Neurobiological links between epilepsy and mood disorders

With increasing realization of the extent and consequences of depressive comorbidity in epilepsy, much human and animal research has focussed on its explanation. Recent studies tackle all three explanatory possibilities: that epilepsy leads to depression; that depression contributes to causation of epilepsy; or that shared causal factors or processes lead to both epilepsy and depression. These are not mutually exclusive; all three probably contribute. Animal models have provided many insights into the interplay between epilepsy and depressive-like behaviours, both associations and mechanisms. Notably, experimental stress potently affects epilepsy endpoints, as well as depressive-like behaviour, having actions at multiple relevant biological levels. Current general (nonepilepsy) depression modelling is biopsychosocial in nature, integrating insights from genetics, epidemiology, psychology and neurobiology; and takes a lifespan developmental perspective, as the causation of depression is a multistage process with origins in early life - as is the case for many epilepsies. These perspectives need to be more fully adopted in the epilepsy/depression field.