Studies indicate that depression is more prevalent among women than it is among men. Genetics and environment seem to be the keys to unlocking this gender-gap mystery, although the complexity of the puzzle makes progress slow.

Women may be more sensitive—physiologically, at least—to certain changes in the environment. And this responsiveness might help explain the high rates of depression in their ranks

The symptoms of depression range from uncomfortable to debilitating: sleep disturbances, hopelessness, feelings of worthlessness, difficulty concentrating, fatigue and sometimes even delusions. Most of us have watched a relative or friend struggle with depression—and many of us have experienced it ourselves. Even so, few people realize just how common depression is, how severe it can be or that it is most prevalent among women. In 1990 the World Health Organization found depression to be the leading cause of 'disease burden' (a composite measure including both illness and death) among women, noting that it affects almost 20 percent of the female population in the developed world. Epidemiological studies indicate that 12 percent of U.S. women—compared with only 6 percent of U.S. men—have suffered from clinically significant depression at some time in their lives.

The big question, of course, is why such a gender gap exists. Over the years various explanations have surfaced to account for the fact that, from one study to the next, depression is between two and three times more common among women than it is among men. Some mental health workers have pointed to psychology, arguing that women are better trained to recognize their feelings and seek help, so they come to the attention of health professionals more often than men. Others have suggested that oppression—in the form of physical or sexual abuse, harassment or discrimination—is to blame. Others still have attributed the increased rates of depression among women to the female reproductive system and the menstrual cycle.

But it isn't that simple. Data from a variety of studies show that depression clearly has psychological, environmental and biological roots. Modern neuroscience is beginning to teach us how these roots can become intertwined and reinforce one another. In other words, an increased risk for depression in women might stem from genetics, the effects of stressful events or social pressures, or some combination of all three. Neuroimaging of the brain's circuitry by PET and MRI scans reveals that psychological phenomena such as anger and sadness have biological underpinnings; we can now see circuits of brain cells becoming activated when these emotions arise.

Similarly, neuroimages demonstrate that environmental and psychological experiences can alter our brain chemistry. For example, Lewis R. Baxter and his colleagues at the University of California at Los Angeles found similar changes on the PET scans of patients with obsessive-compulsive disorder who responded to treatment, regardless of whether the patients were treated with medication or with behavioral therapy.

To figure out why depression is more common among women, scientists have to study how genetics and environment divide the sexes—and how the two conspire to produce the symptoms we describe as depression. It is difficult work, and progress is necessarily slow. But what is coming into focus is that certain environmental factors—including stress, seasonal changes and social rank—may produce different physiological responses in females than they do in males. These findings, are small pieces in what is proving to be an incredibly complex puzzle. Laying them out at this stage does not begin to explain depression's double standard. Nevertheless, it could help scientists develop more effective treatments for depressed individuals—both women and men—in the meantime.