Weaving Conceptual and Empirical Work in Psychiatry: Kenneth S. Kendler, MD

Awais Aftab, MD

Kenneth Kendler, MD

Dr Kendler is a highly respected psychiatrist and genetics researcher, who has been further catapulted into fame over the past two decades through his widely read philosophical commentaries. In this interview with Dr Aftab, he discusses his philosophical and historical approach to psychiatry.

CONVERSATIONS IN CRITICAL PSYCHIATRY

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..

Kenneth S. Kendler, MD, is the Banks Distinguished Professor of Psychiatry and Professor of Human Genetics at Medical College of Virginia, Virginia Commonwealth University. Dr 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, including schizophrenia, major depression, alcoholism, personality disorders and drug abuse and dependence. 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. He has received numerous national and international awards for his work. He is a member of the National Academy of Medicine. He is one of the two editors of the journal Psychological Medicine. He played an active role in the development of DSM-III-R, DSM-IV, and DSM-5 (where he chaired the Scientific Review Committee), and he is currently the Vice-Chair of the APA DSM Steering Committee. He has published over 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.

While Dr Kendler is internationally renowned and highly respected for his work in psychiatric genetics, he has been further catapulted into fame over the past two 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 (edited by Kenneth Kendler and Peter Zachar, Cambridge Scholars Publishing, 2019) and reviewing it for Metapsychology. The book is a selection of 21 of his most important philosophical and historical papers published over the course of his career. These articles address 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 Dr Kendler is no secret at this point. As I write in the review, “Kendler is one of a kind among his psychiatric peers: I am hard-pressed to think of any other living psychiatrist who has the breadth of historical knowledge, rigor of scholarship, excellence in research, and depth of philosophical understanding that Kendler possess.” In the review I also offer a summary of major recurrent themes that are present in Kendler’s philosophical writings. For readers unfamiliar with Kendler’s philosophical work, this interview is best read in the context of the book review.

Aftab: I really like your description of how psychiatric nosology sits in a historically contingent developmental arc. In your opinion, how is this history relevant to on-going 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 two worn maxims: i) if you don’t know where you have been it is hard to see where you are going and ii) 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 with fascination 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 now 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 have to earn their place at the table. It’s 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’ve 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” here? Did the members of the DSM committee tasked with this definition 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, while there is a general idea of what dysfunction means, operationalizing in the way that would give substantial sharp precision to the definition has not proven 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 common-sensical – 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. 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 disorder as a category that no single causal risk factor has dominant explanatory power, but it may be the case for specific depressed individuals 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-19^th 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 which when mutated produce widespread CNS dysfunction, a range of small deletions, and a whole bunch would be non-specific 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 pipedream. I think that lesson applies more broadly.

Aftab: You are widely respected in the field and that has afforded you a certain privilege to advocate for the need to take philosophy of psychiatry seriously. Your philosophical writings are published and featured prominently in leading American psychiatric journals, which don’t usually publish articles related to philosophy of psychiatry. I have wondered if one of the reasons why mainstream journals are so receptive to your philosophical work – aside from the undisputed academic quality and rigor – is that your conclusions don’t 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. What are your thoughts on why leading American psychiatry journals publish so few philosophical articles, are so afraid of controversy, and whether this needs to change?

Kendler: I have made a deliberate attempt over the last 15+ years to try to “crack open” the leading psychiatric journals for articles with a primary philosophical and/or historical content. I have, in the process, been substantially aided by some of the key editors. Nancy Andreasen (prior editor in chief of AJP) was quite supportive of a number of my early efforts and Bob Freedman who succeeded her and Julio Licinio (editor of Molecular Psychiatry) have also been sympathetic. Not every paper was accepted by a long shot, but they listened, were willing to send them out for review and accept a fair proportion.

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 non-scholarly issues impacted on the problems we had with the dopamine hypothesis paper – that was perhaps a special case. I don’t 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 the patients we care for 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’ve 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, or – if you want to go back a century or two – lunacy, insanity etc) 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” back 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’ve 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. Multiple causal risk factors in malignancies converge onto uncontrolled cellular proliferation. 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 – think 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 in my view likely unrealistic.

