Animal Models of Human Anxiety Disorders: Reappraisal From a Developmental Psychopathology Vantage Point

Abstract

ABSTRACT:We are witnessing a tremendous expansion of strategies and techniques that derive from basic and preclinical science to study the fine genetic, epigenetic, and proteomic regulation of behavior in the laboratory animal. In this endeavor, animal models of psychiatric illness are becoming the almost exclusive domain of basic researchers, with lesser involvement of clinician researchers in their conceptual design, and transfer into practice of new paradigms. From the side of human behavioral research, the growing interest in gene-environment interplay and the fostering of valid endophenotypes are among the few substantial innovations in the effort of linking common mental disorders to cutting-edge clinical research questions. We argue that it is time for cross-fertilization between these camps. In this article, we a) observe that the "translational divide" can-and should-be crossed by having investigators from both the basic and the clinical sides cowork on simpler, valid "endophenotypes" of neurodevelopmental relevance; b) emphasize the importance of unambiguous physiological readouts, more than behavioral equivalents of human symptoms/syndromes, for animal research; c) indicate and discuss how this could be fostered and implemented in a developmental framework of reference for some common anxiety disorders and ultimately lead to better animal models of human mental disorders. (Pediatr Res 69: 77R-84R, 2011)

Chronic stress and endothelial dysfunction: mechanisms, experimental challenges, and the way ahead

“…The assessment of whether a preclinical model was successful in terms of inducing stress is currently done by predominantly focusing on behavioral data. Although behavioral assessments such as the sucrose preference test, elevated plus maze test, and the open-field test provide a good indication of whether a protocol induced stress, they only validate the induction of a specific symptom and not necessarily a particular mental disorder (100,167). For example, although the sucrose preference test is a good indicator of anhedonia, it does not necessarily validate the induction of major depressive disorder and its associated molecular derangements (170).…”

Changing perspectives: Towards detailed phenotyping in genetics

“…While the translation from human personality and mood disorders to animal models is challenging, the relevance of animal, and specifically mouse, models for the genetic and neuroscientific study of human psychiatric traits like neuroticism, and to neuroticism-related traits, such as anxiety and depression, is generally acknowledged [237][238][239][240][241] .…”

Gene—Environment Interaction in Panic Disorder and Posttraumatic Stress Disorder

“…Work on CO 2 sensitivity in animal and man 37 suggests that quantitative biometric investigations of gene-environment interaction based on endophenotypes lies midway between the classic biometric quantitative approach, whereby genes are not directly measured but assumed as a latent variable, and the hypothesis-driven molecular-genetic approach, which typically-and sometimes forcibly-focuses on a small number of identified genetic polymorphisms and specified factors of environmental hazard. Interestingly, most biometric-quantitative studies of purely behavioural phenotypes tended to discard gene-environment interaction effects, while several hypothesis-driven molecular-genetic gene-environment interaction studies yielded positive results.…”