Thomas A. Ban
Neuropsychopharmacology in Historical Perspective
Education in the Field in the Post-Neuropsychopharmacology Era.

New Clinical Methodologies in Develooment 2

Nosologic Homotyping*

(Bulletin 78)

         The need for a pharmacologically valid, empirically derived nosology was first expressed in the late 1950s by Fritz Freyhan, a German born, American psychiatrist. He recognized the differential responsiveness to the same psychotropic drug in the same (Kraepelinian) diagnostic category and suggested a pharmacological re-evaluation of psychiatric nosology with the employment of target symptoms and diagnoses (Freyhan 1959).

         Nosologic homotyping is a methodology for the development of an empirically derived, pharmacologically valid, classification of mental disorders.

         Nosologic homotypes are identical in “elementary units” of mental illness and are assigned the same position in the “nosologic matrix” constructed with the employment of nosologic organizing principles (Ban 2002)

         The elementary units of mental illness are psychopathologic symptoms; each psychopathologic symptom has a content derived from past experience and a form characteristic of the illness (Jaspers 1910, 1913). Each psychopathologic symptom represents a distinct pathology in the processing of mental events and each psychopathological symptom profile is a “phenotype” of a mental disorder. The temporal organization of the psychopathologic symptoms reflects the pathological process in its ”dynamic totality” and the “dynamic totality” of the pathological process, together with the “totality” and “polarity” of the clinical picture, provides a “structure” that is determined by the illness (Ban 1987). It is in terms of this “determining structure” that each mental illness is defined and assigned a place in the “nosologic matrix” based on three nosologic organizing principles (Ban 2002).

         The first organizing principle of psychiatric nosology is ”totality,” i.e., the inclusiveness of the psychopathologic process (Ban 2000). It was the organizing principle in the classification of Cullen (1772), Esquirol (1838), Kahlbaum(1863) and many others. On the basis of “totality,” insanity is divided into “universal (“total”) and “partial insanity.” In “partial insanity,” in contrast to “universal insanity,” personality remains preserved. The concept of “partial insanity” was extended to include “abortive” (distinct from “true”), “selective” (distinct from “universal”) and “incomplete” (distinct from “complete”) mental illness (Ban 2000). In “abortive” mental illness patients are aware (have insight) that their thinking and/or feelings and/or actions are pathological. (Westphal 1878); in “selective” mental illness, the pathology of mental integration is restricted to one (or two) of the three field(s) of consciousness, i.e., one that reflects the external world (“allopsychic”), another that reflects the self (“autopsychic”) and the third that reflects the body (“somatopsychic”) (Wernicke 1899); and in “incomplete” mental illness the pathology is restricted to one or two of the three components of the “psychic reflex,” i.e., afferent (“perceptual-cognitive”), central (“relational-affective”) and efferent (“motor-adaptive”) (Leonhard 1957).

         The second organizing principle of psychiatric nosology is the temporal organization of the psychopathologic process, i.e., the “onset” (“sudden” vs. “insidious”), “course” (“episodic” vs. “continuous”) and “outcome” (“recovery” vs. “defect”). It was the organizing principle of mental illness in the sixth edition of Kraepelin’s textbook and has remained the organizing principle in the classifications of mental illness to date (Kraepelin 1899). On the basis of the temporal organization of psychopathologic symptoms “attacks,” i.e., episodes that last from minutes to hours, are distinguished from “phases,” i.e., episodes that last from days to years, and from “periods,” i.e., “phases” that recur with regularity; and “thrusts,” i.e., acute events that yield lasting changes, are distinguished from “continuous process,” i.e., chronic events that yield highly differentiated irreversible “end-states” and from “progressive deterioration,” i.e., chronic events that yield severe dedifferentiation terminating in irreversible dementia (Jaspers 1913).

         The third organizing principle of psychiatric nosology is the spatial organization of the psychopathologic process, i.e., “polarity” of the psychopathological process. The origin of the concept of “polarity” is in Edda Neele’s evaluation of phasic sicknesses diagnosed between 1938 and 1942 in Karl Kleist’s “clinic” in Frankfurt (Neele 1949; Teichmann 1990). Polarity was to become the dominant organizing principle in Karl Leonhard’s classification of endogenous psychoses in which “monopolar” (“simple”) psychoses, such as the phasic psychoses and systematic schizophrenias, were separated from the “bipolar” (“multiform”) psychoses, such as manic-depressive disease, the cycloid psychoses and the unsystematic schizophrenias (Leonhard1957). Within Leonhard’s frame of reference, bipolar illness swings between two poles of mood and/or emotions and/or motility and displays a continuously changing, variable clinical picture, whereas “unipolar” illness is restricted to one pole of mood and/or of emotions and/or of motility and displays the same symptomatology within and across episodes. Each form of “unipolar” illness is distinct and characterized by a syndrome associated with no other forms and not even transitionally related to any other form.

         Nosologic homotypes are more homogenous populations in terms of psychopathology than populations identified by any of the available diagnostic instruments. If nosologic homotyping would identify pharmacologically or genetically homogenous populations it would indicate that phenomenological psychopathology and psychiatric nosology could provide the key for the delineation of biologically meaningful disease categories in psychiatry. By linking the mode of action of psychotropic drugs to pharmacologically homogeneous populations, nosologic homotyping could break the impasse in progress of neuropsychopharmacological research, pharmacotherapy in psychiatry and molecular genetic research in mental illness (Ban 2002).

         Furthermore, considering that “nosological homotypes” are defined in terms of their effect on processing of mental events, and psychotropic drugs are defined in terms of their effects on “signal transduction” in the brain, the empirically derived diagnostic categories could provide clinical entities which are suitable for testing hypotheses relevant to the relationship between processing of mental events and “signal transduction” in the central nervous system. Thus, “nosologic homotyping” could open the path for the development of a psychiatry in which mental pathology is perceived in terms of pathology in “signal transduction” in the brain and for a rational pharmacotherapy of mental illness.

