Animal models for depression and the mismatch hypothesis of disease

Early life stress is one of the best characterized risk factors for psychiatric disorders, including depression, and many animal models have therefore studied the long-term physiological and behavioural consequences of early life stress. In most approaches a very deterministic view of adverse experiences early in life prevails, linking these events inevitably with later pathology. By summarizing literature on early life programming and adaptive phenotypic plasticity the current review proposes that early life challenges may induce changes that prepare an individual for life in a more hostile environment and are therefore predominantly beneficial. Adult diseases as depression might thus not be promoted by early life adversity per se, but by a mismatch of the programmed and the later actual environment in combination with a more vulnerable or resilient genetic predisposition. The present review further discusses the ability of currently available animal models for depression to investigate this novel hypothesis. Finally, a number of criteria and research strategies are outlined that would be necessary to address the mismatch hypothesis of depression.