A mechanism in the brains of mice — specifically, the lack of a protein that is key in adapting to sex hormone fluctuations — might explain why some human mothers experience depression after giving birth, and the discovery could lead to better treatments for postpartum depression.
The study, funded in part by the National Institute of Mental Health, used genetically engineered mice lacking the critical protein; the findings appeared in the July 31 issue of Neuron.
"For the first time, we may have a highly useful model of postpartum depression," said NIMH Director Thomas R. Insel, M.D. "The new research also points to a specific potential new target in the brain for medications to treat this disorder that affects 15 percent of women after they give birth."
Previous studies had suggested that large variations in estrogen and progesterone during pregnancy and childbirth might spur postpartum depression.
"After giving birth, female mice deficient in the suspect protein showed depression-like behaviors and neglected their newborn pups," said Istvan Mody, Ph.D., of the University of California, Los Angeles, who led the research along with Jamie Maguire, Ph.D. "Giving a drug that restored the protein's function improved maternal behavior and reduced pup mortality."
Besides shunning their pups and showing little interest in constructing a proper nest, the genetically altered mice displayed symptoms similar to human mothers with postpartum depression: They were more lethargic and less pleasure-seeking than normal mice.
But this poor mothering was reversed, with pup survival rates increased, when the researchers gave the rodents a drug that targets a subunit of the brain's major inhibitory chemical messenger system, called GABA.
"Improper functioning of the subunit could impair the GABA system's ability to adapt to hormone fluctuations during the highly vulnerable post partum period," Maguire said. "Targeting this subunit might be a promising strategy in developing new treatments for postpartum depression."