It was over 50 years until the end of the neo-Kraepelin framework (NKF). For the sake of clinical practice and scientific investigation, we briefly examine the historical backdrop of the NKF’s emergence in this editorial. Finally, we provide some thoughts on how this framework is adapting to the mechanical theory of biology that developed at the beginning of the 21st century.
Clinical accounts of psychiatry’s work in the 18th and 19th centuries have spawned a voluminous body of work. It was done with the idea that systematic observations constitute the fundamental technique for advancing knowledge, particularly the emerging discipline of behavioral medicine. In his Treatise On Insanity, Philippe Pinel (1745–1826), one of the fathers of modern psychiatry, wrote that the path to success required him to “notice successively every fact, without any other object than that of collecting materials for future use; and to attempt, as far as possible, to divest myself of the influence, both of my own prepossessions and of others. 1 There were no limits to what could be reported and discussed because of the wide range of human behaviors, emotions, and cognitions, as well as their quasi-infinite variations and combination from one subject to another and the limitless ways an observer could interact with and interpret the behavior of their patients.
Even while it’s admirable, the goal of eliminating one’s own influence and that of authority is currently deemed epistemologically incorrect, especially in the human sciences. Even the simplest descriptions and explanations are read/decoded according to a variety of theoretical framework, or discipline matrices,2 that are necessary for all stages of analysis, from descriptions to causal or other organizing principles. These masters of psychiatry contributed to the creation and development of various theoretical frameworks, in which masterfully described cases were used as exemplars to support specific models of psychopathology and were used to understand the life histories of patients, the pathways leading from normal to pathological behavior, the grouping of patients into diagnostic categories, and the treatment offered according to the models at hand.
Psychiatry’s history is littered with notable thinkers, but two in particular, Emile Kraepelin and Sigmund Freud, have had a considerable impact on the field’s development and direction. The birth of the NKF may be traced back to the development of these two frameworks, which are briefly discussed below.
Damian Jacob Sendler
Emile Kraepelin (1856–1922) is often regarded as the most influential contemporary psychiatric researcher.
3 Dementia prcox and manic-depressive illness are two distinct illnesses with distinct pathological processes, genetics, and biochemistry, which he defined as two distinct diseases in the European tradition of correlating signs and symptoms and tracking their evolution through time to define diseases. 4 It’s his method that comes closest to that of a doctor. For the first time in its history, the American Psychiatric Association approved the Kraepelinian categorization system. 5
One of the most prominent and popular theoretical frameworks for the mind and its workings in the 20th century, psychoanalysis, was founded by Sigmund Freud (1856–1939). He didn’t provide an exhaustive list of mental illnesses, but rather developed a theory of the psychic apparatus. The id, the ego, and the superego are three of the three primary human agencies, and the id (unconscious) plays a significant part in human behavior. As a result of conflicts between these agencies and the outside environment, symptoms that are interpreted as maladaptive defense mechanisms are uncovered. Psychoanalytic ideas have grown in popularity over the years, attempting to explain a wide range of indications and symptoms by drawing on Freud’s original psychic topography and all of its incarnations. Some philosophers of science slammed psychoanalysis as a pseudoscience despite its enormous influence on human sciences and psychiatry in particular.
American psychiatry was almost devoured by the ideas of Freud and his adherents in the 1960s and ’70s as a result of the Kraepelinian and other 19th-century frameworks of mental diseases.
7,8 One consequence of this is that there has been an enormous split in the field of psychoanalysis between the United States and the rest of the European continent. That British and American physicians and academics were using a same term to describe wildly different conditions was an epitome of this split. 9,10 Psychiatric diseases such as depression, manic episodes, and personality disorders were all included under the term “schizophrenia” in the United States. As a result of this shocking state of affairs, the American Psychiatric Association (APA) made significant efforts to improve the reliability of the designation of mental disorders, primarily through the creation of operationalized diagnostic criteria for mental disorders that were included in the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) published in 1980. American psychiatrists known as the neo-Kraepelinians spearheaded this effort and it was immediately adopted and used across the globe. For any genuine endeavor to create a scientific knowledge of mental diseases, a homogeneity of the language used by clinicians and researchers was a crucial assumption. The use of criteria with good inter-rater reliability was a key part of the attempt to standardize the language. One of the NKF’s key theoretical foundations was the rejection of any top–down theoretical framework for mental diseases. It was hoped that the use of credible criteria to diagnose diseases would lead to bottom–up theories of mental illnesses via an iterative validation process.
