Isr J Relat Sci - Vol. 48 - No 4 (2011) : It’s Broken and It Can’t Be Fixed. A Conceptual Analysis at the Centenary of Bleuler’s praecox oder Gruppe der Schizophrenien

Jan Dirk Blom, MD, PhD, 1,2 and Herman M. van Praag, MD, PhD3

1 Parnassia Bavo Group, The Hague, The Netherlands 2 Department of Psychiatry, University of Groningen, Groningen, The Netherlands 3 Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands

Background ABSTRACT In 2011 it was 100 years ago that the Swiss psychiatrist Background: In 1911 Bleuler’s Dementia praecox Eugen Bleuler (1857-1939) published his famous book oder Gruppe der Schizophrenien served to launch Dementia praecox oder Gruppe der Schizophrenien schizophrenia as a group of nosological entities (1). The term schizophrenia had been introduced characterized by a “splitting of the psychic functions.” by him three years prior, in a rather inconspicuous Today, at the centenary of this opus magnum, we find paper entitled Die Prognose der Dementia praecox that the term is still in force but not the concept originally (Schizophreniegruppe) (2), but it was his impressive 420- envisaged by Bleuler. page monograph with its myriad clinical descriptions Method: For the sake of this conceptual analysis a that would propagate the name and promote its accep- literature search was carried out in PubMed, Embase, tance throughout the world. As indicated by the APA’s and the historical literature. status reports on the development of the new Diagnostic and Statistical Manual of Mental Disorders (DSM-5), to Results: The current schizophrenia concept, as be published in 2013, the name will be here to stay for operationalized in the DSM and other psychiatric the foreseeable future (3). But the concomitant concept classifications, is primarily indebted to Kraepelin and of a “split” or “fragmented” personality, as originally his degenerationist take on . That envisaged by Bleuler, was discarded a long time ago. approach is now obsolete, but the product still prevents Paradoxically, our present schizophrenia concept bears us from moving beyond the notion of schizophrenia the name coined by Bleuler, although it is based on the as a single-disease concept with multiple etiologies, body of thought of (1856-1926). That multiple clinical expressions, and an unfavorable body of thought derived to a significant extent from the outcome. 19th-century degeneration theory, a poorly discussed Conclusions: If we aim to investigate the biological doctrine which no longer serves as a source of inspira- underpinnings of psychotic symptoms, first a tion for psychiatry’s scientific discourse, but that exerts deconstruction of the schizophrenia concept will need its influence upon our thinking about psychotic disor- to take place. In this paper we highlight a method - called ders up until the present day (4-6). functionalization - which allows for such a deconstruction.

Limitations: Functionalization will probably require Aims a new scientific language, which will be largely discontinuous with our current nosological and In this paper we offer a concise reconstruction of the diagnostic systems. early developmental history of the schizophrenia concept. Our primary aim is to demonstrate that the 19th-century

Address for Correspondence: Jan Dirk Blom, MD, PhD, Assistant Professor of Psychiatry, Director of the Residency Training Program, Parnassia Bavo Group, Paradijsappelstraat 2, 2552 HX The Hague, The Netherlands [email protected]

240 Jan Dirk Blom and Herman M. van Praag degeneration theory should be granted a more significant ting of the psychic functions” may result in an interruption role in its shaping than has hitherto been customary, and of the normal process of association: “Thus the process that this indebtedness constitutes the major reason why of association often works with mere fragments of ideas psychiatry does not succeed in moving beyond the para- and concepts. This results in associations which normal doxical notion of a single-disease concept with multiple individuals will regard as incorrect, bizarre, and utterly etiologies, multiple clinical expressions, and an unfavor- unpredictable. Often thinking stops in the middle of a able outcome. Our secondary aim is to explore possible thought; or in the attempt to pass to another idea, it may directions for the concept’s future development. suddenly cease altogether, at least as far as it is a conscious process (blocking). Instead of continuing the thought, new ideas crop up which neither the patient nor the observer Method can bring into any connection with the previous stream For the sake of this conceptual analysis, a literature search of thought” (1). To Bleuler these two basic mechanisms was carried out in the English, German, French, and constituted the heart of that which he called schizophre- Dutch historical literature, PubMed, and Embase (up to nia. He gave the ensuing symptoms, including hallucina- October, 2010), using the search terms “schizophrenia,” tions and delusions, the status of “secondary” or - from a “dementia praecox,” “Bleuler,” and “Kraepelin.” slightly different vantage point – “accessory” symptoms. As regards the etiology of schizophrenia, Bleuler took a well-considered position in which both organic and psy- Results chological factors were taken into account (7). As to its The genesis of Bleuler’s schizophrenia concept prognosis and outcome, he showed himself somewhat In 1908 Bleuler introduced the term schizophrenia more optimistic than Kraepelin. Whereas Kraepelin because he was dissatisfied with the nomenclature used by reported an inevitable decline in 87 per cent of individuals Kraepelin. As he argued, dementia praecox - as Kraepelin with dementia praecox, Bleuler spoke of periods of remis- called it - was neither characterized by an unavoidable sion and exacerbation (1, 8). Nonetheless, Bleuler was dementia, nor by an unavoidable praecocitas. “For this convinced that the underlying “schizophrenic process” reason,” Bleuler wrote, “and because of the fact that one had a strong tendency to persist, even when superficially cannot derive adjective and substantive noun modi- the patient might appear to be “sane.” fiers from the expression dementia praecox, I take the The notion of an alleged correspondence between liberty of using the word schizophrenia to designate the Bleuler’s schizophrenia concept and Kraepelin’s demen- Kraepelinian notion” (2). Three years later he added, “I tia praecox concept has proved to be quite resistant (9). call dementia praecox ‘schizophrenia’ because (as I hope Apart from Bleuler, who characterized his work on to demonstrate) the ‘splitting’ of the different psychic schizophrenia as “nothing less than the application of functions is one of its most important characteristics. For Freud’s ideas to dementia praecox,” Kraepelin added the sake of convenience, I use the word in the singular to the myth of compatibility through numerous refer- although it is apparent that the group includes several ences to “schizophrenia” and “schizophrenic symptoms” diseases” (1). Thus he suggested that the two terms were in his later work (1, 8). On closer inspection, though, interchangeable, and that they referred to a single noso- Bleuler’s concept differed more from Kraepelin’s than logical category or group of disorders. the two men would openly admit. Thus Bleuler rejected The term schizophrenia (from the Greek wordsσχιζειν the very foundation of Kraepelin’s dementia praecox and φρην) was carefully chosen. It sought to reflect the concept, i.e., the notion of an inevitable deterioration patient’s peculiar loss of unity of the self, or “splitting of towards dementia. However, the greatest source of the psychic functions,” as Bleuler called it, and the ensuing tension between the two concepts would seem to lie emergence of isolated complexes which take turns con- in their level of operationalization. Kraepelin concep- trolling the personality. In Bleuler’s view, without a proper tualized dementia praecox as a -course unit, integration into the rest of the personality, these complexes defining it in terms of overt clinical features developing are bound to result in a fragmentation of the patient’s in a certain direction over time, whereas Bleuler consid- personality. As he asserts, “Thus the patient appears to ered it basically as a weakness of association, i.e., a dis- be split into as many different persons or personalities as turbance of mental functioning which might or might they have complexes” (1). According to Bleuler, this “split- not become manifest in overt clinical features. To him

