Has the Mechanism for Postpartum Depression Been Discovered?

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 depression. Supported in part by the National Institute of Mental Health, 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 protein's 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 a mystery.

Evidence suggested 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.

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 system's 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."

Reference

Maguire J, Mody I. GABAAR plasticity during pregnancy: relevance to postpartum depression. Neuron. 2008 Jul 31; 59

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Ten Great Books on Depression

1. Anxiety & Depression Workbook For Dummies (For Dummies (Psychology & Self Help)) (Paperback) by Charles H., PhD Elliott (Author), Laura L., PhD Smith (Author), Aaron T., MD Beck (Author)
2. Depression for Dummies (Paperback) by Laura L., PhD Smith (Author), Charles H., PhD Elliott (Author)
3. Overcoming Depression One Step at a Time: The New Behavioral Activation Approach to Getting Your Life Back (New Harbinger Self-Help Workbook) (Paperback) by Michael E., Ph.D. Addis (Author), Christopher R. Martell (Author)
4. Overcoming Depression: A Step-by-Step Approach to Gaining Control Over Depression (Paperback) by Paul Gilbert(Author)
5. Overcoming Depression, 3rd edition by Demitri Papolos (Paperback - Jan 10, 1997)
6. Overcoming Depression (Victory Over the Darkness) by Neil T. Anderson and Joanne Anderson (Paperback - Jul 2004)
7. Woman's Guide to Overcoming Depression, A by Archibald Hart and Catherine Hart Weber (Mass Market Paperback - Nov 1, 2007)
8. Overcoming Anxiety and Depression: Practical Tools to Help You Deal with Negative Emotions by Bob Phillips (Paperback - Aug 15, 2007)
9. Overcoming Depression (Overcoming) by Paul Gilbert (Paperback - May 25, 2000)
10. Overcoming Anxiety, Panic, and Depression: New Ways to Regain your Confidence by James Gardner, Arthur H. Bell (Paperback - Feb 1, 2005)

Twelve Resource and Support Groups for Depression

1. Broken Smiles 
2. Journey Towards Freedom
3. Depression Forums
4. Depression Boards  
5. Depression Resources
6. Depression Understood  
7. Depressionsupport1  
8. Yahoo Depression Support Groups
9. The Depression Support Group
10. Depression and Bipolar Support
11. Alliance
12. Families for Depression Awareness

Sources: National Insititute of Mental Health, See also blogposts in Psychiatric Disorders: General and Psychiatric Disorders: Depression

Dr. Jeffrey Speller

Dr. Tanya Korkosz

Psychopharmacology Associates of New England

www.psychopharmassociates.com

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