Elevated Prefrontal Cortex γ-Aminobutyric Acid and Glutamate-Glutamine Levels in Schizophrenia Measured In Vivo With Proton Magnetic Resonance Spectroscopy
Elevated Prefrontal Cortex γ-Aminobutyric Acid and Glutamate-Glutamine Levels in Schizophrenia Measured In Vivo With Proton Magnetic Resonance Spectroscopy
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DOI：
10.1001/archgenpsychiatry.2011.1519
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发表时间：
2012-05-01
影响因子：
--
通讯作者：
Shungu, Dikoma C.
中科院分区：
文献类型：
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作者：
Kegeles, Lawrence S.;Mao, Xiangling;Shungu, Dikoma C.
背景：死后研究发现，精神分裂症患者前额叶皮层快速尖峰、细小蛋白阳性的中间神经元中存在γ -氨基丁酸（GABA）缺失的证据。磁共振波谱研究在未服药的患者报告谷氨酰胺或谷氨酸-谷氨酰胺（Glx）在该地区升高。这些递质的异常被认为在这种疾病的认知障碍中起作用。目的：测定未服药、服药的精神分裂症患者和健康对照者体内2个前额叶脑区GABA和Glx水平。设计：病例对照研究。设置：住院精神病学研究单位及相关门诊。参与者：16名未接受药物治疗的精神分裂症患者，16名接受药物治疗的患者和22名年龄、性别、种族、父母社会经济地位和吸烟情况相匹配的健康对照。方法：3-T体系质子磁共振波谱法和j编辑自旋回波差分法。测量背外侧和内侧前额叶皮层的GABA和Glx水平，并将其归一化为同时获得的水信号。对所有受试者的工作记忆表现进行了评估。主要观察指标：质子磁共振波谱法测定GABA和Glx浓度。结果：内侧前额叶皮质区GABA升高30% (P =。2)和Glx (P =。与对照组相比，未服药患者的水平为03)。服用药物的患者或两组的背外侧前额叶皮层均未发生变化。这两个区域显示了患者和对照组中GABA和Glx水平之间的相关性。与工作记忆表现没有相关性。结论：据我们所知，本研究首次对未服药的精神分裂症患者进行了GABA浓度测量，结果显示内侧前额叶皮层的GABA和Glx水平均升高，而背外侧前额叶皮层则没有升高。服用药物的患者没有出现这些升高，提示抗精神病药物可能使水平正常化。Glx的升高与先前的磁共振波谱文献一致，但GABA的升高是出乎意料的，表明可能涉及死后研究中未发现的中间神经元类别。
Context: Postmortem studies have found evidence of gamma-aminobutyric acid (GABA) deficits in fast-spiking, parvalbumin-positive interneurons in the prefrontal cortex in schizophrenia. Magnetic resonance spectroscopy studies in unmedicated patients have reported glutamine or glutamate-glutamine (Glx) elevations in this region. Abnormalities in these transmitters are thought to play a role in cognitive impairments in the illness.Objective: To measure GABA and Glx levels in vivo in 2 prefrontal brain regions in unmedicated and medicated patients with schizophrenia and healthy controls.Design: Case-control study.Setting: Inpatient psychiatric research unit and associated outpatient clinic.Participants: Sixteen unmedicated patients with schizophrenia, 16 medicated patients, and 22 healthy controls matched for age, sex, ethnicity, parental socioeconomic status, and cigarette smoking.Methods: Proton magnetic resonance spectroscopy with a 3-T system and the J-edited spin-echo difference method. The GABA and Glx levels were measured in the dorsolateral and medial prefrontal cortex and normalized to the simultaneously acquired water signal. Working memory performance was assessed in all subjects.Main Outcome Measures: The GABA and Glx concentrations determined by proton magnetic resonance spectroscopy.Results: In the medial prefrontal cortex region, 30% elevations were found in GABA (P =. 02) and Glx (P =. 03) levels in unmedicated patients compared with controls. There were no alterations in the medicated patients or in either group in the dorsolateral prefrontal cortex. Both regions showed correlations between GABA and Glx levels in patients and controls. No correlations with working memory performance were found.Conclusions: To our knowledge, this study presents the first GABA concentration measurements in unmedicated patients with schizophrenia, who showed elevations in both GABA and Glx levels in the medial prefrontal cortex but not the dorsolateral prefrontal cortex. Medicated patients did not show these elevations, suggesting possible normalization of levels with antipsychotic medication. The Glx elevations agree with prior magnetic resonance spectroscopy literature, but GABA elevations were unexpected and suggest possible involvement of classes of interneurons not found to show impairments in postmortem studies.