Philosophy of psychiatry: rhetoric or reality?

 

“If you laid all philosophers end-to-end it would be a good thing.”  Anonymous philosopher lecturing medical students somewhere in the Midwest in the 1980s. 

 

This post is a partial commentary on a paper about the philosophy of psychiatry (1) that was recently published.  Since I am not a philosopher and do not aspire to be one – I thank the authors for commenting on what they believe the key issues and limitations are. Over the years I have written about philosophical conjecture about psychiatry and consider much of it to be serious overreach. This paper will allow me to make some general observations.  The authors in this case have all published previous work on the subject and given the number of co-authors this is considered a state-of-the art review.  The review is open access and can be read at the link in the reference.

In their introduction the authors – consider metaphysical, epistemological, and ethical issues to be critical at the grey zone between medicine and philosophy.  They mention Karl Jaspers as a seminal figure in the field but emphasize their focus in the paper will be on conceptual competence defined as: “the transformative awareness of the ways by which background conceptual assumptions held by clinicians, patients, and society influence and shape aspects of clinical care” (2).  To their credit they explicitly comment on controversies about what the parameters of good philosophy are and whether progress is made over time.

Their first point is on the boundaries of disorder.  They make the usual observations about Kraepelinian and neo-Kraepelinian and conclude that “neo-Kraepelinians (NKs) claimed that precisely defined diagnostic criteria could be used to discover the specific biological causes of psychiatric syndromes and establish psychiatry as a branch of medicine.”  There is plenty of evidence that the NKs were much more sophisticated than that.  From one of their references (3): 

“The medical model is not based on any assumptions about etiology. It can accept social and psychological causes as well as physical and chemical events.  It can accept single causes or multiple causes.  It can even be applied when the etiology is unknown as in many clinical investigations.”

Guze specifies in several places that the diagnosis is for describing what is known about the patient and treatment planning. He suggests that medicine and psychiatry may evolve to provide more information on pathophysiology and testing but does not link it to diagnostic criteria apart from how it might be studied. He does not suggest that biological causes are necessary to establish psychiatry as a branch of medicine – his entire monograph is about why psychiatry is already a branch of medicine.

The next transition is to Insel and the RDoC.  The criticism seems to be that Insel was criticizing biological psychiatry but I doubt that any biological psychiatrist would see translational neuroscience as being inconsistent with a brain and biological centric psychiatry. The field is described as “lurching from one model to another”.  Excluding homosexuality as a diagnosis is given as a notable example of diagnostic controversy rather than psychiatry (specifically Spitzer) getting it right and leading society in general by about 40 years.  There are still plenty of people who have not caught up.

The first main section of their paper is the nature of mental illnesses.  They define strong naturalism as the factual and value free description of a disorder like what occurs in the natural sciences. They equate biological psychiatry with neurobiological dysfunction – even though those psychiatrists clearly had a much more sophisticated view of psychopathology.  I have quoted their reference to Guze above – here is an additional quote from prominent biological psychiatrists of the 20^th century:

“It should be emphasized…that the demonstration of…[a catecholamine] abnormality would not necessarily imply a genetic or constitutional, rather than an environmental or psychological, etiology of depression…it is equally conceivable that early experiences of the infant or child may cause enduring biochemical changes and that these may predispose some individuals to depressions in adulthood…[and] any comprehensive formulation of the physiology of affective state will have to include many other concomitant biochemical, physiological, and psychological factors.” (4)

That sounds like pluralism rather than naturalism to me.  There are several additional factors that suggest that the idea of strong naturalism is an exaggeration of the position of late 20^th century biological psychiatrists.  Some of those factors include: the concept of heterogeneity in diagnostic categories was widely known at the time, endophenotyping was introduced in 1966 as a purely biological concept (5) that was later applied to medicine and psychiatry (6).  Clinical trialists were certainly aware of heterogeneity and significant problems with recruiting patients into studies based on severity and placebo response.  The general comparison to medical conditions where a significant portion were idiopathic and had speculative pathogenesis and to this day are still diagnosed based on clinical description is an additional factor.  Any intern on medicine or surgery knows pathophysiology and the suggested mechanism of action of medications is typically speculative and no two patients with the same diagnosis are exactly alike.  A key concept in training is that physicians are required to recognize that pattern and make the necessary adaptations.

The authors introduce the definition of strong normativism as basically “no natural, objectively describable set of biological processes that we can characterize as “dysfunctional”, and hence disorder attributions are thoroughly value-laden.”  They do not elaborate – but this definition is clearly counter to the experience of any physician who has treated life threatening or severe illnesses.

Szasz is introduced at that point because of his suggestion that mental illnesses do not exist but rather represent “judgments of deviance based on sociocultural norms”.  They suggest that he is both a strong normativist and a strong naturalist rather than just being wrong.  Szasz’s philosophy (if that is what it was) fails several tests, but for the purpose of this post is probably the best example of controlling the premise rhetoric to prove a point.  The Szasz definition of disease as actual observable pathology allows him to trivialize any condition not meeting that criterion (and there are probably more outside of psychiatry than within) and call it a value judgment.  That is not consistent with diagnostic systems present before him or what historical neuropathologists thought (7).

