Modeling OCD endophenotypes in zebrafish

Obsessive compulsive disorder (OCD) is a pervasive, debilitating neuropsychiatric disorder. Despite over half a century of effort, OCD has remained remarkably resistant to treatment, partly owing to a lack of understanding of the underlying biology. Recently, there has been a growing consensus that in order to understand the basis of neuropsychiatric disorders such as OCD, we should focus on transdiagnostic, observable, measurable behavioral or neural elements, endophenotypes. Zebrafish have the well-characterized neural development and available cutting-edge genetic tools that make them the ideal species for studying psychiatric disorders. In addition, a number of endophenotypes linked to OCD have been observed, and can be objectively measured, in zebrafish. In this chapter, some key behavioral tests of relevance to OCD will be outlined. If the neural substrates underlying these behaviors are elucidated, this may represent significant progress in understanding the biological underpinnings of OCD. This will ultimately lead to increased specificity for drug discovery, as well as providing targets for personalized treatments for one of the most common neuropsychiatric disorders.