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Editorial   |    
An End to Kraepelinian Nosology?
Fred Ovsiew, M.D.
The Journal of Neuropsychiatry and Clinical Neurosciences 2000;12:297-299. doi:10.1176/appi.neuropsych.12.3.297

Kraepelin's dichotomy between manic-depressive illness and dementia praecox has formed the foundation of our current nosology of the functional psychoses, but its validity has been controversial for many years.1 What light do neuropsychiatric data shed?

Kraepelin himself had little doubt that schizophrenia (his dementia praecox) was a brain disease: "We are concerned here with a palpable pathological process in the brain"2 (p. 154). Moreover, he believed that he was initiating the replacement of descriptive psychiatry by a scientific nosology of disease entities, in accord with the accepted notions of clinical-pathological correlation that had established the foundations of modern medicine earlier in the 19th century.3 He fully expected that subsequent research would reveal the nature of the pathological processes, and he used disease course as a proxy.4 Decades after his systematic textbook descriptions of dementia praecox and manic-depressive illness, he recognized that "it is becoming increasingly clear that we cannot distinguish satisfactorily between these two illnesses and this brings home the suspicion that our formulation of the problem may be incorrect." Yet even then he insisted that "we must at all costs adhere to the basic difference between the disease processes concerned"5 (p. 28).

But are dementia praecox and manic-depressive illness distinct disease processes? It must first be noted that psychiatric diagnosis in general developed under the pressure of social factors unrelated to neurobiology.6 Severe forms of mental disorder were geographically and professionally segregated from milder forms because of their social consequences, with the result of obscuring possible continuities in underlying biology and alternative ways of clustering cases. Prognosis and troublesomeness were crucial for asylum decision-makers, neurobiology of no practical importance.7

Discrimination between two forms of functional psychosis cannot be soundly based on symptom clusters, as Kendell and Gourlay showed many years ago.8 Recent work confirms that the phenomenology of psychosis simply does not sort itself out into schizophrenia on the one hand and mood disorder on the other.9 Phenomenological data are supplemented by genetic epidemiological studies, which have been extensive and diverse. A former partisan of the Kraepelinian dichotomy concluded from the recent evidence: "From a familial/genetic perspective, there is no sharp division between schizophrenia and other psychotic disorders"10 (p. 54). Berrettini11 showed that for several of the loci linked by compelling evidence to one of the functional psychoses, strong evidence exists for linkage to the other; he concluded that "both family and molecular studies of these disorders suggest shared genetic susceptibility" (p. 245).

Neurodevelopmental precursors to both schizophrenic and affective psychosis include prenatal famine12 and exposure to influenza,13 winter birth,14 obstetrical complications,15 minor physical anomalies,16 dermatoglyphic anomalies,17 and anomalous social and cognitive development.18 The evidence from pathophysiology and neuropathology is limited by the absence of psychotic control subjects from many studies, but some abnormalities may be shared between supposedly distinct groups.19,20 The neuroimaging data suggestive of shared pathology, along with the neurodevelopmental and genetic data, are discussed in the Neuropsychiatric Practice and Opinion article by Curtis, van Os, and Murray21 that appears in this issue of the Journal. Although the data supporting shared risk are not all replicated and compelling, evidence for specificity of any biological factor is scant.

The issue is not whether Kraepelin described clinical syndromes with exquisite clarity. This he accomplished, even if the evidentiary basis of his research is questionable and the reasons for its domination of nosology for a century are the subject of little historical investigation.22,23 The question is whether these syndromes represent biological natural kinds, disease entities with specific pathological correlates, such that the century-long search for the "causes of schizophrenia" is a sensible project. If not, no shame accrues to Kraepelin, who was operating in the absence of modern statistical and technological methods and of current neuroscientific knowledge. In my opinion, current data, including the neuropsychiatric data, indicate that the psychotic disorders are best understood not categorically but dimensionally,2427 comprising parameters that vary continuously and can appear in various combinations—a "mix-and-match" nosology. From these combinations can certainly emerge the classic clinical pictures described by Kraepelin and seen in daily practice. The claim made here is not that schizophrenia and psychotic mood disorder are the same, with the same antecedents, or that they differ unidimensionally on a spectrum of severity. To the contrary, the analysis of specific symptomatic elements distinguishing various clinical states will be critical to advances in understanding of pathophysiology. But clinging to the idea, outmoded by biological data, that the classic clinical pictures represent distinct disease entities has been and continues to be a brake on progress. It is past time to abandon it.

