Klerman 1978: schizophrenia…

Posted on Monday 19 December 2016

Psychiatry was obviously ripe for the the medicalization ushered in by the neoKraepelinians and the DSM-III released two years after this article. Changes in reimbursement schedules, a burst of new psychotropic drugs certified by industry funded clinical trials, and a focus on neuroscience research soon followed. The disappearance of the public mental hospitals was matched by similar closings in the private sector. And the boundaries between academic psychiatry, guild organizations, and the pharmaceutical industry became increasingly indistinct.

In the period since this chapter was written, the large mental institutions closed for good, replaced, with the reinstitutionalization of many chronic mental patients in our jails and prisons. Psychiatry did indeed medicalize to the point that most psychiatrists became primarily involved in pharmacologic and other biological treatments. And the neuroleptic drugs used in the treatment of psychosis in Klerman’s time were for the most part forgotten, replaced by a string of new Atypical Antipsychotics.

Although The Evolution of a Scientific Nosology] is a broad commentary about nosology in general, it’s in a book called Schizophrenia: Science and Practice, sandwiched among a number of different perspectives [though it would soon become the dominant point of view]. Here’s what Klerman had to say about Schizophrenia in 1978:
What has been the influence of the disease approach on understanding schizophrenia? The neo-Kraepelinian answer has been another question: Does the concept of schizophrenia have any meaning, and if it does, what are the data that give it meaning? In other words, the concern has been with what one might call the epistemology of diagnosis; namely, what are the rules of the game? In the disease approach, there are six steps toward validating a concept of an illness such as schizophrenia.
  1. Define the theoretical bases with clarity. It is very important to make explicit the assumptions on which the many conceptual views of schizophrenia are based. But unfortunately much of psychiatric discourse until the middle of this century* has never moved beyond these theoretical debates. In order to move psychiatry beyond philosophy and into science, the second step must be taken.
  2. Translate the general concept into specific hypotheses that can be operationally tested. For example, what is the meaning of borderline schizophrenia? What are its components? How does it manifest itself?
  3. Put the hypothesis to empirical testing to determine its reliability. How well do several observers agree that a borderline patient does have ego deficits, is using splitting or denial?
  4. Subject the data to various statistical tests to determine whether we are dealing with one syndrome alone or a mixture of syndromes.
  5. Attempt to validate the statistics by follow-up studies, family and genetic investigation, correlates in childhood development, and so on
  6. Undertake epidemiological studies to ascertain the patterns of incidence and prevalence.
How well, then, does schizophrenia meet the criteria of a chronic disease in the medical model? It meets it well but not completely. Before one can conclude definitively that schizophrenia is a disease, conclusive evidence will have to be presented as to etiology and clinical course. While such evidence exists for many other disorders in psychiatry, it does not yet exist for schizophrenia — nor for many other clinical conditions with which medicine deals, such as hypertension, arthritis, and leukemia. That is to say, it is an obviously disordered state with multiple determinants in which there is not certainty as to the exact etiology. Moreover, schizophrenia as we now’ define it is similar to hypertension in that it is likely to comprise various disorders. As the specific etiological principles come into scientific investigation, we will probably reaffirm Bleuler’s concept of a group of schizophrenias. Nevertheless, it is likely that within this group of schizophrenias there is a core group that has a strong genetic component. This genetic factor creates a vulnerability that becomes manifest in psychosis when precipitated by environmental stresses.
In his introduction to the chapter, Klerman had said of Emil Kraepelin…
His textbook was significant in tlie history of psychiatry not because it was the first textbook of psychiatry but because it was one of die first to approach mental illness in terms of causation and etiology, using the principles of modern scientific medicine.
After classifying as many cases of mental illness as possible by etiology — those due to infection, to endocrine disorders, and so on — Kraepelin was left with a large group of patients whose psychoses began in young adulthood and went on for many years but who had relatively few deaths… Kraepelin proposed that these psychotic conditions with no established etiology be further divided into two groups, which he called “dementia praecox” and “manic-depressive insanity.” He justified this division on the basis of clinical features during the acute illness, long term course, and outcome.
… capturing the conundrum that continues to haunt these discussions – from among the psychotic cases with no established etiology, Kraepelin was a pioneer for approaching them in terms of causation and etiology. In the snippet from his section Schizophrenia as a Disease quoted above, he lays out a pathway to define such Diseases.

