Taylor S F, Koeppe R A, Tandon R, Zubieta J K, Frey K A
Departments of Psychiatry, University of Michigan, Ann Arbor, MI 48109-0118, USA.
Neuropsychopharmacology. 2000 Dec;23(6):667-75. doi: 10.1016/S0893-133X(00)00165-2.
Given evidence for excessive striatal dopamine activity in schizophrenia, we sought to test the hypothesis that dopaminergic innervation in the striatum is abnormally elevated, and a secondary hypothesis that age-related loss is accelerated. Twelve schizophrenic subjects on stable doses of medications, along with 12 age and sex-matched healthy control subjects, underwent positron emission tomography (PET) studies with [11C]dihydrotetrabenazine (DTBZ), which binds to the vesicular monoamine transporter, type 2 (VMAT2). DTBZ binding reflects principally dopaminergic projections in the striatum and appears in animal models, over treatment periods as long as two weeks, not to be regulated by antipsychotic drugs. Using an equilibrium analysis, we obtained measurements of the binding potential (BP) of [11C]DTBZ, as well as a transport (K(1)) measure, corresponding to regional cerebral blood flow. BP in the striatum showed no difference between the patient and control groups, and no differential effect of age. We did not find evidence supporting the hypothesis that excessive dopamine activity in schizophrenia could be explained by increased density of striatal dopamine terminals.
鉴于精神分裂症患者纹状体多巴胺活性过高的证据，我们试图验证以下假设：纹状体中多巴胺能神经支配异常增加，以及另一个次要假设，即与年龄相关的神经支配丧失加速。12名服用稳定剂量药物的精神分裂症患者以及12名年龄和性别匹配的健康对照受试者接受了用[11C]二氢四苯嗪（DTBZ）进行的正电子发射断层扫描（PET）研究，DTBZ与2型囊泡单胺转运体（VMAT2）结合。DTBZ结合主要反映纹状体中的多巴胺能投射，并且在动物模型中，在长达两周的治疗期内，似乎不受抗精神病药物的调节。通过平衡分析，我们获得了[11C]DTBZ结合潜能（BP）的测量值以及与局部脑血流量相对应的转运（K(1)）测量值。纹状体中的BP在患者组和对照组之间没有差异，且没有年龄差异效应。我们没有找到证据支持以下假设，即精神分裂症中多巴胺活性过高可由纹状体多巴胺末梢密度增加来解释。
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