Aftab: I’ve always been a bit troubled by the realism assumed by your account of epistemic iteration . . . that there is “something out there” when it comes to psychiatric nosology, and that there is an “unambiguous solution” that can be aimed at. This sort of realism feels at odds with the rest of your work which often tries to demonstrate why psychiatry cannot aspire towards strong realism and why pragmatic factors are important. Given this sentiment, I was delighted to see Kenneth Schaffner’s commentary on epistemic iteration (in Philosophical Issues in Psychiatry II: Nosology), in which he discusses how epistemic iteration can also be understood from an anti-realist perspective. Has that interaction with Schaffner led you to reconsider the realist lens through which you have viewed epistemic iteration?

Kendler: Yes, I was at least partly mistaken in my first take on Hasok’s work. I still make beginner’s mistakes in philosophy. Ken Schaffner was correct that my main points were not critically dependent on the “hard” realism assumptions I made. So, the context of the work was a bit forgiving of my excess initial zeal and naivete. I have been very lucky to have a few well-trained philosophical colleagues who have corrected some of the naïve errors in things philosophical. Recall, I am an auto-didact in this field and I got started late. Therefore, there are big gaps in my knowledge base.

Aftab:Toward a Philosophical Approach to Psychiatry contains a wonderful biographical account of your life written by Peter Zachar, which provides valuable context for your philosophical work. It is mentioned in the bio that you did an outpatient rotation in psychotherapy with Irvin Yalom during your medical school. As someone who has been greatly influenced by Yalom’s work in existential psychotherapy, I am curious if working with Yalom has had any sort of a lasting influence on you.

Kendler: No, not a lot. He was kind to me as a medical student if a bit distant. I have read nearly all of his recent books of case histories – lovely writing, compelling stories. Temperamentally, it was clear to me early in my residency that I was better suited for individual psychotherapy than group or family work. So, I never really engaged with the group psychotherapy writings again in my training.

Aftab: You probably don’t remember this… during the 2016 APA 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 which 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’ve 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 only written for other professional philosophers – that are full of “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 in the history of genetics, cannot get enough of it. I read very little fiction. But I do keep up other lines of reading usually late at night, that helps keep me rounded or listening 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 – a Sophie’s choice that I can’t 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 two parts of what I do apart. My identity is with the whole of it.

Aftab: Thank you!

The opinions expressed in the interviews are those of the participants and do not necessarily reflect the opinions of Psychiatric Times.

Previously in Conversations in Critical Psychiatry

Relentless Warrior for Mental Health: Allen Frances, MD

The Structure of Psychiatric Revolutions: Anne Harrington, DPhil

Skepticism of the Gentle Variety: Derek Bolton, PhD

Explanatory Methods in Psychiatry: The Importance of Perspectives: Paul R. McHugh, MD

Chaos Theory with a Human Face: Niall McLaren, MBBS, FRANZCP

The Rise and Fall of Pragmatism in Psychiatry: S. Nassir Ghaemi, MD, MPH

Integrating Academic Inquiry and Reformist Activism in Psychiatry: Sandra Steingard, MD, and G. Scott Waterman, MD

Social Constructionism Meets Aging and Dementia: Peter Whitehouse, MD, PhD

50 Shades of Misdiagnosis: Susannah Cahalan

Institutional Corruption and Social Justice in Psychiatry: Lisa Cosgrove, PhD

The Impoverishment of Psychiatric Knowledge: Giovanni Fava, MD

Psychiatry and the Human Condition: Joanna Moncrieff, MD

Psychiatric Disorders as an Imperfect Community: Peter Zachar, PhD

Disclosures:

Dr Aftab is a psychiatrist in Cleveland, Ohio, and Clinical Assistant Professor of Psychiatry at Case Western Reserve University. He is a member of the executive council of Association for the Advancement of Philosophy and Psychiatry and 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 Advisory Board. He can be reached at awaisaftab@gmail.com and on twitter @awaisaftab.

Dr Aftab and Dr Kendler have no relevant financial disclosures or conflicts of interest.