Most psychiatrists have traditionally accepted the disease model based on the syndromatic constellation and predictable course, suspecting a biological etiology to show itself sooner or later. The critics are less taken with the homogeneity of the syndromes [see a guest post from Sandy Steingard…], many seeing guild hegemony and medical training as unacknowledged complicating factors. That conflict is, if anything, more intense now than it was in 1978.

Gerald Klerman and the neoKraepelinians had an unprecedented impact on the subsequent course of psychiatry itself. On the other hand, the plight of the patients with the schizophrenias, particularly those with its chronic forms, have not seen much change in the four decades that followed.
    Bernard Carroll
    December 19, 2016 | 5:12 PM

    The US Neo-Kraepelinians came to their position late in the game. Having trained in Australia under teachers from the UK, I can say that the St. Louis model for major psychiatric disorders repeated what was already accepted widely outside the US for decades. And Frank Fish or Max Hamilton or John Wing would not have chosen Klerman’s example of borderline schizophrenia (now called borderline personality disorder) for illustration. They would have chosen what we used to call schizophreniform disorder – acute and often severe psychotic episodes in generally high-functioning young persons who go on to make very good functional recoveries. Those patients would be contrasted with those who follow a deteriorating course, and whose conditions used to be termed hebephrenia or simple schizophrenia.

    Another point, which Klerman did not raise, is what we can learn about the presumptive biological basis of schizophrenia from so-called secondary cases. There is a long list of general medical conditions that are commonly misdiagnosed as schizophrenia. A few examples are temporal lobe epilepsy, stimulant drug intoxication, porphyria, and Wilson’s disease. These look-alikes can be convincing enough to mislead examining physicians. It is interesting that Gerald Klerman overlooked this matter because, also in 1978, he published a much-cited paper on secondary mania. His co-author then was Charles Krauthammer, who is now a television pundit. Go figure.

    December 19, 2016 | 6:05 PM

    Charles Krauthammer! Amazing…

    Thanks for clarifying the Borderline Personality Disorder example attached to Schizophrenia.

    I stifled the impulse to go on a tangent about the issue of disease models in general. There are a lot more of them than are mentioned here. And models have the same relationship to real patients that model airplanes have to 747s – useful, but only as a starting place. Models are most useful for understanding the conditions where they originated, and lose power as they move from that center eg the concrete explanatory power of the medical model of appendicitis is much greater than it is when applied to psychotic conditions eg schizophrenia.

    December 21, 2016 | 2:33 PM

    Comparing schizophrenia to appendicitis is rhetorical. It is highly likely that schizophrenia is a polygenic illness and not comparable to a simple surgical process. Comparing schizophrenia to other polygenic illnesses is fair game and there are a long list of them. In every case there is no “lesion” per se and even endophenotyping has not led to any breakthroughs. I think that there has been significant progress in the treatment of schizophrenia in the past 40 years. Certainly on par with asthma treatment. I have not seen any younger patients with a lobotomy lately. Tardive dyskinesia is rare and when I started out 35 years ago – it was so widespread – I had a subspecialty in treating movement disorders. It is also recognised the ACT keeps patients functioning independently and that talking with patients helps – not in the Harry Stack Sullivan sense but straightforward supportive psychotherapy.

    I personally would not consider Klerman a primary schizophrenia researcher. I think that he is much more well known for interpersonal psychotherapy.

    I had the good fortune to have breakfast with one of my old mentors the other day. He is still active doing research and scaling down his clinical and educational endeavors. Over the decades we had come to the same two basic conclusions:

    1. It is all about the biology (no matter how you want to frame that).
    2. The last thing we need is another research proven psychotherapy – particularly when nobody can get current research proven psychotherapy due to managed care rationing. We both do psychotherapy.