241 Schizophrenia: It’s Broken and It Can’t Be Fixed overt psychotic symptoms, so important to Kraepelin’s (subsequently diagnosed with manic-depressive illness) concept, were merely of secondary importance. and those with an unfavorable one (referred to as the dementia praecox group) (19). Schizophrenia in the DSMs The initial reception of Bleuler’s schizophrenia concept Kraepelin’s ideas on degeneration was one of indifference (10). It took six years before it A fourth, and poorly discussed influence upon elicited any significant response from beyond the circle Kraepelin’s conceptualization of dementia praecox was of Bleuler’s personal collaborators. But during the 1920s, the 19th-century degeneration theory, a pseudo-scientific the usage of the term schizophrenia gradually surpassed doctrine which represented the opposite of evolutionary that of “dementia praecox,” and finally came to replace it. progress, and which dominated scientific thinking at In 1952, when the first DSM appeared, Bleuler’s concept the time (4-6). This idea of a regression towards earlier had been fully incorporated into American psychiatry developmental stages was quite a common notion at (11). Apart from a reference to Menninger’s concept of the time, one which both troubled and delighted 19th- reaction types, derived from the latter’s work with soldiers century Western society. It was troubling because of its in World War II, the name “schizophrenic reactions” fea- association with impending doom, based on the notion turing in the first DSM was a tribute to Bleuler’s idiom that Man, occupying the top rung of the recently discov- (12). Nevertheless, the disorder’s operational definition ered evolutionary ladder, could also take a tumble. On was chiefly a kraepelinian affair. As the authors of the the other hand, the idea was welcomed, because it pro- first DSM stated unambiguously, “This term [i.e., schizo- vided “normal” citizens with an explanatory model for phrenic reactions] is synonymous with the formerly used the occurrence of all kinds of misfortune and wickedness term dementia praecox” (12). The operational definition in society. In the classic reading of Morel, degeneration of schizophrenia in the DSM-IV-TR may be considered a involved a transgenerational process of physical, mental, direct descendent of the 1952 version, in which the bleule- and moral decline, bound to end in extinction of the fam- rian themes “weakness of association” and “splitting of the ily line within four generations (20, 21). In the words of psychic functions” are again nowhere to be found (4, 13). Alexander and Selesnick, “One generation might be sim- In conformity with Kraepelin’s approach, schizophrenia ply nervous, for example; the next generation would be is rather defined in the current DSM as a heterogeneous more nervous; the third might be entirely psychotic; the cluster of overt psychopathological symptoms (A crite- fourth generation would exhibit a full-blown degenerate rion), with a sublimated version of the “inevitable decline” state; and any future generations would be so demented notion in the form of the requirement that the symptoms that the family would become extinct” (22). Kraepelin be present for at least six months (B criterion) (14). was fascinated from an early age onwards with evolu- tionary theory, and later in life he wrote extensively on The origins of Kraepelin’s dementia praecox concept the merits of the degenerationist approach (23-26). He If we wish to become acquainted with the ideas that shared with Morel the lamarckian notion that physical infused our current schizophrenia concept, it is Kraepelin and mental disorders, but also addiction and immoral to whom we must turn. Historical accounts tend to empha- behavior, might affect Man’s hereditary material, and that size three major influences upon his work on dementia this dystrophic material might subsequently be passed on praecox. The first of these is the syndrome-course unit, to its offspring. As he wrote, “Even worse than the imme- as exemplified by Kahlbaum’s concept, which diate effects of alcohol and syphilis is the germ damage Kraepelin incorporated in the fourth edition of his text- [German: Keimschädigung] they bring about, which may book as a conceptual mould for dementia praecox (15-17). cause the degeneration of entire generations… At any Secondly, it has been argued that the concept of General rate, the number of mental defectives, epileptics, psycho- Paralysis of the Insane (GPI) served a similar purpose paths, of criminals, prostitutes, and tramps, who descend (18). The third influence was Kraepelin’s own catamnestic from alcoholic and syphilitic parents, and pass on their study, which he devised to provide empirical confirmation inferiority to their offspring, is interminable” (23). He for the theoretical notion of the syndrome-course unit. considered degeneration such a hazard to society, that This study involved the use of Zählkarten (i.e., “counting he urged the German government to promote scientific vouchers”), with which Kraepelin kept track of his clinical research “to throw light on the degeneration issue, to patients, and sorted out those with a favorable prognosis chart the nature and magnitude of this threat, and to

