“I am now the most miserable man living. If what I feel were equally distributed to the whole human family, there would be not one cheerful face on earth. Whether I shall ever be better, I cannot tell. I awfully forebode I shall not. To remain as I am is impossible. I must die or be better it appears to me.” –Abraham Lincoln

Imagine attending a party with these prominent guests: Abraham Lincoln, Theodore Roosevelt, Robert Schumann, Ludwig von Beethoven, Edgar Allen Poe, Mark Twain, Vincent van Gogh, and Georgia O’Keefe. Maybe Schumann and Beethoven are at the dinner table intently discussing the crescendos in their most recent scores, while Twain sits on a couch telling Poe about the plot of his latest novel. O’Keefe and Van Gogh may be talking about their art, while Roosevelt and Lincoln discuss political endeavors. But in fact, these historical figures also had a much more personal common experience: Each of them battled the debilitating illness of depression.

It is common for people to speak of how “depressed” they are. However, the occasional sadness everyone feels due to life’s disappointments is very different from the serious illness caused by a brain disorder. Depression profoundly impairs the ability to function in everyday situations by affecting moods, thoughts, behaviors, and physical well-being. Twenty-seven-year-old Anne (not her real name) has suffered from depression for more than 10 years. “For me it’s feelings of worthlessness,” she explains. “Feeling like I haven’t accomplished the things that I want to or feel I should have and yet I don’t have the energy to do them. It’s feeling disconnected from people in my life, even friends and family who care about me. It’s not wanting to get out of bed some mornings and losing hope that life will ever get better.”

Depression strikes about 17 million American adults each year–more than cancer, AIDS, or coronary heart disease–according to the National Institute of Mental Health (NIMH). An estimated 15 percent of chronic depression cases end in suicide. Women are twice as likely as men to be affected. Many people simply don’t know what depression is. “A lot of people still believe that depression is a character flaw or caused by bad parenting,” says Mary Rappaport, a spokeswoman for the National Alliance for the Mentally Ill. She explains that depression cannot be overcome by willpower, but requires medical attention.

Fortunately, depression is treatable. In the past 18 years, the Food and Drug Administration has approved several new antidepressants, including Wellbutrin (bupropion), Prozac (fluoxetine), Zoloft (sertraline), Paxil (paroxetine), Effexor (venlafaxine), Serzone (nefazodone), and Remeron (mirtazapine). According to the American Psychiatric Association (APA), 80 to 90 percent of all cases can be treated effectively. However, two-thirds of the people suffering from depression don’t get the help they need, according to NIMH. Many fail to identify their symptoms or attribute them to lack of sleep or a poor diet, the APA says, while others are just too fatigued or ashamed to seek help. Left untreated, depression can result in years of needless pain for both the depressed person and his or her family. And depression costs the United States an estimated $43 billion a year, due in large part to absenteeism from work, lost productivity, and medical costs, according to the National Depressive and Manic Depressive Association.

The three main categories of depression are major depression, dysthymia, and bipolar depression (sometimes referred to as manic depression).

Major depression affects 15 percent of Americans at one point during their lives, according to the U.S. Department of Health and Human Services. Its effects can be so intense that things like eating, sleeping, or just getting out of bed become almost impossible. Major depression “tends to be a chronic, recurring illness,” Laughren explains. Although an individual episode may be treatable, “the majority of people who meet criteria for major depression end up having additional episodes in their lifetime.”

Unlike major depression, dysthymia doesn’t strike in episodes, but is instead characterized by milder, persistent symptoms that may last for years. Although it usually doesn’t interfere with everyday tasks, victims rarely feel like they are functioning at their full capacity. According to the National Alliance for the Mentally Ill, almost 10 million Americans may experience dysthymia each year.

Finally, bipolar disorder cycles between episodes of major depression and highs known as mania. Bipolar disorder is much less common than the other types, afflicting about 1 percent of the U.S. population. Symptoms of mania include irritability, an abnormally elevated mood with a decreased need for sleep, an exaggerated belief in one’s own ability, excessive talking, and impulsive and often dangerous behavior.

Study after study suggests biochemical and genetic links to depression. A considerable amount of evidence supports the view that depressed people have imbalances in the brain’s neurotransmitters, the chemicals that allow communication between nerve cells. Serotonin and norepinephrine are two neurotransmitters whose low levels are thought to play an especially important role. The fact that women have naturally lower serotonin levels than men may contribute to women’s greater tendency to depression. Family histories show a recurrence of depression from generation to generation. Studies of identical twins confirm that depression and genes are related, finding that if one twin of an identical pair suffers from depression, the other has a 70 percent chance of developing the disease. For fraternal twins or siblings, the rate is just 25 percent.

Environmental factors, however, also play an important role in depression. When combined with a biochemical or genetic predisposition, life stressors (such as relationship problems, financial difficulties, death of a loved one, or medical illness) may cause the disease to manifest itself. John (not his real name), 25, was diagnosed with depression for the first time last year when he and his girlfriend ended their three-year relationship. “I couldn’t do anything because I was totally absorbed with the whole break-up issue,” he says. “It was impossible for me to sleep, and I would wake up at 3 or 4 in the morning and literally shake. And when it was time to wake up, I just couldn’t get out of bed.” In addition, substance abuse and side effects from prescription medication may also lead to a depressive episode. And research shows that people battling serious medical conditions are especially prone to depression. According to the U.S. Department of Health and Human Services, those who have had a heart attack, for example, have a 40 percent chance of being depressed.

