Probing into Depression

Research Blogging / by Dave Munger /

Deep brain stimulation, already established as a treatment for stubborn Parkinson’s disease, may also be useful as a therapy for drug-resistant clinical depression.

What would it take for you to allow a surgeon to probe deep into your brain to implant permanent electrodes that would administer behavior-altering electric shocks? Anyone undergoing brain surgery risks stroke and possibly death, and even if the surgery is successful there is the potential for infection, which would require even more surgery with all its attendant risks.

Tens of thousands already have electrostimulation devices implanted in their brains, and millions more may join them if the technique, called “deep brain stimulation” (DBS), gains wider acceptance. DBS was originally developed as a treatment for Parkinson’s disease, and it has been remarkably effective. The primary symptom of Parkinson’s is uncontrollable body tremors that can make it nearly impossible to perform basic daily functions like eating and drinking, writing, and even walking. An acquaintance of mine who has Parkinson’s opted for the DBS procedure and now functions perfectly normally—it’s impossible for the casual observer to notice anything unusual about how he moves. He went from being nearly incapacitated to being renewed as a healthy, fully functional person. Perhaps it’s no wonder that he was willing to submit to such an invasive procedure.

In DBS therapy, one or more electrodes the size of a spaghetti strand are precisely positioned in the patient’s brain, then connected by wire around the skull and through the neck to a pacemaker-like device, a neurostimulator, just below the collarbone. The neurostimulator is activated and deactivated by a magnet that the patient carries, so if a tremor is beginning to become disruptive, DBS can be self-administered in an instant, with near-instantaneous results. A video provided by the manufacturer of a DBS device shows how it works in ideal cases.

Now new uses for the treatment are being tested. One observed side effect of DBS for Parkinson’s is excessive happiness, to the point of uncontrollable elation—the sort of unhealthy, personality-changing reaction that everyone fears when they think of electrodes being implanted in their brain. Tuning the device can minimize this side effect, but its very existence suggests that DBS might be a useful therapy for clinical depression.

The problem has been that, while researchers understand how DBS prevents tremors, they don’t really know why it might work as an antidepressant. That, too, is beginning to change. The pseudonymous UK-based neuroscientist Neuroskeptic points to a study published in the journal Biological Psychiatry in October. “Depression” was induced in rats by forcing them to swim in a cylinder of water from which they couldn’t escape. The amount of time the rats spent immobile, not trying to swim, is seen as a measure of depression. DBS was applied, and, as expected, the rats spent more time swimming and less time contemplating the futility of their situation. What was interesting about the study is that rats swam more even when the brain cells in the area where DBS was applied had been killed. The only way the researchers managed to block the effects of DBS was to deplete the rats’ brains of serotonin. Not coincidentally, many antidepressants work by increasing serotonin levels in the brain.

“Joseph j7uy5” is the pseudonym of a psychiatrist at a US community hospital, who notes that DBS has been tested on a small scale for clinically depressed patients who are resistant to drug treatments. The success rates have been remarkable: Up to 60 percent of patients indicate a positive response, with 35 percent in remission after a full year. Joseph calls these results “astonishingly good”—remember, these are people who are apparently resistant to standard drug-based forms of treatment.

One huge benefit of DBS compared to other types of brain surgery is that it is fully reversible. The electrodes can simply be turned off or even removed if they don’t work or have adverse side effects. But still, the idea of brain surgery is a frightening prospect. Walter van den Broek is a Dutch psychiatrist specializing in treating depression, and two weeks ago he pointed to a new brain stimulation technique that doesn’t require invasive surgery. Instead of implanting electrodes deep in the brain, they are placed just inside the skull—a much safer procedure than full-on brain surgery. Three of five patients responded to the treatment—a similar success rate to the more-invasive DBS.

So if deep brain stimulation isn’t necessary to treat depression, is it possible that even less-invasive procedures might work? Another therapy that is garnering attention is transcranial magnetic stimulation (TCM), which uses an electromagnet to temporarily activate or deactivate regions of the brain without any direct contact. In 2008, the FDA approved the procedure for treatment-resistant depression.

But the pseudonymous blogger at the Clinical Psychology and Psychiatry blog is skeptical, pointing out that the study purporting to show TCM’s effectiveness may have been flawed. A large number of the study participants were excluded from the analysis and results, and there were key differences between the sham TCM and real TCM procedures that may mean the study didn’t have true placebo control.

Nonetheless, the tremendous success DBS has shown as a treatment for Parkinson’s disease and its early promise against treatment-resistant depression suggests that we’ll be hearing much more about electrostimulation of the brain in the future. As scientists learn more about these treatments, look for discussion and analysis of the results on ResearchBlogging.org.

Originally published November 11, 2009

Tags medicine neuroscience research technology

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