Role of murine models in psychiatric illness drug discovery: a dimensional view

The extensive comorbidity among psychiatric disorders underscores the need for a fundamental change in the way psychopathology is classified. An alternative 'dimensional' system classifies disorders based on relationships with respect to heritability patterns and comorbidity. It is from this 'dimensional view' that mouse modeling of neuropsychiatric disorders is presently discussed.

This review describes three proposed dimensions of psychopathology: internalizing (disorders of negative emotions), externalizing (disorders of impulsivity) and schizophrenic. The article, furthermore, presents and explains the concept of endophenotype and discusses the possible endophenotypes relevant to each of these dimensions. Finally, the article also describes mouse behavioral tests that are used for quantifying these endophenotypes and presents examples of recent studies that have used these tests.

Considering animal models within the context of endophenotypes associated with psychopathological 'dimensions', rather than focusing on modeling specific disorders, might facilitate the discovery of new pharmacotherapies. Mouse models will be powerful tools for exploring how environmental factors interact with genetic vulnerability to cause psychopathology, possibly leading to novel preventative treatment strategies. Future pharmacotherapies for neuropsychiatric disorders such as depression might comprise drugs or drug combinations that target key components of multiple systems, including neurotransmitter systems, cytokine production, oxidative stress and the HPA axis.