    In a discussion of the final point he had just read an article stating the average number of psychotherapy sessions in health care systems is 1. I was more optimistic and thought is was about 3 or what was needed to do Viederman’s psychodynamic life narrative approach in crisis situations.

    December 21, 2016 | 3:39 PM

    Reading that last post from Dawson I would love to see a BMJ or Maudsley style debate between Dawson and Steingard. Or, on the topic of clinical neuroscience between Dawson and 1bom.

    Bernard Carroll
    December 22, 2016 | 1:01 AM

    George, you are right about Gerald Klerman not being a primary schizophrenia researcher. That didn’t stop him from expounding on the topic.

    Regarding my comparison of appendicitis and schizophrenia, does it really matter that one is polygenic while the other is a simple surgical disorder? My point was just about how to distinguish complications from essential features of the disorder.

    December 22, 2016 | 6:18 PM

    Barney – I was responding to Mickey’s use of appendicitis as a concrete medical model and not having explanatory power for complex polygenic illnesses. I am perhaps more sensitive to the medical model term than most:


    Like most things in medicine models are dynamic things – most research today is focused on complex phenomena that we could not dream about a decade ago. Now we know that being overweight changes your genetic code in a hundred places and smoking changes it in a thousand places. These are exciting times to be alive and studying the complex phenomena that psychiatrist have been trying to figure out for over a century.

    The medical model is not what it used to be.

    December 22, 2016 | 6:22 PM

    “I would love to see a BMJ or Maudsley style debate” –

    I would suggest pulling up Eric Kandel in the Nobel Laureate lecture and debate at Gustavus Adolphus. I think that they are all available on YouTube. The debate is on whether addiction is a disease or not – another favorite approach by the non-reductionists and non-biologists.


    December 22, 2016 | 7:37 PM

    Would love to hear Neuroskeptic’s take (if they still read the comments section here) on the references to having a “brain centric” view of the world.

    December 22, 2016 | 7:45 PM

    I would concur that much of the blame laid at the feet of the “medical model” is better laid at the feet of the priorities of the funding sources in the system.

    December 22, 2016 | 11:21 PM

    Medical model as defined by the Luddites does not take into account the scientific view of the world and medicine as a changing and dynamic field. For most people using the term it is whatever negative attribute that they want to give it.

    The common dynamic in every teaching/learning endeavor that I have participated in is that physicians want to know how things work and what they need to do to optimize and maintain systems.

    We are finally getting to the point where we realize what the systems are and the view of that landscape is breathtaking.

    December 23, 2016 | 1:13 AM

    “getting to the point where we realize what the systems are and the view of that landscape is breathtaking.”

    You either have a much better sense of the state of science than I, or a much greater sense of optimism as to where we are at in the arc of our collective understanding.

    December 23, 2016 | 11:36 AM

    “You either have a much better sense of the state of science than I, or a much greater sense of optimism as to where we are at in the arc of our collective understanding.”

    It is a sense of where we came from. In the 1980s, molecular biology as it applied to medicine was rudimentary knowledge of receptors, neuroendocrinology and Sutherland’s discovery of cAMP. There was a very basic understanding of nucleic acids. Now you can pick up a copy of the NEJM and read Kandel and Kandel’s article about how nicotine exposure leads to genetic changes that predispose to cocaine addiction and read thousands of articles on similar epigenetic changes.

    There is more relevant molecular biologic and neuroscience published in a couple of months these days than there was between 1980 and 2000. I don’t think it is a mystery or even optimism. I think it logically flows from advancing technology.