What follows is a section on the naturalist-normativist debate including a table of the contrasting points. The basic problem with this dichotomy is that the normativist position as described by the authors is such a caricature when compared with medical and psychiatric training that it really cannot be seen as a viable position by anyone but Szasz.  They produce a couple of examples of hybrid positions as though they have never been considered in the past.  The description of Wakefield’s suggestion that dysfunction that is harmful to the individual is required for disorder, but since depression is an evolutionary response to adversity it is not dysfunction.  That ignores empirical research that suggests that it can be both as well as the problems associated with speculation in evolutionary psychology. The discussion of values in the normative model leaves out a lot and ignores psychiatric training. If the goal is to inform psychiatric practice by this kind of debate there are better ways to go. Psychiatrists walk into the room with a patient and their goal is to understand that patient well and treat that patient well. That involves communication skill, developing a therapeutic alliance, therapeutic neutrality, and providing the patient with enough information so that they can provide informed consent.  That interaction is both scientifically and professionally informed.

The next concept the authors discuss is essentialism or the idea that naturally occurring kinds have an evident essence. They acknowledge that when it comes to medical disorders straightforward classification is generally problematic but for some reason it is more problematic for psychiatry. They suggest that:

“If psychiatric classifications such as the DSM and the ICD were demarcating natural kinds, we would expect each diagnosis to correspond to an entity that exists in the structure of the world, independent of human interests.”

That quote misses the mark at a couple of levels.  First, a classification system is really not a diagnosis. It is more of a hypothesis and general locator (8). The diagnosis takes additional information including some of the validators that they minimize in this section. Second, in looking at these features it is obvious that many of the big ones – like mania “exist in the world independent of human interests.”  They have after all been described since ancient times across multiple diagnostic systems – long before there were psychiatrists.  The same is true of melancholia and several other disorders. Granted – there was no DSM back then but I cannot think of better evidence that there are natural kinds by this definition that have been updated. Third, it should be obvious that many disorders are clearly there for research purposes and this is evidenced by the fact that only about 50% of the diagnoses are used on a clinical basis and many psychiatrists attest to the fact that they doubt a single case of specific disorders exist (9,10).  Finally, essentialism in biology became a casualty of evolution.  Prior to Darwin, Linnaeus suggested that species were distinct and unchanging entities created by God.  That is an essentialist position. Evolutionary theory changed all of that because species change based on individual variation and new species occur (11). 

Whenever I read about the philosophical concepts behind what constitutes psychiatric illness and classification – I am always left considering why philosophy is prioritized over biology.  Medicine is after all firmly rooted in human biology.  There is no better evidence than the biochemistry, anatomy, and physiology courses taken in medical school basic science.  Biology provides a framework for both hierarchical organization as well as individual classification of diseases including mental disorders (see lead graphic). Modern taxonomic classifications of both date back to the mid -18^th century.

A critical question is whether biological classification has advanced to the point where it is not controversial and purely scientific.  The short answer is no. There is ample evidence that the taxonomy of living organisms is problematic and there are ongoing controversies over the past 50 years.  Although species is a fundamental organizational concept in the field of biology that has not prevented the proliferation of up to 24 different species concepts in recent times (12).  Why would medicine be expected to have a more clearly defined classification system than biology?

Rather than comment on the remaining sections that I am sure that I also have problems with – I am going to introduce and idea that I have not seen written about anywhere.  If you read this an think I am wrong please let me know and send references.  That idea is the application of biological theory to psychiatry. Medicine and psychiatry are after all firmly based in human biology and human biology is a subset of biology in general.  When you attend medical school and complete all the basic science training this basic fact is explicit. There is not much discussion of other organisms unless they happen to be pathogens.  There is also not much discussion of the levels of organization in human biology and the implications that has for medicine.

What does the tremendous complexity of biology have to do with psychiatry? It is evident that various mechanisms make it very difficult to classify biological organisms.  That has resulted in many species concepts and that array of concepts has complicate taxonomy at a time when the biodiversity of the planet remains inadequately characterized. Psychiatry is operating only in one species by the same mechanisms that complicate biology at all levels also complicate biology.  To the purpose of this essay the critical question is why they currently seem less important than the increasing presence of philosophy in psychiatry. Frequently the justification seems to be the old quote about “carving nature at the joints.”  Does that mean we philosophize about it and maintain endless arguments?  Or does it mean we consider that human beings and their mental disorders are based in human biology and try to make sense of it by studying biological principles.  And by biological principles – I don’t mean the typical jargon of biological psychiatry used by critics. I mean theoretical biology practiced by biologists.      

I want to touch on just two concepts from biology that have implications for psychiatric controversies.  The first are the classification systems in biology and the second is stochastics.  There are any number of authors offering descriptions about how psychiatry has evolved in the last 200 years. That generally tracing the origins back to 19^th century European schools of thought and bringing those threads forward.  The focus is generally on nosology including diagnostic systems, treatment settings, and how treatments evolved.  The brief discussion of biological classification here touches on a large literature that has been ignored by medicine and psychiatry.  In the debate of categorical versus dimensional diagnoses and the various philosophical labels a significant number of biological classifiers have been left out.

If I am correct what might have caused this significant omission? First, the focus of medicine has been description based on clinical findings.  I have used this characterization previously:

"For several thousand years physicians have recorded observations and studies about their patients.  In the accumulating facts they have recognized patterns of disordered bodily functions and structures as well as forms of mental aberration.  When such categories were sufficiently distinctive, they were termed diseases and given specific names. “

DeGowan and DeGowan, Bedside Diagnostic Examination. 1976, p 1

That has been the historical and primary focus of medicine. Interest in pathogenesis happened in the 19^th century but even then, there were conditions that that escaped that classification.  There has been progress there are still many conditions with no clear pathophysiology and even fewer medications where the mechanism of action is known. One of the primary reasons is that medicine has been based on reductionist biology and even though advances have been made it seems to have reached its limit. What do I mean by reductionist biology?  Simply put it means breaking down complex systems to component parts and studying those parts independently.  In current jargon it has also been referred to as a bottom-up approach.  Second – biological psychiatry is biological in the reductive scientific sense and it needs to be biological in the integrative sense. All biology is not reductive (17,18) – but much of the philosophy I have read seems to think so.  Reductive approaches have led to discrete research programs that produce highly speculative connections to psychiatric disorders. We end up with biological psychiatry as neurochemistry -> neuroendocrinology -> neuroimaging -> genomes, connectomes, proteomes, transcriptomes, metabolomes, etc without any clear underlying connection to all human biology.  Systems biology or network medicine approaches have been used on only a partial basis so far.  Third, rather than make a truly biological connection the field seems to have been sidetracked by philosophy.  Much of that philosophy has been around for 50 years or more and seems satisfied with the role of asking questions and never really providing much of an answer.  Much of the philosophy is vague and untestable.  A secondary role seems to be the criticism of psychiatry with a dependence more on political rhetoric than reality.

