Structural changes after early life adversity in rodents: a systematic review with meta-analysis

Early life adversity (ELA) is a well-documented risk factor for psychiatric illnesses in humans. This risk may, in part, be conferred by structural changes induced by ELA, lasting into adulthood. We here review the evidence for such lasting structural changes in rodent models for ELA involving altered maternal care during the first two postnatal weeks. In total, we extracted data from 64 studies reporting on 260 comparisons in adult rats or mice which experienced ELA or control treatment. Most of the observations concerned structural changes in the hippocampus of adult male rats earlier exposed to maternal separation. A 3-level meta-analysis revealed that ELA reduced hippocampal volume and the number of dendritic branches as well as dendritic length of principal hippocampal cells. No differences were observed across the hippocampal subfields. In terms of adult neurogenesis in the dentate subgranular zone, both staining for BrdU and the early neuronal marker DCX were significantly reduced, while the general proliferation marker Ki67 remained unchanged. The neuronal growth factor BDNF did not show significant changes, although the unexplained heterogeneity was moderate. Generally, the effect of ELA compared to control on structural markers was not affected by additional stressors experienced in life. Overall, the data available support the notion that ELA, at least in the hippocampus of male rats, lastingly reduces volume, hampers dendritic growth and suppresses adult neurogenesis.