The behavioral phenotype of early life adversity: A 3-level meta-analysis of rodent studies

Abstract

Altered cognitive performance is considered an intermediate phenotype mediating early life adversity (ELA) effects on later-life development of mental disorders, e.g. depression. Whereas most human studies are limited to correlational conclusions, rodent studies can prospectively investigate how ELA alters cognitive performance in several domains. Despite the volume of reports, there is no consensus on i) the behavioral domains being affected by ELA and ii) the extent of these effects. To test how ELA (here: aberrant maternal care) affects specific behavioral domains, we used a 3-level mixed-effect meta-analysis, and thoroughly explored heterogeneity with MetaForest, a novel machine-learning approach. Our results are based on >400 independent experiments, involving ∼8600 animals. Especially in males, ELA promotes memory formation during stressful learning but impairs non-stressful learning. Furthermore, ELA increases anxiety-like and decreases social behavior. The ELA phenotype was strongest when i) combined with other negative experiences (“hits”); ii) in rats; iii) in ELA models of ∼10days duration. All data is easily accessible with MaBapp (https://osf.io/ra947/), allowing researchers to run tailor-made meta-analyses, thereby revealing the optimal choice of experimental protocols and study power.