A lesson from the classification of other neuropsychiatric illnesses is that only biological understanding—not clinical syndromes and not even neuropathology—can ultimately organize the data. For example, a single mutation of the prion protein gene can produce varying clinical pictures and variable pathological findings within the same family.28 Similar findings arise from the study of mutations of the tau gene producing frontotemporal dementia.29 Obviously, such biological understanding is not yet available to guide a classification of the functional psychoses. Research to bring it into existence must focus broadly on psychotic disorders;30 no study of the neurobiology of schizophrenia is complete without psychotic controls. Clinicians must move away from traditional but empty debates about whether patients "really" have schizophrenia or mood disorder—debates that often amount to trying to fit a peg with both round and square features into a square or a round hole, at great cost in clinical richness. The challenge is to devise diagnostic dimensions that have heuristic value for neuroscientific research and that can also guide clinical understanding and intervention.

Dr. Ovsiew is Associate Professor of Clinical Psychiatry at the University of Chicago (Department of Psychiatry, 5841 S. Maryland, Chicago, IL 60637; e-mail: f-ovsiew@uchicago.edu).

Jablensky A: The conflict of the nosologists: views on schizophrenia and manic-depressive illness in the early part of the 20th century. Schizophr Res  1999; 39:95—100
[CrossRef] | [PubMed]
 
Kraepelin E: Psychiatry: A Textbook for Students and Physicians, 6th edition (1899). Canton, MA, Science History Publications, 1990
 
Ackerknecht EH: Medicine at the Paris Hospital, 1794—1848. Baltimore, Johns Hopkins Press, 1967
 
Kraepelin E: Ends and means of psychiatric research (1919). J Ment Sci  1922; 68:115—143
 
Kraepelin E: Patterns of mental disorder (1920), in Themes and Variations in European Psychiatry: An Anthology, edited by Hirsch SR, Shepherd M. Bristol, UK, John Wright and Sons, 1974, pp 7—30
 
Ovsiew F, Jobe TH: Neuropsychiatry in the history of mental health services, in Neuropsychiatry and Mental Health Services, edited by Ovsiew F. Washington, DC, American Psychiatric Press, 1999, pp 1—22
 
Turner TH: A diagnostic analysis of the Casebooks of Ticehurst House Asylum, 1845—1890. Psychol Med 1992; monograph supplement 21:1—70
 
Kendell RE, Gourlay J: The clinical distinction between the affective psychoses and schizophrenia. Br J Psychiatry  1970; 117:261—266
[PubMed]
 
McGorry PD, Bell RC, Dudgeon PL, et al: The dimensional structure of first episode psychosis: an exploratory factor analysis. Psychol Med  1998; 28:935—947
[CrossRef] | [PubMed]
 
Kendler KS, Karkowski-Shuman L, Walsh D: The risk for psychiatric illness in siblings of schizophrenics: the impact of psychotic and non-psychotic affective illness and alcoholism in parents. Acta Psychiatr Scand  1996; 94:49—55
[CrossRef] | [PubMed]
 
Berrettini WH: Susceptibility loci for bipolar disorder: overlap with inherited vulnerability to schizophrenia. Biol Psychiatry  2000; 47:245—251
[CrossRef] | [PubMed]
 
Brown AS, van Os J, Driessens C, et al: Further evidence of relation between prenatal famine and major affective disorder. Am J Psychiatry  2000; 157:190—195
[CrossRef] | [PubMed]
 
Machón RA, Mednick SA, Huttunen MO: Adult major affective disorder after prenatal exposure to an influenza epidemic. Arch Gen Psychiatry  1997; 54:322—328
[PubMed]
 
Hultman CM, Sparén P, Takei N, et al: Prenatal and perinatal risk factors for schizophrenia, affective psychosis, and reactive psychosis of early onset: case-control study. BMJ  1999; 318:421—426
[PubMed]
 
Kinney DK, Yurgelun-Todd DA, Tohen M, et al: Pre- and perinatal complications and risk for bipolar disorder: a retrospective study. J Affect Disord  1998; 50:117—124
[CrossRef] | [PubMed]
 
McGrath JJ, van Os J, Hoyos C, et al: Minor physical anomalies in psychoses: associations with clinical and putative aetiological variables. Schizophr Res  1995; 18:9—20
[CrossRef] | [PubMed]
 
