Translational Shifts in Preclinical Models of Depression: Implications for Biomarkers for Improved Treatments

Understanding the neurobiology of major depressive disorder (MDD) remains one of the major challenges in neuroscience. The disease is heterogeneous in nature, and patients present with a varied symptom profile. Studies seeking to identify biomarkers for MDD diagnosis and treatment have not yet found any one candidate which achieves sufficient sensitivity and specificity. In this article, we consider whether neuropsychological impairments, specifically affective biases, could provide a behavioural biomarker. Affective biases are observed when emotional states influence cognitive function. These biases have been shown to influence a number of different cognitive domains with some specific deficits observed in MDD. It has also been possible to use these neuropsychological tests to inform the development of translational tasks for non-human species. The results from studies in rodents suggest that quantification of affective biases is feasible and may provide a reliable method to predict antidepressant efficacy as well as pro-depressant risk. Animal studies suggest that affective state-induced biases in learning and memory operate over a different time course to biases influencing decision-making. The implications for these differences in terms of task validity and future ideas relating to affective biases and MDD are discussed. We also describe our most recent studies which have shown that depression-like phenotypes share a common deficit in reward-related learning and memory which we refer to as a reward-induced positive bias. This deficit is dissociable from more typical measures of hedonic behaviour and motivation for reward and may represent an important and distinct form of reward deficit linked to MDD.