Presynaptic Striatal Dopamine Dysfunction in People at Ultra-high Risk for Psychosis: Findings in a Second Cohort
Presynaptic Striatal Dopamine Dysfunction in People at Ultra-high Risk for Psychosis: Findings in a Second Cohort
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DOI：
10.1016/j.biopsych.2012.11.017
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发表时间：
2013-07-15
影响因子：
10.6
通讯作者：
Howes, Oliver D.
中科院分区：
文献类型：
--
作者：
Egerton, Alice;Chaddock, Christopher A.;Howes, Oliver D.
背景：使用正电子发射断层扫描（PET），我们之前观察到精神病超高风险（UHR）受试者纹状体中 3,4-二羟基-6-[F-18]氟-L-苯丙氨酸（F-18-DOPA）摄取增加，表明突触前多巴胺合成能力升高。本研究的目的是测试这一发现是否会在第二个 UHR 队列中得到复制。 方法：使用 F-18-DOPA PET 来评估全新队列的纹状体中的多巴胺合成能力，该队列由 26 名 UHR 精神病患者（14 名男性，平均 +/- SD 年龄 = 22.7 +/- 4.7 岁）和 20 名年龄和性别匹配的健康志愿者（11 名男性，平均 +/- SD 年龄 = 24.5+/-4.5年）。结果：多巴胺合成能力整体提高[t(44)=2.6； p = .01，效应大小 = .81] 和关联纹状体 [t(44) = 2.6；与对照组相比，UHR 的 p = .01，效应大小 = .73]。当两个样本合并得到 32 名对照组和 50 名 UHR 受试者的最终样本时，UHR 组的多巴胺合成能力水平较高，在整体上达到显着性 [F(1,81) = 11.0； p = .001]，结合 [F(1,81) = 12.7； p = .001]，感觉运动 [F(1,81) = 4.7； p = .03]，但不是边缘 [F(1,81) = 2.1； p = .2]，纹状体。结论：研究结果表明，背侧纹状体多巴胺合成能力升高是 UHR 精神病患者的一个显着特征，并提供了进一步的证据，表明多巴胺能异常先于精神病发作。
Background: Using positron emission tomography (PET), we previously observed increases in 3,4-dihydroxy-6-[F-18]fluoro-L-phenylalanine (F-18-DOPA) uptake in the striatum of subjects at ultra-high risk (UHR) for psychosis, indicating elevated presynaptic dopamine synthesis capacity. The purpose of this study was to test if this finding would be replicated in a second UHR cohort.Methods: F-18-DOPA PET was used to estimate dopamine synthesis capacity in the striatum of an entirely new cohort of 26 individuals at UHR for psychosis (14 males, mean +/- SD age = 22.7 +/- 4.7 years) and 20 healthy volunteers matched for age and gender (11 males, mean +/- SD age = 24.5 +/- 4.5 years).Results: Dopamine synthesis capacity was elevated in the whole [t(44) = 2.6; p = .01, effect size = .81] and associative striatum [t(44) = 2.6; p = .01, effect size = .73] of UHR compared with control subjects. When the two samples were combined to give a final sample of 32 control and 50 UHR subjects, the higher levels of dopamine synthesis capacity in the UHR group reached significance across the whole [F(1,81) = 11.0; p = .001], associative [F(1,81) = 12.7; p = .001], and sensorimotor [F(1,81) = 4.7; p = .03], but not the limbic [F(1,81) = 2.1; p = .2], striatum.Conclusions: The findings indicate that elevated dopamine synthesis capacity in the dorsal striatum is a robust feature of individuals at UHR for psychosis and provide further evidence that dopaminergic abnormalities precede the onset of psychosis.