Striatal dopamine D2/3 receptor binding following dopamine depletion in subjects at Ultra High Risk for psychosis
Striatal dopamine D2/3 receptor binding following dopamine depletion in subjects at Ultra High Risk for psychosis
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DOI：
10.1016/j.euroneuro.2012.04.015
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发表时间：
2013-02-01
影响因子：
5.6
通讯作者：
van Amelsvoort, Therese A. M. J.
中科院分区：
文献类型：
--
作者：
Bloemen, Oswald J. N.;de Koning, Mariken B.;van Amelsvoort, Therese A. M. J.
纹状体多巴胺能神经传递的改变被认为是精神分裂症的基础。突触前多巴胺能活性（[F-18]-DOPA PET）的增加可能早于精神病症状的发作，并且与发生精神病的超高风险（UHR）受试者的临床症状相关。尚未在 UHR 患者中研究突触后多巴胺能神经传递。我们假设 UHR 患者的突触多巴胺浓度会增加，并且突触多巴胺浓度与症状严重程度相关。 14 名 UHR 患者和 15 名年龄和智商匹配的对照者在基线时完成了 [I-123]-IBZM SPECT 扫描，并在用 α-甲基-对酪氨酸 (AMPT) 消耗多巴胺后再次完成。我们测量了放射性示踪剂结合电位的变化，比较了 UHR 患者和对照组之间的变化，并将这些变化与症状严重程度相关联。 UHR 组作为一个整体与对照组没有显着差异。 AMPT 显着降低了 UHR 组的症状严重程度 (p = 0.014)。在 UHR 组中，较高的突触多巴胺浓度预示着消耗后阳性症状的更大程度减少（p = 0.01）。在 UHR 患者中，阳性症状对多巴胺消耗有反应，与精神分裂症中的观察结果相当，表明存在类似的机制。突触多巴胺浓度越高，阳性症状越严重，并且在消耗后这些症状的减轻程度更大。 (c) 2012 Elsevier B.V. 和 ECNR 保留所有权利。
Altered striatal dopaminergic neurotransmission is thought to be fundamental to schizophrenia. Increased presynaptic dopaminergic activity ([F-18]-DOPA PET) may predate the onset of psychotic symptoms and correlates to clinical symptoms in subjects at Ultra High Risk (UHR) for developing psychosis. Postsynaptic dopaminergic neurotransmission has not been investigated yet in UHR patients. We hypothesized that synaptic dopamine concentration would be increased in UHR patients, and that synaptic dopamine concentration would be related to symptom severity. 14 UHR patients and 15 age and IQ matched controls completed an [I-123]-IBZM SPECT scan at baseline and again after dopamine depletion with alpha-methyl-para-tyrosine (AMPT). We measured changes in radiotracer binding potential, compared these between UHR patients and controls, and correlated these to symptom severity. The UHR group as a whole did not differ significantly from controls. AMPT significantly reduced symptom severity in the UHR group (p = 0.014). Higher synaptic dopamine concentration predicted larger reduction of positive symptoms following depletion in the UHR group (p = 0.01). In UHR patients, positive symptoms responded to dopamine depletion, comparable to observations in schizophrenia, suggesting a similar mechanism. Higher synaptic dopamine concentration was associated with more severe positive symptoms and a greater reduction of these symptoms following depletion. (c) 2012 Elsevier B.V. and ECNR All rights reserved.