Animal models of risk factors for suicidal ideation and behaviour

Abstract

In order to predict the risk of a drug-induced side effect prior to the start of a clinic trial, studies in valid pre-clinical models are essential. In the area of neuropsychiatric symptoms, animal models are severely limited and novel approaches are essential if such risks are to be identified before expensive clinical studies are initiated. One of the most serious neuropsychiatric side effects is suicidal ideation and behaviour. A major issue with this area as a whole is that the current methods used in pre-clinical drug safety development are not designed to assess neuropsychiatric side effects, and suitable animal models for suicidal ideation and behaviour have not been well validated. Animal models of depression represent a potentially useful starting point as major depressive disorder (MDD) and bipolar disorder carry the highest risk of suicide. Other behavioural traits associated with suicidal behaviour in man, such as impulsivity and aggression, can also be modelled in animals. This chapter considers the different methodological approaches currently available for rodent studies associated with these behaviours. In particular, translational studies investigating whether changes in cognitive processes implicated in depression may also provide a basis for predicting pro-depressant risk will be considered. We also review the available literature relating to animal studies investigating pro-depressant drug treatments to gauge the degree of predictive validity which these animal models can deliver.