The Serotonergic System and Bone Metabolism During Pregnancy and Lactation and the Implications of SSRI Use on the Maternal-Offspring Dyad

Abstract

Lactation is a physiological adaptation of the class Mammalia and is a product of over 200 million years of evolution. During lactation, the mammary gland orchestrates bone metabolism via serotonin signaling in order to provide sufficient calcium for the offspring in milk. The role of serotonin in bone remodeling was first discovered over two decades ago, and the interplay between serotonin, lactation, and bone metabolism has been explored in the years following. It is estimated that postpartum depression affects 10–15% of the population, and selective serotonin reuptake inhibitors (SSRI) are often used as the first-line treatment. Studies conducted in humans, nonhuman primates, sheep, and rodents have provided evidence that there are consequences on both parent and offspring when serotonin signaling is disrupted during the peripartal period; however, the long-term consequences of disruption of serotonin signaling via SSRIs during the peripartal period on the maternal and offspring skeleton are not fully known. This review will focus on the relationship between the mammary gland, serotonin, and bone remodeling during the peripartal period and the skeletal consequences of the dysregulation of the serotonergic system in both human and animal studies.

The antidepressant fluoxetine (Prozac®) modulates serotonin signaling to alter maternal peripartum calcium homeostasis

“…The decrease in circulating calcium activates endogenous mechanisms for restoration of circulating concentrations of calcium typically by day 2 postpartum. Mechanisms of calcemic adaptations to lactation include bone resorption, increased gastrointestinal absorption, and renal reabsorption mediated by classic endocrine signals (parathyroid hormone, calcitonin, and 1,25-dihydroxyvitamin D) and mammary gland-derived endocrine signals (serotonin and PTHLH) 32 , 34 , 35 . The normal dynamics of circulating calcium homeostasis during the peripartum period is observed in the control group whereas the transient decrease in calcium did not occur in the fluoxetine group.…”