Maternal Care, Hippocampal Glucocorticoid Receptors, and Hypothalamic-Pituitary-Adrenal Responses to Stress

ABSTRACT & COMMENTARY

Synopsis: Variations in maternal care affect the development of individual differences in neuroendocrine responses to stress in rats. As adults, the offspring of mothers that exhibited more licking and grooming of pups during the first 10 days of life showed reduced plasma ACTH hormone and corticosteroid responses to acute stress.

Source: Liu D, et al. Science 1997;277:1659-1662.

More than 40 years ago, levine and colleagues found that neonatal rats that were handled by humans had a lesser endocrine response to stress in adulthood, but the reason for this reduction in endocrine reactivity was puzzling. Glucocorticoid responses to stress are meant to be short-lived, and glucocorticoid excess heightens neuronal degeneration and cognitive decline in rats and humans. The current study suggests that the benefits of human handling of neonatal rats are related to the maternal response it evokes. Specifically, when handled rats are returned to their mothers, they receive extra attention and grooming. Handling approximately doubles the mother’s licking and grooming behavior. Furthermore, rats born to mothers who spontaneously are "high-groomers" also fare better in adulthood when exposed to stressors. Neonatal experience leads to organizational changes in the hippocampus, the site where glucocorticoid receptor occupation truncates the glucocorticoid response to stress.

COMMENT BY SARAH L. BERGA, MD

Is the above study done in rats relevant to human development? Can maternal attention to the human infant protect it from life’s later adversities? Certainly, infants whose mothers suffer from severe postpartum depression show deficits in psychosocial development as children. As reviewed here earlier, early and aggressive antidepressant therapy is recommended for women who do develop postpartum depression because the risks of infant psychosocial neglect are felt to be so much more significant than the risks of exposure to antidepressants during either pregnancy or lactation (Chambers CD, et al. N Engl J Med 1996;335:1010-1015). Antidepressant therapy apparently reduces cortisol secretion (Michelson D, et al. J Clin Endocrinol Metab 1997;82:2601-2606). Recent studies done in elderly humans indicate that if urinary free cortisol levels were persistently elevated in elderly women and men between 70 and 79 years of age over the follow-up interval of 2.5 years; then memory declined (Seeman TE, et al. J Clin Endocrinol Metab 1997;82:2458-2465). Importantly, memory improved in those in whom the urinary free cortisol declined. This was a study of more than 4000 elderly adults funded by the MacArthur Foundation. The senior author of this report also found that higher cortisol responses in anticipation of a stressful experience impaired memory in elderly adults (Lupien SJ, et al. J Clin Endocrinol Metab 1997;82:2070-2075). The good news from these latter studies is that the window of neglect or benefit may never entirely close in humans. Thus, stressful experiences that lead to appropriate psychosocial support and attention could protect not only children but adults from glucocorticoid oversecretion. Neglect at any age is likely to potentiate prolonged endocrine arousal. It probably is never too late to be good to yourself or to your friends and colleagues. Being good to others may have benefits for self. Humans have developed an array of ways to demonstrate concern. The original vision of a physician was as a support in the face of life’s health challenges, not all of which could be reversed. To my way of thinking, one of the greatest fallacies of thinking about medicine as a pharmaceutical transaction is that it omits from the ledger sheet the benefits of simple attention.