Monoamine neurotransmitter interactions in drug-free and neuroleptic-treated schizophrenics.

OBJECTIVE: To study recent suggestions by a number of investigators that interactions between monoamine neurotransmitter systems play an important role in schizophrenia. It has not been clear how hypotheses about interactions might be tested in clinical data. One means for indexing interactions between monoamine neurotransmitter systems may be to compare correlations between cerebrospinal fluid (CSF) monoamine metabolite (homovanillic acid [HVA], 5-hydroxyindoleacetic acid [5-HIAA], and 3-methoxy-4-hydroxyphenylglycol [MHPG]) or ratios of these metabolites (HVA/5-HIAA and HVA/MHPG). DESIGN: We compared these putative measures of monoamine neurotransmitter interaction in 50 drug-free patients with schizophrenia (hospitalized on an inpatient ward of a tertiary care hospital) and 33 normal controls and examined the effects of neuroleptic 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, suggesting that the difference between controls and patients was not due to acute 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 correlations between patients and controls. Metabolite ratios and correlations did not predict subsequent treatment response, but preliminary analyses demonstrated negative relationships between HVA/5-HIAA and HVA/MHPG ratios and Brief Psychiatric Rating Scale rating at that time. CONCLUSIONS: The present findings are consistent with and support hypotheses suggesting that interactions between monoamine systems are altered in schizophrenia and that antipsychotic treatment may affect the functional balance between different monoamine neurotransmitters (although one should keep in mind factors other than interactions between monoamine systems that affect metabolite correlations and ratios.

Suicide and aggression in schizophrenia. Neurobiologic correlates.

In this study of schizophrenic patients, we were unable to find an association between past history of suicide attempt and levels of CSF amine metabolites, response to DST, and ventricular size by CT scan, neurobiologic variables each of which have been reported to be associated with attempted suicide in some patient groups. Our data, however, demonstrate the marked responsiveness of measures of aggressive behavior to neuroleptic treatment, suggesting a dopaminergic involvement in these behaviors when observed in the presence of overt psychotic symptoms. Some support for an association between decreased CNS serotonin function and aggressive behavior was found in drug-free schizophrenics, although difficulty in separating illness from trait factors is an important confounding variable. The need for clinical interventions required to treat severely disturbed and aggressive behavior in the schizophrenic patients studied could not be predicted by any of the neurobiologic variables.