Let’s say you twisted your ankle and it’s causing unbearable pain. You’ll likely go to a doctor, who will examine you and probably order an X-ray. If it’s just a sprain, you’ll be advised to apply ice, elevate and stay off it, and you’ll need crutches to get around for a while. If it’s a break, you might get a cast or a brace, or possibly an appointment with a surgeon, and some time off to heal.

But what happens when your unbearable pain isn’t visible, can’t easily be explained or diagnosed, and doesn’t have a commonly accepted medical treatment? For people who suffer from serious depression, there’s no one cause to pinpoint, no one way to treat it and certainly no definitive solution.

“It’s a basic human need to want a concrete explanation about an illness so it can be predicted and controlled,” says Carolyn Occhipinti, PsyD, a Portland, Oregon–based licensed psychologist in private practice. “The mind and body are intricately connected, and mental illness is related to neurochemical changes in the brain. But being told this isn’t always enough for people, or for their friends and family.”

Major depression is more than just feeling down. Mental health professionals rely on diagnostic criteria that include a persistent sad, anxious or “empty” mood; feelings of hopelessness; irritability; decreased energy or fatigue; difficulty sleeping; and loss of interest in hobbies or activities that were once pleasurable. Generally, if you meet five or more of the criteria, you’ve got some form of depression. After more than two weeks, it’s called major depressive disorder; if it lasts two years or more, it’s named persistent depressive disorder.

A combination of genetic, biological, environmental and psychological factors can cause brain changes, as can unique circumstances like grieving, a serious physical illness, or hormonal changes after childbirth or during menopause. The Journal of the American Medical Association reports that depression affects women at twice the rate as it does men, regardless of racial, ethnic or economic factors. In fact, 20 percent to 26 percent of women will experience depression in their lifetime, compared to 8 percent to 12 percent of men.