Posted by A new book, Shock Therapy, has recently been published, which offers a contrarian take on the history of electroconvulsive therapy, or ECT. I haven’t read the book, but Barron Lerner reviews it in Slate:
The authors believe that electroconvulsive therapy is incredibly effective. And yet for decades, a severely depressed patient–even one on the brink of suicide–might not have been offered the therapy, or if her doctors had proposed it, she or her family might well have declined it. In explaining why, the authors demonstrate that though we may assume medical treatments get adopted or rejected based on objective statistics, in fact data are often misinterpreted and manipulated by outside influences that end up overpowering them.
Scientists are finally beginning to understand the precise mechanisms that make ECT such an effective treatment for severe psychiatric disorders. For the most part, it seems that ECT relies on the same cellular mechanisms as typical anti-depressants, like Prozac. All of these treatments work by increasing the production of a class of proteins known as trophic factors. (The serotonin story is vastly oversimplified, if not flat out wrong.) Trophic factors make neurons grow. What water and sun do for trees, trophic factors do for brain cells.
What does an up-regulation of trophic factors have to do with mood disorders? The simple answer is that nobody quite knows. But there’s some suggestive if preliminary evidence that trophic factors ease depression by increasing neurogenesis, or the birth of new cells, in the hippocampus. Here’s how I described the research in a 2006 article:
In December 2000, Ronald Duman’s lab published a paper in the Journal of Neuroscience demonstrating that antidepressants increased neurogenesis in the adult rat brain. In fact, the two most effective treatments they looked at–electroconvulsive therapy and fluoxetine, the chemical name for Prozac–increased neurogenesis in the hippocampus by 75% and 50%, respectively. Subsequent studies did this by increasing the exact same molecules, especially trophic factors, that are suppressed by stress.
Duman was surprised by his own data. Fluoxetine, after all, had been invented by accident. (It was originally studied as an antihistamine.) “The idea that Prozac triggers all these different trophic factors that ultimately lead to increased neurogenesis is just totally serendipitous,” Duman says. “Pure luck.”
But demonstrating a connection between antidepressants and increased neurogenesis was the easy part. It is much more difficult to prove that increased neurogenesis causes the relief provided by antidepressants, and is not just another of the drugs many side-effects. To answer this question, Duman partnered with the lab of René Hen at Columbia.
The research team, led by post-doc Luca Santarelli, effectively erased neurogenesis with low doses of radiation. All other cellular processes remained intact. If the relief from depression was due to changes in serotonin, then halting neurogenesis with radiation should have had no effect.
But it did. Hen and Duman’s data was unambiguous. If there is no increase in neurogenesis, then antidepressants don’t work in rodents. They stay “depressed.”
Duman and Hen’s work was greeted, as expected, by a howl of criticism. Mice aren’t people. The experiment was flawed. The radiation wasn’t specific enough. Robert Sapolsky, whose work on stress paved the way for much of Duman’s own research, is one of the most incisive skeptics. He argues that neurogenesis researchers have no plausible model for how decreased neurogenesis might cause the symptoms of depression. Why would having a handful fewer new cells in the hippocampus have such an effect? “The more expertise someone has about the hippocampus,” Sapolsky wrote in a review in Biological Psychiatry, “the less plausible they find this novel role.”
Since then, Duman has gone on to show that one trophic factor in particular, VEGF, seems to play a large role in increasing neurogenesis. (Although BDNF also seems to be important.)
Update: Vaughan has a typically superb summary of ECT’s history over at Mind Hacks.
In a nutshell, it [ECT] seems to be the most effective treatment for severe depression, seems to impair memory, is disliked and stigmatised, and is difficult to research. Most notably, as a patient, your mileage may vary. Some people have no benefit, some have huge improvement; some have no side-effects, some have ongoing difficulties. Most have some of each.
January 4, 2008
January 4, 2008
January 4, 2008
January 4, 2008
January 4, 2008