Keeping Tabs on the Serotonin Theory of Depression

Jonathan Leo, PhD / Jeffrey Lacasse, PhD
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In 2008, Philip Cowen published an essay in Trends in Pharmacological Sciences. His essay leads off with the provocative question, “Serotonin and Depression: Pathological mechanism or Marketing Myth?”  To be honest we are not exactly sure on what side of his question he comes down on.  Does he believe that low serotonin is the cause of depression or does he think it is a marketing myth? In his paper he refers to our essay about the disconnect between the advertising and the scientific literature, and in his introduction he appears to put little stock in our thesis.  In his words:

  1. “Some have argued that the 5-HT  hypothesis has been misused by the pharmaceutical industry to promote a simplistic biological model of depression to market selective serotonin reuptake inhibitors (SSRIs) to medical practitioners and the public.”

Since apparently he does not agree with those who come down on the side that the serotonin theory has more to do with marketing than science we assumed that his essay would be a defense of the science. However, as we continued reading we discovered that he provided little scientific evidence in support of the serotonin theory.  In fact when it comes to discussing the evidence in support of the theory, we see little difference between his essay and ours.   For instance, both essays point out that, in contrast to discussions in the popular press, evidence of efficacy does not equate to the idea that low serotonin is the cause of depression.  And both our papers summarize the tryptophan depletion studies and point out similar problems with this line of research.  Namely, that while tryptophan depletion causes depression in recovered depressives, in healthy people it does not cause depression.  The tryptophan depletion studies are rarely used by the press to support the serotonin theory.

One area that we and Dr. Cowen disagree on is his characterization that, “unmedicated depressive patients have abnormalities in aspects of brain 5-HT activity.”  His statement seems to imply that the technology is available to identify a physiological or anatomical marker that differentiates the brains of depressed patients and normals.  We are not aware of any such technology. However, Dr. Cowan apparently does share our view that, even if such a marker was available that it would not automatically lead to proof of causation.  Stressful environments certainly lead to physiological changes, but determining whether those physiological changes caused the depression is much more complicated.

Besides the overlap between the two papers, Dr. Cowen goes beyond our paper and points out further problems with commonly used arguments in support of the serotonin theory.  In our paper we did not discuss the problems with using genetic theories in support of the serotonin theory.   We are pleased that Cowen did point out the problems with using the genetic theories as support for the serotonin theory, as these are often cited in the main stream press.

Since both essays are remarkably similar when it comes to discussing the evidence, we are not exactly sure where Dr. Cowen disagrees with us.  The only conclusion we can come to is that we disagree about who is at fault for the theory becoming such an acceptable and unquestionable theory in the main stream press and popular culture.  Dr. Cowen does not think this is the fault of the pharmaceutical companies but he has not said whose fault it is.

(Note: We wrote this as a letter to the editor but were informed that the journal does not publish letters)