The failure of the schizophrenia concept and the argument for its replacement by hebephrenia: applying the medical model for disease recognition

The present DSM and ICD delineations of schizophrenia do not identify homogeneous populations, and patients with different presentations satisfy the official criteria. Treatment response, illness course, and biological findings vary widely, indicating heterogeneity and not a common pathophysiology. The DSM/ICD construct of schizophrenia does not meet the standard of the medical model. This model for disease recognition delineates syndromes and then attempts to validate them by course and prognosis, response to treatment, and laboratory tests that ultimately lead to a clear picture of the pathophysiology and its etiology. This model has been successfully employed for centuries (1). We examine the historical record and empirical data for schizophrenia from this perspective and find that hebephrenia is a more homogeneous construct with distinctive and reliably identified clinical features and better fits the application of the medical model. Much of the literature on schizophrenia is based on samples that are heterogeneous in constitution. The non-specific findings are best summarized by Tandon et al.: Of 77 variables considered ‘important’ in schizophrenia, only 23 met the standard of support from ‘independent studies with consistent replication and no contradictory findings’ (2). The annual incidence and prevalence of schizophrenia varies fivefold across countries. The condition is highly heritable but with great genetic variability. Several environmental factors of ‘small effect’ play a role. Persons with the diagnosis have reduced brain volume with larger lateral and third ventricles than non-ill comparison groups. Dopamine agonists exacerbate and dopamine D2 antagonists ameliorate hallucinations and delusions. The heterogeneity in neurobiology, clinical manifestations, severity, course, and treatment response is great. No single feature is pathognomonic, and nosologic ‘boundaries between schizophrenia and other psychiatric disorders are indistinct’. The diagnosis is ‘characterized by an admixture of positive, negative, cognitive, and mood symptoms’. Generalized intellectual impairments occur. ‘There is a higher occurrence of obesity and cardiovascular disease’, an ‘increased prevalence of cigarette smoking and other substance use disorders’, and ‘increased suicidality’. The onset of psychotic symptoms usually occurs during adolescence or early childhood and is earlier in men. Mortality risk is doubled. This olio of non-specific observations does not support a syndrome or a disease. Genetic studies yield few positive results despite four decades of effort (3). The most accepted haplotype or allele for the cell protein dysbindin accounts for only 2% of the variance in individual differences in illness presentation (4). In these investigations, the laboratory procedures are better detailed and refined than are the descriptions of the patients studied. Unless a better defined phenotype is delineated, progress is unlikely in identifying an endophenotype or gene for schizophrenia. Traditional subtyping of schizophrenia into paranoid, disorganized, catatonic, undifferentiated, and residual forms focusing on the most prominent feature at the time of examination has not been productive (5, 6). Such sorting is mostly ignored in clinical practice and research studies. Many patients with manic depression are paranoid, catatonic, and behaviourally disorganized, but few exhibit the signs of emotional blunting, avolition, and formal thought disorder, the features that better define a syndrome and prognosis (7–12). The positive–negative symptom dichotomy also yields muddled results (11–13). Positive and negative features are frequently mixed. Patients identified by the presence of positive features also have negative features, resulting in substantial overlap. Formal thought disorder (considered a positive feature) is commonly associated with negative features, guaranteeing a mixture of symptoms in many patients (11). The suggestion of dividing schizophrenia into paranoid and non-paranoid forms, the latter to include catatonia and hebephrenia, has not been adopted (14, 15). Present DSM diagnostic criteria guarantee sample heterogeneity. Should most patients with hallucinations and delusions and without mood disorder or identifiable neurologic disease be labeled schizophrenic? Is schizophrenia a developmental disorder emerging early in life before psychosis or a disease afflicting any age group? Is a residual decline in function always present or can the illness remit? Is a 17-year-old isolating person with long-standing problems of emotional expression, volition, and social and motor awkwardness suffering from the same illness as a 50-year-old person with adequate premorbid functioning, if both meet the cross-sectional criteria? A person with preserved personality and normal emotional expression but experiencing persistent auditory hallucinations of first rank (e.g. voices commenting) and a person with catatonia and delusions of grandeur or disorganized speech both meet the criteria. Do they suffer from the same illness? Any two features permit the DSM diagnosis: hallucinations, delusions, ‘disorganized’ speech, ‘disorganized’ behaviour or catatonia, and negative symptoms. A ‘bizarre’ delusion (e.g. being controlled by electromagnetic waves) or a hallucination of sustained voices discussing or commenting in the third person about the patient is each sufficient alone; but reliance on a single feature to diagnose schizophrenia harkens back to Kurt Schneider’s notion of first rank symptoms (16). These features, while characteristic, are