Conclusion:

When philosophers criticize medicine and psychiatry, they frequently use the term constructs.  From a rhetorical perspective not, all constructs are alike.  In medicine and biology there needs to be at least some real-world observable basis.  

Rather than strong arguments for philosophy in psychiatry – the authors have argued strongly. I have tried to elucidate the rhetoric involved since my observation is that is the nature of most philosophical arguments directed at psychiatry.  The curious aspect is that most people do not even consider this when reading philosophers commenting on psychiatry.  I sent one of my papers to a friend who has been a psychiatrist as long as I have and he told me that he never considered it an area for analysis. I hope that some of the comments here are useful in considering these arguments and why they should not be blindly accepted.

It seems that in all the philosophical criticism and discussion of psychiatry, van Fraassen's empirical adequacy has been ignored (16, 17).  The reasons for that may be less than obvious.  Van Frassen basically states that an empirically adequate model is just that – it is not a comment on the truth of existence or not.  There is a question of whether the model must be based on direct observation.  The criteria for mental disorders require reporting subjective states that are not directly observable. Van Fraassen’s theory includes the outcomes of experiments and isomorphic models – both of which apply to work in psychiatric nosology. The lack of comment on Van Fraasen’s approach is critical because it reflects how psychiatrists are actually trained and directly counters arguments about positivism and realism. Some references suggest that what appear to be diametrically opposed arguments in philosophy are just sustained with no resolution and that is a significant limiting factor when considering what psychiatrists need to know.           

Not all biology is reductionist and not all philosophy is useful.  Empirical adequacy and biological complexity are the future of psychiatry.

 

George Dawson, MD, DFAPA

 

References:

1:  Stein DJ, Nielsen K, Hartford A, Gagné-Julien AM, Glackin S, Friston K, Maj M, Zachar P, Aftab A. Philosophy of psychiatry: theoretical advances and clinical implications. World Psychiatry. 2024 Jun;23(2):215-232. doi: 10.1002/wps.21194. PMID: 38727058; PMCID: PMC11083904.

2:  Aftab A, Waterman GS. Conceptual competence in psychiatry: recommendations for education and training. Acad Psychiatry 2021;45:203-9.

3: Guze SB. Why psychiatry is a branch of medicine. Oxford: Oxford University Press, 1992. p. 38.

4:  Schildkraut JJ, Kety SS. Biogenic amines and emotion. Science. 1967;156 (3771):21-37.

5:  John B, Lewis KR. Chromosome variability and geographic distribution in insects. Science. 1966 May 6;152(3723):711-21. doi: 10.1126/science.152.3723.711. PMID: 17797432.

6:  McGuffin P, Farmer A, Gottesman II. Is there really a split in schizophrenia? The genetic evidence. Br J Psychiatry. 1987 May;150:581-92. doi: 10.1192/bjp.150.5.581. PMID: 3307978.

7:  Pies R.  Did Szasz Misunderstand Virchow’s Concept of disease? Psychiatric Times. Feb 21, 2024.  https://www.psychiatrictimes.com/view/did-szasz-misunderstand-virchow-s-concept-of-disease

8:  Kendler KS. The Phenomenology of Major Depression and the Representativeness and Nature of DSM Criteria. Am J Psychiatry. 2016 Aug 1;173(8):771-80. doi: 10.1176/appi.ajp.2016.15121509. Epub 2016 May 3. PMID: 27138588.

9:  Munk-Jørgensen P, Najarraq Lund M, Bertelsen A. Use of ICD-10 diagnoses in Danish psychiatric hospital-based services in 2001-2007. World Psychiatry. 2010 Oct;9(3):183-4. doi: 10.1002/j.2051-5545.2010.tb00307.x. PMID: 20975866; PMCID: PMC2948730. 

10:  Müssigbrodt H, Michels R, Malchow CP, Dilling H, Munk-Jørgensen P, Bertelsen A. Use of the ICD-10 classification in psychiatry: an international survey. Psychopathology. 2000 Mar-Apr;33(2):94-9. doi: 10.1159/000029127. PMID: 10705253

11:  Hey J.  Genes, categories, and species. NY, NY. Oxford University Press, 2001: p 60-61.

12:  De Queiroz K. Ernst Mayr and the modern concept of species. Proceedings of the National Academy of Sciences. 2005 May 3;102(suppl_1):6600-7.

13:  Mayr E. Biological classification: toward a synthesis of opposing methodologies. Science. 1981 Oct 30;214(4520):510-6. doi: 10.1126/science.214.4520.510.

14:  Mayr E. Biology is not postage stamp collecting. Interview by R. Lewin. Science. 1982 May 14;216(4547):718-20. doi: 10.1126/science.7079730. PMID: 7079730.

