Neuropsychopharmacology: The Interface Between Genes and Psychiatric Nosology

By Thomas A. Ban


4. From DSM-III to DSM-IV

The inconsistent and conflicting findings in molecular genetic research in schizophrenia and manic-depressive illness led to a steadily growing dissatisfaction with psychiatric nosology. By the late 1990s it was recognized that it "would be foolhardy to think" that diagnostic criteria in classifications like the DSM-IV, or its predecessors, the DSM-III and DSM-III-R (American Psychiatric Associations 1980, 1987, 1994), could "select anything that maps into the genome" (Hyman 1999). The DSM-III, and its successors are "consensus-based classifications," i.e., sets of diagnostic formulations agreed upon by a body of well-informed psychiatrists. To accommodate the different orientations in psychiatry, the diagnostic categories in these classifications are broad, and because of the inclusion of different forms of disease in the same category of illness, the populations within the diagnostic categories are heterogenous (Ban 2000a).

In case of depressive illness for example, Kraepelin's (1899) "unitary concept of melancholia" – derived by the pooling together of six distinct syndromes of "melancholia," i.e., "simplex," "gravis," "stuporous," "paranoid," "fantastic" and "delirious" – was adopted in the DSM-III virtually unchanged. In spite of findings in psychopharmacologic, genetic and nosologic studies which indicate that depressive illness is heterogenous (Angst 1966; Overall et al. 1966), the unitary concept of melancholia has been retained in the DSM-III-R and DSM-IV. Depressive disorders in the DSM-IV consists of one core syndrome, i.e., "major depression," which is so broad that in a "composite (polydiagnostic) evaluation" in six of the 25 diagnostic classifications of the diagnostic instrument from 13.5% to 35.5% of the patients did not fit any of the depressive diagnoses (Ban 1992b).

While the diagnosis of "major depression" is eminently suited to reconcile widely different conceptualizations of depressive illness, it is a consensus-based diagnosis that covers up its component diagnoses. Schneider's (1920) "vital depression" – the diagnosis which allowed Roland Kuhn (1957) to recognize imipramine's antidepressant effect – is covered up in the DSM-IV to the extent that even if the patient is so severely ill that he/she displays all the possible symptoms and signs considered for the DSM-IV diagnosis of "major depression," one still would not know whether the patient qualifies for "vital depression." The antidepressant responsive forms of depressive illness are covered up also by the DSM-IV. There is no way to predict, within the framework of the DSM-IV, which 1 (or 2 including placebo responders) of 3 patients with the diagnosis of major depression will respond to treatment with an antidepressant drug (Ban 1987, 1999).

The same applies to the DSM-IV diagnostic concept of "schizophrenia" as to the DSM-IV diagnostic concept of "major depression" (Ban 1987, 1999).