David Healy: The Shipwreck of the Singular
C. Robert Cloninger’s comment
False Dichotomies & the Need for Person-centered Medicine
There is much to admire in what David Healy has eloquently written about the need for more person-centered care in medicine and in psychiatry, in particular. The crucial importance of health promotion through person-centered therapeutics is something about which I have long been a passionate advocate (Cloninger 2004, 2006; Cloninger and Cloninger 2011, 2013). In addition, we agree that randomized controlled trials are inadequate to guide the treatment of the individual patient encountered by a physician because they provide information only about differences between averages of heterogeneous groups.
Where I take issue with him is his focus on a series of commonplace but false dichotomies that undermine an integrated understanding of precise and person-centered care. Specifically, Healy organizes his view of the historical and dynamical trends in healthcare in terms of forces within the individual vs. those outside the individual (nature versus nurture), surgery vs. public health, biomedicine vs. social medicine, and biology vs. numbers/epidemiology. I suggest that his focus on these common but false dichotomies distorts his apprehension and description of the complexity of human ill-being and well-being. His language is artful but could provoke division rather than drawing people to work cooperatively toward integration.
The Complexity of Common Medical Disorders
If we want to improve healthcare, we need to recognize that biological, psychological, social and spiritual influences are each important and interact with one another in complex ways. Whenever multiple variables influence one another through feedback interactions, complex relations arise in which the same causes may have multiple outcomes ("multifinality") and different causes can have the same outcome ("equifinality") (Amedo, Svrakic et al 2015; Cicchetti and Rogosch 1996; Cloninger, Svrakic et al. 1997). Such complexity of non-linear dynamical systems is a strong characteristic of all common medical disorders in general and of healthcare systems (Cloninger, Salvador-Carulla et al. 2014). Consequently, we undermine the possibility of improving healthcare by pitting biological, psychological, and social contributions to health against one another. The work of reductionists in each arena can often be productively integrated if self-defeating antagonism is restrained.
Physical, mental, and social aspects of health are inextricably intertwined. The human brain evolved through a long series of adaptations that allow self-regulation of sexual, physical, emotional, social, cognitive and spiritual aspects of our behavior (Cloninger 2009; Cloninger and Kedia 2011). Measures of physical, mental and social well-being are highly correlated (Cloninger and Zohar 2011). Improving physical fitness enhances emotional and cognitive performance and vice versa (Cloninger and Cloninger 2013; Cloninger, Salloum et al. 2012). As a result, effective treatment of diseases and promotion of health need to be tailored precisely to individuals or subgroups identified as having different needs based on an integrated person-centered consideration of their biology, goals, values and the resources of the community in which they live (Cloninger, Salvador-Carulla et al. 2014; Mezzich, Salloum et al. 2010).
If these broad claims that health and healthcare systems are multifactorial and complex are true, as I think is so, then Healy might be undermining his own hope to improve and re-humanize healthcare by the provocative statement that, "In fact, the reality is that within psychiatry, biology makes little difference, and biology makes less difference than previously in great swathes of the rest of medicine." On its surface, such statements appear outrageous, as if Healy were ignorant that there is strong evidence of the importance of genetic and biological processes in both normal human behavior and in susceptibility to physical and mental disorder. He also makes provocative statements that seem to denigrate the rigor of the psychology of well-being and social science of mental disorders as well. Nevertheless, it would be a mistake, I think, to assume he really dismisses the importance of biology, psychology or social science in medicine. If he did, there would be no scientific foundation for understanding disease or health promotion.
