A Psychiatrist Weaving Conceptual and Empirical Work

CONVERSATIONS IN CRITICAL PSYCHIATRY

Kenneth S. Kendler, MD, is the Banks Distinguished Professor of Psychiatry and professor of human genetics at Medical College of Virginia, Virginia Commonwealth University. Kendler received his medical and psychiatric training at Stanford and Yale University, respectively. Since 1983, he has been engaged in researching the genetics of psychiatric and substance use disorders. He has utilized methods ranging from family studies to large-sample population-based twin and adoption studies to molecular genetic studies, including linkage, genome-wide association studies, and whole genome sequence aimed at identifying specific genes that influence the vulnerability to a variety of psychiatric disorders. Since 1996, he has served as director of the Virginia Institute of Psychiatric and Behavioral Genetics. Kendler has received numerous national and international awards and is an editor of the journal Psychological Medicine. He played an active role in developing DSM-III-R, DSM-IV, and DSM-5 (for which he chaired the Scientific Review Committee), and he is currently the vice-chair of the American Psychiatric Association DSM Steering Committee. He has published more than 1200 articles. Dr Kendler is one of the highest-cited researchers in psychiatry: according to Google Scholar, his academic work has been cited nearly 170,000 times, and his H-index is 196.

Although Dr Kendler is internationally renowned and highly respected for his work in psychiatric genetics, he has been further catapulted into fame over the past 2 decades through his widely read commentaries on the philosophical foundations of psychiatry. I recently had the pleasure of reading the book Toward a Philosophical Approach to Psychiatry: The Writings of Kenneth Kendler. The book is a selection of 21 of his most important philosophical and historical papers published throughout his career, addressing topics such as the classification and nature of mental disorders, mind-body relationship, causality and explanation in psychiatry, and historical studies in psychiatric nosology. My admiration of Kendler is no secret at this point.

AFTAB: I really like your description of how psychiatric nosology sits in a historically contingent developmental arc. How is this history relevant to ongoing nosological debates in psychiatry, and how has ignorance of this history impeded our efforts at making progress?

KENDLER: With respect to psychiatric nosology, there is quite a bit of truth to 2 worn maxims: (1) If you don’t know where you have been it is hard to see where you are going, and (2) if you don’t know your history, you’re are at high risk to repeat your prior mistakes. So, I think history can provide a context and a background for what nosology can do and where it has taken wrong roads in the past.

AFTAB: I read that you collaborated with a translator to obtain English translations of Kraepelin’s previously untranslated works. Will these translations be published or see the day of light in some manner?

KENDLER: They are all sitting on my hard drive, and that of the translator Ms Astrid Klee, but there is a lot more there than just Kraepelin. A very small percentage of the relevant German psychiatric literature of the late 19th and early 20th centuries have been translated. I have thought about trying to set up a website to make these widely available. That will take time, energy, and a bit of resources. If any of these readers want to help, be in touch.

AFTAB: You have argued for a scientific pluralism where there are multiple explanatory perspectives available to us to understand psychiatric disorders, and one perspective cannot be reduced to another perspective. You describe your pluralism as empirical and hard-nosed, by which you mean that risk factors must earn their place at the table. It is a little unfortunate that many discussions of pluralism in psychiatry tend to get stuck in debating the merits and demerits of the biopsychosocial model. For the most part, you have managed to stay away from those controversies and have successfully charted a course for pluralism independent of any baggage that the biopsychosocial model brings. Is it time for our field to abandon the biopsychosocial model?

KENDLER: Its core idea was on target, but its implementation was so non-specific as to blunt any rigor it might have once had and its ultimate utility. I would not mourn its passing, but it did some important historical work.

AFTAB: DSM-5 defines mental disorder as a syndrome that, among other things, “reflects a dysfunction in the psychological, biological, or developmental processes underlying mental functioning.” What is the intended meaning of the term dysfunction? Did the members of the DSM committee have any clarity or consensus regarding what it means?

KENDLER: The hope that we could have a crisp set of inclusion and exclusion criteria for what constitutes a psychiatric dysfunction is a wonderful idea but (in my view, not for lack of trying) impossible. There are too many social and conceptual nuances. So, although there is a general idea of what dysfunction means, operationalizing in the way that would give substantial sharp precision to the definition has not proved possible.

AFTAB: Could you articulate what that general idea of dysfunction is? I am also interested in whether dysfunction necessarily implies that the locus of the problem is primarily inside the individual and not in interpersonal relations and social context? And, if there is such an implication, does this relegate interpersonal and social causal risk factors to a more secondary status?

