DEPRESSION: THE NEXT EPIDEMIC

Better Treatment Is On The Way. Will It Get Here In Time?

Editor's note: Last month Madison Magazine reported on medical advances in
treating drug addiction. Now, in the second of a two-part series, we look
at where science is taking treatment of depression, a mental illness that
afflicts one in three people during their lifetimes.

Emotions have a biology all their own. Scientists have mapped it. Drug
companies have made a six-billion dollar industry of it. And Jennifer M., a
20-something Madison native, came face to face with it a couple of years
ago. "I was going through a horrible, rocky relationship time," she
recalls, "and I just could not get out of a funk. A friend called me up one
weekend and said, 'Maybe you really should talk to your doctor.'" A
self-described "queen of the self-help books," Jennifer was reluctant to
see a physician for such a non-physical problem.

But when her doctor explained that the depression that had laid siege to
her brain was indeed chemical - and treatable - Jennifer followed her
doctor's orders faithfully. For a year, she saw a counselor regularly and
took an anti-depressant daily. Her self-confidence and naturally
even-keeled disposition gradually returned, and she has sailed on with her
life. Today she looks back on that time as "the year that saved my life."

About 21,500 Dane County adults suffer from depression, according to
National Institute of Mental Health estimates. The bad news is that far too
few of them are Jennifer-type success stories. They don't seek help to
begin with, and only one in 10 sees a psychiatrist. Or the drugs they're
prescribed don't work - experts say the symptoms of one-third of depressed
people don't respond to any medications currently available. Or their
insurance coverage runs out midway through psychotherapy. They struggle in
stigmatized silence, costing their employers hundreds of thousands of
dollars in sick time and putting themselves at risk for all kinds of other
illnesses and even death - depression remains the leading cause of suicide.

Yet, what's also true is that depression is more treatable than ever. The
newest drugs are more effective and have fewer side effects. Physicians
like Jennifer's are more informed on how to diagnose depression and
recommend treatment. The stigma is - slowly - fading, and more people who
need help are more likely to seek it. Without a doubt, there have been
remarkable advances in understanding and treating depression during the
past two decades.

But, say researchers, a lot of that progress will soon fall away like a
used-up booster rocket, thanks to explosive new discoveries in what causes
- really causes - depression. At sophisticated labs all over the country,
and especially here at the University of Wisconsin Health Emotions Research
Institute, hard-charging investigations unlock more of the brain's
emotional puzzles daily, suggesting that there are new and vastly better
ways to treat depression - and possibly cure or even prevent it - than
those currently considered state-of-the-art. Now researchers are racing
time to translate those findings into treatments that will be available
when people need them most.

Consider once again, for example, the Baby Boomers. The largest population
swell the nation has ever seen, the Boomers have been in a medical version
of the right place at the right time for most of their lives; an amazing
variety of their diseases have been cured and disabilities eased. Even as
they begin to age - one-fifth of the population will be 65 and older by the
year 2020 - their doctors stand ready with artificial hips, angioplasties,
arthroscopic surgery and more. But the Boomers will also become more
susceptible to geriatric depression as they age, and it's not clear whether
the innovative research will coalesce in time to be of much use to them.

"This gets particularly interesting in the presence of an aging
population," says Dr. Ned Kalin, University of Wisconsin Medical School
Hedberg Professor of Psychiatry and Psychology, of the research he directs
as head of HealthEmotions. "Certainly as people age they have more
likelihood of having medical problems, disabilities, loss of function.
They're more likely to face the loss of a spouse or partner. All these
things contribute to depression. There are going to be more people who are
getting older and who will be more likely to be depressed."

And, because mental health and physical well-being are linked more closely
than even Norman Vincent Peale might have imagined, the health care
consequences of depression could reverberate ever louder in the coming
years. Depression occurs, for example, in only about 5 percent of the
healthy adult population, but in people with old-age illnesses, such as
arthritis and heart disease, that figure jumps to anywhere from 25 to 50
percent. Researchers have discovered that depression may symbiotically
worsen or even help cause such conditions as well.

"These are very important issues in an aging population," says Kalin,
"because not only do you want to be thinking about preventing illness, you
also want to prevent depression because it increases medical problems. It's
a chicken-and-egg thing."

Building A Better Pill

According to a 1999 report published by Bergen Record Corp., the most
popular anti-depressants available today - Prozac, Zoloft and Paxil -
target the way the brain processes serotonin, an emotion-governing chemical
long known to figure prominently in depression. The newest drugs, like
Vestra, target norepinephrine, on the hunch that some 20 percent of
depression is related to this particular neurotransmitter. While another 20
percent of depression is serotonin-related, the drug industry has theorized
that the remaining 60 percent of people suffer from a depression that has
to do with a mixture of the two. As a result, physicians are beginning to
prescribe medications in combination as a first treatment step rather than
trying them sequentially to see which one, if any, will work.

Meanwhile, research at Health Emotions is showing that the current drugs
may actually work harder on the symptoms of depression than they do on the
cause itself.

"Serotonin is important," says Kalin, "but not the essential element. CRH
is a brain chemical that is much more closely related to the cause of
depression, and that likely is at the heart of the problem, than is
serotonin. "A medication to adjust the stress-related CRH," says Kalin,
"would work much faster and better to bring relief from depression."

