Early-life adversity in rodents: Experimental design is of the essence

Early-life adversity (ELA) is a well-documented risk factor for the development of psychiatric illnesses. Prospective investigations in humans are complex and limited in their ability to study the underlying neurobiological mechanisms, which is why many have reverted to animal models to examine the lasting consequences of ELA. In this contribution, we focus primarily on exposure to ELA during the postnatal period and highlight crucial elements of the experimental design that decisively contribute to the observed outcome. These elements include i) aspects of timing, encompassing the developmental stage during which ELA is experienced, the duration and repetitiveness of early-life stressors, and the time point at which the outcomes are investigated; ii) the early-life environment, e.g., the quality and quantity of parental care, the breeding specifics, housing conditions and nutrition, or mitigating interventions; iii) characteristics of later-life readouts, i.e., specific behavioral domains examined, the tasks selected to probe these domains, and the state of the animal at the time of testing; and iv) sex differences. We conclude by discussing how to maximize the advantages of ELA animal models to gain a comprehensive insight into the (neuro)biological mechanisms underlying the lasting consequences of ELA.