Mechanism for Postpartum Depression
Found in Mice
Discovery May Lead to Better Treatments
Researchers have pinpointed a mechanism in the brains of mice
that could explain why some human mothers become depressed following
childbirth. The discovery could lead to improved treatment for postpartum
in part by the National Institute of Mental Health (NIMH), part
of the National Institutes of Health, the study used genetically
engineered mice lacking a protein critical for adapting to the
sex hormone fluctuations of pregnancy and the postpartum period.
"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."
"After giving birth, female mice deficient in the suspect
protein showed depression-like behaviors and neglected their newborn
pups," explained Istvan Mody, Ph.D., of the University of California
at Los Angeles (UCLA), who led the research. "Giving a drug that
restored the proteinís function improved maternal behavior and
reduced pup mortality."
Mody and Jamie Maguire, Ph.D., UCLA, report on their findings
in the July 31, 2008 issue of Neuron.
Researchers had suspected that postpartum depression stemmed from
the marked fluctuations in the reproductive hormones 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
Evidence suggested that the hormones exert their effects on mood
through the brainís major inhibitory chemical messenger system,
called GABA, which dampens neural activity, helping to regulate
when a neuron fires.
Mody and Maguire discovered that a GABA receptor component, called
the delta subunit, fluctuated conspicuously during pregnancy
and postpartum in the brains of female mice, hinting that it might
have pivotal behavioral effects. To find out, they used mice lacking
the gene for this subunit and studied them in situations that can
elicit responses similar to human depression and anxiety.
Much like human mothers suffering from 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.
This abnormal maternal behavior was reversed and pup survival
increased after the researchers gave the animals 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.
"Improper functioning of the delta subunit could
impair the GABA systemís ability to adapt to hormone fluctuations
during the highly vulnerable post partum period," explained Maguire.
"Targeting this subunit might be a promising strategy in developing
new treatments for postpartum depression."
The National Institute of Mental Health (NIMH) mission is to reduce
the burden of mental and behavioral disorders through research
on mind, brain, and behavior. More information is available at
the NIMH website, http://www.nimh.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and its
programs, visit www.nih.gov.
Reference: Maguire J, Mody I. GABAAR plasticity during
pregnancy: relevance to postpartum depression. Neuron. 2008
Jul 31; 59