Wernicke–Kleist–Leonhard Pathway

   (from 1900)

   The central theme in this pathway is classifying psychotic illness not on the basis of outcome, as Kraepelin did, but on the basis of hypothetical underlying neurological impairment or common family history. The pathway had the effect of significantly narrowing the diagnosis schizophrenia and of differentiating a number of schizophrenia-like illnesses and cyclical illnesses—of which Kleist and Leonhard enumerated at least 26 varieties— that may be differentially responsive to treatment.

   Wernicke’s "sejunction" theory (1900). Carl Wernicke (1848–1905), a student of Heinrich Neumann’s (1814–1884) in Breslau, became in 1885 Neumann’s successor to the chair of psychiatry and neurology in Breslau. Wernicke had already established a large name for himself with his discovery in 1874 of the sensory speech center in the temporal lobe. This finding alerted Wernicke all the more to the importance of neurology in understanding behavior and led him to an elaborate hypothesis—later scorned by Karl Jaspers as "brain mythology"—about the underlying brain mechanisms of psychiatric illness. In his textbook of clinical lectures in 1900 (Grundriss der Psychiatrie in klinischen Vorlesungen), Wernicke postulated a "sejunction"—or loosening of the continuity of the association fibers—as the underlying source of psychosis. As he told the medical students, "We shall indicate this process of loosening [Loslösung] with the appropriate term of sejunction, and we cannot avoid seeing in it an [organic] defect, an interruption of continuity, which must correspond to the failure of certain association connections" (p. 109 of the 2nd ed., 1906). Wernicke asserted that "disorientation is the fundamental symptom of all psychoses," best diagnosed clinically by the patient’s expression of "perplexity" (Ratlosigkeit) (p. 210). In 1904, Wernicke became professor of psychiatry in Halle. His contribution to the pathway was really his gift for careful observation.

   Karl Kleist’s cycloid psychoses (1879–1960). Kleist was briefly an assistant of Wernicke’s in Halle before the latter’s death in 1905. Kleist shared Wernicke’s biases both about brain pathology (about half of Kleist’s lifetime writing was neurological in nature) and about psychopathology. Kleist set out to devise "psychic disease systems"; in 1908–1909 he studied with neurologist Ludwig Edinger (1855–1918) in Frankfurt and with Alois Alzheimer in Munich; he wrote his Habilitation thesis with Gustav Specht (1860–1940) in Erlangen, beginning to study systematically the chronic psychoses. In 1920, he became professor of psychiatry in Frankfurt and head of the City Psychiatric Clinic. Here, he founded the Frankfurt Research Institute for Brain Pathology and Psychopathology (Frankfurter Forschungsstelle für Gehirnpathologie und Psychopathologie).

   Kleist held a deep animus against the stark Kraepelinian division between manicdepressive illness and schizophrenia and sought to identify separate illness entities in the borderland between the two large diagnoses. It was Kleist’s idea that all these separate disease entities could, in theory at least, be localized in the brain. As early as 1911, Kleist devised a set of diagnoses regarding motility, running from "hyperkinetic motility psychosis" to stupor ("akinetic motility psychosis"); motility means involving motor symptoms (see his article in the Zeitschrift für die gesamte Neurologie und Psychiatrie, 1911). By 1921, Kleist had proposed a group of recurrent "sudden, fully-formed constitutional psychoses" (autochthone konstitutionelle Psychosen) different from Kraepelin’s manic-depressive illness; the group of psychoses were nondeteriorating, with a stable clinical picture over time, and included principally periodic mania, periodic melancholia, and some circular psychoses. (Kleist used the term "degeneration" as a synonym for constitutional, meaning predisposed; many were demonstrably hereditary. He summarized his work in 1921 in the Zeitschrift für die gesamte Neurologie und Psychiatrie.)

   In 1926, Kleist suggested the concept of the "cycloid degeneration psychoses" in the Archive for Psychiatry and Nervous Diseases (Archiv für Psychiatrie und Nervenkrankheiten) to characterize a wide variety of mental phenomena that circled between two poles (but were not Kraepelin’s manic-depressive illness). There were basically two kinds: the confusional psychoses that alternated between agitated confusion and stupor, and the motility psychoses that alternated between hyperkinesis and akinesis. In further work, he identified several other cyclic psychoses.

   Of the three members of the pathway, it was only Kleist who made a big issue of underlying neurological impairment; Wernicke was more interested in hypothesized brain communication; Leonhard in genetics. (English-speaking readers will find a clear explanation of Kleist’s and Leonhard’s classifications in an article by Gottfried Teichmann of the University of Würzburg—a center sympathetic to the Wernicke–Kleist–Leonhard pathway—in Psychopathology, published in 1990.)

   Frankfurt psychiatrist Edda Neele (1910–) was part of the Kleist team, and she analyzed all patients with "cycloid" psychoses to come through the Frankfurt clinic between 1938 and 1942. Her 1949 monograph, The Phase-like Psychoses According to Presentation and Family History (Die phasischen Psychosen nach ihrem Erscheinungs-und Erbbild), summing up this research provided evidence that Kleist’s disease categories did correspond in part to natural genotypes. (She is, on the basis of this work, apparently the first woman to have written a Habilitation in Germany in psychiatry.) Neele used Kleist’s concepts "one-pole" and "two-pole" disorders ("einpolige und zweipolige Erkrankungen").

