Medtronic to Pursue Major Clinical Trial of Deep Brain Stimulation as Depression Treatment (Business Wire via Yahoo! Finance)

Medtronic to Pursue Major Clinical Trial of Deep Brain Stimulation as Depression Treatment (Business Wire via Yahoo! Finance):

Medtronic, which makes the devices used in many deep brain stimulation treatments, announced it would be launching a large study of the use of DBS in treating severe and intractable depreesion. If conducted well, this will be just the sort of study needed to see if the remarkable results of the Toronto group's small study can hold up/p>

Much Madness about Depression

Before I wrote my Times Magazine story on DBS for depression, several people (including myself) warned me I'd hear complaints about promoting psychosurgery. Those warnings proved fair, Letters to the Times and myself, as well as blogs, opined that the story was "trumpeting psychiatry's latest 'cure' for depression" (The Alliance for Human Research Protection); that the Times was "hyping yet another reckless and scientifically baseless approach for treating depression"; and that we should be doing more talk therapy (agreed) instead of surgery (not necessarily agreed; the latter doesn't rule out the former);

One letter writer, apparently thinking he'd caught me out, noted that a Times story by Benedict cary last October, "Can Brain Scans See Depression," reported that

"After almost 30 years, researchers have not developed any standardized tool for diagnosing or treating psychiatric disorders based on imaging studies."

These complaints assume that I'm hailing this experimental surgery as a cure to recommend — despite that the entire story, beginning with the first sentence, makes clear that the procedure is experimental, its results provisional, and its promise as a direct therapy limited, at best, to a few thousand severely ill patients:

[No] one sees this becoming the new Prozac. The procedure costs too much (around $40,000) to use on anyone who hasn't tried everything else. The appropriate candidates for D.B.S. probably number in the thousands, not the millions. Perhaps the most sensible worry is that if the thing works, doctors might use it too freely, as they tend to do with successful new treatments; witness the problematic boom in D.B.S. for Parkinson's.

In the end, the procedure's greatest clinical value may lie in inspiring less intrusive ways of tweaking key nodes — localized delivery of drug or gene therapies, or other means still to come. Such possibilities probably lie at least a decade away.

Now, that seems pretty plain. That it gets read as a trumpet call for depression's latest wacky cure speaks to how strongly people feel about the patchy history of psychiatry. What with Freud's more bone-headed theories, hack work like lobotomies, and the current excesses of the drug companies, there's plenty of reason for skepticism and anger. To treat shoddily the mentally distressed is malpractice particularly foul. But this DBS trial is being done carefully, using a reversible intervention proven effective and safe in tens of thousands of Parkinson's patients. (That the objections have to do with mental health treatment rather than tweaking the brain is suggested by the utter lack of outcry about the tens of thousands of Parkinson's patients. No one hollers about wiring them up.) No neurons are destroyed, and the voltage is low and affects an area about the size of a pea.

To paint this as kin to lobotomies and early, punitive shock therapy misses the mark.

The story did get some more thoughtful looks. The Neurocritic offers some interesting observations, and Liz Spikol's fascinating blog "The Trouble with Spikol" took notice, and Searchblog posts a lively personal reaction titled "I Am Not a Toaster.. And — my favorite — a concert pianist didn't like my orchestra metaphor.

Merging Genes & Mood Networks

Even as my
New York Times Magazine article about deep brain stimulation for depression went to press, a new study came out throwing more light on the "network model" of depression discussed in the article.

In the article I wrote about (among other things) how some interesting work by Andreas Meyer-Lindenberg has begun the work of linking genetic and neurochemical models of depression to the "network" model that's emerged over the last 5 to 10 years. As the article explains, the neurochemical model, which emphasizes levels of neurotransmitters such as serotonin (the focus of drugs like Prozac), has of necessity focused on brainwide effects so far, while the network or "systems" model focuses on the pathways between particular brain areas.

Meyer-Lindenberg is among those working to merge the two views, and the Times DBS story mentions a paper he did that found that genetic differences affecting the availability of serotonin, the mood-critical neurotransmitter affected by antidepressants such as Prozac, had particular effects in Area 25 — the brain area targeted by the experimental implants described in my Times Magazine story.

Now Meyer-Lindenberg has come out with another paper finding a similar dynamic. In this case, he found that a particular form of the gene — the “L” form — affecting levels of monoamine oxidase (MAO-A) made some people react to stress more violently and aggressively than others. One key difference was that people with the L version often showed more activity in their amygdalas, a mid-brain area associated with fear. (For more on the amygdala, see my story on Joseph LeDoux.) Fear and anxiety, of course, are crucial in depression; they seem to form much of the “active anguish” that William James speaks of, and that makes depression so hard to live with. This MAO-A L variant, though, seemed to turn that fear and anxiety outward.