Theory concerning the aetiology of SCHIZOPHRENIA. The demonstration that effective ANTIPSYCHOTIC drugs have the common property of blocking D2 DOPAMINE receptors led to the idea that hyperactivity of the dopaminergic system may represent the aetiological basis of schizophrenia. However, efforts to demonstrate dopaminergic abnormalities in untreated schizophrenic patients have proved inconclusive, with biochemical, post-mortem, neuroimaging and genetic studies failing consistently to support the hypothesis. The fact that CLOZAPINE, an atypical NEUROLEPTIC, has greater antipsychotic efficacy than traditional neuroleptics, but has less affinity for dopamine receptors further weakens the proposition that schizophrenia is caused by hyperactivity of dopamine. Several reasons have been suggested to account for this.
(1) The antipsychotic effects of traditional neuroleptics may be mediated by mechanisms unrelated to the aetiology of schizophrenia. (2) Other (presently unidentified) factors acting in concert with the dopaminergic system may prove to be important. (3) Dopamine activity in the schizophrenic brain may change in different ways in different structures. It has been suggested for example that dopamine activity in the PREFRONTAL CORTEX may be decreased while activity in the NUCLEUS ACCUMBENS is increased, these changes being reciprocally related to each other. The relationship of these changes to the signs and symptoms of schizophrenia remains uncertain, and what causes the changes in the first place is unknown, but such ideas serve to keep the dopamine hypothesis of schizophrenia tantalizingly viable.
Reference
Davis K.L., Kahn R.S., Ko G, & Davidson M. (1991) Dopamine and schizophrenia: a review and reconceptualization. American Journal of Psychiatry 148:1471–1486.
IAN C.REID
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