Thomas A. Ban
Neuropsychopharmacology in Historical Perspective
Psychopharmacology and the Classification of Functional Psychoses
Neuropsychopharmacology in Historical Perspective
8. Bayle’s Unitary Concept of Psychosis and Endogenous Psychoses
Bayle’s Unitary Concept of Psychosis
The origin of the “unitary” concept of psychosis is in Bayle' s treatise Diseases of the Brain and Its Membranes (Traite des Maladies du Cerveau et de ses Membranes) published in 1826. Bayle postulates that “general paralysis” (cerebral syphilis) has one cause, i.e., “chronic arachnitis,” which is clearly defined in terms of pathological anatomy; has a specific symptomatology which combines motor and mental signs; and, most important, has a specific pattern of development that comprises of three consecutive phases, each marked by different symptoms. These phases are delire monomaniaque, characterized by prevailing exaltation; delire maniaque, characterized by prevailing delusions and overvalued ideas and etat de demence, the terminal phase, characterized by dementia.
Bayle's treatise provided fertile ground for the development of psychiatry as a medical discipline. By linking psychopathology to cerebral pathology (chronic arachnitis) Bayle opened the path for German “somaticism.” One of the most prominent exponents of this approach was Wilhelm Griesinger (1845, 1876) who, in his treatise published in 1845, declared that mental diseases were somatic diseases, that is, diseases of the brain. He also asserted that there was no difference between “organic” and “functional” disorders and that psychiatry and neuropathology are not merely two closely related fields, but one field in which "one language should be spoken" and in which "the same laws prevail."
Griesinger's contentions were further elaborated by Westphal’s (1871 attempt to define the nature of cerebral lesions in psychoses. His contributions, according to Pierre Pichot provided "a bridge between Griesinger, for whom organo-clinical correlations were a particular article of faith,” and psychiatrists like Meynert and Wernicke, “who made use of their anatomical discoveries to work out and formulate general conceptions in psychiatry” (Pichot 1983).
The roots of our current concept of “dementia, i.e., a specific end-state which is the result of chronic organic-neurological changes in the brain regardless of their cause or etiological specificity, are in Bayle’s treatise. It was also Bayle's treatise that focused attention on the importance of the course of illness, determined by the brain pathology intrinsically linked to etiology and progress of the disease.
Endogenous Psychoses
From Kahlbaum to Kraepelin
The greatest impetus for the conceptual development of endogenous psychoses was Kahlbaum's (1874) formulation of his “nosological postulate” that presumes a close correspondence between etiology, brain pathology, symptom pattern and outcome picture (Jablensky 1981). It allowed for the assumption that seemingly disparate clinical states belong to the same nosological entity.
It was Kahlbaum’s nosological postulate that opened the path for Kraepelin (1896) to group together several distinctly different clinical syndromes into two nosological entities: nosological entities: “dementia praecox” (schizophrenia) and “manic depressive insanity” (affective psychoses). By separating “phasic-remitting affective psychoses” from “progressing schizophrenias” Kraepelin laid the foundation for the dichotomy of “endogenous psychoses” that provides basis for our classification of “endogenous psychoses” to date (Jablensky 1981).
The two diagnostic endpoints provided by the dichotomy (i.e., ”dementia praecox” - schizophrenia and “manic-depressive insanity” - affective psychoses) received support from the differential responsiveness within the endogenous psychoses to psychotropic drugs with patients diagnosed as one or another form of schizophrenia responding favorably to “antipsychotic-neuroleptics” whereas patients diagnosed the “affective psychoses” responding favorably to “mood stabilizing lithium salts” and/or “tricyclic antidepressants.”
By following the pharmacological profile of chlorpromazine-type of antipsychotics (neuroleptics) and imipramine-type of antidepressants, a large number of psychoactive drugs with similar action mechanisms were synthesized and introduced into clinical practice for the treatment of schizophrenic and affective (primarily depressive) disorders.
Systematic studies conducted to reveal the action mechanism of antipsychotics and antidepressants contributed greatly to the development of the technology necessary for in vivo exploration of brain mechanisms and brain functions. It remains to be seen whether the newly developed technology will provide the necessary basis for meaningful research in the schizophrenias and affective psychoses.
Kraepelin’s dichotomy proved to be a long step forward in introducing order in a chaotic field. Despite its limitations it has provided the necessary diagnostic endpoints points for the development of drugs with demonstrable therapeutic efficacy in the functional psychoses. Yet, it has fallen short in providing the necessary diagnostic endpoints for the identification of individual patients who will respond to one or another drug.
