“I was going to go home,” says Peggy, “wait until my grandmother went out shopping, take the pills with a bottle of whiskey that she kept hidden in the linen closet. I couldn’t see any other way out.”

Flirting with depression from the age of 5, Peggy’s first year of college had sent her into her blackest downward spiral yet. At 19, she felt helpless and utterly drained. “I thought, ‘Oh God, I’ve flunked everything.’” She’d never had any therapy, never had any help from home, had few friends and had finally just lost hope. Suicide seemed like her only option.

Thirty-six years later, Peggy, who asked that her real name not be used, is a mother of two living in Danville, Calif., and, along with her 15-year-old daughter, is a participant in one of a wave of scientific studies that could help prevent depression in adolescents. It’s an intriguing concept gaining ground within the research community: Identify the adolescents most at risk for depression, and pre-empt it.

“We know rates of depression go up in adolescence. If we want to prevent depression, it makes sense to start early,” says Judy Garber, PhD, professor of psychology and human development at Vanderbilt University. “It seems like a much better way to go,” says Garber, who is testing interventions.

To attack the problem of how, first, to identify these kids, then second, to get them help, scientists are examining brain scans, measuring stress hormone levels, testing prevention programs. The hope is that by better understanding the interplay between human biology and environmental stressors, which together increase vulnerability for depression, researchers can better define those most at risk.

“For most kids, time does heal all,” says Manpreet Singh, MD, a child psychiatrist and associate director of the pediatric bipolar disorders clinic at Lucile Packard Children’s Hospital at Stanford who treats adolescent mood disorders.

“What we want to know is, why do some kids bounce back from stressful life events while some don’t?” says Singh. “What’s different about that subset of kids who don’t do well?”

Much progress has been made over the past 50 years in developing a profile of adolescents who might have a vulnerability to mood disorders, Singh says. What is now known is that depression often first strikes in adolescence, that females are twice as susceptible as males and that children of depressed parents are at a 40 percent increased risk.

“The whole battle between nature and nurture is pretty much over,” explains Victor Carrion, MD, director of the Stanford Early Life Stress Research Program at Packard Children’s Hospital. “We know it’s the interaction between the two. What we now need to figure out is just how environmental factors stimulate certain genes to cause a mood disorder.”

Depressing facts

All people at times feel some degree of sadness in their lives, but clinical depression is something else entirely. It destroys the ability to feel pleasure. It exhausts, both mentally and physically. It makes it impossible to get out of bed, and impossible to fall back asleep. It takes away appetite or causes overeating. It creates obsessive guilt and overwhelming grief. It affects 20 million Americans.

Debate continues over whether rates of adolescent depression are actually rising or whether better awareness has led to increased reporting. According to statistics from the U.S. Surgeon General, clinical depression among children ages 9 to 17 is estimated at 5 percent, making it the most common of psychological ailments.

“Whether it’s rising or not, the rates are really high and nobody is arguing that,” says Jane Gillham, PhD, a research associate in psychology at the University of Pennsylvania and associate professor at Swarthmore University.

Young people who have experienced a major depressive episode are at a greater risk of cycling through depression sometime again within the next five years and are at a higher risk of suicide and other mental health problems.

About 4,400 Americans between the ages of 10 and 24 commit suicide each year, making it the third most common cause of death in that age group, according to the Centers for Disease Control and Prevention. About 60 to 70 percent of this group has had a history of a mental health disorder, most commonly depression, which has typically been present for at least a year prior to their death.

Stanford mental health experts, in particular, have been focusing on the need for early and effective treatments of mood disorders during adolescence in the wake of the suicides of five teenagers in Palo Alto since May last year — a pattern that has stunned the community.

“I had a growing fixation with ending my own life,” is the way an anonymous Stanford University freshman describes his experience with depression. “I had this feeling of being a thousand leagues under the sea — stationary, drowned, crushed by the stillness and pressure, trapped in the dark.”

During adolescence, symptoms of serious depression can be even more confusing and destructive than in adulthood. Irritability, anger, low motivation and boredom are more common in teen depression. Grades can drop, thoughts of suicide occur, substance abuse appears. Diagnosis is often difficult because of our society’s expectations for teens to be moody, irritable and unpredictable.

“It’s hard for us to imagine or fathom that kids can get sad and do something devastating or catastrophic,” Singh says.