    December 23, 2016 | 8:54 PM

    “Advancing technology” is a term that could be applied far before 1980 and 2000. As has the logical assumptions in various eras of where we are in our relative understanding of the brain. That there is definitive evidence at this point of who is panglossian and who is Luddite is something on which I believe we would disagree. There have been many eras where it was believed that we had achieved a fundamental understanding of the “systems” in play and the rest was a steady march of filling in details. This has practical implications on how much money is funneled into the long game of basic research vs translation and 10 year “moon shot” programs. While this is not an either or you often point out that resources are finite. Of course the brain is fundamental. But the translation of “newer and newer” technology should be looked upon with as skeptical an eye as the development of new psychosocial approaches. Dr. Carroll speaks of moving the ball down the field. Researchers do. I remain unconvinced that championing breathless landscapes and that clinicians cannot be as effective without a deep understanding of neuroscience (at this juncture) is another issue.

    December 23, 2016 | 8:57 PM

    What I get for copying and pasting within the last sentence. Boy, mic drops work better (at least by a bit) when the sentence makes sense. Sigh
    Happy Holidays everyone. Hope it’s a safe and peaceful one for y’all.

    December 23, 2016 | 11:52 PM

    “I remain unconvinced that championing breathless landscapes and that clinicians cannot be as effective without a deep understanding of neuroscience (at this juncture) is another issue.”

    I think it is an exercise in futility to think that ideal clinical trials totally devoid of any conflict of interest are going to help clinicians mired in technology from the 1970s and even prohibited from using that by managed care companies.

    If you really think that sitting in an office and prescribing medications or psychotherapy from hopelessly inadequate clinical trials or the 3% of meta-analyses is the psychiatry of the future – that is certainly your prerogative.

    Part of the problem I have with that picture is that the people who maintain that posture complain about it all of the time and yet – that seems like where they are at. Blame drug companies, blame other psychiatrists for not being “good enough” or naive or easily bought off, blame specific researchers for conflict of interest, or critique new paradigms for some technical issue. The problem is not the inadequate technology. The problem is the way it is applied. If we had a perfect drug or psychotherapy trial – everything would be different.

    I don’t understand why all of the cynics don’t want something better. You don’t have to champion anything to side step the constant complaining. It is a breath of fresh air. Science by definition is continuous skepticism and an active process of challenging and rechallenging findings.

    Scientists by definition are skeptics.

    James OBrien, M.D.
    December 24, 2016 | 1:27 AM

    “Scientists by definition are skeptics.”

    That used to be the case when it was science and you didn’t have more journals that good scientists. I know far too many now who are zealots and careerists. Or just plain ignorant fanatics:


    Yes, Prof. Dworkin, that’s it. Women aren’t getting buffed like Arnie in 1973 because they hold back or the patriarchy or something. I’m guessing it’s another independent variable, a certain chemical beginning with a T, but what the hell do us peons in private practice know?

    December 24, 2016 | 6:58 PM

    Any intervention is going to be instantiated within the current system. Access to raw data, thus limiting the ability to juke the stats, and moving away from privileging RCTs as the ultimate source of information for clinical interventions is of importance. I do not view campaigns to try to do that as idle complaining. Whether that intervention is chatting in an office, a drug, an infusion, infecting someone with a genetically modified virus, an implant, whatever.

    To me this is not an either or situation. We get crapier interventions in practice in some part because of the reasons you have complained about (here and on your blog). At the same time, we have a system that has co-opted significant parts of the clinical testing and academic/publishing dissemination of information enterprise as marketing. Whether one argues that the RCTs that gird that system should not be treated as the gold standard they are, or simply that at the very least those RCTs be made more amenable to focused skepticism (such as RIAT), I think both stances are of value. Because otherwise the newer interventions will get funneled through the same system and that system is woefully inadequate to front line clinicians. On top of the enormous amount of damage already in place from managed care.

    Scientists are not by definition skeptics about those views that are their favorites. Appeals to “science” and “technology” don’t address the problems assessing clinical interventions the past 3 decades or so. Carroll and others decry changes that have happened in academic and NIMH culture during that time and I don’t think that just represents cynicism or a belief that there is no evolution in treatment to strive for. The perversion of clinical research, and the perversion of how that information is used, contributes to the problems in the way interventions (technology) are applied.