Even though the NKF has been widely accepted, it is vital to assess some of its repercussions and reflect on its position in light of key breakthroughs in biological psychiatry, including genetics and, to a lesser degree, brain imaging.
Efforts were made to exclude any symptoms or indicators that had a low level of interrater reliability. Since several of these signs and symptoms were critical to the classification of various mental diseases, they weren’t taken into consideration. While Bleuler regarded psychotic ambivalence a key symptom of schizophrenia, the DSM-III and later revisions did not include it because it did not meet the requirement of acceptable inter-rater reliability. However, phenomenologically tuned doctors may clearly detect ambivalence in certain patients, and this can be quite useful in understanding the patient and relating to their issues. Another characteristic, delusional mood, that was formerly prominent in the understanding of the early stages of psychotic disease, has all but gone from current psychiatric literature. Individuals who are experiencing the early collapse of the structure of consciousness as a result of the psychotic process often have this feeling of deluded mood. Delusions, for example, are defined in the DSM system as “false beliefs with some modifiers,” which contrasts with the sophisticated phenomenological analyses offered by some masters of psychopathology who consider delusion a “particular type of existence in the world, which should be analyzed on a case-by-case basis and not defined in advance by its non-reality,” as cited in the article. 11,12,13
Some of the rich clinical and semantic information that psychiatrists and researchers have laboriously uncovered over the previous two centuries has been lost as a consequence of the list-oriented psychiatry we’ve discussed here. The objective here is not to throw the finger at the DSM and its subsequent revisions for the deterioration of clinical psychiatry. Although the NKF never claimed the DSM as a clinical textbook for psychiatry and empathy, it was never meant to be used for that purpose. However, as Nancy Andreasen observed a few years ago, the “death of phenomenology” in America is an unpleasant unintended effect of the NKF. 1
Criterion-oriented research, despite its unintended consequences, has made an important contribution to research in the field of mental health because patients could be grouped under relatively reliable labels, studied with modern and tremendously sophisticated technology that has revolutionized the field of medicine (e.g., molecular biology, genetics, high-resolution brain imaging, high-throughput computational power). Our field would have devolved into a cacophony if we’d stuck with the muddled jargon we employed before the NKF. Psychiatry researchers were able to employ cutting-edge technology created in the previous 40 years to verify these criterion-defined diseases using this strategy (this is what most papers published in JPN attempt to do). The NKF’s second and most important goal is to raise awareness about these issues. In 1970, prominent neo-Kraepelinists Robins and Guze released the “manifesto” of this validation procedure. 14 For the validation of psychological illnesses, they recommended five criteria: a clinical description, laboratory testing, elimination of other diseases, follow-up research, and family research. A family research led them to conclude that “good prognosis’schizophrenia’ is not mild schizophrenia, but a different illness,” according to them. In light of recent advances in genetic and brain imaging research, we feel it is appropriate to ask if any major mental condition has acquired additional validity, as stated by Rubins and Guze, compared to our basic clinical understanding. However, it is possible to generalize from these instances to all mental diseases without losing generality.
In the late ’80s, the revelation of large gene effects related with schizophrenia15 and bipolar disorder16 was received with excitement, only to be severely challenged later on. Even while just a few instances may be significantly affected by a single gene mutation, it is now clear that no big mutations are responsible for any mental disorders (e.g., complement C4, RNA-motif binding 12, and SETD1A in schizophrenia). For the National Kidney Foundation (NKF), the picture painted by a massive worldwide joint effort (the Psychiatric Genetic Consortium; PGC) that collected and analyzed the genetic variations of thousands of patients and controls is gloomy. 113 single nucleotide polymorphisms (SNPs) were shown to be substantially linked with schizophrenia in a recent genome-wide association study (GWAS) including 36 180 Chinese subjects and a concurrent analysis of PGC data, 17 and each of these variations had a small impact. To account for the combined influence of hundreds of loci that might be involved in an illness in the context of a polygenic model, genome-wide association studies have created and validated the notion of the “polygenic risk score.” Genetic comorbidity between the most common mental diseases studied has been convincingly confirmed in this study. 18–21 One of the most remarkable findings came from a recent, huge research that examined the genetic similarities across 25 different types of brain illnesses (265 218 patients and 784 643 controls). Neurologic and psychiatric illnesses do not exchange genetic variations, creating a distinct line between the two categories of brain disorders. Psychiatric diseases do not have obvious borders between them like neurologic disorders do, according to the findings of this research. There is a strong genetic link between schizophrenia and ADHD, anorexia nervosa, bipolar disease, autism, and major depressive disorder. 22 In addition to SNPs’ lack of specificity, studies of genomic copy number variations (CNVs) have shown that these nonspecific genetic impacts on a wide range of mental diseases are also present. 23 These pathogenic CNVs are, in fact, thought to raise the likelihood of neurodevelopmental abnormalities and a variety of mental health issues (e.g., ADHD, autism, intellectual disability, learning disabilities, epilepsy).
