Washington, July 31 : Researchers from University of California at Los Angeles have uncovered a brain mechanism that may be responsible for postpartum depression in women.
The team has identified a suspect protein in mice that may promote depression-like behaviours.
"For the first time, we may have a highly useful model of postpartum depression," said NIMH Director Dr Thomas R. Insel.
"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," he added.
During the study the researchers used a genetically engineered mice lacking a protein critical for adapting to the sex hormone fluctuations of pregnancy and the postpartum period.
"After giving birth, female mice deficient in the suspect protein showed depression-like behaviors and neglected their newborn pups," said Istvan Mody, Ph.D., lead researcher, of the University of California at Los Angeles,
"Giving a drug that restored the protein's function improved maternal behavior and reduced pup mortality," Mody added.
Researchers Mody and Jamie Maguire assumed that postpartum depression was the result of marked fluctuations in estrogen and progesterone that accompany pregnancy and childbirth
Yet manipulating the hormones experimentally triggers depression only in women with a history of the disorder. The roots of their vulnerability remain a mystery.
Previous studies have made it evident that the hormones exert their effects on mood through the brain's major inhibitory chemical messenger system, called GABA, which dampens neural activity, helping to regulate when a neuron fires.
They found the GABA receptor subunit fluctuated conspicuously during pregnancy and postpartum in the brains of female mice, hinting that it might have pivotal behavioural effects.
Similar to human mothers with postpartum depression, the genetically altered mouse mothers were more lethargic and less pleasure-seeking than normal mice. They also shunned their pups and failed to make proper nests for them.
The researchers then treated the mice with a drug called THIP that acts on the receptor in a way that specifically restores its function in spite of the reduced number of subunits.
They found that the abnormal maternal behaviour was reversed and pup survival increased.
"Improper functioning of the subunit could impair the GABA system's ability to adapt to hormone fluctuations during the highly vulnerable post partum period," said Maguire.
"Targeting this subunit might be a promising strategy in developing new treatments for postpartum depression," she added.
The findings appear in the July 31, 2008 issue of Neuron.