not pathognomonic of schizophrenia, even in the absence of coarse brain disease, nor do they predict treatment response or long-term prognosis (11, 17, 18). These weaknesses in the present formulation of schizophrenia led to our review. Applying general paresis as a model for a single disease frequently expressed as several syndromes, Wilhelm Griesinger (1817–1868) championed the mid-nineteenth century notion of what was later called a ‘unitary psychosis’– different syndromes considered stages of a single disease rather than expressions of different pathophysiologies (19). Sufferers were believed to pass through stages of melancholia, mania, and amentia (delirium), ending in dementia, although it was understood that some patients experienced several forms, while others experienced only one (20). With only one form of psychosis to consider, the profession’s energies were directed at determining etiology, not classification. Karl Ludwig Kahlbaum (1828–1899) rejected the unitary model and re-focused attention on delineating specific syndromes, seeking to link psychiatric disorders to biological turning points in life (21–23). ‘Paraphrenia hebetica’ was identified as the psychosis of youth and adolescence. He coined the term ‘hebephrenia’. Kahlbaum classified behaviour disorders by symptom patterns and illness course in 1863. Basing his studies on the 19th century’s tripartite image of the mind consisting of will, emotion, and intellect, he recognized an idiopathic progressively deteriorating condition affecting all spheres that became Kraepelin’s model for dementia praecox. He defined a postpubescent circumscribed illness affecting only emotion that is recognized in today’s mood disorders. Melancholia was included in this category, but he used the term ‘dysthymia’ for it. The concept of ‘cyclothymia’ was introduced as a low-grade form of what became ‘manic-depressive illness’. His disorders of intellect (e.g. paranoia, dementia paranoides) are today’s delusional disorder, and his disorders of will are exemplified by catatonia (23). At the Reimer Sanitarium in Görlitz, Kahlbaum was joined in 1866 by Ewald Hecker, a junior clinician (21, 22). In 1874, Kahlbaum published his monograph on catatonia, separating catatonia and hebephrenia (24). He presented catatonia’s distinctive clinical features, course, and a variety of non-specific brain autopsy findings as validation for catatonia being a discrete disease. Catatonia is now recognized as a syndrome associated with many conditions (25). A chronology is cited in Table 1. In 1871, Ewald Hecker (1843–1909) described ‘hebephrenia’ as a discrete illness by its symptoms and course, acknowledging Kahlbaum as the originator of the concept (26, 27). Hecker wrote: ‘Of course, not all mental illness appearing at puberty show the same development. Nearly all the clinical forms (mania, melancholia, etc.) can be found in this age group without appearing much different than they do at other ages. Hebephrenia, however, stands out as possessing both a specific course and a distinct symptomatology’. After presenting a typical case history, he concluded that ‘Hebephrenia… is a disease that always rises in connection with the development of puberty’ (27). Among his patients, the onset was between ages 18 and 22, the course distinctive, always ending in ‘hebephrenic dementia’; the disease process ‘limits further intellectual and emotional development and produces a particular form of mental disability’. The disease began with symptoms of melancholia but then psychosis set in. Amidst the symptoms of melancholia, ‘these patients often exhibit an irrepressible impulse to laugh and tell silly jokes’. [Witzelsucht] After discharge from the hospital, many subjects became vagabonds. Some philosophized grandly about life and science. Non-sequiturs and poorly constructed logical sentences crept into their speech. Some spoke and wrote in strange jargons. While all the symptoms would not be present in every patient, ‘the characteristic course that is invariably present, the early onset that is unmistakable, and the peculiarly silly form of dementia together make for a secure delineation of this type of illness’. As the illness advanced, the silliness was replaced by ‘hebephrenic dementia’, a state that did not approach the dementia of neurosyphilis (which was well recognized), but which corresponded to ‘an intermediate level of mental deterioration’. Hallucinations emerged. Later, listless apathy replaced the silliness. The distinctive and historically new element in Hecker’s description was the downhill course of an illness that began as melancholia, rapidly ending in intellectual deterioration, often over a period of a few months (26, 27). This concept was quickly accepted (28–30). Emil Kraepelin (1856–1926) adopted Kahlbaum’s classification system: ‘I got the starting point of the line of thought which in 1896 led to dementia praecox being regarded as a distinct disease, on the one hand from the overpowering impression of the states of dementia quite similar to each other which developed from the most varied initial clinical symptoms, on the other hand from the experience connected with the observations of Hecker that these peculiar dementias seemed to stand in near relation to the period of youth’ (31). Also: ‘I kept Kahlbaum’s and Hecker’s ideas in mind and tried to collect those cases, which inclined toward dementia as ‘mental degeneration processes’. Apart from Kahlbaum’s catatonia, I differentiated between dementia praecox, which essentially corresponded with hebephrenia, [our emphasis] and dementia paranoides with hallucinations, which quickly developed into mental deficiency’ (32, 33). Relying heavily on illness course, Kraepelin conflated