Evidence that neuropsychological deficits following early life adversity may underlie vulnerability to depression

Early life adversity (ELA) is a risk factor for major depressive disorder (MDD), however the underlying mechanisms are not well understood. Clinical studies suggest that negative affective biases (the process, whereby cognitive processes such as learning and memory and decision-making are modified by emotional state) represent a vulnerability factor for MDD. In this study we investigate the impact of ELA on affective biases and reward-associated behaviours in rats. Sprague Dawley rat pups underwent 14 days of postnatal maternal separation (180 min/day from postnatal day 1: MS180) whilst control pups remained unhandled. In adulthood, affective biases associated with reward learning and decision-making were assessed using the affective bias test (ABT), or judgement bias task (JBT) respectively. Changes in motivation and reward sensitivity were tested in a progressive ratio (PR) schedule of operant responding and the sucrose preference test (SPT) respectively. We observed that MS180 animals expressed enhanced negative biases in response to acute corticosterone treatment but without effects on antidepressant-induced positive biases. ELA animals were impaired in their ability to develop appropriate biases in response to changes in reward value in a modified ABT but in the absence of any changes in reward sensitivity or motivation. No effects on decision-making were observed in the JBT but MS180 animals failed to develop the same more optimistic behavioural profile as controls in response to an increase in reward value. These findings suggest that ELA in rats increases vulnerability to negative affective biases and impairs animals' ability to appropriately learn reward value, independent of a reward sensitivity or changes in motivation. These data provide important evidence linking ELA with relevant neuropsychological impairments that may explain increased risk of developing MDD.