Will such a drug be invented? We're working on it, say the experts. "There
are a number of projects under way to see if you can develop specific
medications to block the effects of the hormone that starts the stress
cascade," says Dr. John F. Greden, who runs the University of Michigan
Depression Center. "So instead of trying to treat the depression that comes
later by changing neurotransmitters that have already been altered, this
would be a strategy to alter things at the front end."

Even when it does arrive, though, it's certain to be a cure - but not a
cure-all. Researchers have picked up many of the threads of how depression
forms and festers, but they're still in the process of unraveling this
tangled knowledge. Scientists have known for years, for instance, that
there are different types of depression, which in turn have different
causes and results. Pinning them down and developing the right therapy for
each is a different matter.

Depression can be caused by alcohol abuse or drug addiction, for example,
but it will differ in how it changes the workings of the brain from the
depression that may have actually sparked the "self-medicating" addiction
in the first place. The symbiotic relationship between depression and
addiction is increasingly understood as a profound one. "It's pretty
straightforward," says Sherry Martin, a top-level certified alcohol and
drug counselor who assesses the severity of teen-age substance abuse as
part of her work at the UW Adolescent Intervention Program. "Of my
caseload, probably 25 percent to 33 percent are people who are clinically
depressed and self-medicating with substances."

Drug-related depressions, in turn, differ from hormonally linked
post-partum depressions and from the post-adolescent depressions that
strike girls three times as often as boys. There is also the depression
that is thought to be caused by age related changes in the brain's
hippocampus and the stress-related depression that strikes with illness or
loss.

"The work that's going to be crucial is in parsing the homogeneity of
depression," says Richard Davidson, a UW-Madison psychologist who directs
the W.M. Keck Laboratory for Functional Brain Imaging and Behavior. "Saying
depression is a single disorder would be like saying cancer is a single
disorder. It's very clear from the research that depression has subtypes."

That's the reason pills or psychotherapy make some depressed people feel
better but not others. It has also led to some serendipitous breakthroughs
on what does work, if not why it works. One of these occurred a few years
ago when doctors noticed that certain epilepsy medications seemed to
relieve depression in some of their patients, even when the patients'
seizures weren't prevented. As a result, the drugs are currently being
given in clinical trials to people diagnosed with depression but not with
epilepsy, and the early results indicate that it is actually quite an
effective treatment. It may prove especially important for Boomers in light
of a recent study showing that clinically depressed older adults are six
times as likely to have a seizure as their non-depressed peers.

Finding The Cranial Sore Spot

What's on the horizon - and Kalin, Davidson, Greden and others say they can
already see it from where they stand - are increasingly fine-tuned
medications and increasingly high-tech diagnostic tools and treatments,
thanks to breakthroughs in computerized technology.

MRI and PET scans let researchers actually watch computerized images of the
brains of people who are depressed. Researchers can see metabolism and
blood flow. They can track electrical impulses. Soon, they'll even be able
to tell how much serotonin or CRH is concentrated and in which part of the
brain. And, thanks to the mapping of the human genome, scientists can see
more clearly than ever the genetic links to depression.

"I think we're going to be able to develop more specific interventions that
are based upon what we know is wrong with the brain," says Davidson.
"Drugs, for example, affect chemical systems throughout the brain. They're
not terribly specific." As scientists learn more about the different
components of emotional circuitry, Davidson envisions the development of
medication that will act only upon a given sore spot in the brain. A
pacemaker-like device that uses electrical pulses to stabilize people with
epilepsy is already being investigated for use in treating depression. The
therapy is called vagus nerve stimulation, and in a recent pilot study it
helped 40 percent of the patients who tried it. It may be reviewed and
approved for treatment of depression by the end of this year.

Transcranial magnetic stimulation is a high-tech answer to traditional
electric shock therapy, which has always shown some promise in treating
severe depression but requires anesthesia and has serious side effects.
TMS, though, uses an electric current and an electromagnetic coil to
depolarize neurons in the brain, so it's painless and has no known side
effects. Presently being evaluated as a treatment for depression in several
studies worldwide, TMS will be in use here, Greden estimates, within a year
or two.

Much of the research will also improve low-tech treatments for depression,
such as cognitive behavioral therapy and talk therapy, predicts Davidson.
"It will help us to better design behavioral interventions that may affect
very specific areas of the brain," he explains. "We shouldn't think of
behavioral treatments as any less biological." Indeed, psychotherapy is
expected to remain an important treatment component; not only is it a
drug-free way to create healthy biological and chemical change in the
brain, it is crucial in helping reduce the impact of stress-related depression.

The other promise of technology lies in diagnosing depression; advancing
research may well allow doctors of the future to find it in a patient just
by performing a simple lab test. Technology will undoubtedly create the
ability to screen for depression - Kalin has said he'd like to see this
done in childhood - as well as to predict it and possibly prevent it.

"Inevitably, we'll have medications that attempt to turn off certain genes
that get and keep depression going," says Greden," and to turn on certain
genes that actually promote well being."

Along with the coming bulge in depression rates that the aging Boomers will
cause, overall rates of depression are expected to rise - not because more
people are expected to become depressed but because more of the ones who
already are will be diagnosed.

A key aspect of whether any of them will get the help they need, though,
will be their willingness to seek it. "Most people don't start with the
viewpoint that it's an illness," says Greden. "They don't necessarily
believe that it's treatable." With research-driven advances in dealing with
depression approaching warp speed, says Greden and others, it's a good time
for people to start changing their minds.

Mary Feingold is a senior writer for Madison Magazine.