Seasonal affective disorder, often called “SAD,” is a striking example of an environmental factor playing a major role in depression. SAD usually starts in late fall, with the decrease in daylight hours and ends in spring when the days get longer. The symptoms of SAD, which include energy loss, increased anxiety, oversleeping, and overeating, may result from a change in the balance of brain chemicals associated with decreased sunlight. The exact reason for the association between light and mood is unknown, but research suggests a connection with the sleep cycle. Several studies have suggested that light therapy, which involves daily exposure to bright fluorescent light, may be an effective treatment for SAD.

Medical professionals generally base a diagnosis of depressive disorder on the presence of certain symptoms listed in the American Psychiatric Association’s Diagnostic and Statistical Manual. The DSM (presently in the fourth edition) lists the following symptoms for depression: depressed mood loss of interest or pleasure in almost all activities changes in appetite or weight disturbed sleep slowed or restless movements fatigue, loss of energy feelings of worthlessness or excessive guilt trouble in thinking, concentrating, or making decisions recurrent thoughts of death or suicide. The diagnosis depends on the number, severity and duration of these symptoms. Even with this list of symptoms, diagnosing depression is not simple. According to the National Alliance for the Mentally Ill, it takes an average of eight years from the onset of depression to get a proper diagnosis. In making a diagnosis, a health professional should also consider the patient’s medical history, the findings of a complete physical exam, and laboratory tests to rule out the possibility of depressive symptoms resulting from another medical problem. The symptoms of the depressive part of bipolar disorder are the same as those expressed in major (unipolar) depression. Because of the similarities in symptoms and the fact that manic episodes usually don’t appear until the mid-20s, some people with bipolar disorder may mistakenly be diagnosed with unipolar depression. This may lead to improper treatment because antidepressants carry the risk of triggering a manic episode.

One major approach for treating depression is the use of antidepressant medications. The older antidepressants include tricyclic antidepressants such as Tofranil (imipramine) and monoamine oxidase inhibitors such as Nardil (phenelzine). Antidepressants approved more recently include the selective serotonin reuptake inhibitors Prozac, Paxil and Zoloft, and the other newer antidepressants Wellbutrin, Effexor, Serzone, and Remeron. The effects of antidepressants on the brain are not fully understood, but there is substantial evidence that they somehow restore the brain’s chemical balance.

These medications usually can control depressive symptoms in four to eight weeks, but many patients remain on antidepressants for six months to a year following a major depressive episode to avoid relapse. Different drugs work for different people, and it is difficult to predict which people will respond to which drug or who will experience side effects. So it may take more than one try to find the appropriate medication. Since the mid-1950s, tricyclic antidepressants have been the standard against which other antidepressants have been measured. Monoamine oxidase inhibitors were discovered around the same time as tricyclic antidepressants, but were prescribed less because, if mixed with certain foods or medications, the drugs sometimes resulted in a fatal rise in blood pressure. Laughren describes Prozac as the “first of a new type of more selective antidepressants.” The older antidepressants had unpleasant and sometimes dangerous side effects, such as insomnia, weight gain, blurred vision, sexual impairment, heart palpitations, dry mouth, and constipation. Prozac, other selective serotonin reuptake inhibitors, and other recently approved antidepressants have had generally safer side effect profiles.

Other types of therapy, such as natural substances extracted from plants, are currently being studied. Although not approved by FDA, some people believe St. John’s wort, for example, is extremely helpful in alleviating their depressive symptoms.

For severe depressive episodes, medications are often the first step because of the relatively quick relief they can bring to physical symptoms. For the long term, however, psychotherapy may be needed to address certain aspects of the illness that drugs cannot. “Although the biological features of depression may respond better to drugs,” Laughren says, “people may need to relearn how to interact with their environment after the biological part of the depression is controlled.”

“I wanted to talk things out and get better in that way,” John says. “And even after the first couple of times I saw my therapist, I could do a little bit more. Talking with her gave me some reality that how I was feeling wasn’t so abnormal, so unusual, or so terrible.”

Anne explains, “It’s just comforting sometimes to share the little day-to-day happenings in my life with someone who doesn’t get to see them first-hand.”

Some find support groups to be invaluable in helping them cope with their depression. “It’s through talking with others with similar experiences,” says Mary Rappaport, “that you can better understand what you’re going through.”

Changes in lifestyle are also important in the management of depression. Exercise, even in moderate doses, seems to enhance energy and reduce tension. Some research suggests that a rush of the hormone norepinephrine following exercise helps the brain deal with stress that often leads to depression and anxiety. A similar effect may be obtained through meditation, yoga, and certain diets.

Like many others who have not had to face depression themselves, John’s friends lacked knowledge about the disease. “I think the whole thing really affected my relationships with people,” he says. “I was pretty much a jerk all of the time. I didn’t want to talk to anybody. I just wanted them to leave me alone.”

With the growing awareness of the seriousness of the disorder and the biological causes, the understanding and support of family and friends may be easier to come by. “The future looks very bright for individuals who in the past have often had to suffer alone,” says Rappaport. “More and more people are coming out, which encourages people to talk about it.” Among those who have “come out” recently to publicly discuss their personal bouts with depression are comedian Drew Carey and “60 Minutes” correspondent Mike Wallace.

Experts say that no one, young or old, has to accept feelings of depression as a necessary part of life. By trying different options for facing their personal challenges, Anne and others have learned what treatments help them most. “All in all,” Anne says, “I think my ability to weather the ups and downs of life has gotten better.”

Researchers continue to make great strides in understanding and treating depression. For example, scientists are beginning to learn more about the chromosomes where affective disorder genes appear to be located. “While there is a long way to go in coming up with even more effective drugs,” Laughren says, “there’s much ongoing research and reason for optimism.”