Diagnosing depression in rodents with epilepsy

Many patients with epilepsy suffer from debilitating mood disorders, including depression. These psychiatric conditions are the major determinants of Quality of Life of patients, but there is little known about why these patients get depression, and no epilepsy-specific treatments for depression in epilepsy. This project will develop and characterise new methods for diagnosing depression in a rodent model of epilepsy, which will aid in understanding the biological changes which occur to cause depression in this patient population. Traditionally, diagnosing depression in rodents has been done using a variety of unconditioned tasks which have recently come under intense scrutiny. Here we will use alternative tests based on cognitive affective biases to objectively identify affective bias - a core feature of depression - in rodents with epilepsy. These tests are conducted in advanced computerised touchscreens, and incorporate assessments which are based on analogous tasks in humans, allowing both for objective assessment of cognitive bias, and translation into humans. We will use a rat rodent model of epilepsy, whereby rats experience a brain injury which causes epilepsy over the ensuing weeks. Control animals do not get epilepsy. All rats are then subjected to the ambiguous cue task to assess negative affective bias and slowed processing speed, symptoms identified in patients with depression. We will then test rats on a probabilistic reversal learning task to examine reward-based cognitive function. All tests will compare epileptic rats vs controls to determine whether there exist affective biases or reward-learning impairments. These results will promote a new wave of research thinking regarding the assessment and diagnosis of depression symptoms in rodents based on objective, computerised tasks which are translatable to human tasks.