Progressive Changes in Glutamate Concentration in Early Stages of Schizophrenia: A Longitudinal 7-Tesla MRS Study.
Progressive Changes in Glutamate Concentration in Early Stages of Schizophrenia: A Longitudinal 7-Tesla MRS Study.
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DOI：
10.1093/schizbullopen/sgaa072
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发表时间：
2021-01
期刊：
影响因子：
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通讯作者：
Palaniyappan L
中科院分区：
文献类型：
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作者：
Jeon P;Limongi R;Ford SD;Mackinley M;Dempster K;Théberge J;Palaniyappan L
逐渐减少的神经递质传递已被认为是精神分裂症疾病轨迹的重要组成部分。尽管这一概念很受欢迎，但迄今为止，这一概念尚未在精神分裂症早期患者中得到令人信服的检验。在纵向7 T磁共振波谱（1H-MRS）中，我们量化了21名中位寿命抗精神病药物暴露少于3天的参与者背侧前扣带皮层的谷氨酸盐，并在治疗6个月后对其进行了随访。10名健康对照也在2个时间点进行扫描。虽然患者的总体谷氨酸水平显著低于健康对照组（F（1，27）= 5.23，P = 0.03），但我们没有观察到患者谷氨酸浓度的进行性变化（F（1，18）= 0.47，P = 0.50），并且组与时间的相互作用不显著（F（1，27）= 0.86，P = 0.36）。平均而言，接受治疗的早期精神病患者显示MRS谷氨酸水平增加0.02 mM/y，而健康对照显示MRS谷氨酸水平降低0.06 mM/y。贝叶斯分析我们的观察不支持精神分裂症的早期，发病后谷氨酸损失。有趣的是，它提供的证据支持我们的精神分裂症样本中缺乏渐进的谷氨酸变化，表明疾病发作时的谷氨酸水平是治疗后6个月水平的最佳预测因子。一个更微妙的观点，谷氨酸能生理学，与早期皮质成熟，可能需要了解谷氨酸介导的动力学在精神分裂症。
Progressive reduction in glutamatergic transmission has been proposed as an important component of the illness trajectory of schizophrenia. Despite its popularity, to date, this notion has not been convincingly tested in patients in early stages of schizophrenia. In a longitudinal 7T magnetic resonance spectroscopy (1H-MRS), we quantified glutamate at the dorsal anterior cingulate cortex in 21 participants with a median lifetime antipsychotic exposure of less than 3 days and followed them up after 6 months of treatment. Ten healthy controls were also scanned at 2 time points. While patients had significantly lower overall glutamate levels than healthy controls (F(1,27) = 5.23, P = .03), we did not observe a progressive change of glutamate concentration in patients (F(1,18) = 0.47, P = .50), and the group by time interaction was not significant (F(1,27) = 0.86, P = .36). On average, patients with early psychosis receiving treatment showed a 0.02 mM/y increase, while healthy controls showed a 0.06 mM/y reduction of MRS glutamate levels. Bayesian analysis of our observations does not support early, post-onset glutamate loss in schizophrenia. Interestingly, it provides evidence in favor of a lack of progressive glutamate change in our schizophrenia sample—indicating that the glutamate level at the onset of illness was the best predictor of the levels 6 months after treatment. A more nuanced view of glutamatergic physiology, linked to early cortical maturation, may be required to understand glutamate-mediated dynamics in schizophrenia.