Adrenarche as a regulator of sensitivity to early adversity.

The human brain is highly sensitive to early adversity, which can have long-term consequences for later mental health. It is also a time of rapid learning of social, motor and other skills, including language. It is proposed that pre-adrenarche, the only epoch in human development in which cortisol is not accompanied by dehydroepiandrosterone (DHEA) and its sulphated derivative (DHEAS), represents the sensitive period but this is subsequently moderated by the advent of adrenarche and the surge of DHEA(S) at 6-8 years. Cortisol enhances plasticity and the formation of new memories as well as personality traits such as emotionality. DHEA(S) is well known to oppose many of the actions of cortisol on the brain, including those on learning, memory and synaptic function, all reflecting altered plasticity; adrenarche is therefore a time of moderated cortisol activity. Several endocrine-dependent neural mechanisms respond to the neuroendocrine transition at adrenarche, including alterations in perineuronal nets, gene expression of growth factors, serotonin activity, cytokine release and synaptic adaptability. Adrenarche will reduce the detrimental impact of adverse events but stabilise memories and psychological traits acquired during the cortisol-dominated pre-adrenarche epoch. The transition from pre- to post-adrenarche is therefore a highly significant neuroendocrine event in early life, with both potentially beneficial and disadvantageous consequences. This suggests a primary role for adrenarche, for which no function has yet been established.