15:  Ho CC, Lau SK, Woo PC. Romance of the three domains: how cladistics transformed the classification of cellular organisms. Protein Cell. 2013 Sep;4(9):664-76. doi: 10.1007/s13238-013-3050-9. Epub 2013 Jul 19.

16:  Van Fraassen.  BC.  The Empirical Stance.  New Haven: Yale University Press, 2002.

17:  Monton, Bradley and Chad Mohler, "Constructive Empiricism", The Stanford Encyclopedia of Philosophy (Summer 2021 Edition), Edward N. Zalta (ed.), URL = <https://plato.stanford.edu/archives/sum2021/entries/constructive-empiricism/>.First published Wed Oct 1, 2008; substantive revision Tue Apr 13, 2021

18:  Loscalzo J, Kohane I, Barabasi AL. Human disease classification in the postgenomic era: a complex systems approach to human pathobiology. Mol Syst Biol. 2007;3:124. doi: 10.1038/msb4100163. Epub 2007 Jul 10. PMID: 17625512; PMCID: PMC1948102.

19:  Van Regenmortel MH. Reductionism and complexity in molecular biology. Scientists now have the tools to unravel biological and overcome the limitations of reductionism. EMBO Rep. 2004 Nov;5(11):1016-20. doi: 10.1038/sj.embor.7400284. PMID: 15520799; PMCID: PMC1299179.

 

Dedication:  This post is dedicated to my undergraduate biology Professors at Northland College including Lee Stadnyk, Richard Verch, John Brennan, and Mallanpali Rao. I spent many months studying the comparative anatomy and physiology of invertebrates and the taxonomy and population dynamics of sphagnum moss plant species, aquatic invertebrates, and freshwater plankton with these professors and they were the best.  I also had the pleasure of working on Loblolly Pine (Pinus taeda) and Douglas Fir (Pseudotsuga menziesii) species in Don Durzan’s lab at the Institute of Paper Chemistry. Experience in biology is a grounding in the complexity of living organisms.

Another Round of Addiction As A Brain Disease

 

A new open access article looking at the issue of addiction as a brain disease was recently published by Neuropsychopharmacology.  The authors point out that since this original claim as made 20 years ago (7) and subsequently reinforced (8) there have been a flurry of critical articles. On this blog I have examined several of these articles in the past. They parallel typical arguments that are used against psychiatric diagnoses, particularly the concept of psychiatric disorders as diseases.  Interestingly, in this paper that entire issue was summarily addressed:

“Few, if any healthcare professionals continue to maintain that schizophrenia, rather than being a disease, is a normal response to societal conditions. Why, then, do people continue to question if addiction is a disease, but not whether schizophrenia, major depressive disorder or posttraumatic stress disorder are diseases?”  (p. 3)

Any casual observer of the constant arguments on this issue will note a constant flux of how psychiatric disorders are described.  Disorders, conditions, and constructs come to mind.  I always like to point out that actual surveys of both the general public and health care professionals finds that both groups typically classify severe mental illnesses and substance use disorders as diseases, but to varying degrees.  The best surveys of this problem have been done in Finland (4,5) with large sample of doctors, nurses, psychiatrists, laypersons, and politicians included.  In two separate studies the authors asked respondents to consider 60 general conditions and 20 psychiatric conditions.  Respondents were asked to rank the disorders according to which were more similar to disease conditions and different cut offs were used for both samples. In the larger survey of 60 medical and psychiatric conditions – schizophrenia and autism met the survey requirements for disease.  In the second survey, 75% of the respondents considered schizophrenia and autism as diseases and 50% considered Depression, Anorexia, Panic disorder, Generalized Anxiety Disorder, Bulimia, Attention deficit hyperactivity disorder, and Personality disorder to be diseases.  There was more disagreement on Alcoholism and Drug Addiction but 64% of physicians and 74% of psychiatrists considered alcoholism to be a disease.  On the issue of drug addiction 50% of physicians and 65% of psychiatrists considered that condition to be a disease. The authors generally discuss the implications of these opinions from a practical and public policy perspective rather than a medical or philosophical one. The common arguments that persist is that disease status confers social legitimacy on a disorder leading to more treatment resources and hopefully decreasing stigma.  In the case of addictions there are longstanding moral defect or choice theories that essentially equate addiction to willful misconduct. Since large corporations have taken over the healthcare systems in the United States many of these biases are less visible since proprietary rules determine who gets treatment resources and how they are treated. A recent court ruling details how these rules are seriously flawed (6).  An important perspective from the discussion and that is personal experience with the illness by the patient, family members, friends, and employers– a subject I will elaborate on further.

The previous posts on this blog addressed a New England Journal of Medicine article suggesting that addiction was a problem in learning rather than a disease in two separate posts.  Before that I addressed a 2015 article that listed 10 reasons why addictions were not a disease. Responding to these articles highlighted their rhetorical aspect.  Many of the arguments against a disease model of addiction have three basic flaws.  First, they consider the concept of disease to be clearly defined and it is not. Second, they use their more precise definitions for comparison and as a way to prove addiction is not a disease.  And third, they suggest that psychosocial variables are relevant only if the condition in question is not a true disease.  They suggest that real diseases are self-contained and self-perpetuating and that interpersonal relationships and environmental factors cannot modify diseases.  By extension only a medication or a surgical intervention can modify or cure a real disease.  There are many examples of diseases that illustrate why that premise is not true.  In my practice over the past 30 years the most common examples have been diabetes mellitus Type 2, hypercholesterolemia, and hypertension. I have seen many people with extreme cholesterol elevations who were “cured” by a simple dietary change and starting to exercise.  My two previous articles discuss these lines of argumentation.