Concluding remarks

         Recognition of a possible relationship between drug-induced changes in psychopathology and in the concentration of monoamine neurotransmitters and their metabolites in the brain led to the formulation of the hypothesis that the psychotropic effects of drugs are related to their action on the transmission (processing) of impulses at the synaptic cleft (Ban 2000, 2002, 2006; Brodie, Shore and Pletscher 1956a,b; Pletscher, Shore and Brodie 1955, 1956; Shore, Silver and Brodie 1955a,b). The notion that drugs exert their psychotropic effects through the modification of transmission of impulses from one neuron to another has far reaching heuristic implications for psychiatry. The cerebral cortex of the human brain contains about 10 billion neurons, with about one million billion connections, of which the majority communicates only with each other (Edelman 1992). The lack of consistent biological manifestations in mental illness has raised the possibility that the site of mental pathology is the major compartment of the cerebral cortex that has no direct contact with either sensory input or behavioral output (Ban 2004). If this is the case, the primary manifestations of the psychiatric disease process are psychopathological symptoms and nosologic entities, i.e., patterns of psychopathologic symptoms (Ban1987) and nosologic homotyping is a suitable methodology for rendering the morphologic substrate of mental pathology accessible to scientific scrutiny.

References:

Ban TA. Prolegomenon to the clinical prerequisite: Psychopharmacology and the classification of mental disorders. Progress in Neuro-Psychopharmacology & Biological Psychiatry 1987; 11: 527-80.

Ban T.A. Nosology in the teaching of psychiatry. J bras psiquiatr 2000; 49: 39-49.

Ban TA. .Neuropsychopharmacology: the interface between genes and psychiatric nosology. In: Lade B, editor. Pharmacogenetics of Psychotropic Drugs. Cambridge: Cambridge University Press; 2002, pp. 36-56.

Ban TA. Neuropsychopharmacology and the history pf pharmacotherapy in psychiatry. A review of developments in the 20th century. In: Ban, T.A., Healy, D., Shorter, E. (2004), Reflections on Twentieth-Century Psychopharmacology. Budapest: Animula; 2004, pp. 697-720.

Ban TA. Academic psychiatry and the pharmaceutical industry. Progress in Neuro- Psychopharmacology & Biological Psychiatry 2006; 30, 429-41.

Brodie BB, Shore PA Pletscher A. Limitation of serotonin-releasing activity to those alkaloids possessing tranquilizing action. Science 1956a; 123, 992-3.

Brodie BB, Pletscher A, Shore PA. 1956b. Possible role of serotonin in brain function and in reserpine action. J Pharmacol Exp Therap 1956b; 123: 116 - 9.

Cullen W. Synopsis Nosologiae Methodicae. Edinburgh: A. Kincaid & Creech; 1772. Esquirol, J.E.D., 1838. Des maladies mentales. vol.2. Paris, Bailliere.

Edelman GM. Bright Air, Brilliant Fire. On the Matter of the Mind. New York: Basic Books; 1992.

Freyhan, F., Selection of patients from the clinical point of view. In: Cole JO, Gerard RW, editors. Evaluation of Pharmacotherapy in Mental Illness. Washington: National Academy of Sciences; 1959, pp. 372-89.

Jaspers K. Eifersuchtswahn : Entwicklung einer Persoenlichkeit oder Prozess. Z.Ges. Neurol. Psychiatr. 1910; 1: 567-37.

Jaspers K. Allgemeine Psychopathologie. Berlin/Heidelberg: Springer; 1913.

Kahlbaum K. Die Gruppierung der psychischen Krankheiten und die Enteilumg der Seelenstoerungen. Danzig: A.W. Kaufman; 1863.

Kraepelin E. Psychiatrie. Ein Lehrbuch für Studierende und Ärzte. 6 Aufl. Leipzig: Barth; 1899.

Leonhard K. Aufteilung der endogenen Psychose. Berlin: Akademie-Verlag; 1957.

Neele, E. Die phasischen Psychosen nach ihrem Erscheinungs- und Erbbild: Leipzig; 1949.

Pletscher A, Shore PA, Brodie BB. Serotonin release as a possible mechanism of reserpine action. Science 1955; 122: 374-5.

Pletscher A, Shore BB, Brodie BB. Serotonin as a modulator of reserpine action in brain. J.Pharmacol Exp Ther.1956; 116, 84-9.

Sauvages de la Croix BF. Nosologia Methodica Sistems Morborum Classes, Genera et Species, Juxta Sydenhami Mentales Botanicorum Ordinem. Amsterdam: Frat de Tournes; 1769.

Shore PA, Silver SL, Brodie BB. Interaction of serotonin and lysergic acid diethylamide in the central nervous system. Experientia 1955a; 11, 272-3.

Shore PA, Silver SL, Brodie BB. Interaction of reserpine, serotonin and lysergic acid diethylamide in brain. Science 1955b; 122: 284-5.

Teichmann G. The influence of Karl Kleist on the nosology of Karl Leonhard. Psychopathology 1990; 23, 267-76.

Wernicke C. Über die Klassifikation der Psychosen. Breslau: Slettersch Bucchandlung; 1899. Westphal C. Über Zwangsvorstellungen. Arch. Psychiatr. Nervenkrank. 1878; 8: 734-50. 

*Based on Thomas A. Ban: Nosology in the teaching of psychiatry. J bras psiquiatr (2000; 49: 39-49). Thomas A. Ban: Towards a clinical methodology for neuropsychopharmacology research, published in Neuropsychopharmacologia Hungarica (2007; 9: 81-90).

July 25, 2019