Gutierrez B, van Os J, Valles V, et al: Congenital dermatoglyphic malformations in severe bipolar disorder. Psychiatry Res  1998; 78:133—140
[CrossRef] | [PubMed]
 
van Os J, Jones P, Lewis G, et al: Developmental precursors of affective illness in a general population birth cohort. Arch Gen Psychiatry 1997:625—631
 
Rosoklija G, Toomayan G, Ellis SP, et al: Structural abnormalities of subicular dendrites in subjects with schizophrenia and mood disorders: preliminary findings. Arch Gen Psychiatry  2000; 57:349—356
[CrossRef] | [PubMed]
 
Benes FM: Emerging principles of altered neural circuitry in schizophrenia. Brain Res Rev  2000; 31:251—269
[CrossRef] | [PubMed]
 
Curtis VA, van Os J, Murray RM: The Kraepelinian dichotomy: evidence from developmental and neuroimaging studies. J Neuropsychiatry Clin Neurosci  2000; 12:398—405
[CrossRef] | [PubMed]
 
Weber MM, Engstrom EJ: Kraepelin's "diagnostic cards": the confluence of clinical research and preconceived categories. History of Psychiatry  1997; 8:375—385
[CrossRef] | [PubMed]
 
Roelcke V: Biologizing social facts: an early 20th century debate on Kraepelin's concepts of culture, neurasthenia, and degeneration. Cult Med Psychiatry  1997; 21:383—403
[CrossRef]
 
Maziade M, Roy M-A, Marinez M, et al: Negative, psychoticism, and disorganized dimensions in patients with familial schizophrenia or bipolar disorder: continuity and discontinuity between the major psychoses. Am J Psychiatry 1995; 152:1458—  1463
 
van Os J, Fahy TA, Jones P, et al: Psychopathological syndromes in the functional psychoses: associations with course and outcome. Psychol Med  1996; 26:161—176
[CrossRef] | [PubMed]
 
van Os J, Gilvarry C, Bale R, et al: A comparison of the utility of dimensional and categorical representations of psychosis. Psychol Med  1999; 29:595—606
[CrossRef] | [PubMed]
 
Verdoux H, van Os J, Maurice-Tison S, et al: Increased occurrence of depression in psychosis-prone subjects: a follow-up study in primary care settings. Compr Psychiatry  1999; 40:462—468
[CrossRef] | [PubMed]
 
Mallucci GR, Campbell TA, Dickinson A, et al: Inherited prion disease with an alanine to valine mutation at codon 117 in the prion protein gene. Brain 1999; 122:1823—  1837
 
Bird TD, Nochlin D, Poorkaj P, et al: A clinical pathological comparison of three families with frontotemporal dementia and identical mutations in the tau gene. Brain  1999; 122:741—756
[CrossRef] | [PubMed]
 
McGorry P: A treatment-relevant classification of psychotic disorders. Aust NZ J Psychiatry  1995; 29:555—558
[CrossRef]
 
+

References

Jablensky A: The conflict of the nosologists: views on schizophrenia and manic-depressive illness in the early part of the 20th century. Schizophr Res  1999; 39:95—100
[CrossRef] | [PubMed]
 
Kraepelin E: Psychiatry: A Textbook for Students and Physicians, 6th edition (1899). Canton, MA, Science History Publications, 1990
 
Ackerknecht EH: Medicine at the Paris Hospital, 1794—1848. Baltimore, Johns Hopkins Press, 1967
 
Kraepelin E: Ends and means of psychiatric research (1919). J Ment Sci  1922; 68:115—143
 
Kraepelin E: Patterns of mental disorder (1920), in Themes and Variations in European Psychiatry: An Anthology, edited by Hirsch SR, Shepherd M. Bristol, UK, John Wright and Sons, 1974, pp 7—30
 
Ovsiew F, Jobe TH: Neuropsychiatry in the history of mental health services, in Neuropsychiatry and Mental Health Services, edited by Ovsiew F. Washington, DC, American Psychiatric Press, 1999, pp 1—22
 
Turner TH: A diagnostic analysis of the Casebooks of Ticehurst House Asylum, 1845—1890. Psychol Med 1992; monograph supplement 21:1—70
 
Kendell RE, Gourlay J: The clinical distinction between the affective psychoses and schizophrenia. Br J Psychiatry  1970; 117:261—266
[PubMed]
 
McGorry PD, Bell RC, Dudgeon PL, et al: The dimensional structure of first episode psychosis: an exploratory factor analysis. Psychol Med  1998; 28:935—947
[CrossRef] | [PubMed]
 
