ORIGINAL

Abstract

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are etiologically complex conditions thought to stem from interactions between biological and environmental factors. The established early life stress (ELS) paradigm proposes a “two-hit” stress model, wherein mouse maternal separation in the early postnatal period leads to heightened depression- and anxiety-like behavior upon a second hit of stress during adulthood. However, the mechanisms by which maternal separation induces these behavioral changes remain ambiguous, as both tactile stimulation and nutrition are depleted during separation. The present study disentangles the nutritional and tactile aspects of ELS by investigating the effects of early-life nutritional and tactile care environments on behavioral outcome measures and epigenetic markers. We confirmed that ELS increases susceptibility to adult stress, and observed male-specific main effects of early experience on mouse depression- and anxiety-like behavior. Human cohort analysis revealed that quality nutrition is predictive of decreased depression only when accompanied by tactile care. Additionally, nutrition and tactile factors are implicated in synergistically slowing the process of methylation aging, though these effects are small among teenagers. These results inform future work which will contribute to a more complete understanding of early-life programming of the long-term stress response across mice and humans.