Another disease feature of substance use disorders is that they can occur in discrete epidemics.  Although epidemics are typically thought of as being associated with infectious diseases, the CDC description is careful to point out that they can also occur as a result of non-infectious diseases like obesity and diabetes mellitus. They also describe 5 conditions that lead to epidemics including an increase in exposure in terms of total amount or increased virulence, introduction of a novel agent, enhanced transmission, a change in host response, or increased host exposure that can occur by new portals of entry.  All 5 of these factors are relevant in drug epidemics.  Substance use disorder epidemics have these features as evidenced by the 20-year opioid epidemic that started with excessive availability of prescriptions opioids and transitioned to more potent illicit opioids. The widespread availability of these compounds come from illicit importation and supply chain proliferation often by opioid users selling these compounds in order to assure that they have an adequate supply.  Over the past 25 years there have been a clear pattern of increased geographic availability of multiple drug classes – leading to increased morbidity and mortality from substance use disorders in these areas.  

Does the current paper add anything to the argument for addiction as a brain disease?  The authors review the history of the more public airing of the concept – an original article by Leshner (7) asserting “addiction is a brain disease” and a follow up article by McClellan (8). The fact that both of these declarations are only about 20 years old should not be lost on anyone. The authors get derailed from the basic concept of disease in the very next paragraph by suggesting “To promote patient access to treatments, scientists need to argue that there is a biological basis beneath challenging behaviors of individuals suffering from addiction.”  The social utility of a diagnosis is separate from its medical and scientific utility. All three are conflated at times (even to the point of suggesting that laypersons should have input into what is a diagnosis), but in my opinion without medical and scientific utility – there is not social utility.

They review the definition of disease – starting with Jellinek’s “The Disease Concept of Alcoholism”.  Jellinek made the argument that diseases were not self-contained “entities” but it is more of an agreed upon label “to describe a cluster of substantial deteriorating changes in the structure or function of the human body and the accompanying deterioration in biopsychosocial functioning”.  That definition is very close to the one I came up with reviewing the work of philosophers Munson and Resnick who defined disease as a “failure of normal functioning”. The main difference is that these two philosophers predicated the definition on the premise that biological systems were programmed processes and those processes failing is what causes the disease.  Adaptive reward based learning can certainly be considered a programmed process in brain biology.  

They take a close look at the idea that any definition of addiction should account for spontaneous remission and non-relapsing states. One of the typical arguments against addiction as a disease is that a significant number of heavy drinkers (and probably cannabis smokers) stop after they graduate from college.  In many ways, excessive alcohol and drug use in college is considered a rite of passage by many Americans.  That rite of passage has a considerable mortality and morbidity on its own that is usually not considered by the addiction as disease critics.  The vast majority of these people are not the people seen by addiction specialists later in life. The people seen in their 40s or 50s will typically give a history of knowing that their pattern of drinking was problematic.  As an example: “I knew from the very first time that I drank a lot more and I drank faster than anyone else. I drank more in college and I did not stop after I graduated”.  And they elaborate on the consequences of excessive alcohol use at every life stage.  Binge use or even fairly continuous use of drugs or alcohol in college is not the same as an addiction.  

The authors point out that some of the epidemiological data used to justify the remission argument is dependent on methodology and population.  For example, a population recruited from a residential treatment facility and interviewed with a standardized interview will yield much different results than a community sample. The diagnosis of addiction (or severe alcohol use disorder) will be stable in the former case but not the latter.  They reference NESARC (National Epidemiological Survey on Alcohol and Related Conditions) as the community sample and using that methodology the baseline lifetime prevalence of non-remitting alcohol dependence was 10% (p. 9).  They also point out that opioid use disorder when observed for 10-30 years has a stable abstinence rate of < 30%.  The fact that some people stop using excessive amounts of drugs or alcohol is not an argument that there is not a large population of people who clearly have a chronic relapsing course and incur significant mortality and morbidity along the way.

The authors proceed to the genetic argument and point out that family and adoption studies point to a heritability of ~50% for addictive disorders. They highlight typical misunderstandings of genetics, specifically the concept of polygenic risk and that fact that some polygenic disorders lead to pathological states – addiction being one of them.  An additional argument is that although the first 20 years of human genome study have been very productive for Mendelian disorders, it has been far less productive for more complex disorders (11). Understanding the human genome is far from complete at this point and some research groups are just beginning to understand the relationships between genetics, addiction, and medication effects (12, 13, 14).

The lesion argument is the next disease straw man to fall. It should be obvious to anyone that diseases do not necessarily produce a discrete lesion either on imaging studies or autopsy.  An yet it remains a favorite to anyone who claims that addictions or psychiatric disorders are not diseases.  They review how imaging is currently used clinically.  This is a reality that most of the critics seem to miss.  If I see brain imaging consistent with small vessel ischemic disease – that alone is insufficient to make the diagnosis. It also requires an adequate history and examination of the patient. The critics apparently have not see radiology reports that point out “clinical correlation is necessary”.  The authors briefly review the functional imaging of alcohol and stimulant use disorders that point to problems with frontal-striatal circuitry, structural changes with alcohol, and demonstrable and expected changes in dopamine signaling. Brain imaging in addiction at this point (apart from the necessary clinical imaging) is useful from a heuristic standpoint – looking for relevant mechanism and treatments, but there is no imaging of addictive disorders per se. 

A popular viewpoint these days is that there is not enough of an investment in psychosocial factors in funded research. Many of those critics make the argument that the trade off should be reduced funding for biological research and those funds should be diverted to psychosocial research. The authors here acknowledge the importance of social factors, their incorporation in more complex research designs, and the fact that a view of addiction as a brain disease in no way negates the importance of other environmental factors. 