From Wernicke to Leonhard via Kleist
Carl Wernicke (1894, 1900) recognized the limitations of Kraepelin’s dichotomy and focused attention on the low prognostic validity of Kraepelinian diagnoses. He also set the foundation for the development of a “differentiated psychopathology” of “endogenous psychoses” that seemed to provide biologically more homogeneous diagnostic end points than Kraepelin’s. (Leonhard 1961).
Karl Kleist (1921), a disciple of Wernicke, succeeded, in the early years of the 20th century, to demonstrate that some of the syndromes Wernicke described are distinct forms of psychiatric illness. He had also shown that these “diseases,” he subsumed under the heading “degeneration psychoses,” could only be partially allotted to one or the other of Kraepelin's two diagnostic groups. Included among them “are several "affective," "conative" and "intellectual" illnesses which follow either a simple-monopolar or a multiform-bipolar pattern of course (Hassler 1861).
Recognition of the difficulties in separating schizophrenic (dementia praecox) and affective (manic depressive) psychoses by cross-sectional assessment of psychopathological symptoms created a diagnostic crack with a considerable percentage of patients not fitting either of the two diagnoses.
There are some indications that at least some of the shortcomings of Kraepelin’s dichotomy might be overcome by adopting the classification developed by the Wernicke school and presented by Karl Leonhard in 1957 in his Classification of Endogenous Psychoses.
Leonhard's (1957, 1979) classification of “endogenous psychoses” divides “schizophrenia” into “systematic schizophrenias” and “unsystematic schizophrenias” and “affective-phasic psychoses” into “unipolar affective psychoses” and “bipolar affective psychoses” with several distinct subpopulations in each of these diagnoses. Furthermore, it also identifies a distinct group of psychoses referred to as “cycloid psychoses” that resemble the phasic psychoses in their course and unsystematic schizophrenias in their symptomatic manifestations.
At first sight Leonhard's classification appears to be bewilderingly complex. Yet, if its basic tenets are understood, it becomes rational and simple. The classification is based on a four-dimensional model of psychiatric diagnosis with emphasis on the final stage of psychiatric illness which ranges from full recovery (phasic psychoses) to moderate or marked defect states (systematic schizophrenias) with personality transformation (cycloid psychoses) and mild to moderate defect states (nonsystematic schizophrenias) in between.
Leonhard recognized that endogenous psychoses may follow an episodic (phasic psychoses, cycloid psychoses and unsystematic schizophrenias) or a continuous (systematic schizophrenias) course and noted that “phasic psychoses” may appear in the form of unipolar (mania or depression) or bipolar (manic-depressive psychosis) illness.
Insofar as cross-sectional psychopathology is concerned, Leonhard follows the principles of Wernicke's (1881, 1900, 1906) structural approach that considered the reflex arc as his functional working unit and saw the cerebral cortex as the organ of "associations." In his "reflex pathology" Wernicke recognized that he dealt with three functional components of the reflex arc: sensory input, inter neuronal associations and motor output. He also noted that any of the three components could be disturbed separately and also in various combinations.
Within Wernicke’s frame of reference psychopathological syndromes are perceived as a decrease, increase or a dysfunction in the activity of respective structures which become manifest through the effect of the disturbance on "transcortical associations."
Nyiro’s Structural Psychopathology
Wernicke’s structural approach to psychopathology was further elaborated by Julius (Gyula) Nyiro (1958, 1962), a Hungarian professor of psychiatry, who conceptualized, with the adoption of an ontogenetic model, the three components of the reflex arc as three "pyramidal structures": perceptual-cognitive (sensory input), relational-affective (central intrapsychic) and motor-adaptive (motor output). Within his frame of reference psychopathological syndromes which affect primarily one of the three structures, as the syndromes of systematic schizophrenia in Leonhard’s classification are distinguished from psychopathological syndromes which affect more than one structure, as the syndromes of nonsystematic (unsystematic) schizophrenia and psychopathological syndromes which are characterized by dissociation among the three "structures" as the syndromes of nonsystematic and systematic schizophrenia are separated from the syndromes in which the functioning of the three "structures" is congruent, i.e., harmonious, as the syndromes of phasic and cycloid psychoses.
Nyiro brought to attention that both groups of schizophrenias and some of the cycloid psychoses are characterized by prevailing changes in perceptual-cognitive structures (systematic paraphrenias, cataphasia and confusion psychosis), whereas other disorders and groups of disorders are characterized by prevailing changes in relational affective structures (systematic hebephrenias, affect-laden paraphrenia and anxiety-elation psychosis) and others again by prevailing changes in motor-adaptive structures (systematic catatonias, periodic catatonia and motility psychosis). In phasic psychoses, the primary disturbance is in the relational-affective structure (mood). Yet, in some forms and sub-forms of “phasic psychoses,” as manic-depressive psychosis, pure melancholia and pure mania, there are corresponding disturbances in the other two structures; and in some of the other sub-forms, as in the pure euphorias and pure depressions, there are disturbances in one additional structure only, i.e., perceptual-cognitive or motor-adaptive.