Furthermore, new findings from genetic and molecular investigations provide insight on the underlying mechanisms of mental illness. Most of the genetic variations associated with schizophrenia are non-coding variants with minimal enrichment in functional gene categories,24 according to a recent study in the journal Genome Research. The “omnigenic” model was developed as a result of these findings, which were found to be common to a wide range of complex human diseases. It proposes that disease risk is primarily a result of genetic variants that are not specific to any one disease, but that their effects are nonetheless distributed widely through pleiotropic effects on transcription. We still have a long way to go in understanding how these widely dispersed impacts culminate in a particular illness. 25
The genetic architecture of the main mental illnesses therefore did not support the well-delimited entities reified as diseases using highly reliable criteria as a result. Molecular genetic studies show that the main mental diseases form a big group, with unclear boundaries between the various disorders. It is thus reasonable to say that even afflicted individuals of the same family would vary in thousands of genetic variations involved in the condition under the highly polygenic nature and complex genetic architecture of mental disorders. Even in the case of monozygotic twins, who share 100% of their DNA, the concordance for mental problems seldom reaches 50%. This, of course, raises the problem of nongenetic contribution, which has been shown to be nonshared in character in the majority of psychiatric diseases (as opposed to shared environmental risk factors within families). Given that our access to environmental variables is retroactive and polluted by different biases and circular causation, analyzing these nonshared components may be several orders of magnitude more complicated than genetic factors. Perhaps the non-shared environmental elements are not limited to physical environments, but encompass all of the “decisions” each individual makes throughout their life.
Empiricism has been a major epistemological force in science from its inception in the 17th century and has dominated the epistemology of science until the late 20th century, with a goal of discovering the laws of nature on which to base our knowledge of occurrences. Psychiatrists of the past aimed to achieve the same goal in their writings. Neuroscience and psychology, as well as other biological disciplines, spawned a new mechanical philosophy of science (NMP) that evolved around the turn of the century. NMP was sparked by the lack of universal rules in biological sciences, as opposed to those in physics and chemistry. In a publication by Machamer and colleagues published in 2000, the idea of mechanism was fully defined. 30 “Mechanisms are sought to explain how a phenomenon arises or how some significant process works,” according to this seminal publication. Entities and activities structured in such a way that they produce regular changes from the start or set-up to end or termination circumstances are known as mechanisms. There is a fairly broad definition of mechanisms in this NMP that encompasses various levels of analysis. A Cartesian machine isn’t always a “cogwheel” if it’s a “cogwheel” in the strictest sense of the word. A mechanism is an artifact, not a universal rule that governs everything.
A key point is that we aren’t criticizing NKF or its accomplishments in any way; rather, we feel that the NKF has been crucial to the advancement of mental health research over these last 50 years and has shown that mental illnesses are genuine and not just social constructions. Although genetic and brain imaging studies have been the most often used to validate the mental diseases in this paradigm, their findings show very limited specificity and very few consequences for individual patients. Phenomenological studies of patients’ experiences need and merit more education, study, and appreciation. New avenues for research on psychological/phenomenological mechanisms will open up as a result of this, and not just as “epiphenomena” that can be discarded once they are correlated to some molecular or brain activity phenomenon. This is a very useful clinical point of view (at the individual level). The NKF will have helped to the revival of common sense in that way.
