Neuropsychopharmacology: The Interface Between Genes and Psychiatric Nosology

By Thomas A. Ban


9. Nosologyc Matrix

Whether the DCR, the CODE-DD, or any other diagnostic instrument in preparation would provide suitable populations for genetic research is not known. Until the time such an instrument becomes available, the use of "nosologic homotypes" is an essential prerequisite of obtaining interpretable findings in research in the genetics of mental illness. Nosologic homotypes are identical in "elementary units" of mental illness and are assigned the same position in the "nosologic matrix" constructed with consideration of Esquirol's (1838), Kraepelin's (1896, 1899) and Leonhard's (1957) "nosologic organizing principles" (Ban 2000b).

The elementary units of mental illness are psychopathologic symptoms (Jaspers 1913, 1962). Each psychopathologic symptom represents a distinct pathology in the processing of mental events (Wernicke 1900) and each distinct "psychopathologic symptom profile" (syndrome) is a potential "phenotype" of mental disorder. The formal characteristics of the "onset" (sudden or insidious), "course" (episodic or continuous) and "outcome" (recovery or defect) of the mental syndrome reflect the pathological process in its "dynamic totality" and the "dynamic totality" of the pathological process, together with the "holistic character" (Petho 1990) of the clinical picture ("monomorphous," "polymorphous," "amorphous"), provide a "structure" that is "determined by the illness" (Ban 1987). It is in terms of this structure, that each mental illness is defined and assigned a distinct place in the "nosologic matrix," based on the three nosologic organizing principles.

The first organizing principle of psychiatric nosology is the "inclusiveness" of the psychopathological process. Its origin is in Esquirol's (1838) distinction between "insanity proper" and "partial insanity." The prototype of "insanity proper" is Morel's (1860) "demence precoce" and the prototype of "partial insanity" is Lasegue's (1852) "persecutory delusional psychosis." The concept of "partial insanity," i.e., insanity with preserved personality, was extended to include "abortive insanity." Patients with "abortive insanity" are fully aware (cognizant) that their thinking, feelings or actions are pathological. The prototype of "abortive insanity" is Westphal's (1878) diagnostic concept of "obsessional neurosis."

The second organizing principle of psychiatric nosology is the "course" and "outcome" of the psychopathological process. Its origin is in Kraepelin's (1899) separation of "manic-depressive insanity," an episodic and remitting illness, from "dementia praecox, a continuous and progressing disease. It is within the frame of reference of the second nosologic organizing principle that "attacks,” i.e., episodes with brief duration (from minutes to hours), encountered in "panic disorder," are distinguished from "phases," i.e., episodes with long duration (from days to years), encountered in the "phasic psychoses," and from "periods," i.e., phases recurring with regularity, encountered in with regularity, encountered in "seasonal affective disorder"; and "thrusts," i.e., acute events, which yield lasting changes, encountered in the "unsystematic schizophrenias," are distinguished from "continuous process," i.e., chronic events, which yield highly differentiated end states, encountered in the "systematic schizophrenias," and from "progressive deterioration," i.e., chronic events which yield increasingly severe "dedifferentiation," encountered in the "organic dementias."

The third organizing principle of psychiatric nosology is "polarity." Its origin is in Leonhard's (1957) distinction between "polymorphous (multiform) bipolar" and "monomorphous (pure) unipolar" psychiatric disorders. "Bipolar illness" swings between two poles of mood (emotions and motility), and displays a continuously changing (variable) clinical picture, whereas "unipolar illness" is restricted to one pole of mood (emotions and motility), and displays the same symptomatology within and across episodes. Each distinct form of "unipolar illness is characterized by a syndrome associated with no other form and not even transitionally related to any other forms."

While "nosologic homotypes," based on a specially devised "nosologic matrix,” are biologically more homogenous populations than any of the diagnostic population identified by the available diagnostic instruments today, the information collected by the use of the "nosologic matrix" would allow the completion of the re-evaluation (of diagnostic concepts) started by a group of psychiatrists at the "Heidelberg Clinic" in the 1920s. The information collected by the use of the "nosologic matrix" could also serve as the starting point for an empirically derived classification of mental illness.

Considering that "nosologic homotypes" are defined in terms of their effect on "processing of mental events, " and psychotropic drugs are defined in terms of their effect on "signal transduction" in the brain (Bloom 2001), the empirically derived diagnostic categories 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, employment of the "nosologic matrix" could open up a new perspective for the development of a psychiatry in which mental pathology is perceived in terms of pathology in "signal transduction" in the brain and for the development of a rational pharmacotherapy of mental illness. Within the new frame of reference, genetic research in mental illness would enter a new phase.