KENDLER: The general idea of dysfunction is commonsensical—that the relevant psychobiological system is not doing what it is supposed to do. Examples might include providing your higher centers with an approximately veridical sense of the world around you, keeping levels of anxiety roughly appropriate to the real dangers being confronted, producing mood states approximately congruent to the environmental situation, etc. The DSMs have traditionally seen disorders as existing within individuals and, for example, avoided providing diagnoses for dysfunctional marriages or families. So, in that sense, the underlying disturbance is seen to exist within individuals. I do not see that definition having much of anything to do with the causes. Environmental experiences like severe childhood sexual abuse can clearly cause dysfunctional mood-modulation systems as well as a high genetic vulnerability.

AFTAB: To what extent is the dappled distribution of causal risk factors of psychiatric disorders a result of the heterogeneity of constructs? For example, a discussion of the distribution of causal risk factors of chronic fever disorder is not likely to be very meaningful. Furthermore, it is true for major depressive disorderas a category that no single causal risk factor has dominant explanatory power, but it may be the case for specific individuals with depression that there are causal risk factors of large explanatory power. What are your thoughts?

KENDLER: I don’t buy it. Most psychiatric disorders are, I think, multifactorial all the way down. I also think that for a few affected individuals they do suffer from disorders largely as a result of one major cause. I sometimes call your model the mental handicap model. Imagine you were a physician in the mid-19th century caring for what would then have been called idiots or imbeciles. If you could apply modern diagnostic methods to that group, a fair proportion would have a range of specific causes: Down syndrome, fragile X, a host of autosomal recessive disorders impacting on all kinds of brain-relevant genes that, when mutated, produce widespread central nervous system dysfunction, a range of small deletions, and a whole bunch would be nonspecific multifactorial. That is, a lot of your cases (but far from all) would have largely monocausal conditions. This has been long postulated for psychiatric illness. It has, in my judgment, been largely a pipe dream. I think that lesson applies more broadly.

AFTAB: Your philosophical writings are published and featured prominently in leading American psychiatric journals, which do not usually publish articles related to philosophy of psychiatry. I have wondered if one of the reasons mainstream journals are so receptive to your philosophical work—aside from the undisputed academic quality and rigor—is that your conclusions do not threaten or destabilize the status quo in a way that conclusions of some of the other philosophical commentators do. It was interesting to me that one of your more controversial articles—on the dopamine hypothesis of schizophrenia—was also the one that had a difficult time getting accepted. Why are leading American psychiatry journals publishing so few philosophical articles and so afraid of controversy?

KENDLER: I have made a deliberate attempt over the past 15-plus years to try to crack open the leading psychiatric journals for articles with a primary philosophical and/or historical content.

I agree with you that my ability to do that has been, in part, a result of the fact that I have achieved some standing in empirical areas of psychiatric research. To be vernacular, I have accumulated some street cred. I also think the papers were written in a way the audience could understand and that spoke to their concerns. I did not consciously edit the papers to make them less controversial. I still think that nonscholarly issues impacted on the problems we had with the dopamine hypothesis paper—that was perhaps a special case. I do not want to blow up psychiatry. I believe quite deeply in our clinical and research mission, but we surely can think more clearly about a number of issues in our clinical work, nosology and research.

AFTAB: Some critics hold the view that if a classification can be misused, it will be misused. To what extent should the concern for misuse constrain classification decisions? Do the creators of DSM have a responsibility to make academic as well as public educational efforts to reduce the ways in which the diagnostic manual is misunderstood and misused?

KENDLER: Our primary responsibility on DSM is to our patients and the research community that we assist. But possible misuse does, appropriately, arise in nosologic debates. For example, it played a key role in the opposition to the late-luteal-phase dysphoric debate in DSM-IV—that the diagnoses would be used in ways prejudicial to women. So, it would be unrealistic for DSM to ignore completely the possible misuse of the document. But, if the chips are down, I think serving our patients and research is the more important mission. It is impossible to control all the possible misuses of DSM and, if you took that concern too far, it would be paralyzing.

AFTAB: You have argued persuasively that the conditions we call psychiatric disorders are not merely constructed by individuals and cultures, and that these conditions have some basis in the objective reality, but what do you say about the construct of mental disorder itself? To what extent are concepts of health and disease, and characterizations of disorder grounded in objective reality?

