BACKGROUND Abnormal glutamate and GABA (gamma-aminobutyric acid) levels have been found in the early phase of schizophrenia and may underlie cognitive deficits. However, the association between cognitive function and levels of glutamatergic metabolites and GABA has not been investigated in a large group of antipsychotic-naïve patients. METHODS In total, 56 antipsychotic-naïve patients with schizophrenia or psychotic disorder and 51 healthy control subjects underwent magnetic resonance spectroscopy to measure glutamate, glutamate+glutamine (Glx), and GABA levels in dorsal anterior cingulate cortex (ACC) and glutamate and Glx levels in left thalamus. The cognitive domains of attention, working memory, and IQ were assessed. RESULTS The whole group of antipsychotic-naïve patients had lower levels of GABA in dorsal ACC (p = .03), and the subgroup of patients with a schizophrenia diagnosis had higher glutamate levels in thalamus (p = .01), but Glx levels in dorsal ACC and thalamus did not differ between groups. Glx levels in dorsal ACC were positively associated with working memory (logarithmically transformed: b = -.016 [higher score indicates worse performance], p = .005) and attention (b = .056, p = .035) in both patients and healthy control subjects, although the association with attention did not survive adjustment for multiple comparisons. CONCLUSIONS The findings suggest a positive association between glutamatergic metabolites and cognitive function that do not differ between patients and healthy control subjects. Moreover, our data indicate that decreased GABAergic levels in dorsal ACC are involved in schizophrenia and psychotic disorder, whereas increased glutamate levels in thalamus seem to be implicated in schizophrenia pathophysiology. The findings imply that first-episode patients with cognitive deficits may gain from glutamate-modulating compounds.

中文翻译：

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精神分裂症或精神病患者的认知功能与谷氨酸能代谢物和 GABA 水平之间的关联

背景 已在精神分裂症的早期发现异常的谷氨酸和 GABA（γ-氨基丁酸）水平，并且可能是认知缺陷的基础。然而，认知功能与谷氨酸能代谢物和 GABA 水平之间的关联尚未在一大群抗精神病药初治患者中进行过研究。方法 总共对 56 名精神分裂症或精神病性精神障碍患者和 51 名健康对照受试者进行了磁共振波谱测量，以测量背侧前扣带皮层 (ACC) 中的谷氨酸、谷氨酸+谷氨酰胺 (Glx) 和 GABA 水平以及谷氨酸和 Glx 水平在左丘脑。评估了注意力、工作记忆和智商等认知领域。结果 整组未接受过抗精神病药物治疗的患者背部 ACC 中的 GABA 水平较低 (p = .03)，诊断为精神分裂症的患者亚组在丘脑中的谷氨酸水平较高 (p = .01)，但背侧 ACC 和丘脑中的 Glx 水平在组间没有差异。背部 ACC 中的 Glx 水平与患者和患者的工作记忆（对数转换：b = -.016 [得分越高表示表现越差]，p = .005）和注意力（b = .056，p = .035）呈正相关健康对照受试者，尽管与注意力的关联在多重比较调整后无法幸存。结论 研究结果表明，谷氨酸能代谢物与认知功能之间存在正相关关系，患者与健康对照受试者之间没有差异。此外，我们的数据表明，背部 ACC 中 GABA 能水平的降低与精神分裂症和精神病有关，而丘脑中谷氨酸水平的增加似乎与精神分裂症的病理生理学有关。研究结果表明，具有认知缺陷的首发患者可能会受益于调节谷氨酸的化合物。