242 Jan Dirk Blom and Herman M. van Praag establish which measures can be taken to avert it.” As he posthumously published ego document, Persönliches, continued, “The signs are certainly ominous enough; it “All measures which have as their goal an improve- is up to us to alert the people and the government, and ment of our race, must… be directed at future rather to show them the way that should be taken to restore the than present generations, and seek to prevent the accu- health of our race” (23). mulation of an unfavorable hereditary constitution, germ With this recommendation, Kraepelin did not skate damage, and developmental disorders… From all these on thin ice. Over the years he had become an expert on considerations followed the exceptional meaning I had degeneration, ending up with a somewhat subtler version to attribute to determined racial selection. Apart from of the doctrine than Morel, in the sense that he envisaged many other unfavorable influences, of which I here only a certain protective influence from Nature itself against mention the undermining of natural selection through this invisible but devastating process, speculating that the economic measures, and the burdening of competent dystrophic material running in families might become individuals with the responsibility for the incompe- “diluted” by admixture with “healthy blood,” and arguing tent ones, it seemed precarious to me for the future of that “the damage will be partially compensated for by [the our people that our own nature was threatened ever degenerate’s] reduced life expectancy” (25). And yet his more by Jewry. It was the often discernable inclination fear of degeneration seemed to be even more acute than of the Semitic race to strive forwards not for the sake Morel’s. In addition to its direct threat through the propa- of intrinsic gratification, but for the sake of external gation of acquired pathogenic characteristics, he discerned advantages; their deftness, toughness, industriousness, an indirect threat posed by “domestication” (23,25,26,27). self-abnegation, the indissoluble solidarity; on the other As he wrote, “A second major type of cultural damaging hand, also the ruthlessness in the pursuit of goals and the can be summarized under the common name of domesti- choice of resources, which made it understandable that cation, a breaking away from the natural conditions of life” they gained victories at the cost of their more indolent, (25). As Kraepelin explained, Man’s increasing dependency peculiar, dreamy, indecisive, and agreeable compatriots. upon community life turned him into a dependent and Anxiously I saw how in science, too, the influence of the helpless creature, unaccustomed to physical strain and to Jews far surpassed their share in the population, and how the hardships encountered in a natural environment (25, disastrous this was in so far as here also the pursuit of 26). In his opinion, this entailed a state of Verweichlichung, success and recognition came to the fore rather than the i.e., a general weakening of the body, of which the weak- pursuit of truth and knowledge. That is why, although I ening of the brain was only a single aspect. This would had personal contacts with many Jews, and had a high in turn lead to a further susceptibility to degeneration regard for many of them, I could only look upon them as through reduced fertility and life expectancy, reduced the salt of the earth which may well have been necessary resistance against disease, increase of sexual aberrations, for the development of our own powers. A preponder- and increase of suicidal ideations (27). ant influence of the Jewish spirit upon German science, From 1899 onwards, Kraepelin arranged the noso- which unfortunately became ever more appreciable, logical categories in his psychiatric classification in appeared to me an exceptionally grave hazard, which accordance with their supposed indebtedness to degen- should especially be countered through the systematic eration, arguing that all mental disorders are caused by sustenance of the undeniable talents of the German race” it to a greater or lesser extent (27). In an effort to neu- (27, translation: JDB). tralize this virtually omnipresent threat, he called for These words, written down around 1924, indicate immediate action from the government, the scientific the extent to which Kraepelin had committed himself community, and society at large, advocating large-scale to degenerationism. With hindsight now, it may be epidemiological surveys and all kinds of preventive hard to look past the ideas that helped the U.S. govern- measures, ranging from the abstinence of alcohol to ment around 1900, as well as the Nazis during World positive eugenic measures (24, 25, 27). War II, to justify the negative eugenic measures they undertook against population groups designated by Kraepelin’s ideas on eugenics them as “degenerative” (28). But this is not the issue These eugenic measures involved a program of racial that should concern us here, nor are we to judge the way selection, aimed at the sustenance and promotion of the Kraepelin’s ideas may or may not have been misused talents of the German race (26). As Kraepelin wrote in his by others. Instead, we should keep firmly in mind that

243 Schizophrenia: It’s Broken and It Can’t Be Fixed his version of the theory had its roots in contemporary It has been argued that these figures may well reflect evolutionary thought, that his ideas on degeneration a genuine increase in the prevalence of the disorder, but and racial selection were not as extreme as those of they would seem to follow naturally from the increasing many of his contemporaries, and that, in his writings at looseness of Kraepelin’s diagnostic criteria. In any case, least, he never advocated any negative eugenic measures within 20 years what started out as an intriguing but rarely against any population groups. And yet we cannot avoid diagnosed disorder had grown into the most common the question whether these private reflections indicate diagnostic category in clinical psychiatry. Meanwhile, as that he had given in to the belief that certain groups of Boyle noted, it was as if everyone, including Kraepelin people can be intrinsically inferior to others, in a moral himself, had lost sight of the concept’s shaky foundations as well as a psychophysical sense, and that individuals (30). A man as brilliant as Kraepelin must have known within these groups may well be beyond help, simply that his critics were right. In the light of the above reflec- because of their membership of the groups in question. tions there is good reason to believe, then, that the demen- Which, if true, would be a far cry from the basic prin- tia praecox concept was designed as a prime example of ciples of natural science defended by him so vehemently degeneration. As Kraepelin wrote to Wundt as early as throughout the rest of his work. 1881, he was from the outset determined “to operational- ize the notion of degeneration in psychophysical terms” Degeneration and dementia praecox (32). Accordingly, he introduced dementia praecox in the Kraepelin’s thinking was steeped in degenerationism, like fourth edition of his textbook under the heading of the that of so many of his contemporaries. But how exactly psychische Entartungsprocesse (i.e., “mental degenerative did that affect his conceptualization of dementia praecox? processes”) (17). Although it would take another 15 years Kraepelin claimed that the disorder’s chief characteristic before Bleuler would pitch the term schizophrenia, it was was its unfavorable outcome, and that he had established there and then, in 1893, that the schizophrenia concept that fact by empirical means, with the aid of his Zählkarten. commenced its long and prosperous life (27). During the 1970s the International Follow-up Study of Schizophrenia (29) famously challenged the notion that The quest for a lathomenology deterioration was characteristic of schizophrenia, but The 19th-century degeneration theory has long ceased to it was also contested by Kraepelin’s contemporaries. As be a source of inspiration for psychiatry’s scientific dis- stated by men such as Meschede, Mendel, Siemerling, Jolly, course. However, if it is true that this pseudo-scientific and Grashey, his approach entailed a circular argument in doctrine helped to shape the dementia praecox concept, which clinical diagnosis served as a prognostic tool, and which in turn served as a conceptual mould for the first prognosis as a diagnostic tool (4, 19). This methodological DSM’s “schizophrenic reactions,” the diagnostic features fallacy was discussed at length by Boyle, who explained of our current schizophrenia concept are still largely clus- that Kraepelin did not follow the correspondence rules for tered together in a degenerationist fashion. Owing to the inferring hypothetical constructs, and that his concept was APA’s measure to allow no changes in the operational therefore invalid (30). Boyle also observed that each edi- definitions of the DSM’s diagnostic categories without tion of his textbook allowed for more and more symptoms any substantial support from empirical research find- associated with the disorder, thus steadily enlarging the ings, Kraepelin’s degenerationist outlook is exerting its group of matching cases without making the case for the influence up until the present day. This is why, on the concept itself any stronger. Table 1 reflects the accompa- eve of the DSM-5 era, psychiatry finds itself holding a nying increase in the number of diagnoses of dementia rich legacy of empirical data in the one hand, and a neo- praecox among inpatients at Kraepelin’s clinic (31). degenerationist concept in the other, asking itself how to relate the two. Which is an impossible task, as numerous Table 1. The prevalence of dementia praecox among inpatients authors have pointed out (4, 5, 30, 33-40). at Kraepelin’s clinic between 1892 and 1900 (adapted from Andreasen aptly portrays schizophrenia research as a Kuilman 1971) quest for the disorder’s lathomenology (41). That is to 1892 5% say, as the search for a neurobiological “lath” or narrow 1895 25% bottleneck that connects the established etiologies and 1900 50% risk factors for the development of with the observed at the phenomenologi-