The authors address the issue of reductionism.  They use the term determinism instead. Over the past two decades molecular biologists have moved firmly away for the idea that all complex biological systems can be reduced to the basic laws of chemistry and physics. The does not mean that with the appropriate tools biological complexity can not be understood and explained.  Many physicists see the brain as deterministic.  In other words because the brain is made up of particles and those particles must follow the laws of physics, the future (or past state) of any brain can be determined by the right differential equation. Deterministic states can be chaotic and in that situation they are not predictable.  If you believe the brain is deterministic based on physical laws – it follows that there is no free will and that free will is an illusion.  The real limiting factors with describing the brain as deterministic include the following problems:

1.  There are known stochastic factors that introduce random events – some of which are relevant for the addiction.

2.  Complexity – as noted above.  There is so much structure and so many particles that must be considered in these complex systems that there is a clear measurement problem and the most difficult problems are solved by computer modeling approximations rather than mathematically.  I have not seen it discussed but whenever I consider the complexity of biological systems, I see them as an almost infinite set of microenvironments - each with their own physical and chemical parameters. If there was an equation to describe all of those microenvironments acting at one - it would be exceedingly complex.

3.  Brain changes occurring during the addiction process (a large number of which are unknown at this time) alter the deterministic nature of the system.  I suppose the response by the physical determinists would be that the new altered system would be determined by the laws of physics and chemistry. That does not alter the fact that it is a new system with different physical and chemical componenets.

The authors contend that the system is indeterministic because of these factors and therefore free will is allowed.  An associated physics and philosophical question is whether it is really deterministic but unpredictable and why.  Overall, these philosophical arguments do not really seem to add much to the debate.  The critical piece is whether either deterministic or reductionist is used in a pejorative manner.  That use is typically coupled with arguments that other social or psychological theories is what is really happening.  Scientists and physicians are generally interested in knowing all of the details and mechanisms of action. The is the real driver of knowing what is happening at the molecular level.  This paper does a good job of explaining why people who use that approach do not exclude everything else that is going on in the environment.

They end on the issue of compulsivity (or more accurately uncontrolled use) in addiction. It is not the case that this does not happen, but the degree at which it happens.  In the people who I work with practically all of the negative outcomes are associated with uncontrolled use/compulsivity.   That does not mean that people with addictions are automatons. The major treatment modality anywhere is some form of group therapy.  Those groups would not exist if there was an assumptions that people with substance use disorders could not choose to change their thought patterns and behavior.  They continue to have some flexibility, but the probabilities during an active addiction is that the substance use will continue despite negative and in many cases life threatening outcomes. Intact decision making in other areas or even in the focal area of continued substance use with episodes of abstinence does not mean that normal decision making occurs in all areas of life.

In their conclusion, the authors suggest that progress can occur from integrating a number of scientific perspectives including those outside the field of neuroscience.  They advocate for consilience and input from a plurality of disciplines. They also suggest that no single discipline has exclusive ownership of the field.

As a clinician who is used to constant criticism of psychiatry from people who don’t know anything about it – I have a different position.   First, we need to acknowledge the severity of addictions specifically that they kill and disable large numbers of people.  Family members trying to help an afflicted persons know that as well as the difficulty in trying to help them stop.  Second, in rankings of disability compared with other disease states – addictions are consistently in the top 10.  When combined with psychiatric diseases they are ranked second.  There are few other diseases as disabling or lethal.  Third, there have been treatments that are based on the underlying biological factors that are thought to be relevant to addiction that have worked.  Four, it is very clear that individuals with addictions are no longer functioning normally – defined as their normal baseline.  That can start at any point in the life cycle – and at some point most people are aware that they have a severe problem and cannot stop.

All of those factors point to a disease state and it is good to see a paper supporting that opinion.   But even beyond this opinion, consider the people you have known with addictions and make up your own mind based on that experience.  Carefully consider how you interact with people if you consider addiction to be a disease or intentional decision-making.

 

 George Dawson, MD

 

References:

1:  Heilig M, MacKillop J, Martinez D, Rehm J, Leggio L, Vanderschuren LJMJ. Addiction as a brain disease revised: why it still matters, and the need for consilience. Neuropsychopharmacology. 2021 Feb 22. doi: 10.1038/s41386-020-00950-y. Epub ahead of print. PMID: 33619327.

2:  Heilig M, Augier E, Pfarr S, Sommer WH. Developing neuroscience-based treatments for alcohol addiction: A matter of choice? Transl Psychiatry. 2019 Oct 8;9(1):255. doi: 10.1038/s41398-019-0591-6. PMID: 31594920; PMCID: PMC6783461.

3:  Venniro M, Banks ML, Heilig M, Epstein DH, Shaham Y. Improving translation of animal models of addiction and relapse by reverse translation. Nat Rev Neurosci. 2020 Nov;21(11):625-643. doi: 10.1038/s41583-020-0378-z. Epub 2020 Oct 6. PMID: 33024318.

4:  Tikkinen KA, Leinonen JS, Guyatt GH, Ebrahim S, Järvinen TL. What is a disease? Perspectives of the public, health professionals and legislators. BMJ Open. 2012 Dec 2;2(6):e001632. doi: 10.1136/bmjopen-2012-001632. PMID: 23204142; PMCID: PMC3533011.

5:  Tikkinen KAO, Rutanen J, Frances A, Perry BL, Dennis BB, Agarwal A, Maqbool A, Ebrahim S, Leinonen JS, Järvinen TLN, Guyatt GH. Public, health professional and legislator perspectives on the concept of psychiatric disease: a population-based survey. BMJ Open. 2019 Jun 4;9(6):e024265. doi: 10.1136/bmjopen-2018-024265. PMID: 31167856; PMCID: PMC6561450.

