Towards zebrafish models of personality disorders

Personality disorders (PDs) are increasingly recognized and highly prevalent, yet remarkably poorly understood, diagnosed and treated mental conditions. Common PDs include antisocial, avoidant, borderline, dependent, histrionic, narcissistic, obsessive-compulsive personality, and paranoid disorders. Experimental (animal) models are a valuable tool to study various brain illnesses, including PDs. However, characterized by complex and frequently overlapping aberrant behaviors, PDs pose major challenges for their preclinical modeling. Here, we discuss the potential utility of zebrafish (Danio rerio) as complementary translational models relevant to studying PDs. Paralleling clinical symptoms and traits of PDs to specific behavioral phenotypes, biomarkers and paradigms in these fish, we critically evaluate the existing challenges and limitations of such models, and provide a conceptual framework for further research in this field. Despite clear conceptual and practical challenges, we argue that zebrafish models not only provide a powerful platform for elucidating neurobiological mechanisms of a wide range of key PD traits (e.g., impulsivity, aggression, emotional dysregulation), but may markedly accelerate both translational modeling of these disorders and therapeutic discovery.