Erica Duncan, M.D. and her co-investigators have been using plasma catecholamine metabolites as a tool to estimate central dopaminergic and noradrenergic turnover in schizophrenics and normals. Recent studies have found that schizophrenics who improve after treatment with neuroleptics have a brisk increase in homovanillic acid (HVA), a metabolite of dopamines, after their first dose of neuroleptic. In contrast, those patients who do not improve with treatment have no change in their HVA after their first dose of medication. This differential change in HVA likely reflects a difference in the plasticity of the dopamine system in these two groups of schizophrenics. Ongoing studies are examining the response of MHPG, a norepinephrine metabolite, to neuroleptic treatment. In another series of subjects, the researchers have found that normals have a natural fall in HVA over the morning. Unmedicated schizophrenic patients lack this normal pattern. This study will be extended to include the effects of medication.
In another study, neuroleptic nonresponsive schizophrenics were stabilized on neuroleptics. Alpha-methylparatyrosine (AMPT) was added in order to block dopamine synthesis. As expected, their HVA fell to very low levels. The subjects did not change clinically, despite dramatically reduced dopaminergic neurotransmission. This data suggests that, at least in this group of neuroleptic nonresponsive schizophrenics, hyperdopaminergia is not a satisfactory explanation for their symptoms.
Other projects currently being developed include the use of a 2-deoxyglucose as a metabolic stress paradigm to probe dopaminergic and nondopaminergic stress response in schizophrenics and normals; and the use of metachlorophenylpiperazine (mCPP) as a serotonergic probe in the investigation of schizophrenia, PTSD, and anxiety disorders.
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