We are glad that Dr. Alexander has looked into how the chemical imbalance theory has been portrayed. One question that we think his blog raises is: If the pharmaceutical companies and psychiatrists have not promoted this theory then who did? It is hard to argue that it has not become imbedded in pop culture? How did this happen? The misguided media? One thing that we would like to point out is that for the most part the terms “chemical imbalance theory” and “serotonin theory” are pretty much interchangeable in the popular press. Over the past several decades the profession’s focus has moved from implicating norepinephrine, to dopamine, to serotonin, to a combination of all three, or two, etc.. Some in the media use the term “chemical imbalance” while others use the term “serotonin imbalance.” And even then they all fall under the “biological theories” of mental illness. Of all the transmitters, serotonin has probably gotten the most credit simply because of the commercial success of Prozac. In our papers, whatever we have said about the serotonin theory applies equally to all the other transmitters. To say that an alteration in dopamine is the cause of depression is just as problematic as saying an alterations in serotonin is the cause. We imagine that when it comes to the companies, their belief in which transmitter is the most important is strongly correlated with the mechanism of the drug they are promoting. But more importantly, we think the way Dr. Alexander presented the theory is subtly, but importantly, different from how the theory was originally proposed. In the original presentation, the chemical imbalance was presented as the cause of the depression, but Dr. Alexander presents it as a result of the depression. I think there are very few people who would argue that emotional stress can lead to biological changes. However, this is not what the “chemical” or “biological theories” have stated. Here is how it is worded in Up-To Date: “Mood disorders, such as depression and bipolar disorder, are caused by chemical imbalances in the brain.” As Seymour Kety, the biological psychiatrist behind the schizophrenia adoption studies, stated: “there are now substantial indications that serious mental illnesses derive from chemical rather than psychological, imbalances” (See Kety, It’s Not All in Your Head, Saturday Review, 1976). Here is the wording from Nancy Andreasen’s 1983 book Blaming the Brain. The important point here is how she stresses that altered biology is the cause: “1) The major psychiatric illnesses are diseases. 2) These diseases are caused principally by biological factors and most of these reside in the brain. 3) As a scientific discipline, psychiatry seeks to identify the biological factors that cause mental illness. 4) The treatment of these diseases emphasizes the use of somatic therapies.” (See page 29 in her book for a more complete discussion). All of her statements are up for debate, yet she lays out a simplistic set of steps that leads readers to the idea that emotional distress is caused by faulty biology, which needs to be treated with a medication. Granted, she doesn’t use the word “chemical imbalance” in the above quote but in 1983 when it came to “biological factors” the dominate theories of psychopathology were in reference to transmitters. Later on in her book she refers to the Catecholamine Hypothesis as the “cause of affective disorder.” Her statements are very much in line with the famous Zoloft ad of the miserable ovoid creature with a chemical imbalance who is miraculously cured by a medication. We agree that when it comes how the profession currently discusses depression that it has moved beyond transmitters and onto other theories, such as alterations in circuits. However it is important to point out that just these are also only theories. As just one example of how comments about circuits have replaced the old promises of chemical imbalances, in a 2012 blog post Thomas Insel stated: “mental disorders appear to be disorders of brain circuits…” Yet, later on in the very same blog post he states, “In truth we still do not know how to define a circuit.” If it was wrong to tell patients that their depression was caused by a chemical imbalance, then it would seem to be wrong to tell them that their depression is caused by faulty circuits. For an excellent discussion of the Biomedical Model we recommend this paper by Brett Deacon titled: “The Biomedical Model of Mental Disorder: A Critical Analysis of its validity, utility and effects on psychotherapy research.” Available at: http://jonabram.web.unc.edu/files/2013/09/Deacon_biomedical_model_2013.pdf We welcome any evidence from Dr. Alexander that alterations in serotonin or any other neurotransmitters are the cause of depression.