244 Jan Dirk Blom and Herman M. van Praag cal level. So far, this search for a final common pathway psychotic disorder. More recent attempts to nibble away has proved to be rich yet unsatisfactory. One reason for parts of the territory traditionally attributed to schizo- this may be the lack of specificity of the empirical “facts” phrenia include a proposal to grant catatonia an inde- assembled over the past century (33, 42-45). One of the pendent nosological status (50), and the introduction painful conclusions from a meta-analysis of the results of the notion non-affective acute remittent psychosis of 20 years of empirical research into the neurobiologi- (NARP) for a prognostically favorable subgroup of psy- cal and neuropsychological correlates of schizophrenia is chotic disorders (51). In addition, schizophrenia’s con- that the effect size of these findings is very small, and that ceptual boundaries have been called in dispute because findings presented as “typical” for schizophrenia can also of its overlap with other psychiatric disorders and with be found in individuals with entirely different disorders, experiences of individuals without any psychiatric or with no psychiatric disorder at all (42). For this reason, diagnosis (52-54). In the light of today’s technological current empirical research tends to focus more and more advances there is good reason to expect an acceleration on subtypes and (endo-)phenotypes of schizophrenia, of schizophrenia’s conceptual deconstruction in the near as well as on individual signs and symptoms (46-48). future (55, 56). Neuroimaging techniques, as well as However, the more important reason why psychiatry is localizing techniques such as electro-encephalography waiting in vain for a proper lathomenology would seem (EEG) and magneto-encephalography (MEG), have to be that the constellation of signs and symptoms as brought back a lively interest in classical produced by Kraepelin’s degenerationist approach can- such as Capgras’ syndrome and other misidentification not be reproduced via alternative approaches such as the syndromes (57), autoscopy and out-of-body experi- dopamine hypothesis or, for that matter, any other non- ences (58), hallucinations (59), and metamorphopsias degenerationist approach (4, 49). (60), which would all seem to have neurobiological cor- relates that defy the boundaries of diagnostic categories Directions for future development as defined in the DSM and related classifications. Along At this stage it would seem paramount that the scien- with the promises of molecular biology, genetics, epi- tific community formulate a blueprint for programs that demiology, psychopharmacology, and neuropsychiatry, encourage further progress in schizophrenia research (33). these techniques hold the promise of generating a wealth To dispose of the concept altogether, or to exchange it for of fresh data in the near future that may serve as the a purely dimensional approach, would not seem to be an raw material for a new understanding of the biological appropriate solution. After all, an important virtue of the underpinnings of mental pathology. DSM and related psychiatric classifications is that they Practically, there are a number of conceivable ways provide psychiatry with a common language and uniform to deconstruct “schizophrenia” and arrive at empirically diagnostic criteria, which are both prerequisites for any validated disease entities, syndromes or psychopatho- coordinated international research program. Therefore, logical dimensions. They all involve the letting go of rather than getting rid of the notion schizophrenia, it psychiatric nosological categories as they are currently would seem advisable to work towards an awakening to defined, and a shift of our scientific focus towards the concept’s legitimate status, namely, that it is nothing underlying levels of conceptualization such as clinical more and nothing less than a working hypothesis. symptomatology, neuropsychology, neurophysiology, In this context we may remind ourselves that Bleuler psychopharmacology, and molecular biology. Starting himself was not too confident about the epistemic value from those levels, there are basically two different of his schizophrenia concept. As he wrote in 1911, he approaches, which we call the bottom-up and top-down had proposed the name for lack of a better one, mean- research paradigms. The bottom-up research paradigm while realizing that it might well have bearing on a group is exemplified by genomics, with its search for locations of disorders rather than on a single disease. The history in the genome that are associated with diseases. By tak- of psychiatry has proved Bleuler right, in the sense that ing patterns in the genome as its point of departure, this empirical findings and conceptual considerations have procedure is capable of detecting abnormalities which yielded a gradual fragmentation of the original concept may subsequently turn out to have consequences at the into smaller, separate concepts. Some classical examples level of clinical psychopathology. It is unlikely that such of such “splinter” concepts are dementia paralytica, dis- abnormalities will ever be linked one-on-one to any sociative identity disorder, autism, and alcohol-induced psychiatric disorder as we know them today, but they

