Perinatal programming of adult hippocampal structure and function; emerging roles of stress, nutrition and epigenetics.

Early-life stress lastingly affects adult cognition and increases vulnerability to psychopathology, but the underlying mechanisms remain elusive. In this Opinion article, we propose that early nutritional input together with stress hormones and sensory stimuli from the mother during the perinatal period act synergistically to program the adult brain, possibly via epigenetic mechanisms. We hypothesize that stress during gestation or lactation affects the intake of macro- and micronutrients, including dietary methyl donors, and/or impairs the dam's metabolism, thereby altering nutrient composition and intake by the offspring. In turn, this may persistently modulate gene expression via epigenetic programming, thus altering hippocampal structure and cognition. Understanding how the combination of stress, nutrition, and epigenetics shapes the adult brain is essential for effective therapies.