CLINICAL INVESTIGATION OF MONOAMINE NEUROTRANSMITTER INTERACTIONS

Monoamine neurotransmitter systems are widely thought to be involved i n the pathophysiology of affective disorders and schizophrenia and the mechanism of action of antidepressant and antipsychotic drugs. Previo us clinical studies have focused on individual monoamine function in i solation, even though a large number of preclinical studies have demon strated that monoamine neurotransmitter systems interact with one anot her. In the present paper, preclinical data on monoamine neurotransmit ter interactions are reviewed, and two methods for examining monoamine neurotransmitter system interactions in clinical data are presented. One of the best replicated findings in biological psychiatry is that m onoamine metabolites in CSF correlate with one another. The degree of correlation may be in part a measure of the degree of interaction betw een the parent monoamine neurotransmitter systems. Another approach to studying interactions is the use of HVA/5HIAA and HVA/MHPG ratios as an index of interactions between 5HT-DA and NE-DA. When these methods are applied in schizophrenia, patients are found to have decreased mon oamine metabolite correlations compared to normal controls. Metabolite correlations increase significantly after antipsychotic treatment, an d the HVA/5HIAA and HVA/MHPG ratios also increase, suggesting that neu roleptics may act in part by strengthening interactions between monoam ines. BPRS ratings are negatively correlated with HVA/5HIAA and HVA/MH PG so that patients with higher ratios have fewer symptoms, particular ly after treatment. These results provide direct experimental support for hypotheses suggesting that interactions between monoamine neurotra nsmitters are important in schizophrenia. Some of the effects of the a typical neuroleptic, clozapine, on metabolite correlations and ratios are also discussed.