Elevated Striatal Dopamine Function Linked to Prodromal Signs of Schizophrenia
Elevated Striatal Dopamine Function Linked to Prodromal Signs of Schizophrenia
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DOI：
10.1001/archgenpsychiatry.2008.514
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发表时间：
2009-01-01
影响因子：
--
通讯作者：
Grasby, Paul M.
中科院分区：
文献类型：
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作者：
Howes, Oliver D.;Montgomery, Andrew J.;Grasby, Paul M.
背景：精神分裂症生物标志物开发和新型干预措施发展的一个主要限制是其发病机制不明。尽管纹状体多巴胺活性升高被认为是精神分裂症的根本原因，但不清楚这种神经化学异常是在疾病发作的何时出现的，以及它与精神分裂症前驱症状个体中出现的症状和神经认知损害有何关系。
目的：确定在精神病发作前有精神分裂症前驱症状的个体中纹状体多巴胺功能是否升高，并评估其与症状和神经认知损害的关系。
设计：体内纹状体多巴胺能功能的病例对照研究。
地点：学术研究。
患者：患者从社区精神卫生服务机构招募。将24名有精神分裂症前驱症状的患者与7名精神分裂症患者以及来自同一社区的12名匹配的健康对照受试者进行比较。
主要观察指标：使用正电子发射断层扫描（18）F - 多巴成像测量纹状体6 - 氟 - L - 多巴F18 - 多巴摄取量。
结果：有精神分裂症前驱症状的患者纹状体（18）F - 多巴摄取量升高（效应量为0.75），与精神分裂症患者相比处于中等程度（效应量为1.25）。两组的升高都局限于联合纹状体。此外，有精神分裂症前驱症状的患者纹状体（18）F - 多巴摄取量与前驱精神病理学和神经心理学损害的严重程度相关，但与焦虑或抑郁症状的严重程度无关。
结论：这些发现表明，在有前驱精神病性症状的个体中，多巴胺过度活动早于精神分裂症发作，主要局限于联合纹状体，并且与症状和神经认知功能障碍的严重程度相关。
Context: A major limitation on the development of biomarkers and novel interventions for schizophrenia is that its pathogenesis is unknown. Although elevated striatal dopamine activity is thought to be fundamental to schizophrenia, it is unclear when this neurochemical abnormality develops in relation to the onset of illness and how this relates to the symptoms and neurocognitive impairment seen in individuals with prodromal symptoms of schizophrenia.Objectives: To determine whether striatal dopamine function is elevated in individuals with prodromal symptoms of schizophrenia before the onset of psychosis and to assess how this relates to the symptoms and neurocognitive impairment.Design: Case-control study of in vivo striatal dopaminergic function.Setting: Academic research.Patients: Patients were recruited from a community mental health service. Twenty-four patients having prodromal symptoms of schizophrenia were compared with 7 patients having schizophrenia and with 12 matched healthy control subjects from the same community.Main Outcome Measure: Striatal 6-fluoro-L-dopa F 18-dopa uptake measured using positron emission tomographic (18)F-dopa imaging.Results: Striatal (18)F-dopa uptake was elevated in patients with prodromal symptoms of schizophrenia (effect size, 0.75) to an intermediate degree compared with that in patients with schizophrenia (effect size, 1.25). The elevation was localized in the associative striatum in both groups. Moreover, striatal (18)F-dopa uptake in patients with prodromal symptoms of schizophrenia was correlated with the severity of prodromal psychopathologic and neuropsychological impairment but not with the severity of anxiety or depressive symptoms.Conclusions: These findings indicate that dopamine over-activity predates the onset of schizophrenia in individuals with prodromal psychotic symptoms, is predominantly localized in the associative striatum, and is correlated with the severity of symptoms and neurocognitive dysfunction.