Relevance of Rodent Models of Depression in Clinical Practice: Can We Overcome the Obstacles in Translational Neuropsychiatry?

Abstract

The diagnosis of a mental disorder generally depends on clinical observations and phenomenological symptoms reported by the patient. The definition of a given diagnosis is criteria based and relies on the ability to accurately interpret subjective symptoms and complex behavior. This type of diagnosis comprises a challenge to translate to reliable animal models, and these translational uncertainties hamper the development of new treatments. In this review, we will discuss how depressive-like behavior can be induced in rodents, and the relationship between these models and depression in humans. Specifically, we suggest similarities between triggers of depressive-like behavior in animal models and human conditions known to increase the risk of depression, for example exhaustion and bullying. Although we acknowledge the potential problems in comparing animal findings to human conditions, such comparisons are useful for understanding the complexity of depression, and we highlight the need to develop clinical diagnoses and animal models in parallel to overcome translational uncertainties.

Figure 1.

Scheme of exposures (arrows) and vulnerabilities (circles) that increase risk of depression. By combining risk factors for depression identified in the clinic with specific neurobiological manipulations in animal models, we will achieve a better understanding of the pathophysiology of depression.

Figure 2.

To be able to study relevant mechanism of depression, we need to find a common context for clinical and experimental work. For most, if not all, diseases it will be impossible to generate animal models that can serve as faithful models of a specific diagnosis that could be used to test treatments. Instead, animal models should be seen as experimental tools where hypothesis regarding biological correlations or mechanisms can be investigated and where new hypothesis regarding the clinical condition can be tested. It is only by combining findings from the clinical and experimental fields that we will achieve better diagnosis and treatment.