The relationship between grey matter volume and striatal dopamine function in psychosis: a multimodal (18)F-DOPA PET and voxel-based morphometry study.
The relationship between grey matter volume and striatal dopamine function in psychosis: a multimodal (18)F-DOPA PET and voxel-based morphometry study.
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DOI：
10.1038/s41380-019-0570-6
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发表时间：
2021-04
影响因子：
11
通讯作者：
Howes OD
中科院分区：
文献类型：
--
作者：
D'Ambrosio E;Jauhar S;Kim S;Veronese M;Rogdaki M;Pepper F;Bonoldi I;Kotoula V;Kempton MJ;Turkheimer F;Kwon JS;Kim E;Howes OD
精神分裂症和相关精神障碍的一个主要假说认为，大脑皮层破坏导致皮层下多巴胺能功能障碍，这是大多数对治疗有反应的患者出现精神病的基础。尽管临床前研究结果支持前额皮质病变导致纹状体多巴胺失调，但尚未在精神病患者中测试前额叶结构体积与纹状体多巴胺功能之间的关系。因此，我们研究了对治疗有反应的精神病患者纹状体多巴胺合成能力和前额叶灰质体积之间的体内关系，并将其与治疗无反应的患者进行了比较，其中多巴胺能机制不被认为是中心机制。在两个独立的队列中，40名精神病患者接受了18F-DOPA PET扫描，以测量多巴胺合成能力（以流入速率常数Ki - cer为指标）和结构3T MRI。PET，而不是MR，数据之前已经报道过。采用DARTEL-VBM对结构图像进行处理。在SPM12中进行GLM分析以测试前额叶灰质体积与纹状体Ki的关系。治疗应答者显示前额叶灰质和纹状体多巴胺合成能力呈负相关，但这在治疗无应答者中并不明显。具体来说，我们发现治疗反应、整个纹状体多巴胺合成能力和左（pFWE）和右（pFWE）前额皮质灰质体积之间存在相互作用。我们在独立样本中重复了右前额叶皮层的发现（pFWE相关性= 0.031）。总效应量为0.82。我们的研究结果与长期存在的纹状体多巴胺能系统失调与精神分裂症的前额叶皮层病理有关的假设是一致的，但也批判性地扩展了这一假设，表明它只适用于治疗反应性精神分裂症。这表明治疗反应性和治疗抵抗性精神分裂症的病理生理机制不同。
A leading hypothesis for schizophrenia and related psychotic disorders proposes that cortical brain disruption leads to subcortical dopaminergic dysfunction, which underlies psychosis in the majority of patients who respond to treatment. Although supported by preclinical findings that prefrontal cortical lesions lead to striatal dopamine dysregulation, the relationship between prefrontal structural volume and striatal dopamine function has not been tested in people with psychosis. We therefore investigated the in vivo relationship between striatal dopamine synthesis capacity and prefrontal grey matter volume in treatment responsive patients with psychosis, and compared them to treatment non-responsive patients, where dopaminergic mechanisms are not thought to be central. 40 patients with psychosis across two independent cohorts underwent 18F-DOPA PET scans to measure dopamine synthesis capacity (indexed as the influx rate constant Ki cer) and structural 3T MRI. The PET, but not MR, data have been reported previously. Structural images were processed using DARTEL-VBM. GLM analyses were performed in SPM12 to test the relationship between prefrontal grey matter volume and striatal Ki cer. Treatment responders showed a negative correlation between prefrontal grey matter and striatal dopamine synthesis capacity, but this was not evident in treatment non-responders. Specifically, we found an interaction between treatment response, whole striatal dopamine synthesis capacity and grey matter volume in left (pFWE corr.= 0.017) and right (pFWE corr.= 0.042) prefrontal cortex. We replicated the finding in right prefrontal cortex in the independent sample (pFWE corr.= 0.031). The summary effect size was 0.82. Our findings are consistent with the long-standing hypothesis of dysregulation of the striatal dopaminergic system being related to prefrontal cortex pathology in schizophrenia, but critically also extend the hypothesis to indicate it can be applied to treatment-responsive schizophrenia only. This suggests that different mechanisms underlie the pathophysiology of treatment-responsive and treatment-resistant schizophrenia.
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影响因子：
6.6
作者：
Allen, Paul;Luigjes, Judy;McGuire, Philip
通讯作者：
McGuire, Philip
影响因子：
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作者：
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影响因子：
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作者：
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作者：
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