“I had a growing fixation with ending my own life.”

And even when teens are diagnosed, only 30 percent receive treatment, such as antidepressants or talk therapy or a combination of the two.

New research is also exploring the possibility that mood disorders such as depression leave a trail of damage in the brain, interfering with its normal growth, Carrion says.

“The environment can have a detrimental effect on brain development,” Carrion says. “But I also believe very strongly that psychotherapeutic interventions can have a palliative effect on the brain. The more we look at the brain, the more we realize how plastic it is. And the earlier we intervene, the higher the chances for this to work.”

Feeling protective

“Anxiety and depression is something I’ve dealt with on and off for years,” says Sarah, 37, who lives in Dublin, Calif., and who also asked that her real name not be used. She knows that depression runs in families so she’s watching her teenage daughter closely. “I try to mask it but sometimes my daughter is a casualty of it. She’ll ask me, ‘Mom, are you OK?’ She’ll try to make me feel better. She’ll be really good. She’s a great kid, but I see more sadness than happiness in her. I feel a lot of guilt and worry.”

Singh sees talk therapy as one way to reach out to families with mood disorders who want to prevent similar problems from occurring in their children. She conducts family-focused therapy sessions in which she teaches the family about mood disorders and promotes improved communication between family members.

“The kids who don’t do well develop maladaptive coping strategies,” Singh says. “In these kids, stress actually begets more stress. It compounds itself. They’re not able to detach themselves from a particular stressor.”

Signs of impending gloom

Peggy’s and Sarah’s teenage daughters are among those participating in studies at the Stanford Mood and Anxiety Disorders Laboratory directed by investigator Ian Gotlib, PhD, professor of psychology. Halfway through a five-year grant from the National Institute of Mental Health, Gotlib and colleagues at the university and medical school are comparing the responses to stress of 100 young girls with depressed mothers with a control group of 100 girls whose mothers have not suffered from depression. These researchers are continuing to recruit mothers and daughters into their study, with the goal of finding better predictors of which teens will get hit with the deep blues.

At the lab, the girls undergo tests that can detect high levels of the stress hormone cortisol, reduced hippocampus size (the brain structure that stores and retrieves memories) and susceptibility to negative moods — all of which have been linked to depression. Every 18 months, the girls come back for another round of these and other tests.

Measuring hormone levels and hippocampus size is straightforward enough, but how does one pin a number on negative mood? In Gotlib’s lab, each of the daughters takes turns sitting with a researcher in a small room in Jordan Hall, the psychology building just off the main quad. They watch 10-minute clips of sad movies (including the death of Bambi’s mother, and the part in Dead Poets Society where the best friend commits suicide), answer a series of difficult math questions and discuss problems they’re having at home or in school or with friends. The tests are intended to cause a sad mood or a stressful response. During the tests, researchers take saliva samples at 15-minute intervals to measure cortisol levels.

Another test quantifies the girls’ susceptibility to negativity by measuring how quickly they recognize a sad face versus a happy face on a computer screen.

The results have been surprising, Gotlib says. Initially researchers thought they’d have to wait for the at-risk girls, that is, the daughters of depressed mothers, to become depressed themselves before they saw physiological or psychological differences between the groups. But it turns out that even before ever experiencing depression, the at-risk girls are generally more reactive to stress than are the control girls. They already have higher levels of cortisol, they’re perceiving more stress day to day and they have smaller hippocampi than the control group.

Gotlib has published a series of studies to support these findings. One paper currently in press at the Archives of General Psychiatry shows a decreased hippocampus volume in healthy girls at risk for depression. Another study, published in 2007 in the Journal of Abnormal Psychology, finds that girls at risk for depression are already primed to see negative aspects of their environment. And a 2008 study in the journal Biological Psychiatry reports that girls with a particular serotonin-transporter gene linked with depression produced higher and more prolonged levels of cortisol in response to stress.

A simple way of looking at the results is that when many of the at-risk girls watch a sad movie, it takes them longer to feel better. These girls have a higher physiological, neural and endocrine response to stressful experiences than do the girls without depressed mothers. Gotlib believes that this provides evidence that a certain response to stress may push these girls over the edge into depression.

