Data_Sheet_1_Metabolite Alterations in Adults With Schizophrenia, First Degree Relatives, and Healthy Controls: A Multi-Region 7T MRS Study.docx

Proton magnetic resonance spectroscopy (MRS) studies in schizophrenia have shown altered GABAergic, glutamatergic, and bioenergetic pathways, but if these abnormalities are brain region or illness-stage specific is largely unknown. MRS at 7T MR enables reliable quantification of multiple metabolites, including GABA, glutamate (Glu) and glutamine (Gln), from multiple brain regions within the time constraints of a clinical examination. In this study, GABA, Glu, Gln, the ratio Gln/Glu, and lactate (Lac) were quantified using 7T MRS in five brain regions in adults with schizophrenia (N = 40), first-degree relatives (N = 11), and healthy controls (N = 38). Metabolites were analyzed for differences between groups, as well as between subjects with schizophrenia with either short (<5 years, N = 19 or long (>5 years, N = 21) illness duration. For analyses between the three groups, there were significant glutamatergic and GABAergic differences observed in the anterior cingulate, centrum semiovale, and dorsolateral prefrontal cortex. There were also significant relationships between anterior cingulate cortex, centrum semiovale, and dorsolateral prefrontal cortex and cognitive measures. There were also significant glutamatergic, GABAergic, and lactate differences between subjects with long and short illness duration in the anterior cingulate, centrum semiovale, dorsolateral prefrontal cortex, and hippocampus. Finally, negative symptom severity ratings were significantly correlated with both anterior cingulate and centrum semiovale metabolite levels. In summary, 7T MRS shows multi-region differences in GABAergic and glutamatergic metabolites between subjects with schizophrenia, first-degree relatives and healthy controls, suggesting relatively diffuse involvement that evolves with illness duration. Unmedicated first-degree relatives share some of the same metabolic characteristics as patients with a diagnosis of schizophrenia, suggesting that these differences may reflect a genetic vulnerability and are not solely due to the effects of antipsychotic interventions.

针对精神分裂症的质子磁共振波谱（Proton magnetic resonance spectroscopy, MRS）研究已证实其存在γ-氨基丁酸能（GABAergic）、谷氨酸能（glutamatergic）及生物能量通路异常，但此类异常是否具有脑区特异性或疾病阶段特异性，目前仍不明确。7特斯拉磁共振（7T MR）下的MRS技术可在临床检查的时间限制内，对多个脑区的多种代谢物进行可靠定量，包括γ-氨基丁酸（GABA）、谷氨酸（Glu）与谷氨酰胺（Gln）。
本研究采用7T MRS技术，对40名精神分裂症成人患者、11名精神分裂症一级亲属（first-degree relatives）及38名健康对照（healthy controls）的5个脑区代谢物进行定量分析，检测指标包括GABA、Glu、Gln、Gln/Glu比值及乳酸（Lac）。
本研究分析了三组间的代谢物差异，同时对比了按病程长短划分的精神分裂症患者亚组差异：短病程组（<5年，n=19）与长病程组（>5年，n=21）。三组比较分析显示，前扣带回皮层（anterior cingulate cortex）、半卵圆中心（centrum semiovale）及背外侧前额叶皮层（dorsolateral prefrontal cortex）存在显著的谷氨酸能与γ-氨基丁酸能代谢物差异；前扣带回皮层、半卵圆中心及背外侧前额叶皮层的代谢物水平与认知测评结果存在显著相关性。
此外，长病程与短病程精神分裂症患者在前扣带回皮层、半卵圆中心、背外侧前额叶皮层及海马区（hippocampus）均存在显著的谷氨酸能、γ-氨基丁酸能及乳酸代谢物差异。最后，阴性症状严重程度评分与前扣带回皮层及半卵圆中心的代谢物水平呈显著相关。
综上，7T MRS技术揭示了精神分裂症患者、一级亲属与健康对照者在多个脑区的γ-氨基丁酸能与谷氨酸能代谢物差异，提示此类异常呈现相对弥漫性分布且随病程进展而变化。未接受抗精神病药物治疗的一级亲属与精神分裂症患者存在部分共通的代谢特征，表明上述差异可能反映了遗传易感倾向，而非仅由抗精神病药物干预（antipsychotic interventions）所致。