    To some of us the relative value of the psychiatric literature to front line clinicians has decreased over the past 30 years. To me restoring that value is a lot of what 1bom’s blog is about. That seems important, regardless of whether you or I have the better sense of the potential immediately available benefits of new technology translation.

    December 25, 2016 | 5:12 PM

    I’m only going to nibble around the edges of this debate, because I know I don’t yet have the chops for the main course, but…

    I’m not sure that the average number of sessions provided by managed care is quite so low (though I realize we’re dealing in back-of-the-envelope metrics.)

    I have no problem maintaining a 15 client-per-week caseload at our group insurance practice (three days per week), and I rarely see anyone for less than a half dozen sessions, more typically 12 to 26, and several clients are north of 30 sessions. It’s certainly true that some of those clients have to be relatively high-functional just to figure out how to get their carrier to pay for sessions, or realize that their carrier WILL pay for sessions, and some of them have to wait a while.

    The problem is, I can only manage to do that for a variety of reasons: I have a non-insurance private practice two days a week that pays better, I happen to work with an excellent group practice that employs a billing staff that roll like operatives for a well-trained counterinsurgency, I’ve only been practicing for a year, we bought our house in 1997, and– weirdly– in my later ’50s I seem to have developed the patience of a monk. I’m also well-enough capitalized that I can dip into savings when the insurance companies are slow to pay, and then top the accounts back up when the money starts flowing again.

    The larger problem is, I have so much damn paperwork I can’t do as mush research and consulting as I would like to.

    That’s why I often show up here: I need to refine my skills for ferreting out junk science and research so I don’t waste an instant of the little time I have to spend on EBSCO host or conferring with my long-suffering cohort.

    So let me just say how thankful I am that you guys are all still here and… kicking it, as my younger colleagues would say! Happy holidays and Merry Christmas to all!


    Sandra Steingard
    December 26, 2016 | 9:31 AM

    Dr. Dawson,
    What does it actually mean, or what are the implications, of “it’s all about biology”?
    I suspect people read into it that this means to help people we need certain kinds of treatments that are inherently “biological”. Perhaps not for you, but for many, this means some drug or procedure to fix the abnormal biology.
    But as you point out in later comments, modern conceptualizations of organisms accept that we are in a constant flux both internally and with our environment.
    The question of therapeutic intervention rests not so much on the particular etiology but at what level one wants to intervene.
    One reason I am drawn to practices such as Open Dialogue is that this allows for a framework that acknowledges the uncertainty and humility that seems appropriate for our field. That it also seems to hold some specific therapeutic action only adds to its appeal.
    There is also the issue of resource allocation. Our focus on what most consider “biological”, i.e., brain function, seems like an unfortunate missed opportunity for us to learn how to be more effective at helping people.

    Matty H.
    December 27, 2016 | 2:26 PM

    I believe that there is a fundamental philosophical problem in the psychiatric science that is, quite frankly, crippling it severely. I believe that for as long as this problem is not resolved, there will not be accurate explanations of psychological phenomena. This problem is philosophical materialism and is part of the general culture of the modern world. I have written this on another blog already, and I think it would be good to raise the point here as well:

    Here’s the problem: There isn’t a single element in the human brain that you don’t find in the rest of the universe. There isn’t a special type of atomic particle that makes these brains conscious. So how do we explain this?

    1.One idea is that of panpsychism. Every single particle in the universe is conscious in some way, it just becomes more complex when neurology is involved. But this is really a terrible way to explain the unitary nature of our individual minds. It’s a stretch to imagine that these small conscious particles could form our unified self-reflections. Not to mention our rationality, our values, etc. So I would intuitively say that panpsychism is false.

    2.Emergentism. The mind emerges out of complex arrangement of matter. So we can investigate which arrangements lead to this happening. But this is a lazy, ad hoc explanation. Why, exactly, should these arrangements lead to consciousness? No matter how it’s arranged, how and why should the material give rise to something so radically different from it, a subjective, self-aware experiencce?