245 Schizophrenia: It’s Broken and It Can’t Be Fixed are nevertheless highly informative. The clinical presen- chic dysfunctions. This is what Bleuler meant when he tation of the 22q11 deletion syndrome, for example, is designated hallucinations and delusions as symptoms far from identical with that of schizophrenia or autism. “secondary” to thought disorders. But the method of And yet this genetic disorder is associated with an ele- functionalization goes one step further, in the sense vated risk for both psychotic and autistic symptoms, and that in the final assessment, it seeks to link psychic dys- may thus yield novel insights into their mediation (61). functions to their biological determinants, which, after Likewise, the study of 5-hydroxytryptamine metabolism all, are more likely to correspond with disturbances in has yielded important novel insights into mood, aggres- psychological regulatory systems than with largely man- sion, and anxiety regulation, with all due consequences designed categorical entities (34). for our understanding of disorders as diverse as schizo- Because this method cuts across existing nosological phrenia, depression, anxiety disorders, and alcoholism, categories such as schizophrenia, depression, bipolar dis- without pretending to throw light on each and every order, autism, and so on, it has been proven to be much aspect of them (62). more fruitful than the search for biological determinants of psychiatry’s nosological categories (65). Ultimately, it Functionalization might well allow us to attain a psychiatric physiology, i.e., The top-down research paradigm involves a dissection a detailed chart of brain dysfunction underlying abnor- of diagnostic categories into their constituent parts, mally functioning psychological regulatory systems (33). and a subsequent search for relationships between Thus it holds the promise of rooting psychiatric diagnosis psychological and biological dysfunctions. We wish to much more firmly in its scientific discourse, and doing illustrate this paradigm by highlighting a method called much more justice to the individual patient with his or functionalization, introduced in 1965 by Van Praag and her unique psychopathology. The same holds true for Leijnse (63). Functionalization, or functional psychopa- treatment, which might benefit from this approach by the thology, involves a stepwise diagnostic procedure which possibility to offer tailor-made drug treatment, psycho- allows for a gradual transition from clinically relevant to therapy, and physical treatment, aimed at specific symp- scientifically relevant foci. It comprises (i) clinical diag- toms and psychic dysfunctions rather than at “disease nosis, (ii) syndrome diagnosis, (iii) functionalization of packages.” An obvious drawback is that this method will the diagnosis, and (iv) linkage to biological determi- force clinicians and researchers to learn a new scientific nants. The first step, clinical diagnosis, is the one used language which will be largely discontinuous with our by psychiatrists in their day-to-day practice. It involves current nosological and diagnostic systems. Nosological the assignment of given mental states to preconceived categories such as “schizophrenia” and “depressive disor- diagnostic categories such as schizophrenia, depression der” will need to be replaced by categories such as “hal- or ADHD, i.e., what doctors call “diagnosis,” and biolo- lucinatory syndrome with excess dopaminergic activity,” gists “identification.” The second step, syndrome diag- “hallucinatory syndrome with sensory deprivation and nosis, represents a departure from the traditional quest deafferentiation,” “ with serotonergic dys- for an underlying substrate of nosological entities such regulation,” and “mood and anxiety disorder with excess as these. Rather than aiming at unraveling the biological dopaminergic activity,” to name a few hypothetical exam- underpinnings of whole “disease packages,” it involves ples. Combined functional-biological categories such as the assessment of the symptoms or syndromes involved. these will not feature in the upcoming DSM-5. But if we Examples of these are highly specific ones such as verbal succeed in identifying them, DSM-6 might well come to auditory hallucinations, misidentification and mania, represent a first step towards a truly biologically based but also rather unspecific ones such as anxiety, fatigue, psychiatry. In that case, health insurance companies and apathy and insomnia. The third step, functionalization governments will be forced to develop new ways to decide of the diagnosis, is the cardinal one. It involves the list- which treatments will be refunded for which indications, ing of the psychopathological symptoms constituting and which ones will not. In short, life will become more the syndrome, and the examination, and – if possible complex for professionals and health insurers alike. But – quantification of the psychic dysfunctions involved the individual patient will no longer need to hear about a in their mediation (33, 64). After all, psychopathologi- so-called disease with multiple etiologies, multiple clini- cal symptoms – so important to kraepelinian nosology cal expressions, and an unfavourable outcome – which – are considered expressions of their underlying psy- certainly strikes us as a goal worth pursuing.

