Monoamine Neurotransmitter Interactions in Drug-Free and Neuroleptic-Treated Schizophrenics

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Abstract
Objective: To study recent suggestions by a number ofinvestigators that interactions between monoamine neu-rotransmitter systems play an important role in schizo-phrenia. It has not been clear how hypotheses about in-teractions might be tested in clinical data. One meansfor indexing interactions between monoamine neu-rotransmitter systems may be to compare correlationsbetween cerebrospinal fluid (CSF) monoamine metab-olite (homovanillic acid [HVA], 5-hydroxyindoleaceticacid [5-HIAA], and 3-methoxy-4-hydroxyphenylglycol[MHPG]) or ratios of these metabolites (HVA/5-HIAAand HVA/MHPG). Design: We compared these putative measures of monoam-ine neurotransmitter interaction in 50 drug-free patientswith schizophrenia (hospitalized on an inpatient ward ofa tertiary care hospital) and 33 normal controls and ex-amined the effects of neuroleptic antipsychotic treatmenton these measures in 41 patients (22 of whom had an-tecedent drug-free CSF data). Results: Drug-free patients with schizophrenia had sig-nificantly smaller correlations between CSF monoaminemetabolites than normal controls. Longer drug-free timewas associated with even smaller correlations between me-tabolites, suggesting that the difference between controlsand patients was not due to acute drug withdrawal. Aftertreatment with neuroleptic antipsychotics there were sig-nificant increases in the HVA/5-HIAA and HVA/MHPGratios, as well as increases in correlations between monoam-ine metabolites. After treatment, there were no significantdifferences in metabolite correlations between patients andcontrols. Metabolite ratios and correlations did not pre-dict subsequent treatment response, but preliminary anal-yses demonstrated negative relationships between HVA/5-HIAA and HVA/MHPG ratios and Brief Psychiatric RatingScale rating at that time. Results: Neuroleptic treatment significantly raised HVA concentrations and significantly increased the ratio between HVA and 5-HIAA. The increase in HVA was not related to symptomatic improvement, whereas the increase in the HVA/5-HIAA ratio was significantly correlated with reduction in overall symptomatology. Conclusions: The present findings are consistent withand support hypotheses suggesting that interactions be-tween monoamine systems are altered in schizophreniaand that antipsychotic treatment may affect the func-tional balance between different monoamine neurotrans-mitters (although one should keep in mind factors otherthan interactions between monoamine systems that affectmetabolite correlations and ratios).

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