Reduced GABA/glutamate in the thalamus of individuals at clinical high risk for psychosis
Reduced GABA/glutamate in the thalamus of individuals at clinical high risk for psychosis
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DOI：
10.1038/s41386-020-00920-4
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发表时间：
2020-12-03
影响因子：
7.6
通讯作者：
Ferrarelli, Fabio
中科院分区：
文献类型：
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作者：
Quinones, Gonzalo M.;Mayeli, Ahmad;Ferrarelli, Fabio
青少年临床高危人群（CHR）是一个独特的人群，富含主要精神疾病的前体，特别是精神分裂症（SCZ）。最近的神经影像学发现表明SCZ患者的丘脑异常，包括慢性和早期病程患者，以及CHR个体相对于健康对照组，因此表明丘脑功能障碍甚至在发病前就存在。此外，建模数据表明，兴奋性和抑制性控制之间的改变，如GABA能和谷氨酸能平衡（即GABA/Glu）的改变所反映的，可能是与精神病风险和发展相关的丘脑缺陷的基础。然而，在CHR状态下缺乏GABA/Glu丘脑异常的体内证据。磁共振波谱成像（MRSI） 7特斯拉（7t）为量化CHR个体丘脑中GABA和Glu水平提供了更高的分辨率。在这项研究中，我们对15名CHR参与者和20名健康对照（HC）参与者进行了7次磁共振成像。我们发现，与HC组相比，CHR组的右侧内侧前丘脑和右侧内侧后丘脑的GABA/Glu明显降低。GABA/Glu减少与右侧内侧后丘脑的一般症状以及右侧内侧后丘脑的紊乱症状呈负相关。总之，这些发现表明，GABA/Glu异常在全面精神病发作之前就存在于丘脑中，并与症状严重程度相关，因此为CHR青少年早期干预提供了假定的分子和神经元靶点。
Youth at clinical high risk (CHR) are a unique population enriched for precursors of major psychiatric disorders, especially schizophrenia (SCZ). Recent neuroimaging findings point to abnormalities in the thalamus of patients with SCZ, including chronic and early course patients, as well as in CHR individuals relative to healthy comparison groups, thus suggesting that thalamic dysfunctions are present even before illness onset. Furthermore, modeling data indicate that alteration between excitatory and inhibitory control, as reflected by alteration in GABAergic and glutamatergic balance (i.e., GABA/Glu), may underlie thalamic deficits linked to the risk and development of psychosis. There is, however, a lack of in vivo evidence of GABA/Glu thalamic abnormalities in the CHR state. Magnetic resonance spectroscopic imaging (MRSI) 7 Tesla (7 T) provides enhanced resolution to quantify GABA and Glu levels in the thalamus of CHR individuals. In this study, we performed 7 T MRSI in 15 CHR and 20 healthy control (HC) participants. We found that GABA/Glu was significantly reduced in the right medial anterior and right medial posterior thalamus of CHR relative to HC groups. The GABA/Glu reduction was negatively correlated with general symptoms in the right medial anterior thalamus, as well as with disorganization symptoms in the right medial posterior thalamus. Altogether, these findings indicate that GABA/Glu abnormalities are present in the thalamus before the onset of full-blown psychosis and are associated with symptom severity, thus providing putative molecular and neuronal targets for early interventions in youth at CHR.