development of novel therapeutic approaches. The 2018 ACNP meeting provided the ideal audience for a discussion centered on this topic, offering a professional setting in which diverse viewpoints could be presented, and allowing voices from all arenas of basic and translational neuroscience to be heard. At its core, there is a growing and healthy discussion about the degree of confidence we have that our preclinical animal models and their behavioral endpoints can predict the success of new drugs in clinical trials. While it is clear that we cannot completely model complex neuropsychiatric and neurodevelopmental disorders in animals, there is certainly agreement across domain criteria and endophenotypes of disease that have proven informative, particularly when multiple levels of outcome measures, including genomics, epigenomics, cellular properties, circuits, network dynamics, and behaviors are included. This issue is now of critical importance with the arrival of big ‘omics data sets that provide novel and informative insights about genetic risk and molecular pathophysiology. How can we best examine these insights into disease risk and resilience using preclinical measures? Similarly, while genome-wide association studies and genome sequencing studies provide valuable clues into the genes and pathways that are associated with disease risk, how can we determine how these loci interact with each other as well as with the environment to assess their importance across developmental and life stages? Most importantly, we seek to identify ways to develop novel therapeutic approaches to improve the lives of those with neuropsychiatric disorders including those of neurodevelopmental origins, a challenge that remains even after decades of intensive research.