KENDLER: As an aggregate concept, I think psychiatric illness (or mental illness) is a real thing out in the world. Going from that to specific disorders, be it schizophrenia or narcissistic personality disorder, that is harder, and the role of social construction or historical accident becomes greater. A metaphor (not my own) is to imagine rewinding the tape of history, say, to 20 centuries BCE and re-running it 100 times until society and medicine developed enough to establish something like what we call psychiatry. I would bet that some construct like insanity/schizophrenia would be there almost all the time. I would not say that for a number of more specific disorders in our manual.

AFTAB: You have stated that psychiatric disorders are multicausal, similar to how coronary artery disease, hypertension, and type 2 diabetes are multicausal in medicine. Multifactorial disorders can still have final common pathways onto which those risk factors converge, and those final common pathways provide a lot of explanatory power.

For example, multiple causal risk factors for diabetes converge onto insulin production or insulin resistance. Do you imagine that various causal risk factors for psychiatric disorders also converge onto final common pathways? If it turns out that psychiatric disorders are more like homeostatic property clusters, then it may very well be the case that there may be no final common pathway. In that situation would it still be fair to say that psychiatric disorders are multicausal in the same way as diabetes mellitus is?

KENDLER: Great question and topical. I have been involved with a research team trying to determine the biological coherence of the signals emerging from genome-wide association studies. This is a question rather closely related to the one you pose. I guess my main answer is “I hope so.” As you note, that is the case for lots of other complex disorders. To be a bit more precise, I think it is realistic that our “big” syndromes (eg, schizophrenia, alcohol use disorder, depression, anxiety disorders) reflect broad syndromes with some meaningful subtypes within them for which different therapies might have different success. It is awfully optimistic to think that all of them go through one tight final common pathway at which an intervention, properly designed, could be nearly curative for all cases. But similarly, the idea that there are hundreds of kinds of each disorder, each with its own needed therapy, is both very pessimistic and likely unrealistic.

AFTAB: You may not remember during the 2016 American Psychiatric Association Annual Meeting, I approached you nervously after a session to express my admiration of your philosophical work. I was a second-year resident at that time. You gave me advice that was something along the lines of “It is very important that you read a lot and that you read very widely.” That often comes to my mind because every day I discover that there is so much more to learn. I am impressed by how you have managed to apply ideas from other areas of philosophy of science to psychiatry. Given that you have limited time, how do you prioritize and decide what you will read?

KENDLER: There is never enough time to read everything of interest; I often think of the metaphor of trying to drink a waterfall. I am rather disciplined in what I read. I am good at skimming, and if the first 20 pages don’t look good, then I bail. The older I have gotten, the less patient I am with philosophical books written for other professional philosophers, filled with philosophy-speak. If they are not interested in communicating with me, I have to be very, very interested in what they are saying to soldier on.

I read 5 or 6 books at once. I am now reading about the history of genetics and cannot get enough of it. I read very little fiction. But I do keep up other lines of reading, usually late at night, that help keep me rounded, or listen to Audible when I bike or commute. Recently, I have been reading more history of psychiatry than philosophy. I have lots of bookshelves at my home and work office, but I am running out of space.

AFTAB: This may be an unfair question: If posterity could remember you predominantly for either your research work in psychiatric genetics or your philosophical work in psychiatry, what would you prefer it to be?

KENDLER: I have to laugh—yes unfair—Sophie’s choice that I cannot answer. I hope I am remembered, if at all, as someone who has tried to weave together empirical and conceptual work. It has been a wonderful career, and the older I get, the harder it is to pull these 2 parts of what I do apart. My identity is with the whole of it.

Conversations in Critical Psychiatry is an interview series that explores critical and philosophical perspectives in psychiatry and engages with prominent commentators within and outside the profession who have made meaningful criticisms of the status quo. The opinions expressed in the interviews are those of the participants and do not necessarily reflect the opinions of Psychiatric Times^TM.

Interviews published in this series can be accessed at www.psychiatrictimes.com/series/critical-conversations-in-psychiatry.

Dr Aftab is a psychiatrist in Cleveland, Ohio, and clinical assistant professor of psychiatry at Case Western Reserve University. He has been actively involved in initiatives to educate psychiatrists and trainees on the intersection of philosophy and psychiatry. He is also a member of the Psychiatric Times^TM Advisory Board.❒

An earlier version of this article, Weaving Conceptual and Empirical Work in Psychiatry: Kenneth S. Kendler, MD, was published online ahead of print on May 26, 2020. -Ed