Rather, what I think he is saying is that a proper understanding of the complex interactions of biological, psychological and social influences is being handicapped by the limitations inherent in biomedicine, psychological medicine and evidence-based medicine (EBM) when any one of them is elevated to a position of dominance rather than being integrated in a balanced way. For example, evidence-based medicine proclaims itself the gold standard to guide practice, but it relies on simplistic case-control design in randomized trials that can only inform treatment of a mythical average person, not the particular individual who comes to a physician and visits for consultation in search of diagnosis and treatment. Healy says, "The reason for this [i.e., that biology makes little difference] is that social medicine in the form of Evidence Based Medicine, sometimes called the Epidemiological Paradigm, has taken over." In fact, Healy recognizes that the biology of the brain is important in understanding intrapersonal and interpersonal processes in clinical practice: "Clinical practice is becoming degraded and there is an increasing need for clinicians to relearn the skills of listening to, seeing and touching patients. It will have to engage with a biology that recognizes the brain as a social organ [underline added for emphasis] rather than with biobabble. It will have to shape an epidemiology that accepts you cannot design a proper controlled trial without understanding the biology being investigated. It will have to be able to take the dynamics of industrial power into account. Until such treatment becomes possible, individual patients will be left shipwrecked."
Emerging Opportunity for Person-centered Precision Medicine
In the USA, today, there is a major initiative in biomedicine that is being called Precision Medicine (Collins and Varmus 2015). Precision medicine is a medical model that proposes the customization of healthcare, with medical decisions, practices and/or products being tailored to the individual patient. It focuses on identifying subpopulations that differ in susceptibility to diseases and responses to various treatments, so that it tries to optimize precision of treatment and health outcomes within the joint constraints of optimizing outcomes, through consideration of molecular diversity, while being consistent with the goals and values of individuals and the resources of a public health system. This is similar to Personalized Medicine except that personalized medicine is often misinterpreted as implying that it is desirable or possible to design unique treatments for each individual and seldom is viewed from a public health perspective that needs to consider personal goals and values as well as public health resources.
Following the completion of sequencing of the human genome in 2003, there was a great expectation that many cures for human diseases would rapidly emerge because we then had the complete sequence. However, that did not occur. Highly heritable disorders, including all the Big Five chronic diseases, failed to yield their mysteries despite our knowing the complete human DNA sequence. What we found instead was that the average effects of individual genes account for only a minority of the heritability estimated from twin and adoption studies -- this is called the "missing" or "hidden" heritability problem. For example, liability to schizophrenia has a heritability of 81% but only 24% had been explained by the average effects of specific genes until September 2014, when my colleagues and I made a major advance in solving the hidden heritability problem (Arnedo, Svrakic et al. 2015). We showed that a person-centered approach was needed, in which we considered the interactive effects of many genetic and environmental events in subpopulations of people. We identified 8 subtypes of schizophrenia with distinct clinical features associated with specific clusters of genes. We were able to identify people with risk of 70 to 100% for developing schizophrenia, in contrast to the best effects of individual genes, which only increase risk from 1% in the general population to 2% or less. We were able to replicate the findings in three independent samples. Being able to identify whether a particular individual is a very high risk is essential for precision medicine, and simply was impossible previously. It lays the foundation for sensitive and specific laboratory tests of susceptibility and for causally-based prevention and treatment. In order to do so, it is crucial to take a whole person perspective in order to understand the interactions of many genetically regulated processes underlying the complex adaptive systems involved in common diseases (Arnedo, Svrakic et al. 2015). Then such options for diagnosis and treatment can be considered in terms of priorities in an integrated healthcare system, using people-centered approaches (Cloninger, Salvador-Carulla et al. 2014).
Essentially, the linear contrasts involved in early genome-wide association studies (GWAS) associated with the early personalized medicine era were inadequate to support person-centered or people-centered healthcare, just as EBM is inadequate to inform treatment planning of a specific individual. The limitation of EBM, early personalized medicine and linear GWAS is the same -- they are all based on average effects of individual variables and do not address the complex non-linear interactions involved in common disorders. There is little precision or reliability in predicting disease causation or outcome when only average effects of variables are considered. Now we are entering a new era in which the paradigm of precision medicine will fundamentally change what we can do, but for that to be effective for individual people and the population as a whole, we must retain our commitment to the principles of person-centered and people-centered healthcare (Cloninger, Salvador-Carulla et al. 2014). Otherwise, we risk domination of healthcare by profit motives and prejudices that perpetuate health inequities.
