Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Center Glostrup, University of Copenhagen, Glostrup, Denmark.
Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Center Glostrup, University of Copenhagen, Glostrup, Denmark.
Biol Psychiatry. 2021 Feb 1;89(3):278-287. doi: 10.1016/j.biopsych.2020.06.027. Epub 2020 Jul 10.
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.
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.
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.
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.
在精神分裂症的早期阶段发现谷氨酸和 GABA（γ-氨基丁酸）水平异常，这可能是认知缺陷的基础。然而，在一大群未经抗精神病药物治疗的患者中，尚未研究认知功能与谷氨酸代谢物和 GABA 水平之间的关系。
共有 56 名未经抗精神病药物治疗的精神分裂症或精神病患者和 51 名健康对照者接受磁共振波谱检查，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，以及左丘脑的谷氨酸和 Glx 水平。评估注意力、工作记忆和智商等认知领域。
整个未经抗精神病药物治疗的患者组背侧 ACC 的 GABA 水平较低（p =.03），而精神分裂症诊断亚组的丘脑谷氨酸水平较高（p =.01），但背侧 ACC 和丘脑的 Glx 水平在组间无差异。背侧 ACC 的 Glx 水平与工作记忆（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，尽管这种与注意力的关联在经过多次比较调整后并未成立。
研究结果表明，谷氨酸代谢物与认知功能之间存在正相关，而这种相关性在患者和健康对照者之间没有差异。此外，我们的数据表明背侧 ACC 中的 GABA 能水平降低与精神分裂症和精神病有关，而丘脑中的谷氨酸水平升高似乎与精神分裂症的病理生理学有关。这些发现意味着有认知缺陷的首发患者可能会从谷氨酸调节化合物中受益。
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