The miracle of birth is one of life's greatest joys, but paradoxically many women suffer serious depression after delivering their new baby. Surprisingly, one in seven women will be stricken with postpartum depression, making it the most common medical complication of birth. "Baby blues" can develop into a serious condition, with such tragic consequences as child abandonment, infanticide, or suicide.

The cause of postpartum depression is unknown. Theories range from reactions to hormonal swings after birth to stressful psychological pressures of adjusting to a new life. The added responsibility of caring for a new child will force changes in life-style, impact career, remodel family relationships, and affect finances. These are understandable pressures that could trigger depression, but there seems little doubt that there is also a biological underpinning to this illness. What that biological mechanism might be has remained elusive. A new study investigating blood samples taken from women diagnosed with postpartum depression provides long-awaited insight into the biological cause of this puzzling illness, and a surprising twist--the findings have nothing to do with neurons.

As with most psychiatric illnesses, there is no equivalent of a blood test to diagnose postpartum depression or aid in treating it. Doctors cannot run a lab test to identify which new mother is at risk of suffering postpartum depression, and when a woman is stricken with depression, doctors must settle for managing the symptoms of her illness rather than attacking its root cause.

In a study just published in the journal Molecular Psychiatry, scientists from Hadassah-Hebrew University in Jerusalem examined white blood cells from new mothers to determine which genes in them were being activated or inactivated. They found that different genes were switched on in white blood cells from mothers with postpartum depression compared with blood cells from healthy new mothers. In the mothers with depression, a large category of genes controlling the generation of new cells was suppressed together with genes that stimulate the immune response that protects our body from infection. Moreover they found that this genetic analysis could predict the severity of her illness and her prognosis. The findings move the search for origins of psychiatric illnesses beyond neurons, to include non-neuronal brain cells, called glia, and to cells of the immune system.

The findings raise a number of puzzling questions. Are the changes in genes in white blood cells the cause or result of the illness? Secondly, white blood cells do not enter brain tissue (unless it is damaged), so how could the immune system disrupt neural networks controlling mood and motivation?

Interestingly, the distinctive pattern of genes that are activated and inactivated in mothers with postpartum depression closely matches the gene profile found in people suffering posttraumatic stress disorder, pointing to suppression of cell division and immune response in both mental illnesses. Human brain imaging and microscopic analysis of brain tissue taken at autopsy have confirmed that indeed proliferation and survival of certain brain cells is impaired in people suffering depression, and similar results are found in animal studies. This new research into the biological basis for psychiatric illnesses shows that stress and depression shrink the amount of brain tissue in critical areas necessary for thought and mood. One of the most recent surprises from this line of research is the discovery that antidepressant drugs used for treating depression stimulate the birth of new brain cells.

The loss of neurons is now being seen as an underlying feature of depression. Most of the cells in the brain are not neurons, but rather they are cells called glia, which have been largely overlooked because they do not generate electrical impulses. However, recent research shows that new neurons are born not from other neurons, but instead from immature glial cells. Once neurons mature, they can no longer divide to generate new neurons. Thus, glia are implicated in the cause of depression and in effective treatments for it.

The changes in white blood cells suggest that systemic effects on the entire body are contributing to depression, but inside brain tissue white blood cells are absent because they cannot escape from the blood. Instead a different type of glial cell, called microglia, defend brain tissue from infection just as our white blood cells do in our body. Microglia attack invading organisms in much the same way as white blood cells.

One of the main chemical signals marshalling a cellular response to infection are called cytokines. Genes for several cytokines were suppressed in women with postpartum depression. Cytokines are released into the blood by white blood cells, but microglia release cytokines in brain tissue. Cytokines have powerful effects on the excitability of neurons and they regulate cell division and cell development. Recent research, for example, has shown that cytokines released by microglia contribute to chronic pain and addiction to opiate drugs. (See

Postpartum depression may be triggered in part by the emotional stresses and responsibilities confronting a new mother, but these new studies show that there is indeed a real biological basis for the illness. As scientists broaden their search beyond neurons, non-neuronal cells are being found to have critical roles in normal brain function, disease, and even psychiatric illnesses that have for a very long time been difficult to explain.

Segman, R.H. et al., (2010) Blood mononuclear cell gene expression signature of postpartum depression. Molecular Psychiatry 15, 93-100.

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