Depression has many faces — from the common sad mood variety to major psychotic depression. Major depression, defined as a severely depressed mood that goes on for two weeks or more, is one of the most common mental disorders in the United States and includes symptoms such as sadness, sleep problems, suicidal feelings and a general inability to feel pleasure.

Studies show that rates of depression for Americans have risen dramatically in the past 50 years. Each year, about 1 in 5 adults (43.8 million or 18 percent) experiences mental illness and 1 in 25 adults (10 million or 4 percent) suffers with a serious mental illness that interferes with daily life.

Women are 70 percent more likely than men to experience depression during the course of their lifetimes due to hormones during pregnancy, menstruation and menopause. The lifetime prevalence of major depressive disorder is between 10 to 20 percent of the population.

Treating mood disorders can help people manage other illnesses and improve their general health. But treating depression can be complex, involving multiple risk factors, and treatment-resistant depression remains challenging, intensifying the need for relevant research involving newer drugs and treatment options.

Exactly what biochemical changes in the brain lead to depression remain unclear.

Prozac (fluoxetine) and tricyclics target and inhibit a pathway in the hippocampus — the BMP signaling pathway — triggering stem cells in the brain to produce more neurons called hippocampal neurogenesis. Because Prozac acts on multiple mechanisms, however, scientists have been unclear whether blocking the pathways contributed to the drugs' antidepressant effect.

But a study published this month in Molecular Psychiatry confirms the importance of the BMP pathway in depression.

At Northwestern University Feinberg School of Medicine, Sarah Brooker, M.D., and colleagues have been looking at how current antidepressants work in the brain in an effort to help those not getting relief from existing drugs. Bone morphogenetic proteins (BMPs) are a group of signaling molecules that belong to the transforming growth factor-beta (TGF-β) super family of proteins.

In this groundbreaking research, the scientists found that treatment with the selective serotonin reuptake inhibitor Prozac suppressed BMP signaling in the adult mouse hippocampus both by decreasing levels of BMP4 ligand and increasing production of the BMP inhibitor Noggin, a brain protein. After injecting the mice, the scientists observed the effect on mood by testing for depression and anxiety behavior.

Depression was measured by whether the mice tried to get upright when held by their tails or remained immobile. Those injected with noggin were more likely to try to get upright than the control mice.

To test for anxiety, the mice were placed in a maze, parts of which were secluded and other parts less secluded. The noggin-injected mice explored the maze and were less anxious than the control mice that remained in the secluded parts of the maze.

For decades, the effectiveness of antidepressants has been debated. The findings of this novel study not only help to understand the causes of depression but also may provide a new biochemical target for developing more effective therapies.