    Now here are some viable explanations:

    1.Dualism: There are two fundamentally different substances that interact with one another.

    2.Idealism: There is only consciousness.

    Both of these are anti-materialistic, and as such, are not taken seriously in the current intellectual climate. And yet, that intellectual climate is nothing other than the triumph of ideology over common sense. It is completely intellectually, factually and logically bankrupt.

    There are people who can explain the problem better than I can, but I think that’s the gist of it.

    Bernard Carroll
    December 27, 2016 | 3:21 PM

    I am not sanguine that either dualism or idealism are viable explanations. One compelling reason is because consciousness tracks with brain complexity over evolution. Why or how could a more complex brain have conferred evolutionary advantage in a dualistic order or an idealistic order?

    A second reason comes from psychopathology. Just as general pathology teaches us a lot about normal bodily processes, so also psychopathology can teach us about normal operations of the mind. The clearest examples are in the realm of psychopathology associated with medical conditions and with brain damage or impaired brain development.

    Matty H.
    December 28, 2016 | 12:11 AM

    I don’t know about evolutionary advantage. If you’re referring to Darwinian evolution, it has serious problems and limitations of its own (and I accept that many will now call me a loon, but that’s life). Some type of evolution obviously exists, but I believe the Darwinian interpretation is fundamentally inadequate and missing something. For example, it simply cannot account for the rapid formation of new forms. That’s why you now have so-called evo devo theorists who question its validity (even though they assume the materialist position, usually). If Darwinism doesn’t fit reality, then so much worse for Darwinism.

    Also: Even if Natural Selection guides evolution, it can only explain why consciousness survived: it cannot explain how something so different from matter can arise in the first place. And we often do forget how fundamentally different the purely objective is from the subjective. For example, can you explain the redness of red using biochemical explanations?

    Oh and speaking of psychopathology, let’s take one extreme example: Near Death Experiences. Why is it that people who report such intense and life-changing experiences actually have minimal brain activity levels (by the way, the same is the case for tripping on psychedelics, as Bernardo Kastrup notes)? From a materialistic perspective, this makes no sense at all. And if you add reports where people report things that happened in the room they clearly would not be able to report “normally”, you start to a get a very interesting picture of the phenomenon.

    Then there is the extensive research on paranormal phenomena such as telepathy and other variants strongly indicating something very interesting is going on (e.g. Dean Radin is a good reference).

    Now add the Anthropic Cosmological Principle: The notion that if conditions were even slightly different at the beginning of the Universe, human life would never evolve. It is telling that Francis Crick, the co-discoverer of DNA (of all people!), was well-aware of the problem. He put forward the “directed panspermia” hypothesis, the idea that an advanced civilization from outer space planted the seeds of life on Earth, based on the premise that other planets had more favorable conditions for life to evolve much before ours (although even he admits that he has absolutely no hard data for such a claim).

    Also, here’s something Thomas Nagel has to say about congnition present in “higher” forms of life, and then later of the problem of value: “Just as consciousness cannot be explained as a mere extension or complication of physical evolution, so reason cannot be explained as a mere extension or complication of consciousness. To explain our rationality will require something in addition to what is needed to explain our consciousness and its evidently adaptive forms, something at a different level. Reason can take us beyond the appearances because it has completely general validity, rather than merely local utility. If we have it, we recognize that it can be neither confirmed nor undermined by a theory of its evolutionary origins, nor by any other external view of itself. We cannot distance ourselves from it….

    This, then is what a theory of everything has to explain: not only the emergence from a lifeless universe of reproducing organisms and their development by evolution to greater and greater functional complexity; not only the consciousness of some of those organisms and its central role in their lives; but also the development of consciousness into an instrument of transcendence that can grasp objective reality and objective value.”

    On value: “The most important metaphysical aspect of a realist view of practical reason is that consciousness is not epiphenomenal and passive but that it plays an active role in the world…Whether practical reason is emergent or reducible to activity at the micro level through some form of psychological monism, value realism requires consciousness to be active and rules out epiphenomenalism in human action.”

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