Mechanism For Postpartum Depression Found In Mice

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 (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 protein’s function improved maternal behavior and reduced pup mortality.”
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.”

The Magic Drug for Depression and Anxiety? Exercise

Two new studies released recently have highlighted the positive influence that exercise can have in lifting depression and quelling anxiety. Researchers encourage mental health providers to begin prescribing exercise in addition to other standard therapies of medication and therapy.
The first study, published in the Archives of Internal Medicine in February, found that in physically inactive patients with chronic health conditions such as heart disease or arthritis, exercise training may significantly reduce anxiety. The research, from the University of Georgia in Athens, found that sessions of at least 30 minutes a day had lasting effects on the participants.
In the second study, Jasper Smits, director of the Anxiety Research and Treatment Program at Southern Methodist University in Dallas and Michael Otto, psychology professor at Boston University, analyzed dozens of studies and meta-analytic reviews related to exercise and mental health. Individuals who exercise reported fewer symptoms of anxiety and depression and lower levels of stress and anger.
Exercise affects certain neurotransmitters systems in the brain and can re-establish positive behaviors which may have been put aside. It can also reduce the fear and physical symptoms of anxiety.
Because the standard treatments of cognitive behavioral therapy and pharmacotherapy (medications such as anti-depressants), do not reach everyone who needs them, all physicians should encourage those who can to perform daily exercise to help ease the symptoms of depression and/or anxiety.
"Exercise can fill the gap for people who can't receive traditional therapies because of cost or lack of access, or who don't want to because of the perceived social stigma associated with these treatments," says Smits. "Exercise also can supplement traditional treatments, helping patients become more focused and engaged." The research suggests that patients work up to 150 minutes of moderate-intensity exercise a week for mental health benefits.
Smits emphasizes that the benefits are seen immediately for those who suffer from depression and anxiety. "After just 25 minutes, your mood improves, you are less stressed, you have more energy - and you'll be motivated to exercise again tomorrow. A bad mood is no longer a barrier to exercise; it is the very reason to exercise."
Depression and anxiety can either occur together or separately. Depression is a serious medical condition that can potentially affect every part of a person’s life, such as the physical body, mood, thoughts, and eating and sleeping patterns. It is not a “case of the blues” and it does not relate to a specific situation, such as grief or sadness. Anxiety in itself is not harmful – it is a normal reaction to stress. However, when anxiety becomes and “excessive, irrational dread of everyday situations”, it can be disabling.
There are five major types of anxiety. Generalized Anxiety (GAD) is characterized by chronic anxiety, exaggerated worry and tension, even when there is nothing to provoke it. Obsessive Compulsive Disorder (OCD) is characterized by recurrent and unwanted thoughts and/or repetitive behaviors. Panic disorder is the unexpected and repeated episode of intense fear that is accompanied by physical symptoms, such as chest pain, heart palpitations, shortness of breath or abdominal distress. Post-Traumatic Stress Disorder (PTSD) is an anxiety that can develop after a terrifying event in which grave physical harm occurred or was threatened, such as disasters, accidents, or military combat. Social Anxiety Disorder is the overwhelming feeling of anxiety and excessive self-consciousness in everyday social situations.
The researchers presented their findings March 6 in Baltimore at the annual conference of the Anxiety Disorder Association of America. Their workshop was based on their therapist guide "Exercise for Mood and Anxiety Disorders," with accompanying patient workbook (Oxford University Press, September 2009).