Monoamines and schizophrenia

Abstract

The hypothesis that central biogenic amines may play a role in the pathophysiology of schizophrenia was originally based upon the fact that hallucinogenic and antipsychotic drugs have profound effects on central transmitter pathways where dopamine, noradrenaline and serotonin are involved. The structural similarities between hallucinogenic drugs such as amphetamine and mescaline, and catecholamines on the one hand and lysergic acid diethylamide (LSD) and indolamines such as serotonin on the other hand have by direct experimentation been shown to explain their important effects on the transmitter systems. The marked effect of several classes of chemically different antipsychotic drugs on central dopamine receptor function formed the basis for the dopamine hypothesis regarding the mechanisms of action of these drugs and also for the hypothesis that dopamine D2 receptor function played a significant role in the pathophysiology of schizophrenia. Direct experimental analysis of aminergic functions in the brain of schizophrenic patients, both during life and post mortem, has been and will for the foreseeable future continue to be a rational approach to the further elucidation of the validity of these hypotheses. Analysis of metabolite levels in the cerebrospinal fluid and plasma of schizophrenic patients has shown great variation in the results with reports of both elevated and reduced release of amines in the brains of schizophrenic patients. Analysis of the aminergic receptor structures in the postmortem human brain has relatively consistently revealed an increased density of D2 receptors in the major basal ganglia of schizophrenic patients. Whether these alterations represent a primary feature of brain structure in schizophrenia or a drug-induced effect still remains to be shown. Positron emission tomographic (PET) scan studies of D2 receptors in schizophrenia have demonstrated both increased densities and absence of change in the characteristics of D2 receptors in the patients as compared to matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)