Samson Genelle D, Maximo Jose O, Nelson Eric A, Kraguljac Nina V, Armstrong William P, Benningfield Branden, Adnani Seyedeh Nasim, Bashir Adil, Lahti Adrienne C
Department of Psychology, University of Alabama at Birmingham, Birmingham, United States.
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, United States.
Schizophr Bull. 2025 Jun 30. doi: 10.1093/schbul/sbaf079.
Converging evidence from animal and human studies has implicated gamma-aminobutyric acid (GABA)-ergic dysfunction in the pathophysiology of psychosis spectrum disorders. However, little is known about GABA's role in the early illness stages. Based on prior research, we hypothesized that GABA levels would already be altered in first episode psychosis patients (FEP), and that they would be associated with patients' cognitive function and response to treatment.
We used magnetic resonance spectroscopy with a MEGA-PRESS sequence to quantify GABA in the dorsal anterior cingulate cortex (ACC) at baseline and over the course of antipsychotic treatment with risperidone. We compared GABA levels between 79 medication-naïve FEP and 113 healthy controls (HC) longitudinally over a period of 16 weeks and examined their relationships to cognition and treatment response.
We found significantly lower GABA levels in FEP compared to HC at all 3 time points (baseline, 6 weeks, 16 weeks), but did not observe a significant main effect of time or an interaction of group by time. We found no significant correlations between GABA and cognitive scores. Baseline GABA levels of patients considered treatment nonresponders significantly differed from HC, whereas responders did not.
Our findings suggest that GABA dysfunction in the ACC may be an important feature of the core pathophysiology of psychosis. This dysfunction does not appear to be attenuated by conventional antipsychotic treatment, though baseline levels may be indicative of clinical prognosis in FEP.
来自动物和人类研究的越来越多的证据表明，γ-氨基丁酸（GABA）能功能障碍与精神病谱系障碍的病理生理学有关。然而，关于GABA在疾病早期阶段的作用知之甚少。基于先前的研究，我们假设首发精神病患者（FEP）的GABA水平已经发生改变，并且它们与患者的认知功能和治疗反应相关。
我们使用具有MEGA-PRESS序列的磁共振波谱来量化背侧前扣带回皮质（ACC）在基线时以及在使用利培酮进行抗精神病治疗过程中的GABA水平。我们在16周的时间内纵向比较了79名未接受过药物治疗的FEP和113名健康对照（HC）的GABA水平，并研究了它们与认知和治疗反应的关系。
我们发现，在所有3个时间点（基线、6周、16周），FEP的GABA水平均显著低于HC，但未观察到时间的显著主效应或组间与时间的交互作用。我们未发现GABA与认知分数之间存在显著相关性。被认为治疗无反应的患者的基线GABA水平与HC有显著差异，而有反应的患者则没有。
我们的研究结果表明，ACC中的GABA功能障碍可能是精神病核心病理生理学的一个重要特征。这种功能障碍似乎不会被传统抗精神病治疗所减轻，尽管基线水平可能预示FEP的临床预后。