the syndromes of catatonia, paranoia, and hebephrenia into the single condition: ‘I was forced to realize that in a frighteningly large number of patients, who at first seemed to have the syndrome of mania, melancholia, insanity, amentia or madness, the syndrome changed fairly quickly into a typical progressive dementia and in spite of some differences, the syndromes became increasingly similar. I soon realized that the abnormalities at the beginning of the disease had no decisive importance compared to the course of the illness’ (32). Kraepelin’s interpretation of dementia as a necessary outcome compounded a faulty reliance on catatonia and hebephrenia as one disorder. Many patients with severe mood disorder appear demented, and a large number become chronically dysfunctional when inadequately treated. Without effective treatments, severity and chronicity were common in Kraepelin’s experience, encouraging him to incorporate manic and melancholic patients, particularly those with catatonia, into his notion of dementia praecox. Outcomes for the different variations of dementia praecox were grim: ‘I must consider excluding the possibility of any recovery from this illness’. He reserved the label of hebephrenia only for those cases in which the presence of ‘agitation’ creates ‘the more unfavorable kinds of prognoses’ (34). The image shifted in successive editions of his textbook. In the sixth edition, Kraepelin divided dementia praecox into hebephrenic, catatonic, and paranoid forms. He retained Hecker’s ideas of hebephrenia (35). In 1899, he included délire chronique (36) within dementia praecox. In the seventh edition (1904), he all disorders that led to and intellectual dementia was included but the were by delusions without or of emotional In the edition Kraepelin introduced the term to The term has the as did not but rather a into in and with of emotional expression was also Hecker’s of the Kraepelin descriptions of highly in with and and all in dementia with few The patients with silly dementia to of the cases of dementia praecox Among other patients with dementia praecox, Kraepelin recognized that some (31). The of Kraepelin’s concept of dementia praecox on both catatonia and hebephrenia being of a single disease with a deteriorating the of his he had dementias before age and all forms of mania, melancholia, and mood disorders into the two of dementia praecox and This formulation became the of the ICD and DSM conditions with the same course have similar and faulty construct of the illness on the tripartite mind determining to psychiatric of in Kraepelin’s concept of dementia praecox in it symptoms were identifiable in all the patients, with symptoms in Kraepelin one disease. the possibility of several with ‘hebephrenia’ as the form In that dementia was a of the He rejected the notion of and hebephrenia at any age rejected silly behaviour as a for the diagnosis and the concept of ending in He retained the term ‘hebephrenia’ it no to the accepted and the dementia praecox He used the of and features to the His and were he had the to in before two that in being and the of as the of and His were not in and are not commonly in psychiatric The heterogeneity of samples identified by approach led to to from prognosis patients the of the disorder and disorder and psychosis each of with These are now conflated as psychotic disorder. has been the heterogeneity patients with schizophrenia, some to the image of In the Karl of at the of found hebephrenia to be symptoms. wrote of in hebephrenia, an illness symptom is not silliness. was not a group of syndromes but a single disease, the of progressive dementia with symptoms’. and catatonia were its symptoms Karl of at the in regarded and being as the characteristic of hebephrenia, one of his While has not been his description of psychosis of hebephrenia is consistent with Hecker’s model. Kurt the notion of rank as specific features in the absence of coarse brain disease, were pathognomonic of schizophrenia with its prognosis first rank symptoms are found in and melancholia as well as in schizophrenia, they form the for the DSM for schizophrenia. occurrence is considered pathognomonic as the schizophrenia diagnosis is if the patient only the of sustained voices discussing or commenting in the third person about the patient or has a ‘bizarre’ delusion (e.g. a has been in a that The features of hebephrenia are in Table features are not have been historically associated with hebephrenia, and the motor and features are to brain of emotional expression, avolition, and are features of the syndrome function are an accepted of the brain particularly to environmental as and in who later schizophrenia The diagnosis of hebephrenia four of emotional expression and formal thought disorder as speech and delusions of or auditory and in or motor cognitive, emotion, and problems are commonly Catatonia is not a feature of the it is defined and is treated. presence in mania, or melancholia in the of the present illness or in the attention to the mood disorders and the diagnosis of is historical and support for schizophrenia as a single disease. The historical however, the concept of hebephrenia and its specific criteria. Hecker’s model of hebephrenia was of a brain illness with in emotional expression, volition, motor functioning, speech and and in childhood with emerging and was in adolescence and by hallucinations and other and delusions and then by a persistent but not progressive decline in cognitive, and The syndrome is The negative features and formal thought disorder are found together in of psychotic patients who have mood disorder nor defined neurologic disease patients as syndrome and studies support the of hebephrenia but find