People used to think that depression is a kind of personal weakness,
something you can will away. Research has helped lift the stigma
attached to it by showing that depression has measurable physical
effects. It raises the risk of heart disease, high blood cholesterol
and high blood pressure; in fact, the chance of someone dying after
a heart attack is 4 times greater if he or she is depressed. Our
understanding of what's actually going on in the brain during depression
has also taken remarkable strides. Researchers are now using this
new knowledge in the hope of changing the way depression is treated
in the future.
Advanced imaging techniques showing activity within the brain
have revealed areas that behave differently in depressed people.
This knowledge is guiding researchers in designing newer methods
for treating depression that target particular brain regions. In
one technique called deep brain stimulation, thin wires are surgically
implanted into an area called the subgenual cingulate region. A
small current run through the wires improved depression in a small
study. Such surgery may be impractical for large numbers of people,
but it proves the principle that a small electric current in this
area of the brain can help treat depression.
Another technique that doesn't require surgery is called transcranial
magnetic stimulation. In TMS, a small electromagnet rests on the
scalp and induces a current in the brain. The device can be fairly
well focused on specific brain regions and doesn't seem to cause
side effects. TMS has been promising in small studies, and a large-scale
NIMH-funded study is now under way to test it more rigorously.
Other research teams are making progress using molecular approaches.
Scientists were intrigued by the fact that it often takes people
days or weeks to get better with selective serotonin reuptake inhibitors
(SSRIs) even though these drugs work very quickly to block serotonin
reuptake from synapses. Dr. Husseini Manji, director of NIMH's
Mood and Anxiety Disorders Program, explained that we now know
these medications ultimately work by affecting signaling pathways
within neurons that alter gene expression.
The genes that account for the improvements these antidepressants
bring seem to be those involved in cell growth and survival. While
nerve cells in the brain don't die with depression, they do "shrivel
up," as Manji put it — they have fewer dendritic branches
and the dendritic spines onto which synapses are made. Drugs targeting
these neuroplasticity and cellular resilience pathways are now
being developed and tested. Manji is optimistic that new medications
will be available within the next few years.
Researchers hope that understanding the genes involved in depression
will also help doctors make better treatment decisions. Antidepressants
like SSRIs and talk therapy are currently the most common treatments
for depression, but different people respond differently to them
and doctors often have little guidance in designing effective treatment
regimens. Manji believes that as few as 4 or 5 genes might one day
enable doctors to predict, with a simple blood test, which treatments
will work best for which people.