246 Jan Dirk Blom and Herman M. van Praag

14. American Psychiatric Association. Diagnostic and statistical manual Conclusion of mental disorders. Fourth edition, text revision. Washington, DC: American Psychiatric Association, 2000. As Bleuler spoke wisely, “Errors are the greatest obstacle 15. Kraepelin E. Psychiatrie. Ein Lehrbuch für Studirende und Ärzte. III. to the progress of science; it is of greater practical value to Band. Klinische Psychiatrie. II. Teil. Achte, vollständig umgearbeitete correct them than to achieve new knowledge” (66). One Auflage. Leipzig: Johann Ambrosius Barth, 1913. hundred years after the publication ofDementia praecox 16. Kahlbaum KL. Die Katatonie oder das Spannungsirresein. Berlin: Verlag von August Hirschwald, 1874. oder Gruppe der Schizophrenien, psychiatry should 17. Kraepelin E. Psychiatrie. Ein kurzes Lehrbuch für Studirende und face the fact that its schizophrenia concept is heavily Ärzte. Vierte, vollständig umgearbeitete Auflage. Leipzig: Verlag von indebted to the 19th-century degeneration theory, and Ambrosius Abel, 1893. 18. Peters UH. The German classical concept of schizophrenia. In Howells that empirical research into the nature and biological JG, editor. The concept of schizophrenia: Historical perspectives. underpinnings of psychosis is irreconcilable with its Washington, DC: American Psychiatric Press, 1991. ongoing use. Bleuler’s initial intention was to grant the 19. Berrios GE, Hauser R. The early development of Kraepelin’s ideas on term schizophrenia nothing but the status of a working classification: A conceptual history. Psychol Med 1988;18:813-821. 20. Morel B-A. Traité des dégénérescences physiques, intellectuelles et title. There should be no reason for us to do otherwise, morales de l’espèce humaine. Paris: Baillière, 1857. meanwhile allowing the concept’s gradual deconstruc- 21. Hermle L. Die Degenerationslehre in der Psychiatrie. Fortschr Neurol tion to take place while novel empirical and conceptual Psychiatr 1986;54:69-79. insights become available. The method we advocate to 22. Alexander FG, Selesnick ST. The history of psychiatry. An evaluation of psychiatric thought and practice from prehistoric times to the present. speed up the process of deconstruction is functional Northvale, N.J.: Jason Aronson, 1966. psychopathology or functionalization. Meanwhile, there 23. Kraepelin E. Zur Entartungsfrage. Centralblatt für Nervenheilkunde would seem to be little harm in maintaining the term und Psychiatrie 1908;19:745-751. schizophrenia for clinical purposes as long as we bear in 24. Kraepelin E. Die Erscheinungsformen des Irreseins. Zeitschrift für die gesamte Neurologie und Psychiatrie 1920;62:1-29. mind its preliminary status. 25. Kraepelin E. Hundert Jahre Psychiatrie. Ein Beitrag zur Geschichte menschlicher Gesittung. Berlin: Verlag von Julius Springer, 1918. References 26. Kraepelin E. Persönliches. Selbstzeugnisse. Burgmair W, Engstrom EJ, 1. Bleuler E. Dementia praecox oder Gruppe der Schizophrenien. Leipzig: Weber MM, editors. Munich: belleville Verlag, 2000. Franz Deuticke, 1911. 27. Van Bakel AHAC. Kraepelin over zichzelf. Een becommentarieerde 2. Bleuler E. Die Prognose der Dementia praecox (Schizophreniegruppe). uitgave van "Persönliches." Amsterdam: Uitgeverij Candide/Wrede Allgemeine Zeitschrift für Psychiatrie und psychischgerichtliche Veldt, 2001. Medizin 1908;65:436-464. 28. Meyer J-E. The fate of the mentally ill in Germany during the Third 3. www.dsm5.org/ProposedRevisions/Pages/SchizophreniaandOther Reich. Psychol Med 1988;18:575-581. PsychoticDisorders.aspx 29. World Health Organization. Schizophrenia. An international follow-up 4. Blom JD. Deconstructing schizophrenia. An analysis of the epistemic study. New York, N.Y.: John Wiley & Sons, 1979. and nonepistemic values that govern the biomedical schizophrenia 30. Boyle M. Schizophrenia. A scientific delusion? Second edition. London: concept. Amsterdam: Boom, 2003. Routledge, 2002. 5. Blom JD. Honderd jaar schizofrenie. Van Bleuler naar de DSM-V. 31. Kuilman M. Klinische en psychopathologische beschouwingen over Tijdschr Psychiatr 2007;12:887-895. de endogenie. Een literatuurstudie met betrekking tot de endogene 6. Pick D. Faces of degeneration. A European disorder, c. 1848-c. 1918. psychosen. Lochem: De Tijdstroom, 1971. Cambridge: Cambridge University Press, 1989. 32. Kraepelin E. Letter to Wundt, 1881. Universitätsarchiv Leipzig, Wundt- 7. Bleuler E. Lehrbuch der Psychiatrie. Sechste Auflage. Berlin: Julius Nachlaß, letter 299. Quoted in Van Bakel AHAC. Een psychologie van Springer, 1937. de endogenie. Over de theoretische pijlers van de Kraepeliniaanse 8. Kraepelin E. Psychiatrie. Ein Lehrbuch für Studirende und Ärzte. nosologie. Tijdschr Psychiatr 1998;40:752-764. I. Band: Allgemeine Psychiatrie. Sechste, vollständig umgearbeitete 33. Van Praag HM. “Make believes” in psychiatry or the perils of progress. Auflage. Leipzig: Johann Ambrosius Barth, 1899. Clinical & experimental psychiatry monograph no. 7. New York, N.Y.: 9. Adityanyee [no initials], Aderibigbe YA, Theodoridis D, Vieweg WVR. Brunner/Mazel, 1993. Dementia praecox to schizophrenia: The first 100 years. Psychiatry Clin 34. Shorter E, Van Praag HM. Disease versus dimension in diagnosis. Can Neurosci 1999;53:437-448. J Psychiatry 2010;55:59-64. 10. Müller C. Rezeption der Bleuler’schen Schizophrenielehre in der 35. Fischer AA. About concept formation in relation to treatment in zeitgenössischen Fachliteratur. In Hell D, Scharfetter C, Möller A, eds. schizophrenia. Some considerations from the viewpoint of the theory Eugen Bleuler. Leben und Werk. Bern: Hans Huber, 2001. of science. In Lader MH, editor. Studies of schizophrenia. Ashford: 11. Kline NS. Synopsis of Eugen Bleuler’s Dementia praecox or the group of Headley Brothers, 1975. . 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with many of the authors’ specific points, I find some of Schizophrenia: Cracked but their statements concerning Kraepelin’s work to be tenuous or wanting in factual accuracy. They seem to overplay the on the Way to Repair influence of the mid-19th century theory of degeneration Assen Jablensky, MD, Perth, Australia on Kraepelin’s outlook. Indeed, like many of his contem- [email protected] poraries, Kraepelin used arguments broadly derived from degeneration theory but he remained ambivalent towards The provocative title and “deconstructivist” discourse its highly speculative character (1). The authors’ claim that on schizophrenia in the article by Blom and van Praag the placement of dementia praecox under the heading of invites a commentary. Basically, the authors’ conceptual mental degeneration (psychische Entartungsprocesse) in the analysis is focused on: (i) a juxtaposition of Kraepelin’s 4th edition of Kraepelin’s textbook was definitive needs to original ideas about the nature of dementia praecox and be corrected. In fact, dementia praecox was removed from Bleuler’s reformulation of the latter under the name “degeneration” and placed under “metabolic diseases” in schizophrenia; (ii) a critique of the DSM-IV definition and the 5th edition of 1896 (2). Far from being an inveterate diagnostic criteria of schizophrenia (it remains unclear “degenerationist,” Kraepelin was much more “Darwinian” why the authors make no reference to ICD-10); and (iii) in his theoretical allegiance and can be regarded, with some a proposal of “deconstructing” schizophrenia by means of justification, as the progenitor of evolutionary psychiatry. a “functionalization” of the diagnostic approach. In one of his late articles – Patterns of Mental Disorders While agreeing with the general tenor of the article, and (Die Erscheinungsformen des Irreseins) (3), he referred to