Kendler KS, Karkowski-Shuman L, Walsh D: The risk for psychiatric illness in siblings of schizophrenics: the impact of psychotic and non-psychotic affective illness and alcoholism in parents. Acta Psychiatr Scand  1996; 94:49—55
[CrossRef] | [PubMed]
 
Berrettini WH: Susceptibility loci for bipolar disorder: overlap with inherited vulnerability to schizophrenia. Biol Psychiatry  2000; 47:245—251
[CrossRef] | [PubMed]
 
Brown AS, van Os J, Driessens C, et al: Further evidence of relation between prenatal famine and major affective disorder. Am J Psychiatry  2000; 157:190—195
[CrossRef] | [PubMed]
 
Machón RA, Mednick SA, Huttunen MO: Adult major affective disorder after prenatal exposure to an influenza epidemic. Arch Gen Psychiatry  1997; 54:322—328
[PubMed]
 
Hultman CM, Sparén P, Takei N, et al: Prenatal and perinatal risk factors for schizophrenia, affective psychosis, and reactive psychosis of early onset: case-control study. BMJ  1999; 318:421—426
[PubMed]
 
Kinney DK, Yurgelun-Todd DA, Tohen M, et al: Pre- and perinatal complications and risk for bipolar disorder: a retrospective study. J Affect Disord  1998; 50:117—124
[CrossRef] | [PubMed]
 
McGrath JJ, van Os J, Hoyos C, et al: Minor physical anomalies in psychoses: associations with clinical and putative aetiological variables. Schizophr Res  1995; 18:9—20
[CrossRef] | [PubMed]
 
Gutierrez B, van Os J, Valles V, et al: Congenital dermatoglyphic malformations in severe bipolar disorder. Psychiatry Res  1998; 78:133—140
[CrossRef] | [PubMed]
 
van Os J, Jones P, Lewis G, et al: Developmental precursors of affective illness in a general population birth cohort. Arch Gen Psychiatry 1997:625—631
 
Rosoklija G, Toomayan G, Ellis SP, et al: Structural abnormalities of subicular dendrites in subjects with schizophrenia and mood disorders: preliminary findings. Arch Gen Psychiatry  2000; 57:349—356
[CrossRef] | [PubMed]
 
Benes FM: Emerging principles of altered neural circuitry in schizophrenia. Brain Res Rev  2000; 31:251—269
[CrossRef] | [PubMed]
 
Curtis VA, van Os J, Murray RM: The Kraepelinian dichotomy: evidence from developmental and neuroimaging studies. J Neuropsychiatry Clin Neurosci  2000; 12:398—405
[CrossRef] | [PubMed]
 
Weber MM, Engstrom EJ: Kraepelin's "diagnostic cards": the confluence of clinical research and preconceived categories. History of Psychiatry  1997; 8:375—385
[CrossRef] | [PubMed]
 
Roelcke V: Biologizing social facts: an early 20th century debate on Kraepelin's concepts of culture, neurasthenia, and degeneration. Cult Med Psychiatry  1997; 21:383—403
[CrossRef]
 
Maziade M, Roy M-A, Marinez M, et al: Negative, psychoticism, and disorganized dimensions in patients with familial schizophrenia or bipolar disorder: continuity and discontinuity between the major psychoses. Am J Psychiatry 1995; 152:1458—  1463
 
van Os J, Fahy TA, Jones P, et al: Psychopathological syndromes in the functional psychoses: associations with course and outcome. Psychol Med  1996; 26:161—176
[CrossRef] | [PubMed]
 
van Os J, Gilvarry C, Bale R, et al: A comparison of the utility of dimensional and categorical representations of psychosis. Psychol Med  1999; 29:595—606
[CrossRef] | [PubMed]
 
Verdoux H, van Os J, Maurice-Tison S, et al: Increased occurrence of depression in psychosis-prone subjects: a follow-up study in primary care settings. Compr Psychiatry  1999; 40:462—468
[CrossRef] | [PubMed]
 
Mallucci GR, Campbell TA, Dickinson A, et al: Inherited prion disease with an alanine to valine mutation at codon 117 in the prion protein gene. Brain 1999; 122:1823—  1837
 
Bird TD, Nochlin D, Poorkaj P, et al: A clinical pathological comparison of three families with frontotemporal dementia and identical mutations in the tau gene. Brain  1999; 122:741—756
[CrossRef] | [PubMed]
 
McGorry P: A treatment-relevant classification of psychotic disorders. Aust NZ J Psychiatry  1995; 29:555—558
[CrossRef]
 
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