Howes Oliver D, Montgomery Andrew J, Asselin Marie-Claude, Murray Robin M, Valli Isabel, Tabraham Paul, Bramon-Bosch Elvira, Valmaggia Lucia, Johns Louise, Broome Matthew, McGuire Philip K, Grasby Paul M
Section of Neuroimaging, Institute of Psychiatry, King's College London, England.
Arch Gen Psychiatry. 2009 Jan;66(1):13-20. doi: 10.1001/archgenpsychiatry.2008.514.
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.
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.
Case-control study of in vivo striatal dopaminergic function.
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.
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.
These findings indicate that dopamine overactivity 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.
精神分裂症生物标志物及新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，但尚不清楚这种神经化学异常在疾病发作时何时出现，以及它与有精神分裂症前驱症状个体的症状和神经认知障碍有何关联。
确定在精神病发作前有精神分裂症前驱症状的个体纹状体多巴胺功能是否升高，并评估其与症状和神经认知障碍的关系。
体内纹状体多巴胺能功能的病例对照研究。
学术研究。患者从社区精神卫生服务机构招募。将24例有精神分裂症前驱症状的患者与7例精神分裂症患者以及12名来自同一社区的匹配健康对照者进行比较。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（18）F - 多巴摄取量。
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（效应大小为0.75），与精神分裂症患者相比处于中等程度（效应大小为1.25）。两组的升高均局限于联合纹状体。此外，有精神分裂症前驱症状患者的纹状体（18）F - 多巴摄取量与前驱精神病理和神经心理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。
这些发现表明，多巴胺过度活跃在有前驱精神病症状的个体中早于精神分裂症发作出现，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。