6:  Wit v. United Behavioral Health.  Full text of ruling.

7:  Leshner AI. Addiction is a brain disease, and it matters. Science. 1997 Oct 3;278(5335):45-7. doi: 10.1126/science.278.5335.45. PMID: 9311924.

8:  McLellan AT, Lewis DC, O'Brien CP, Kleber HD. Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation. JAMA. 2000 Oct 4;284(13):1689-95. doi: 10.1001/jama.284.13.1689. PMID: 11015800.

9:  Koob GF, Volkow ND. Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry. 2016 Aug;3(8):760-773. doi: 10.1016/S2215-0366(16)00104-8. PMID: 27475769; PMCID: PMC6135092.

10:  Volkow ND, Morales M. The Brain on Drugs: From Reward to Addiction. Cell. 2015 Aug 13;162(4):712-25. doi: 10.1016/j.cell.2015.07.046. PMID: 26276628.

11:  Koob GF, Powell P, White A. Addiction as a Coping Response: Hyperkatifeia, Deaths of Despair, and COVID-19. Am J Psychiatry. 2020 Nov 1;177(11):1031-1037. doi: 10.1176/appi.ajp.2020.20091375. PMID: 33135468.

12.  Miga KH. Breaking through the unknowns of the human reference genome. Nature. 2021 Feb;590(7845):217-218. doi: 10.1038/d41586-021-00293-8. PMID: 33568817.

13:  Ho MF, Zhang C, Zhang L, Wei L, Zhou Y, Moon I, Geske JR, Choi DS, Biernacka J, Frye M, Wen Z, Karpyak VM, Li H, Weinshilboum R. TSPAN5 influences serotonin and kynurenine: pharmacogenomic mechanisms related to alcohol use disorder and acamprosate treatment response. Mol Psychiatry. 2020 Aug 4:10.1038/s41380-020-0855-9. doi: 10.1038/s41380-020-0855-9. Epub ahead of print. PMID: 32753686; PMCID: PMC7858703.

14:   Nguyen TTL, Liu D, Ho MF, Athreya AP, Weinshilboum R. Selective Serotonin Reuptake Inhibitor Pharmaco-Omics: Mechanisms and Prediction. Front Pharmacol. 2021 Jan 11;11:614048. doi: 10.3389/fphar.2020.614048. PMID: 33510640; PMCID: PMC7836019.

 

 

Reductionism Is Not A Dirty Word...

A recent opinion piece in the New York Times, by George Makari, MD has me shaking my head.  The thesis was that a recent headline grabbing story (what's wrong with that criteria?) on the effects of comprehensive treatment of psychosis as opposed to treatment as usual surprised many and highlighted the problem with reductionism.  He bemoans the fact that the reaction to the story was one of surprise.  He doesn't specify who was surprised.  I certainly was not surprised.  I attended recent meeting and somebody in the audience asked Daniel Weinberger if he was surprised.  His response: "They spent $15 million dollars showing that good treatment is better than bad treatment."    He certainly was not surprised.  I have not heard about Eric Kandel's response, but based on his 1979 paper on plasticity and what happens in psychotherapy - I doubt that he would be surprised.  The exact population of who might be surprised by these findings seems poorly defined at this point in time but I doubt that it included any psychiatrists.

Speaking for myself, I will elaborate on why I was not be surprised.  At one point, I was the Medical Director of a community support program of a group of about 100 outpatients in the State of Wisconsin.  According to the state statutes, access to the program depended on diagnosis and degree of psychiatric disability.  You could only apply if you had a diagnosis of Bipolar Disorder, Major Depression, Schizophrenia,  or Borderline Personality Disorder had significant associated disability or were at high risk for hospitalization.  The clinical goal of the program was to reduce hospitalizations, maintain independent living, and facilitate employment.  The program was staffed by a psychologist, 2 social workers, three nurses and me.  When I arrived, one of the early dynamics was to frame problems in terms of medication needs.  That translated to increasing the dose of a medication (typically an antidepressant or antipsychotic) in crisis situations or other emotional crises.  The patients in the program had chronic problems and symptoms that did not necessarily respond to medication.  One of my first steps was to start to discuss problems and solutions with the patients.  I met with all of the patients and did supportive psychotherapy when possible.  We had team meetings every morning and problem solved around the needs of the patients in the community, how to solve any crises, and how to approach people in ways other than medications.  I tracked the total dose of antipsychotic medication and days of hospitalization as outcome measures.  At the end of three years, the days in hospital had gone down from about 14 days per person to less than 1, and the total dose of antipsychotic medication had gone down a total of 600 mg chlorpromazine equivalents.

My point is obviously that comprehensive care of patients with severe problems results in improved outcomes.  In this case lower doses of medications were used and the patients spent less time in the hospital and more time at home.  My orientation and ability to implement such a program was not an accident.  I was trained by Len Stein, MD at the University of Wisconsin.  Dr. Stein was a pioneer in the area defined as community psychiatry.  He was motivated by realizing that once people were in large state hospitals - it was very easy to warehouse them in overcrowded conditions.  Nobody seems to recognize it but overcrowding and suboptimal conditions were the state hospital equivalent of managed care rationing.  Once your state hospital is on the spreadsheet of a state bean counter with no accountability to patients or their families rationing and fewer and fewer resources are the order of the day.   In a community psychiatry seminar, Dr. Stein projected a slide of a gymnasium-sized room populated by male patients with hundreds of cots aligned edge to edge.  There was no room to walk between the cots.  That was his motivation for moving people out of these state facilities and into their own housing.  When I trained, there were three programs with independent living and quality of life as the primary goals and the staff involved in the programs was very good at it.  My effort just extended that skill set.  Contrary to the "surprising" results of the quoted study - I did the same thing back in 1986!