Historical Notes on Psychiatry in St. Louis
In order to foster cooperation and integration across biological, psychological and social sectors of healthcare, it is important that we avoid the false dichotomies that Healy emphasized in his analytical comments. When we accept or tolerate false paradigms, we often unintentionally color our perceptions and distort our conclusions. For example, consider Healy's assertions about DSM-III, in 1980 and the "invention" of biological psychiatry, in the 1980’s. He makes many contentious statements, but I will focus on this example because of my intimate knowledge of the details from having lived them myself. Healy says that DSM-III "was primarily an effort by an epidemiological movement within American psychiatry to corral psychoanalysis. The creators of the DSM (other than the St. Louis Department who were on the margins of the exercise) bridled at the slur of Neo-Kraepelinians that was thrown at them."
I am in a position to comment on this personally because I have been associated with the Department of Psychiatry at Washington University in St. Louis throughout my career. As a medical student (1966-1970) and throughout my psychiatry residency, I conducted research that I have continued from 1969 to the present on psychiatric diagnosis in close association with the psychiatrists, Sam Guze and Eli Robins and also with Eli's wife, the sociologist, Lee Robins. Already in 1969, we used semi-structured interviews with explicit diagnostic criteria that had been developed by clinical psychiatrists for use in both research and clinical practice (Cloninger and Guze 1970). The early biological neuropsychiatrist, Mandel Cohen (1907-2000), had initiated this approach at Harvard University between 1942 and 1953, where he developed operational criteria for manic-depressive disorder, anxiety neurosis and hysteria, in addition to mentoring Eli Robins, beginning in 1943 ( Cassidy, Flanagan et al. 1957; Cohen, Consolazio et al. 1947; Cohen, Robins et al. 1953; Cohen and White 1951, Cohen, Robins et al. 1953). On advice from Mandel Cohen, in 1949, Eli (1921-1994) and his wife Lee Robins moved to Washington University in St. Louis, where the head of psychiatry Edwin Gildea was also a biological psychiatrist (Gildea 1942, 1948; Landau 2009) and Eli could study neurochemistry with Oliver Lowry, the head of pharmacology (Landau 2009). The succession of chairmen following Gildea was Eli Robins in 1963, Sam Guze in 1975, and then me in 1989. By 1969, Guze and colleagues had developed a comprehensive diagnostic interview and set of diagnostic criteria for research in psychiatric outpatients, which I used in my early work (Cloninger and Guze 1970, Guze, Cloninger et al. 1983; Woodruff, Clayton et al. 1969). In 1970, Eli Robins and Sam Guze (1923-2000) articulated their basic principles for establishing the validity of psychiatric diagnoses, which they had already been using for several years (Robins and Guze 1970). Following these principles, a set of criteria for 14 psychiatric disorders that were judged to have been adequately validated were later synthesized in a publication organized by the chief resident in the department at the time, John Feighner (Feighner, Robins et al. 1972; Cloninger 1989). These 14 diagnoses were sufficient to diagnose at least 80% of people with the remaining 20% in a residual category, requiring further information or research (Cloninger 1989). From these earlier foundations and as part of a collaborative study of mood disorders involving Washington University in St. Louis and Columbia University in New York, the Research Diagnostic Criteria were developed in collaboration between Bob Spitzer, Jean Endicott and Eli Robins (Spitzer, Endicott et al. 1978). It was designed to improve reliability of diagnosis in clinical research, "particularly those related to genetics, psychobiology of selected mental disorders, and treatment outcome" and expanded the criteria to include 25 psychiatric illnesses (Spitzer, Endicott et al. 1978). Only later, in 1981, did Lee Robins develop the NIMH Diagnostic Interview Schedule for use by lay interviewers in order to make studies like the Epidemiological Catchment Area Study financially feasible (Robins, Helzer et al. 1981).
