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

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  • 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-Åsberg 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.


  • Daniels, Stephen
  • Horman, Thomas
  • Lapointe, Thomas
  • Melanson, Brett
  • Storace, Alexandra
  • Kennedy, Sidney H
  • Frey, Benicio
  • Rizvi, Sakina J
  • Hassel, Stefanie
  • Mueller, Daniel J
  • Parikh, Sagar V
  • Lam, Raymond W
  • Blier, Pierre
  • Farzan, Faranak
  • Giacobbe, Peter
  • Milev, Roumen
  • Placenza, Franca
  • Soares, Claudio N
  • Turecki, Gustavo
  • Uher, Rudolf
  • Leri, Francesco

publication date

  • February 2020