Dopamine Synthesis Capacity in Patients With Treatment-Resistant Schizophrenia

作者：Arsime Demjaha, Robin Murray, Philip McGuire, Shitij Kapur, Oliver Howes · 发表于：American Journal of Psychiatry · 年份：2012 · DOI：10.1176/appi.ajp.2012.12010144 · 被引用次数：350 · 研究领域：Schizophrenia research and treatment、Neurotransmitter Receptor Influence on Behavior、Parkinson's Disease Mechanisms and Treatments

OBJECTIVE: Elevated presynaptic striatal dopaminergic function is a robust feature of schizophrenia. However, the relationship between this dopamine abnormality and the response to dopamine-blocking antipsychotic treatments is unclear. The authors tested the hypothesis that in patients with schizophrenia the response to antipsychotic treatment would be related to the severity of presynaptic dopamine dysfunction, as indexed using [(18)F]-DOPA uptake positron emission tomography (PET). METHOD: Twelve patients with treatment-resistant schizophrenia, twelve patients with schizophrenia who had responded to antipsychotics, and twelve healthy volunteers matched for gender, age, ethnicity, weight, and cigarette smoking underwent [(18)F]-DOPA PET scanning. [(18)F]-DOPA influx rate constants (K(i)(cer) values) were measured in the striatum and its functional subdivisions. RESULTS: Patients who had responded to antipsychotic treatment showed significantly higher K(i)(cer) striatal values than did patients with treatment-resistant illness (effect size=1.11) and healthy volunteers (effect size=1.12). The elevated [(18)F]-DOPA uptake was most marked in the associative (effect size=1.31) and the limbic (effect size=1.04) striatal subdivisions. There were no significant differences between patients with treatment-resistant illness and healthy volunteers in the whole striatum or any of its subdivisions. CONCLUSIONS: In some patients with schizophrenia, antipsychotic treatment may be ineffecti...