Therefore, it is inaccurate for Healy to suggest that operational diagnostic criteria, like those adopted in DSM-III, were "primarily an effort by an epidemiological movement within American psychiatry to corral psychoanalysis". The structured interviews and operational criteria were developed by psychiatrists for clinical and biological research more than 3 decades before the first epidemiological effort to adapt them for use by lay interviewers. It is true that Cohen, Robins, and Guze objected to the subjectivity of psychoanalytic formulations and sought diagnoses based on signs and symptoms that were more reliably rated (Landau 2009). The animus toward psychoanalysis was scientific, not personal.
The role of Robins and Guze in DSM-III was marginal, as stated by Healy, in one sense. Spitzer was in the head of DSM-III and was charged with producing a classification system that had a diagnosis for every patient that psychiatrists might encounter. He was also much more of a splitter and focused on specifying checklist criteria for hundreds of overlapping diagnoses, compared to 14 well-differentiated syndromes that were considered validated by Robins and Guze. In addition, in St. Louis, we always began our interviews with open-ended questions to allow the patient to tell his or her life narrative, in order to gain a sense of their development across their full life span, to record their spontaneous statements and to observe their mental status. Only after that would the lists of specific items or questions be checked in order to be sure that everything of interest for diagnosis had been covered already. That style of semi-structured interviews by skilled observers changed in epidemiological research with its reliance on lay interviewers who required highly structured interview schedules to attain reliability.
In addition, Eli Robins had a rule of "one person, one diagnosis". If someone qualified for multiple syndromes, then they would be rated as having uncertain diagnoses (i.e., "undiagnosed", or not otherwise specified, in DSM-III terms). The only exceptions to the rule of one diagnosis per person were that depressive syndromes or alcoholism that occurred secondary to a clearly preexisting disorder was diagnosed as "secondary depression" or "secondary alcoholism". As a result, the approach to diagnosis at Washington University was much more person-centered than what was popularized in DSM-III (Cloninger, Svrakic et al. 2006). Robins and Guze were always person-centered, whereas DSM fragmented the person into multiple comorbid syndromes under Spitzer's influence (Maser and Cloninger 1990). I did not think the differences in approach between Washington University and DSM were large or problematic initially, but Eli and Sam disliked the differences. I could not imagine that anyone would consider interviewing people without allowing them to tell their story, in narrative fashion, before commencing a checklist. Unfortunately, I have seen a marked deterioration in interviewing skills as trainees who rely on DSM begin checklists as their means to elicit information about their patients and focus almost exclusively on what leads to hospitalization without knowing the past history or their personal and social background well, especially when they begin their training on short-stay inpatient units. Consequently, in my experience, diagnosis in clinical practice is now often, but not always, dehumanized, impoverished and unreliable compared to the rich information previously available, when people actually listened to their patients in a person-centered manner.
Moving Forward with Person-centered Healthcare
In summing up, let me say that Healy is rightly concerned about the negative influence of market forces on what we do in clinical practice, but that does not mean person-centred and people-centred principles cannot help us move forward to establish a balance among biological, psychological and social approaches to healthcare. Profit motives increasingly constrain everything that physicians do, and business managers who are not dedicated to human well-being seek to reduce physicians to interchangeable units, thereby sacrificing the benefits of professional dedication to excellence and continuity of care. We often handle acute procedures well, but most of the cost of medical care is related to the treatment of chronic disease, which we are ineffective at preventing or managing in a procedure-focused payment system optimal for surgeons but not for primary care-takers (Cloninger 2013). Nevertheless, I remain hopeful that both ethical imperatives and the excessive cost of procedure-oriented practice must lead to change toward person-centred care, as has been called for by the National Academy of Medicine in the USA (IOM 2001, 2012). That hopeful view is most likely, in my opinion, to come from an integration of biological, psychological and social considerations in healthcare. Each of these components of well-being has a crucial role in developing an effective person-centred and people-centred healthcare system. We need to avoid perpetuation of the false dichotomous thinking that lies at the root of the current inadequacies in healthcare. Only then will we refloat the ship of person-centred and people-centred healthcare.
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Robert C. Cloninger
April 14, 2016