MONOAMINE NEUROTRANSMITTER INTERACTIONS IN DRUG-FREE AND NEUROLEPTIC-TREATED SCHIZOPHRENICS

Objective: To study recent suggestions by a number of investigators th at interactions between monoamine neurotransmitter systems play an imp ortant role in schizophrenia. It has not been clear how hypotheses abo ut interactions might be tested in clinical data. One means for indexi ng interactions between monoamine neurotransmitter systems may be to c ompare correlations between cerebrospinal fluid (CSF) monoamine metabo lite (homovanillic acid [HVA], 5-hydroxyindoleacetic acid [5-HIAA], an d 3-methoxy-4-hydroxyphenylglycol [MHPG]) or ratios of these metabolit es (HVA/5-HIAA and HVA/MHPG). Design: We compared these putative measu res of monoamine neurotransmitter interaction in 50 drug-free patients with schizophrenia (hospitalized on an inpatient ward of a tertiary c are hospital) and 33 normal controls and examined the effects of neuro leptic antipsychotic treatment on these measures in 41 patients (22 of whom had antecedent drug-free CSF data). Results: Drug-free patients with schizophrenia had significantly smaller correlations between CSF monoamine metabolites than normal controls. Longer drug-free time was associated with even smaller correlations between metabolites, suggest ing that the difference between controls and patients was not due to a cute drug withdrawal. After treatment with neuroleptic antipsychotics there were significant increases in the HVA/5-HIAA and HVA/MHPG ratios , as well as increases in correlations between monoamine metabolites. After treatment, there were no significant differences in metabolite c orrelations between patients and controls. Metabolite ratios and corre lations did not predict subsequent treatment response, but preliminary analyses demonstrated negative relationships between HVA/5-HIAA and H VA/MHPG ratios and Brief Psychiatric Rating Scale rating at that time. Conclusions: The present findings are consistent with and support hyp otheses suggesting that interactions between monoamine systems are alt ered in schizophrenia and that antipsychotic treatment may affect the functional balance between different monoamine neurotransmitters (alth ough one should keep in mind factors other than interactions between m onoamine systems that affect metabolite correlations and ratios).