   In 1953, Kleist introduced the terminological refinement of calling circular psychoses either "unipolar" or "bipolar" (for the group of psychoses that he called "Phasophrenien") in the Monatsschrift für Psychiatrie und Neurologie. This later became a fundamental terminological bulwark of the DSM system.

   In sum, Kleist’s contribution to the pathway was to construct diseases from Wernicke’s syndromes and then attempt to validate them in follow-up studies. Besides the Kraepelinian schizophrenia and manic-depressive illness, Kleist distinguished a number of "grey-area psychoses" (Randpsychosen) having a good outcome.

   Karl Leonhard’s endogenous psychoses (1957). Leonhard continued Kleist’s efforts to identify "good-outcome" (gutartige) psychoses.

   Karl Leonhard (1904–1988) joined Kleist at the Frankfurt City Psychiatric Clinic in 1936, and in 1937 produced his own monograph on anxiety-depression among older patients (Involutive und idiopathische Angstdepression). It was this work on the genetics of catatonia, cycloid psychoses, and paranoid schizophrenia that led to the startling new synthesis of all bipolar and psychotic phenomena that Leonhard achieved in 1957: The Classification of Endogenous Psychoses (Die Aufteilung der endogenen Psychosen)—published as he was still professor of psychiatry at Erfurt (the year in which he left to become professor of psychiatry at the Charité Hospital of the Humboldt University in East Berlin). Leonhard was fundamentally in agreement with Kraepelin’s move up from syndromes to "actual diseases" in the form of manicdepressive illness and dementia praecox. "Unfortunately," he said in a lecture in Leipzig in 1957, "this progress was achieved with a terrible simplification of the clinical realities."

   To better refine upon Kraepelin, Leonhard distilled the Wernicke–Kleist teachings into three great groups of "endogenous psychoses": (1) the affective, or phasic, psychoses ("bipolar" distinguished from "monopolar"); "phasic" means either mania or depression; (2) the cycloid psychoses (which include motility psychosis); and (3) the schizophrenic psychoses, which Leonhard divided into "systematic" (meaning that the symptoms underwent no marked change once established) and the nonsystematic psychoses (meaning fluctuating severity and symptom picture). The system is notable for rehabilitating the term "melancholia," Leonhard’s "pure melancholia" being distinct from his "pure depressions" of various kinds.

   In formulating these subtypes, Leonhard first began with chronic patients, then validated the subtypes in patients at earlier stages of illness. As Gabor Ungvari commented in 1993, "His diagnoses imply prognostic prediction, that is, they are true life-time diagnoses. This ‘backward’ direction of his classification system enabled Leonhard to identify the most persistent signs and symptoms as characteristics of a particular subtype during its natural history" (Biological Psychiatry, 1993, p. 750). Frank Fish of Edinburgh University gave the following account of the schizophrenias in the Leonhard system in Psychiatric Quarterly (1964): Among the systematic psychoses were the systematic paraphrenias (including seven subforms), the hebephrenias (four subforms), and the systematic catatonias (six subforms). Leonhard divided the nonsystematic psychoses into affect-laden paraphrenia (widely considered to be the diagnosis of the mathematician John Nash in the book and movie A Beautiful Mind); cataphasia (which Leonhard had once called schizophasia); and periodic catatonia. Affect-laden paraphrenia, as the term suggests, was characterized by a high affective loading of the symptoms ("bitter" complaints about persecution, "enthusiasm" about grandiose delusions); cataphasia by a breakdown of speech and thought while the patients otherwise continued to behave more or less rationally; periodic catatonia by its shift-like course, with alternating stupor and excitement.

   "The Leonhard system is not easy to use," noted Fish in a touch of understatement. In fact, the system called for very careful observation of the patients and the ability to discern small differences among the subcategories, many of which blended into one another. Yet, the alert clinician might find that the effort repayed itself, for the main groups of psychoses had quite different prognoses: the systematic ones being poor, the nonsystematic rather better. Even more interesting, after the introduction of chlorpromazine and the other phenothiazine antipsychotics in 1952, the nonsystematic psychoses turned out highly responsive to drug treatment, whereas the systematic psychoses responded scarcely at all. Christian Astrup (1921–1989) discovered this in research he did at Gaustad Hospital in Oslo, Norway, where he was later joined by Frank Fish. Astrup’s initial findings appeared in the Acta Psychiatrica Scandinavica in 1959, where, using a five-illness model of the Leonhard scheme, he found that chronic schizophrenics with "slight paranoid defects" responded well, those with "systematic catatonias" poorly; Fish then published additional cases in L’Encéphale in 1964. These findings, once widely overlooked in the psychiatric literature, are being rexamined attentively today. (Astrup’s work on conditional reflexes in the Leonhardstyle psychoses was published as Schizophrenia: Conditional Reflex Studies in 1962.) For a comprehensive assessment of the ideas of this pathway, and the evidence that gives them at least some credence, the reader may consult the book edited by Würzburg University psychiatry professor Helmut Beckmann (1940–), Endogenous Psychoses: Leonhard’s Impact on Psychiatry (1995).

   The diagnoses of the Wernicke–Kleist–Leonhard pathway have made almost no impact on DSM-style U.S. psychiatry. Yet, they have had a small echo in the World Health Organization’s International Classification of Diseases, tenth edition (ICD-10), which describes "acute polymorphic psychotic disorder without symptoms of schizophrenia" (F23.0) and will accept either Valentin Magnan’s bouffée délirante or nonschizophrenic "cycloid psychosis" in fulfilment of the diagnosis.