If it is true that we have known for 30 years that comprehensive care for psychiatric disorders trumps "treatment as usual" what is all of the rhetoric about?  Dr. Makari seems to want to make this into a mind-brain argument.  In other words, the biopsychosocial approach and the uncertain effect it has on the mind as opposed to a brain based approach that looks at specific mechanisms of action and seems to be focused on psychopharmacology.  He points out for example that the highlighted study would possible not qualify for current NIMH funding unless it looked at specific brain mechanisms.  He throws around the word "reductionism".  Anytime reductionistic or reductionism is used rhetorically in the same sentence with psychiatry it is pejorative.  My old psychoanalytic teacher would refer to anyone who talked about brain biology as a "dial twister".  The implication is that the reductionists are somewhat simple minded largely because they cannot accept the uncertainty of dealing with an organ that has poorly defined inputs and outputs.  Kind of a double whammy of rhetoric - you are a unsophisticated reductionist and you really can't see the big picture.  Are things really that simple?  Are these arguments accurate?  Are there problems with equating reductionism with "bad".

Of course there are major problems.  The first is the statement that inherent to the proposition that mental illness is a brain disease is "the implication that psychological and social events somehow are not also brain events."  This is a serious misreading of the definition of plasticity or experience dependent changes in the brain.  When I give my neurobiology of the brain lectures. I use Kandel's original New England Journal of Medicine article that discusses brain changes in a patient and a therapist conducting psychotherapy and how those changes are associated with brain plasticity.  I give further examples - weightlifting,  playing the violin, and how the typical stream of consciousness is profoundly altered by drug addiction.  There is no neuroscientist or biological psychiatrist I know who would suggest that psychological and social events are not brain events and there are numerous experimental paradigms that look specifically at how these events occur in the brains of animals.

The second aspect of Dr. Makari's argument has to do with reductionism.  His specific comment is:

"With luck, studies like Dr. Kane’s, which undermine these suppositions, will help move us away from such narrow thinking and embolden the substantial community within psychiatry that has never accepted such reductionism."

The suppositions in this case are that mental illness is a brain disease and that social or psychological events have no brain representation.  The argument is based on that false premise.  But further the use of the term "reductionism" is instructive here as previously noted.  By definition reductionism applies to many proposed etiologies of psychiatric disorders.  Those etiologies can be studied at a molecular level or at a higher level.  Schaffer (2) says that a model is reductive if it "employs standard biochemical and molecular entities to account for psychiatric symptoms and disorders".  Non-reductive models discuss "causal connections at higher levels of aggregation."  He illustrates these definitions by looking at Kendler's non-reductive account of major depression.  Kendler has used path analysis to look at clinical variables relevant to psychiatric disorders and although I do not have access to the one used in the book, here is a typical example.  The model looks at life stages, familial factors and psychological factors and all are higher levels of aggregation than molecular mechanisms.  At the reductive side of things he examines Harrison and Weinberger's proposed genetic susceptibility genes for schizophrenia.  At the time the book was written the author limited the discussion to 5 genes.  He also looked at the continuum of psychiatric genetic models ranging from basic and advanced genetic epidemiology being non-reductive, gene finding partially reductive, and molecular genetics fully reductive.  It seems perfectly logical to me that the study of brain biology proceeds in the same way that the biology of all living organisms proceeds.  The difference is that we are studying an infinitely more plastic organ with significant computational power.  There is clearly a lot of phenotypic heterogeneity that is unexplained in psychiatric diagnostic categories.  It is highly unlikely that refining diagnostic descriptors or applying clinical methods will lead to any significant change in the diagnostic or treatment process.  I don't understand the reluctance to go after more specific mechanisms or treatments.

The idea that a molecular or clinical focus in psychiatry is the problem with psychiatric services is also misleading.  As I hoped to point out by my mental health center example, psychiatrists know all about comprehensive care but they are rarely able to provide it.  They have known about how to provide it for decades.  State asylums became overcrowded and not therapeutic due to the financial management of the system by state governments.  The bean counters have moved out of the asylum and they are now integrated at every level in the health care system.  They all have a very strong bias against the comprehensive treatment of mental illness.  They insist that patients with severe psychiatric problems do not get comprehensive evaluations, that they are discharged before they have been adequately treated, and that any associated addictions are poorly treated.  They do not have the same biases against people hospitalized for medical or surgical illnesses.  They have in effect, moved the poorly run, overcrowded asylum model into the general health care system.  Any comprehensive care for severe mental disorders in such a system is an advertising phenomenon rather than reality.

The reductionism argument is good for New York Times opinion pieces.  It may sell a few more papers or get a few more clicks online.  Unfortunately it perpetuates an old pattern of blaming people and psychiatrists in particular for the shortcomings of a non-system of mental health care in this country that is set up to favor large health care businesses.  You can blame psychiatrists all you want for that - but until people realize that the real problems are the product of business and politics - and not the scientific interests of psychiatrists - nothing will change.


George Dawson, MD, DFAPA

References:

1.   George Makari.  Psychiatry’s Mind-Brain Problem.  New York Times.  November 11, 2015.

2.  Scaffner KF.  Etiological Models in Psychiatry - Reductive and Nonreductive Approaches in  Philosophical Issues in Psychiatry.  Kenneth Kendler, Josef Parnas (Eds), The Johns Hopkins University Press, Baltimore, 2008:  pp 48-98.

Attribution:

Image is Microscope 1 by Bill3t Hughes on Flickr.  Reposted as noncommercial via Creative Commons License on 11/14/2015.  The original work is not modified.