Zebrafish models for personalized psychiatry: Insights from individual, strain and sex differences, and modeling gene x environment interactions

Abstract

Currently becoming widely recognized, personalized psychiatry focuses on unique physiological and genetic profiles of patients to best tailor their therapy. However, the role of individual differences, as well as genetic and environmental factors, in human psychiatric disorders remains poorly understood. Animal experimental models are a valuable tool to improve our understanding of disease pathophysiology and its molecular mechanisms. Due to high reproduction capability, fully sequenced genome, easy gene editing, and high genetic and physiological homology with humans, zebrafish (Danio rerio) are emerging as a novel powerful model in biomedicine.Mounting evidence supports zebrafish as a useful model organism in CNS research.Robustly expressed in these fish, individual, strain, and sex differences shape their CNS responses to genetic, environmental, and pharmacological manipulations. Here, we discuss zebrafish as a promising complementary translational tool to further advance patient-centered personalized psychiatry. K E Y W O R D Sgene-environment interactions, individual differences, personalized psychiatry, zebrafish | 403 VOLGIN et aL.

Boldness in Male and Female Zebrafish (Danio rerio) Is Dependent on Strain and Test

“…In conclusion, profound strain differences have been reported in a variety of behavioral studies using zebrafish (Maximino et al, 2013; Kalueff et al, 2014; Volgin et al, 2019). Here we demonstrate that behavioral characteristics including those associated with boldness differ in a complex pattern depending on strain and test.…”

Which Zebrafish Strains Are More Suitable to Perform Behavioral Studies? A Comprehensive Comparison by Phenomic Approach

“…Offering several advantages including low husbandry costs, easy maintenance, and small size, these freshwater fish have become an excellent model organism for effective experimental use [15,16]. Furthermore, because of their vast use in research, some inbred zebrafish strains are available, differing not only morphologically, but also physiologically, genetically, and behaviorally, in both the larval and adult stages, and these differences may cause differences in the behavioral test outcomes [17,18]. However, while one can have vast knowledge about the feature of different outbred and inbred strains in rodents, only a few studies focused on strain variation in zebrafish, especially in their behavior [1].…”

Zebrafish models of impulsivity and impulse control disorders

“…Likewise, zebrafish commonly display individual and strain differences in their neuroendocrine and behavioral responses (Egan et al., 2009; Toms & Echevarria, 2014; Volgin et al., 2019) that may directly or indirectly impact their impulsive behaviors. For example, motor hyperactivity may non‐specifically exaggerate zebrafish performance in impulsivity tasks, whereas motor and/or social deficits may indirectly impair their performance in ICD‐like aggression paradigms by affecting motor (but not motivational) domain.…”

“…For example, cortisol is an important glucocorticoid hormone involved in stress and impulsivity in humans (King, Jones, Scheuer, Curtis, & Zarcone, 1990) and is also utilized by zebrafish (unlike rodents that release corticosterone) (Demin et al., 2020). Finally, the availability of comprehensive behavioral catalogs (Kalueff et al., 2013), as well as multiple strain, sex and individual differences in zebrafish, offers further important practical and conceptual advantages of this aquatic model (Genario et al., 2019; Volgin et al., 2019), potentially applicable to translational ICD research.…”