The behavioral phenotype of early life adversity Bonapersona, V.; Kentrop, J.; Van Lissa, C. J.; van der Veen, R.; Joels, M.; Sarabdjitsingh, R. A. Citation for published version (APA): Bonapersona, V., Kentrop, J., Van Lissa, C. J., van der Veen, R., Joels, M., & Sarabdjitsingh, R. A. (2019). The behavioral phenotype of early life adversity: A 3-level meta-analysis of rodent studies. Neuroscience and Biobehavioral Reviews, 102, 299-307. https://doi.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.

Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

Adverse early life events are a well-established risk factor for the precipitation of behavioral disorders characterized by anomalies in the dopaminergic system, such as schizophrenia and addiction. The correlation between early life conditions and the dopaminergic system has been causally investigated in more than 90 rodent publications. Here, we tested the validity of the hypothesis that early life stress (ELS) alters dopamine signaling by performing an extensive 3-level mixed effect meta-analysis. We included several ELS models and biochemical indicators of the dopaminergic system in a variety of brain areas, for a total of 1009 comparisons. Contrary to our expectations, only a few comparisons displayed a significant effect. Specifically, the striatal area was the most vulnerable, displaying decreased dopamine precursor and increased metabolites after ELS. To make all data openly accessible, we created MaDEapp (https://osf.io/w25m4/), a tool to explore data of the meta-analysis with the intent to guide future (pre)clinical research and allow power calculations. All in all, ELS induces a few yet robust changes on biochemical indicators of the dopaminergic system.