5 - New dimensions in animal modeling of neuropsychiatric disorders

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The categorical view of mental illness, which implies the existence of discrete neuropsychiatric disorders that are distinguishable from each other as well as from the healthy state, is evolving into a more realistic “dimensional” view. The dimensional view explains neuropsychiatric symptoms in terms of natural phenotypical variance along certain independent dimensions that are continuous with “normal.” This view can account for the comorbidity and extensive symptom sharing that is observed among categorically defined disorders. Classic animal models of neuropsychiatric disorders—very much in line with the categorical model of psychopathology—explicitly or implicitly attempt to replicate the human disorder in the animal subject, and the validity of the model hinges on how closely the animal model match the human condition. As the conceptualization of mental illness shifts from categorical to dimensional, approaches to animal modeling of mental illness must also change. Dimensional approaches to animal modeling include the “domain interplay” approach proposed by Kalueff and colleagues (Kalueff et al., 2008a,b; LaPorte et al., 2010), the “behavioral domain” approach proposed by Kas and colleagues (Kas et al., 2007, 2009, 2011). A common theme running through these newer ideas is that psychopathology represents dysfunction in specific cognitive, emotional, or behavioral domains (such as fear and stress responsiveness, motivation, hedonic capacity, and social interaction). These domains comprise adaptive responses and behaviors that are conserved among mammalian and nonmammalian species. Identifying the genetic and environmental factors associated with phenotypic variation within these domains should provide clues to understanding the etiology of neuropsychiatric disorders. Likewise, the “domain interplay” approach aims to identify factors that are associated with dysfunction in multiple domains and those that underlie the tendency for certain domain dysfunctions to co-occur.