“Reducing reactivity to stress, therefore, should be a critical target for prevention efforts,” Gotlib says. “We could assess stress reactivity within a sample of children at risk for depression (for example, by virtue of having a depressed parent) and offer prevention programs to those with the highest levels of reactivity.”

By simply measuring heart rate changes in response to stressors or even using self-reported reactivity to stress — rather than quantifying cortisol or conducting expensive brain scans — “at-risk” teens could be targeted for prevention programs.

“We have clues now about who and what to target,” Gotlib says.

Heading off depression

In theory then, stress reduction programs such as yoga, meditation, self-hypnosis or exercise could help prevent depression in adolescents. That’s what researchers like Vanderbilt’s Garber are exploring. She published a study last summer in the Journal of the American Medical Association showing that relatively modest intervention — fewer than a dozen group sessions — goes a long way to prevent episodes of depression in high-risk teens.

The study, published June 3, 2009, focused on teens whose parents had a history of depression. All 316 of the teens had experienced some symptoms of depression themselves. Half were randomly assigned to attend eight weekly group sessions of a cognitive behavioral intervention. After nine months, teens who attended the sessions were less likely to have had an episode of depression than teens who didn’t. Less than 12 percent of those who got the therapy suffered a depressive episode — while of those in the non-therapy group, 21 percent had one.

“Basically, you’re trying to teach kids to evaluate the way they view the world,” says Garber, whose colleague, Frances Lyndh, PhD, is now conducting a cost analysis of the program. “For example, when something bad happens, like you lose your job, a person at risk for depression might think: ‘My God, my life is over. I’m never going to get another job. It’s all my fault I lost the job.’ Someone else might see this as an opportunity to try something new.”

Research into similar prevention programs has exploded in the past few years, says Gillham, co-director of the Penn Resiliency Project at the University of Pennsylvania. Programs designed to prevent depression in young people such as Gillham’s and Garber’s are popping up across the country — from an interpersonal psychotherapy-based program at Rutgers University in New Jersey to a family-based model at the Children’s Hospital of Philadelphia.

“When I did a review of the literature 10 years ago, there wasn’t much out there,” Gillham says. “Now I’m finding that it’s hard to keep up with all the literature. There are two or three papers out just this month,” she says in the December 2009 interview. “That’s huge in this field.”

“It teaches kids to be more realistic, not to be so hard on themselves.”

Gillham’s school-based program trains teachers and counselors to teach coping skills during 12 two-hour lessons either during or after school. Originally designed in the 1990s to prevent depression in adolescents, it has since branched out to include children between the ages of 10 and 14.

In a meta-analysis of 19 controlled studies co-authored by Gillham and published in December in the Journal of Consulting and Clinical Psychology, the program was found to successfully reduce and prevent symptoms of depression in adolescents.

“It teaches kids to be more realistic, and not to be so hard on themselves, and to cope with problems more effectively and more assertively,” Gillham says. “It teaches life skills that are helpful to most kids.”

Breaking the cycle

For people with chronic depression, like Peggy, preventing depression in young people before it has the chance to spiral out of control makes the most sense. She’s hoping for any tips that would help her own children avoid the periods of depression that she’s cycled through most of her life.

“I know I’m going to be dealing with depression on and off,” Peggy says. “I have gotten better. I think what helps me the most is to have somebody to talk to, whether it’s a good friend or somebody you pay $80 an hour.”

Peggy never took those sleeping pills when she was a freshman at Berkeley. She went on to graduate. She worked many years as a magazine editor, and now is successfully raising a family. And she remains vigilant in watching for signs of depression in her own kids.

About six years ago, she was driving in the family car with her seventh-grade son when he confided in her. He was going through a tough time. He has a mild form of autism, and the social stresses of junior high had become overwhelming.

“Sometimes I think about killing myself,” he told his mom.

“I just about fell out of the car,” Peggy says. “I immediately just started talking. ‘If you’re that sad, we’re here to help you. I know this is an emotionally sensitive time for you. This is not the answer.’” She took him seriously, got him the therapy he needed. Today her son is an 18-year-old freshman at the University of California, and she can’t help but be nervous. She remembers her freshman year of college all too clearly.

“It’s hard for kids,” she says. “All they think is, ‘I want my pain to stop. I’m miserable,’ and sometimes they don’t see any way out. They don’t realize that life does get better.”

 

E-mail Tracie White