248 Jan Dirk BloAmssen and J Habermanlensk M.y van Praag phylogenetically ancient, preformed brain mechanisms of sistent with his hypothesis about hierarchically structured reaction that could be released by pathological processes “registers” of syndromes that might recombine in their and find expression in three hierarchically ordered classes, clinical presentation in a “lawful” manner, determined or “registers” of symptoms and syndromes, including by the hypothetical extent of “destruction of nerve tissue” affective, schizophrenic and encephalopathic forms. This – the “encephalopathic” forms could easily incorporate construct bears close resemblance to Hughlings Jackson’s features of the schizophrenic and affective “registers,” but theory of dissolution of higher nervous function (4) with the reverse was not true – i.e., a primary affective disorder which Kraepelin undoubtedly was familiar. But, while could only occasionally attract symptoms belonging to the heeding to such meta-theories, Kraepelin essentially underlying “schizophrenic” register and never symptoms remained an empirical scientist in his attempts at “bring- from the “encephalopathic” register. This was retained as ing order to the confusing diversity of mental disorders” the Schichtenregel (the strata rule - that has been completely and “understanding their essential structure” (3). Thus, lost in the DSM “atheoretical approach” to psychopathol- he adopted Kahlbaum’s proposal for a syndrome-course ogy). Thus, Kraepelin’s long journey from the initial for- entity as the basic unit of a ‘natural’ classification of mental mulation of dementia praecox to the later and wider view of disorders but elaborated it further by blending into it the the complexity of the manifestations of the “forms” of men- role of pathoplastic factors including, above all, personal- tal illness remain pertinent for the research agenda today, ity traits, age and cognition. along with Bleuler’s reformulation of the concept to include Kraepelin’s concept of dementia praecox was conceived, non-psychotic (latent) forms and the important distinction in its early versions, as an amalgamation of Kahlbaum’s between fundamental and accessory symptoms. catatonia, Hecker’s hebephrenia, and Morel’s dementia Regarding the statement of Blom and van Praag that paranoides – all three developing in the course of time an Kraepelin’s “degenerationist” approach to the classifica- irreversible pattern of cognitive deficit and personality tion of psychoses cannot be reproduced via alternative deterioration. The criterion of outcome, defined in terms approaches, I should mention that back in 1987, I was of “curability” and “incurability” was the cornerstone of granted access to the Kraepelin archive at the Munich his nosological system and was largely a matter of conve- Department of Psychiatry. With my collaborators (5) nience – he realized that knowledge of aetiology and brain we selected one volume of Kraepelin’s counting cards pathology at the time could offer little guidance, while (Zählkarten) filled in for all 721 admissions to the depart- outcome was a variable accessible to the clinician and ment during the year 1908, the time when his nosological could be described with considerable refinement. Later system was already mature. Notably, only 53 (7.4%) of the on, Kraepelin acknowledged the diversity of the clinical patients were diagnosed as dementia praecox, as compared pictures subsumed under dementia praecox and articu- to 134 (18.6%) cases of manic-depressive insanity. The lated nine different “clinical forms,” ranging fromdementia majority (66.3%) of these cases were first admissions, and praecox simplex to circular, agitated and periodic forms, with the exception of 13 forensic patients, were voluntary thus anticipating what today is labelled as schizoaffective admissions. It is important to note that Table 1 in the Blom disorder. This certainly widened the scope of the original and van Praag article, which shows increasing proportions concept, and Kraepelin was faced with the boundary issue of inpatients being diagnosed as dementia praecox from between dementia praecox and manic-depressive insanity. In 1892 to 1900 and is claimed to reflect “the increasing loose- his 1920 article (3), he acknowledged that “it is becoming ness of Kraepelin’s diagnostic criteria,” is based on data from increasingly clear that we cannot distinguish satisfactorily the Heidelberg clinic where all admissions were involuntary between these two illnesses and this brings home the sus- (Kraepelin left Heidelberg for Munich in 1903). We ana- picion that our formulation of the problem may be incor- lyzed the content of the 187 cards for the two disorders by rect.” The solution of the problem was in recognizing that coding the symptoms and any other recorded clinical fea- “the affective and schizophrenic forms of mental disorder tures using the syndrome checklist and glossary definitions do not represent the expression of particular pathological of the Present State Examination (PSE) and processed the processes, but rather indicate the areas of our personality in data with the CATEGO computer classification algorithm which these processes unfold…it is conceivable that these which assigned ICD-9 diagnoses to the cases (6). We found two illnesses may…at times spread beyond the framework an overall concordance of 80.2% between Kraepelin’s origi- of their usual syndromes.” This was the first acknowledge- nal diagnoses and the computer-assigned ICD-9 diagnoses. ment of the existence of a continuum of psychoses, con- Furthermore, stepwise discriminant analysis revealed that

249 ScSchihizozophreniaphrenia:a Cra:u Itth’sc oBkedrsro'ken respbut and oonnse the It Can Way’t tBoe RFepairixed flat affect, fantastic delusions and catatonic signs had the phenotypes cutting across the conventional classificatory highest discrimination weights in the separation of demen- categories may be a signpost for future developments. As tia praecox from manic-depressive insanity (5). At a next suggested by Blom and van Praag, the mapping of clinical step, we applied grade of membership analysis (a form of phenomenology on specific brain dysfunction is becoming latent class analysis which generates “pure types”) to obtain feasible and the resulting functional psychopathology may a purely statistical grouping of the patients based on their in the future help recast the present nosology (9). symptom profiles and ignoring the original diagnoses (7). This independent taxonomic analysis produced three “pure References 1. Hoff P. Kraepelin and degeneration theory. Eur Arch Psychiatry Clin types,” clearly corresponding to , recurrent Neurosci 2008; 258 (Suppl 2): 12-17. unipolar depression, and dementia praecox, suggesting a 2. Kraepelin E. Psychiatrie. Ein Lehrbuch für Studirende und Aerzte. consistent “goodness of fit” between Kraepelin’s typology Fünfte, vollständig umgearbeiterte Auflage. Leipzig: Barth, 1896. and the actual clinical material on which it was based. 3. Kraepelin E. Die Erscheinungsformen des Irreseins. Zeitschrift für die gesammte Neurologie und Psychiatrie 1920; 62:1-29. English translation Finally, is the diagnostic concept of schizophrenia really by Marshall H. patterns of mental disorder. In Hirsch SR, Shepherd M, “broken” beyond repair? Despite the ever-increasing vol- editors. Themes and Variations in European Psychiatry. Bristol: John ume of research data, the search for causes of schizophre- Wright & Sons, 1974: pp. 7-30. 4. Jackson J Hughlings. Remarks on evolution and dissolution of the nia remains inconclusive and this raises doubts about the nervous system. J Ment Sci 1887; 33:25-48. validity of the diagnostic concept as presently defined. 5. Jablensky A, Hugler H, von Cranach M, Kalinov K. Kraepelin revisited: Such doubts are not without reason. However, simply A reassessment and statistical analysis of dementia praecox and manic- depressive insanity in 1908. Psychol Med 1993; 23:843-858. dismantling the concept is unlikely to result in an alter- 6. Wing JK, Cooper JE, Sartorius N. Measurement and Classification of native model that could account for the host of clinical Psychiatric Symptoms. An Instruction Manual for the PSE and Catego phenomena and research data consistent with a working Program. London: Cambridge University Press, 1974. hypothesis of schizophrenia as a broad syndrome com- 7. Jablensky A, Woodbury MA. Dementia praecox and manic-depressive insanity in 1908: A Grade of Membership analysis of the Kraepelinian prising aetiologically different subtypes, as anticipated by dichotomy. Eur Arch Psychiatry Clin Neurosci 1995; 245:202-209. Bleuler. The dissection of the syndrome with the aid of 8. Cuthbert BN, Insel TR. Toward new approaches to psychotic disorders: intermediate phenotypes is beginning to be perceived as The NIMH Research Domain Criteria project. Schizophr Bull 2010; 36:1061-1062. a viable strategy, and a recent proposal (8) to link genom- 9. Jablensky A. The diagnostic concept of schizophrenia: Its history, evolution, ics and neural circuit functioning as “hubs” for a range of and future prospects. Dialogues Clin Neurosci 2010; 12:271-287.

