Mental Health Centre and Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Brain Research Center, West China Hospital, Sichuan University, Chengdu, China.
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, Section of Psychiatry, University of Genoa, Genoa, Italy.
Schizophr Bull. 2018 Feb 15;44(2):419-431. doi: 10.1093/schbul/sbx067.
OBJECTIVE: The dopamine hypothesis is one of the most influential theories of the neurobiological background of schizophrenia (SCZ). However, direct evidence for abnormal dopamine-related subcortical-cortical circuitry disconnectivity is still lacking. The aim of this study was therefore to test dopamine-related substantia nigra (SN)-based striato-thalamo-cortical resting-state functional connectivity (FC) in SCZ. METHOD: Based on our a priori hypothesis, we analyzed a large sample resting-state functional magnetic resonance imaging (fMRI) dataset from first-episode drug-naïve SCZ patients (n = 112) and healthy controls (n = 82) using the SN as the seed region for an investigation of striato-thalamo-cortical FC. This was done in the standard band of slow frequency oscillations and then in its subfrequency bands (Slow4 and Slow5). Results: The analysis showed in SCZ: (1) reciprocal functional hypo-connectivity between SN and striatum, with differential patterns for Slow5 and Slow4; (2) functional hypo-connectivity between striatum and thalamus, as well as functional hyper-connectivity between thalamus and sensorimotor cortical areas, specifically in Slow4; (3) correlation of thalamo-sensorimotor functional hyper-connectivity with psychopathological symptoms. Conclusions: We demonstrate abnormal dopamine-related SN-based striato-thalamo-cortical FC in slow frequency oscillations in first-episode drug-naive SCZ. This suggests that altered dopaminergic function in the SN leads to abnormal neuronal synchronization (as indexed by FC) within subcortical-cortical circuitry, complementing the dopamine hypothesis in SCZ on the regional level of resting-state activity.
目的:多巴胺假说 是精神分裂症(SCZ)神经生物学背景的最有影响力的理论之一。然而,仍然缺乏异常多巴胺相关的皮质下-皮质电路连接断开的直接证据。因此,本研究的目的是测试精神分裂症患者基于黑质(SN)的多巴胺相关纹状体-丘脑-皮质静息状态功能连接(FC)。
方法:基于我们的先验假设,我们使用 SN 作为种子区域,分析了来自首发未经药物治疗的 SCZ 患者(n = 112)和健康对照者(n = 82)的大型静息态功能磁共振成像(fMRI)数据集,以研究纹状体-丘脑-皮质 FC。这是在慢频振荡的标准频带中进行的,然后在其亚频带(Slow4 和 Slow5)中进行。
结果:分析表明,在 SCZ 中:(1)SN 与纹状体之间的功能连接性降低,Slow5 和 Slow4 呈现出不同的模式;(2)纹状体与丘脑之间的功能连接性降低,以及丘脑与感觉运动皮质区域之间的功能连接性增加,特别是在 Slow4 中;(3)丘脑-感觉运动功能连接性与精神病理学症状相关。
结论:我们在首发未经药物治疗的 SCZ 中证明了慢频振荡中基于多巴胺的 SN 纹状体-丘脑-皮质 FC 的异常。这表明 SN 中多巴胺功能的改变导致了皮质下-皮质电路内神经元同步性的异常(以 FC 为指标),在区域静息状态活动水平上补充了精神分裂症的多巴胺假说。
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