Psychopharmacology and the Classification of Functional Psychoses 

By Thomas A. Ban and Bertalan Pethö

Four-Dimensional Classification

Affective Psychoses

Schizophrenic Psychoses

Neuroleptics and Etiological Speculations

One of the most important contributions to schizophrenia research which has resulted from psychopharmacologic progress is the verification that schizophrenia consists of a biologically heterogenous population. In view of this it is paradoxical that the most extensively explored biochemical hypothesis, the DA excess hypothesis, deals with "schizophrenia" instead of one or another subtype of the schizophrenias.

Dopamine Excess or Deficiency

The finding that "clinical potencies" (mg/kg therapeutic dose requirements of neuroleptics) correlate well with binding affinities at DA2 receptors prompted several laboratories to search for alterations in the levels of DA and/or DA receptors in post-mortem brains of schizophrenic patients. As a result, a significantly increased number of DA2 receptors (Owen et al., 1978), as well as a 50% increase in DA content was found in schizophrenic brains (Bird et al., 1977). There are indications, however, that the increase in the number of DA2 receptors may be related to prior treatment with neuroleptic drugs.

In favor of the hypothesis that DA excess is related to the psychopathology in schizophrenic patients are the findings that schizophrenic psychopathology may be precipitated and/or aggravated by the administration of DA releasers, such as methylphenidate or ethanol. In favor also is that the therapeutic effects of neuroleptics may be potentiated by adding substances which interfere with the formation and/or action of DA to the treatment regime such as alphamethyl-paratyrosine (a specific tyrosine hydroxylase inhibitor) or alphamethyldopa (a non-specific dopa decarboxylase inhibitor) (Snyder, 1976). On the other hand, and in variance with the DA excess hypothesis are the findings that the time of onset of amphetamine psychosis (which serves as the model psychosis for schizophrenia) coincides more closely with DA depletion than with increased DA availability. In variance also are the findings that in some schizophrenic patients, amphetamine administration alleviates psychotic symptomatology and in others it enhances the therapeutic effect of neuroleptics (Fukuda and Mitsuda, 1979; Van Kammen et al., 1982).