Defining Depression and Bipolar Disorder

Cutting a wide swath across all communities and cultures, major depression is more common in women and is characterized by a variety of psychic and physical signs that persist over several weeks or longer, including lowered mood, decreased energy, sleep disturbances, anxiety, self-destructive thoughts, poor concentration, and chronic pain. Bipolar disorder affects men and women equally and is characterized by episodes of mood highs and lows, each lasting at least one week. Although the onset of both disorders tends to be in adulthood, children can also be affected.

Tracing Genetic Roots

What causes mood disorders? Scientists now understand that these illnesses occur when biological or genetic vulnerability intersects with environmental stress. Stanford experts are in the process of unraveling these interactions using unprecedented discovery techniques made possible by the mapping of the human genome over the past decade.

Since 1996, Stanford has been an institutional leader in the Pritzker Network for the Study of Depression, a collaborative forum established by the Pritzker family to study the root causes of depression and to improve treatment of the disorder. Now known as the Pritzker Consortium, Stanford—in partnership with investigators from the University of Michigan, Cornell University, and the University of California—is focused on identifying genes that contribute to bipolar disorder and depression and on the development of new treatments for patients with major mood disorders.

Scientists once thought they would be able to attribute mood disorders to a single genetic alteration in a single neurotransmitter system. They now know that the genetics of these disorders is complex. Genes may have an impact on many different functions that can all feed into depression or bipolar disorder—for example, by affecting how our brains respond to stress, modulate mood, or maintain cognitive performance. One Stanford effort enables scientists to look at a large number of genes simultaneously in specific regions and circuits of the brain. Combined with similar preclinical examinations, these studies will determine which circuits and structures in the brain play key roles in mood disorders—the first step in developing novel, better-directed, more effective treatments.

To explore the genetic origins of mood disorders, Stanford is also investigating these diseases across generations—collecting data on families in which both adults and children have depression or bipolar disorder. Using the latest in genetic analytic technologies, these studies promise to reveal which genes connote increased risk for developing one or more mood disorders.

Seeing and Healing the Brain

Can stress damage the brain and make it more vulnerable to mood disorders? What portions of the brain are affected by depression and bipolar disorder? How do antidepressants affect the brain? To answer these questions, scientists must be able to study the living brain in real time. And scientists at Stanford are internationally renowned for exploring and developing innovative technologies that reveal mood disorders at the biological level and promise to transform the way brain disorders are diagnosed and treated.

Among the advanced technologies developed by Stanford scientists is functional magnetic resonance imaging (fMRI) technology that can monitor activity in a difficult-to-image brain region—the subgenual cortex—thought to be associated
with deep depression. Other researchers are looking at high-risk children of women with depression and are combining fMRI explorations with genetic studies to determine how particular genes and the neuronal circuits they affect might influence emotional regulation and how to use imaging to develop effective treatments and prevention strategies.

Several teams are using fMRI to explore how changes in emotion are associated with the activation of neuronal circuits in various parts of the brain. Some are investigating how neurotransmitters respond to current therapies. Others are looking at how certain hormones affect parts of the brain associated with severe depression. Another novel investigation is combining imaging with externally administered brain stimulation to understand the circuits involved in pathogenesis and to develop new treatments.