samples of to be heterogeneous In a of a large and et identify as by both and symptoms, outcome with deterioration, no or manic symptoms, of and and a illness of manic depression but more schizophrenia they a ‘hebephrenia’ group with a of deterioration, and or The better fits the hebephrenia While syndrome schizophrenia a consistent other of psychotic disorders exhibit features are over even between of psychosis Such patients have in with social and and to to Formal thought disorder, speech and is also associated with in response to illness course, and similar in Hecker’s detailed formal thought disorder was by the speech patterns of his Patients with hebephrenia function poorly in their many function well to lead and to the with negative features and early onset of illness are most to become chronically Patients with and reduced before psychosis to to have persistent symptoms, and chronically function poorly Hecker’s of childhood in hebephrenia are consistent with described reduced emotional expression and volition, social and motor and as features of schizophrenia. the with schizophrenia exhibit these childhood The are heritable who exhibit emotional expression, social and problems experience a characteristic syndrome later in Genetic and factors (e.g. to the The more these the more severe are the childhood abnormalities and the later psychotic While and social are associated with hebephrenia, the of a course the first is patients with schizophrenia, and manic depression are compared on these no points of the are found outcome is in each group with substantial chronicity in of symptoms and decline in in those with a syndrome Mortality are higher than Kraepelin’s concept of a prognosis dementia praecox and a prognosis manic depression is found only at the of a when the present DSM criteria are to patient While dementia is nor even the most common outcome of schizophrenia, are recognized particularly those consistent with The even when with the most The are associated with negative features and formal thought disorder, but not with hallucinations and delusions Some to be a diagnostic for schizophrenia, but while most have problems consistent with these are not pathognomonic the of hebephrenia to a of patients and then course has not been often but several the of psychotic disorders from a et used patterns with the features described in the in a sample to successfully predict to psychosis over a in with a positive for had clinical features as and thought and and et a clinical model for psychosis in a sample of and also at risk of at risk of psychosis were or had and were to have These patterns are consistent with the image of hebephrenia While for schizophrenia ameliorate symptoms to some to of the typical and and the symptoms of hallucinations and delusions No treatment the symptoms of of emotional expression, and Of the present of schizophrenia, effective are for the and paranoid Patients with catatonia well to and to usually the signs of catatonia, and often the associated signs of psychiatric illness (25). was the of catatonia as a syndrome and not as a type of schizophrenia that clinical which developed its present treatment delusions be by and by although than the studies of treatment response in hebephrenia are but it would We a or identifying The results from patients being with consistent with development are for the Kraepelin described and motor signs in his patients and a of dementia praecox volume is in patients with schizophrenia negative features, even in and abnormalities in and function are also and signs are in The abnormalities are associated with the negative features of the condition patients with negative features also exhibit and a to disease The are found early in the condition The and are of a that also the motor features of the severe forms of schizophrenia can be understood as expressions of in this the of the progress is in identifying of for schizophrenia. yield positive results (4). The studies for schizophrenia no clear findings (3). The results are by the of patients with the The in the for schizophrenia has been to the and for the the of several different and the possibility that the be expressed as a toward a psychotic illness but not for a specific psychotic condition A more of the for ‘the of is that schizophrenia, as now is not a single disease. The is to the for the of mental Kraepelin that of his patients with dementia praecox had a for psychosis and many studies for psychosis of psychotic patients and of as and are consistent with a genetic A few however, identified patients by criteria specific for Among those that the for hebephrenia as or symptom is with a between the forms and mood disorder studies that define by criteria for hebephrenia can this Unless hebephrenia as a genetic and biological studies will The historical record does not support schizophrenia as a diagnostic from Kahlbaum and Kraepelin to a disease that does not as a single which much psychiatric and to the notion do not a homogeneous and are to on and non-specific criteria to identify who are and who or who are but who do not into a clear criteria and effective to the diagnosis are without mood disorder or identified neurologic would well as the present criteria. The only condition in the schizophrenia that has not been rejected by is hebephrenia or schizophrenia. is a syndrome and be considered a for the present construct of schizophrenia. of the of psychotic conditions support the hebephrenia but the of the syndrome to be hebephrenia as a of schizophrenia will not is not a of schizophrenia. is schizophrenia. are well defined and its the construct of schizophrenia. We are to of the of who the and the

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