Neurosteroids and early-life programming: An updated perspective

Early-life stress can lead to detrimental offspring outcomes, including an increased risk for mood disorders and hypothalamic–pituitary–adrenal axis dysregulation. Neurosteroids bind to ligand-gated neurotransmitter receptors, rapidly modulating neuronal excitability and promoting termination of stress responses. Reduced neurosteroidogenesis underlies some of the aberrant neuroendocrine and behavioural phenotypes observed in adult prenatally stressed rodents. During development, disruptions in neurosteroid generation and action also lead to long-term programming effects on the offspring's brain and behaviour. Here, we review recent advances in the field, focusing on the interaction between neurosteroids and early-life stress outcomes in adulthood and in the perinatal period. We also discuss the direction of future research, with emphasis on quantification methods, sex differences, and neurosteroids as targets for therapeutic intervention.