Reverse translation of major depressive disorder symptoms: A framework for the behavioural phenotyping of putative biomarkers

Background Reverse translating putative biomarkers of depression from patients to animals is complex because Major Depressive Disorder (MDD) is a highly heterogenous condition. This review proposes an approach to reverse translation based on relating relevant bio-behavioural functions in laboratory rodents to MDD symptoms. Methods This systematic review outlines symptom clusters assessed by psychometric tests of MDD and antidepressant treatment response including the Montgomery–Asberg Depression Rating Scale, the Hamilton Depression Rating Scale, and the Beck Depression Inventory. Symptoms were related to relevant behavioural assays in laboratory rodents. Results The resulting battery of tests includes passive coping, anxiety-like behaviours, sleep, caloric intake, cognition, psychomotor functions, hedonic reactivity and aversive learning. These assays are discussed alongside relevant clinical symptoms of MDD, providing a framework through which reverse translation of a biomarker can be interpreted. Limitations Certain aspects of MDD may not be quantified by tests in laboratory rodents, and their biological significance may not always be of clinical relevance. Conclusions Using this reverse translation approach, it is possible to clarify the functional significance of a putative biomarker in rodents and hence translate its contribution to specific clinical symptoms, or clusters of symptoms.