Endogenous Psychoses in the KDK
The KDK Budapest (Pethö, Ban, Kelemen et al., 1984) adopts Leonhard’s (1957) classification with some modifications primarily by shifting the point of departure from the end-state to the first or index psychosis and by characterizing outcome, not only in terms of psychopathological symptoms, but also in terms of personality characteristics and social adjustment. In the KDK a prerequisite for the diagnosis of schizophrenic psychosis is the dissociation among the perceptual-cognitive, affective-relational and motor-adaptive structures, expressed in psychopathological symptoms.
Unlike the schizophrenic psychoses, which are characterized by an irreversible process, cycloid psychoses are characterized by complete recovery from each phase, although personality changes may remain. Patients with cycloid psychoses are diagnosed on the basis of a number of distinctive characteristics in the KDK. Among them probably the most important is that the whole field of patient's experience is transformed (protopathic change of Gestalt) with a change in the state of mind and depth of emotions.
Similar to the cycloid psychoses, which usually display complete recovery from each phase, affective-phasic psychoses are characterized by a fully remitting course with periodicity and/or rhythmicity. An essential prerequisite, although not necessarily exclusive criterion for this diagnosis, is that experience, behavior and performance are in keeping with mood.
Validity of KDK (Leonhard’s) Diagnoses
The “heredofamilial” distinctiveness of unipolar and bipolar illnesses within the phasic psychoses was supported by Angst and Perris (1968, 1972) and the “genotypical” distinctness of cycloid psychoses and systematic schizophrenias by Ungvari (1984). This genetic distinctness of systematic schizophrenias and cycloid psychoses was also substantiated by multiple threshold analyses which rejected the possibility of identical liability and confined the separateness of these diagnostic categories. In the same study the nonsystematic schizophrenic category displayed a considerably greater genotypical overlap with the cycloid psychoses ("as if it were a connecting link" between the “nonsystematic” and “systematic schizophrenias”).
In favor of Leonhard's schizophrenic sub-types are the findings of a high correlation between the distribution of subtypes in the original sample of Leonhard from the late 1930s and early 1940s and in Astrup's sample 20 years later (Wilson and Ban 1983). In favor also are the statistically significant correlations in rank order of frequency of occurrence of the six paraphrenic, four hebephrenic and six catatonic subtypes in eight countries in a study carried out in the late 1970s and early 1980s (Ban, Guy and Wilson 1984a). The finding of differential therapeutic responsiveness to phenothiazine neuroleptics in the systematic and the nonsystematic schizophrenic populations and within both populations among the different types and subtypes of patients by Fish (1964c) is also in support of Leonhard's system.
Leonhard's classification is important because it opens a new perspective for neuropsychopharmacological research by providing more discriminate new diagnostic end-points. While three-dimensional Kraepelinian psychiatric classifications are suitable only to establish the therapeutic efficacy of drugs with an accepted level of statistical probability, four-dimensional classifications as Leonhard’s might be suitable to demonstrate therapeutic effectiveness by identifying the treatment responsive subpopulations, i.e., .diagnostic subtypes or even patients responsive to a particular drug with a reasonable clinical accuracy. Thus, four-dimensional classifications, by providing new, more discriminate clinical end-points than the end-points provided by three-dimensional classifications, might open the path for neuropsychopharmacological research in which a pharmacologically homogenous population is prerequisite.
Four-dimensional classifications might also newly facilitate the development of a new class of drugs, e.g., "transition compounds" (les produit de transition). Drugs which belong to this category include carbamazepine, an anticonvulsant which is structurally related to tricyclic antidepressants which may have a place in the treatment of bipolar affective disorders and/or cycloid psychoses; and carpipramine and chlorcarpipramine, i.e., dibenzazepines (tricyclic antidepressant structure) with a butyrophenone (antipsychotic) side chain, which may have a place in the treatment of cycloid psychoses and/or affect-laden paraphrenia, one of the three diagnostic types of the nonsystematic schizophrenias. The same applies to the dibenzoxazepines, such as loxapine, an antipsychotic which demethylates in part to amoxapine, an antidepressant, which in turn hydroxylates into a dopamine receptor blocking antipsychotic drug. The dibenzoxazepines today are profiled as traditional antipsychotics (loxapine) and a traditional antidepressant (amoxapine) because of their common pharmacological properties with prototype antipsychotics and antidepressants. By this, special emphasis is placed on some of their possible adverse effects without full appreciation of their unique therapeutic potential in certain diagnoses that require the combined administration of an antipsychotic with an antidepressant for optimal treatment.
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May 27, 2021