A yes or no answer

Abstract

Medical students are chosen, at least largely, for academic and scholarly potential, and most physicians enjoy reading and keeping up in the literature of their field. However, since medicine is a practical art, physicians read with the goal of updating their knowledge to maximize their treatment of their patients. The literature on biological pathophysiology of depression has expanded exponentially over the last 30 years, and physicians who completed their training in the 1970s, 1980s and 1990s have been faced with a huge amount of literature promising insights into depression, one of their most common areas of professional activity 1. Sophisticated molecular genetics, revolutionary imaging technology, erudite neuroendocrine analyses and numerous other approaches have strained the ability of many clinicians to feel that they are up-to-date in their field. In the last few years, a creeping feeling of doubt has entered the hearts and minds of numerous clinicians around the world as to whether the mountain of new data is really of any value to the clinical practitioner of psychiatry. The title of G. Hasler‘s paper, therefore, is guaranteed to attract a huge audience, as is appropriate for World Psychiatry. However, in my opinion, this paper does not bite the bullet and avoids giving an answer to its own question. The abstract states that antidepressant treatments should be tailored for individual patients and disease states, but nowhere in the paper does the author say how to do this. The conclusion relates to a table where the various neurobiological hypotheses are presented and an argument made against a unified hypothesis of depression. Fair enough. The paper goes on to state that “this encourages research on predictors of response” and that “the identification of reliable predictors will allow for the development of personalized medicine”. Promises, promises, promises. I had hoped this article was going to tell me whether we have any solid evidence of interest to clinicians now. Personally, I think the answer is no and that we must bravely face this fact. I share Hasler’s belief that depression is heterogeneous and his hope that future research will allow for better treatments. However, clinicians will be more honest with themselves, their patients and our society if we answer this paper’s question with a clear “no”. There is no genetic test, blood test, spinal fluid test or imaging test today that can aid in the diagnosis of depression. There are many findings reported in groups of depressed patients of changes in spinal fluid or blood metabolites or proteins or in brain functional imaging. However, few if any are consistently replicable. Many could be secondary to the powerful lifestyle changes induced by depression, such as weight loss, inactivity, and poor sleep 2. Even more important for a clinician to understand is that a mean difference reported as a finding in a research paper, even when highly statistically significant, often conceals a large overlap between patient and control populations that makes diagnostic use of the finding impossible. I have sometimes been told by those who agree with the previous statement that my views should be hidden from the public, so as not to endanger the prestige of psychiatry or our rightful share of research funding. Such an opinion, of course, has more to do with ethics and values than with science. However, the psychoanalytic tradition that the truth makes one free has always seemed to me even more relevant in biological psychiatry. Our trainees, patients and public are increasingly confused by contradictory claims to have found the biological basis of depression in genetics, imaging, neuroendocrinology, or neurotrophic factors. We must create a new style of discourse where research results, exciting as they are, are translated into a proper understanding of the long slow road we are likely to travel in order to understand depression pathophysiology 3.