criteria. Unfortunately, however, such a clinical and Functionalization Revisited. statistical “goodness of fit” does not suffice to remedy the lack of validity of the schizophrenia concept. On A Reply to Jablensky’s the basis of Jablensky’s work we are convinced that, in “Schizophrenia: Cracked clinical practice, Kraepelin applied his own typology of psychotic disorders with unwavering rigor, and that he but on the Way to Repair” indeed lent the highest discrimination weights to flat Jan Dirk Blom and Herman M. van Praag affect, fantastic delusions, and catatonic signs in his attempts to distinguish between dementia praecox and We are grateful to Professor Jablensky for bringing manic-depressive insanity. And yet we wonder whether to our attention his own reanalysis of the data derived Kraepelin himself was aware of the extent to which he from Kraepelin’s Zählkarten, the outcome of which relied on this diagnostic algorithm. If so, he might well beautifully demonstrates the remarkable concordance have designated the symptoms at hand as “first rank between the diagnoses established by Kraepelin in symptoms” in the vein of Kurt Schneider, or he might 1908 and the way they can be established on the basis at least have mentioned them as symptoms of particular of ICD-9 criteria (1). We consider that concordance as diagnostic value – which he never did. further proof of the extent to which our current schizo- But let us assume, for argument’s sake, that the triad phrenia concept is indebted to Kraepelin’s nosological of flat affect, fantastic delusions, and catatonic signs work, not only when it is operationalized in terms of might indeed help us to devise a nosology of psychotic DSM criteria but also when this is done in terms of ICD disorders similar to Kraepelin’s, and that we would

250 Jan Dirk Blom and Herman M. van Praag thus be able to “reproduce” the operational criteria of from writing extensively on the subject, and from publicly dementia praecox (or “schizophrenia”) without taking warning the German government that something should recourse to any speculations about an unavoidable unfa- be done about it to avert its disastrous effects. vorable outcome, whether inspired by degenerationism All in all we are grateful to Jablensky for his thoughtful or not. Would that help us to increase the validity of the commentary on our conceptual analysis of the biomedical dementia praecox concept? Or of our current schizo- schizophrenia concept. Elsewhere, the concept was desig- phrenia concept? And even more importantly, perhaps, nated by him as “an overinclusive diagnostic category for would it alter the historical facts about the concept’s which no specific biological substrate is identifiable, proba- indebtedness to Kraepelin’s degenerationist outlook? bly because of admixture between different underlying dis- Jablensky expresses his concern that we may well have ease subtypes” (7). That characterization pretty much sums overplayed the influence of the 19th-century degenera- up our own position on the subject, although we would tion theory on Kraepelin’s work. We will leave it up to the like to add that at present even the existence of “underlying reader to decide whether that is what we did. We agree disease subtypes” must be considered uncertain. Maybe, with Jablensky that Kraepelin was thoroughly darwinian and hopefully, such subtypes will be identified in the near in his theoretical allegiance. He was introduced to evolu- future. But for as long as the concept has been around, cli- tionary thought by his brother Karl while he was still in nicians and researchers have been forced to do their jobs elementary school, only a few years after the first German without having them at their disposal. For that reason, the translation of the Origin of Species had been published. method of functionalization that we advocate seeks to link That introduction, along with the enthusiasm for evolu- psychic dysfunctions rather than “disease subtypes” to tionary thought expressed by his later teacher Wilhelm their biological determinants. This method, described in Wundt, sparked a life-long fascination with the subject some detail in our paper (8), does not involve a quest for (2). But at the time evolutionary thought was tightly a novel nosological concept but rather a sophistication of interwoven with the degeneration theory, and Kraepelin our current diagnostic approach. In the everyday practice freely mixed up elements from both discourses in his of cardiologists a diagnosis of myocardial infarction serves theoretical work. This is especially clear in his later writ- as a starting point for a detailed analysis of its biological ings, such as his 1920 article Die Erscheinungsformen des determinants. Functionalization seeks to allow for similar Irreseins (“The manifestations of madness”), in which he analyses in the area of psychiatric symptoms, thus paving unfolds his ideas on human evolution and on the role of the way for tailor-made treatments for individual patients, remnants from earlier developmental stages in the media- aimed at alleviating their specific symptoms and psychic tion of psychopathological symptoms (3). An overview of dysfunctions rather than broad “disease packages” such as his ideas on the nature and causes of degeneration is to “schizophrenia” or any of its alleged “endophenotypes.” be found in his 1908 essay Zur Entartungsfrage (“On the question of degeneration”) (4), as well as in his ego docu- References ment, Persönliches (5), written only a few years before his 1. Jablensky A, Hugler H, von Cranach M, Kalinov K. Kraepelin revisited: death. It is unfortunate that van Bakel’s richly annotated A reassessment and statistical analysis of dementia praecox and manic- translation of that ego document (2) was only published in depressive insanity in 1908. Psychol Med 1993;23:843-858. 2. van Bakel AHAC. Kraepelin over zichzelf. Een becommentarieerde Dutch, because in that edition we find an extensive treat- uitgave van "Persönliches." Amsterdam: Uitgeverij Candide/Wrede ment of Kraepelin’s reflections on the causes and nature of Veldt, 2001. degeneration, as well as on the threats it allegedly posed 3. Kraepelin E. Die Erscheinungsformen des Irreseins. Zeitschrift für die to public health. It may be true that Kraepelin remained gesamte Neurologie und Psychiatrie 1920;62:1-29. 4. Kraepelin E. Zur Entartungsfrage. Centralblatt für Nervenheilkunde ambivalent about the doctrine’s speculative character, and und Psychiatrie 1908;19:745-751. that empirical science is the field with which he deserves 5. Kraepelin E. Persönliches. Selbstzeugnisse. Burgmair W, Engstrom EJ, to be associated foremost in our collective memory. After Weber MM, eds. Munich: belleville Verlag, 2000. all, he was an exceptionally gifted and versatile man: a 6. Blom JD. Deconstructing schizophrenia. An analysis of the epistemic and nonepistemic values that govern the biomedical schizophrenia clinician, empirical scientist, taxonomist, progenitor of concept. Amsterdam: Boom, 2003. evolutionary psychiatry, transcultural psychiatrist, phi- 7. Jablensky A. Resolving schizophrenia’s CATCH 22. Nat Genet 2004;36: losopher, poet, musician, husband, father, and networker 674-675. 8. Blom JD, Van Praag HM. Schizophrenia: It’s broken and it can’t be fixed. avant la lettre (6). But however ambivalent he may have A conceptual analysis at the centenary of Bleuler’s Dementia praecox oder been about the degeneration theory, it did not keep him Gruppe der Schizophrenien. Isr J Psychiatry Relat Sci 2011;48:229-247.

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