Background

Salience network (SN) connectivity is altered in schizophrenia, but the pathophysiological origin remains poorly understood. The goal of this multimodal neuroimaging study was to investigate the role of glutamatergic metabolism as putative mechanism underlying SN dysconnectivity in first episode psychosis (FEP) subjects.

Methods

We measured glutamate + glutamine (Glx) in the dorsal anterior cingulate cortex (dACC) from 70 antipsychotic-naïve FEP subjects and 52 healthy controls (HC). The dACC was then used as seed to define positive and negative resting state functional connectivity (FC) of the SN. We used multiple regression analyses to test main effects and group interactions of Glx and FC associations.

Results

dACC Glx levels did not differ between groups. Positive FC was significantly reduced in FEP compared to HC, and no group differences were found in negative FC. Group interactions of Glx-FC associations were found within the SN for positive FC, and in parietal cortices for negative FC. In HC, higher Glx levels predicted greater positive FC in the dACC and insula, and greater negative FC of the lateral parietal cortex. These relationships were weaker or absent in FEP.

Conclusions

Here, we found that positive FC in the SN is already altered in medication-naïve FEP, underscoring the importance of considering both correlations and anticorrelations for characterization of pathology. Our data demonstrate that Glx and functional connectivity work differently in FEP than in HC, pointing to a possible mechanism underlying dysconnectivity in psychosis.

中文翻译：

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首次用药初治患者的显着网络谷氨酸和大脑连接——多模态磁共振波谱和静息状态功能连接 MRI 研究

背景

精神分裂症的显着网络 (SN) 连通性发生了改变，但其病理生理学起源仍然知之甚少。这项多模式神经影像学研究的目的是调查谷氨酸能代谢作为首发精神病 (FEP) 受试者 SN 连接障碍的推定机制的作用。

方法

我们测量了 70 名未使用抗精神病药 FEP 受试者和 52 名健康对照 (HC) 的背侧前扣带皮层 (dACC) 中的谷氨酸 + 谷氨酰胺 (Glx)。然后将 dACC 用作种子来定义 SN 的正和负静息状态功能连接 (FC)。我们使用多元回归分析来测试 Glx 和 FC 关联的主要影响和组交互。

结果

dACC Glx 水平在各组之间没有差异。与 HC 相比，FEP 的阳性 FC 显着降低，阴性 FC 未发现组间差异。在 SN 中发现了 Glx-FC 关联的组相互作用，用于阳性 FC，在顶叶皮质中发现阴性 FC。在 HC 中，较高的 Glx 水平预示着 dACC 和岛叶的正 FC 较大，而外侧顶叶皮层的负 FC 较大。这些关系在 FEP 中较弱或不存在。

结论

在这里，我们发现 SN 中的阳性 FC 在未经药物治疗的 FEP 中已经改变，强调了考虑相关性和反相关性对病理学表征的重要性。我们的数据表明，Glx 和功能连接在 FEP 中的工作方式与在 HC 中不同，这表明了精神病中连接障碍的可能机制。