Sklar Alfredo L, Blazer Annie, Snover Warren, López-Caballero Fran, Curtis Mark, Coffman Brian A, Hetherington Hoby H, Moon Chan-Hong, Salisbury Dean F, Sarpal Deepak K
Department of Psychiatry Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Department of Psychological and Brain Sciences, Washington University, St. Louis, Missouri, USA.
Brain Behav. 2025 Aug;15(8):e70735. doi: 10.1002/brb3.70735.
Excitatory/inhibitory (E/I) imbalance is a proposed neural disruption in schizophrenia supported by magnetic resonance spectroscopic imaging (MRSI) evidence of altered gamma-aminobutyric acid (GABA) and glutamate (Glu) levels. However, there exists a paucity of data linking these abnormalities to impaired in vivo brain function putatively reflecting E/I imbalance. Here, associations between GABA/Glu and the evoked early auditory gamma-band response (EAGBR) were examined in first-episode schizophrenia (FESz).
Twelve FESz underwent resting-state 7T-MRSI and magnetoencephalography (MEG) recorded during an auditory oddball task. MRSI spectra and source-localized MEG data were extracted from overlapping regions of left (LH) and right (RH) superior temporal sulcus. Associations between evoked EAGBR power and GABA/Glu, GABA/Cre, and Glu/Cre ratios were assessed. The Brief Psychiatric Rating Scale (BPRS) and Global Functioning: Role/Social (GF: Role/Social) scales were collected.
GABA/Glu ratios were inversely correlated with EAGBR power (LH: ρ = -0.87; RH: ρ = -0.85). LH GABA/Glu ratios were also inversely correlated with BPRS scores (ρ = -0.64) and positively correlated with GF: Social (ρ = 0.64) scores while RH EAGBR power was positively correlated with BPRS scores (ρ = 0.70). Stepwise linear regressions suggest these relationships were driven primarily by GABA concentrations.
Associations in FESz between GABA/Glu ratios, clinical ratings, and EAGBR power suggests this evoked gamma-band response reflects cortical hyperexcitability within the auditory system that is closely tied to disease debility at this early illness stage. These data highlight the potential of merging high-precision, in vivo neuro-chemical assays via 7-Tesla MRSI and physiological measures from MEG to validate established cellular models of disease.
兴奋性/抑制性（E/I）失衡是精神分裂症中一种被提出的神经功能紊乱，磁共振波谱成像（MRSI）显示γ-氨基丁酸（GABA）和谷氨酸（Glu）水平改变为其提供了证据。然而，将这些异常与可能反映E/I失衡的体内脑功能受损联系起来的数据却很匮乏。在此，我们在首发精神分裂症（FESz）患者中研究了GABA/Glu与诱发的早期听觉γ波段反应（EAGBR）之间的关联。
12名FESz患者在进行听觉oddball任务期间接受静息态7T-MRSI和脑磁图（MEG）检查。从左（LH）和右（RH）颞上沟的重叠区域提取MRSI光谱和源定位MEG数据。评估诱发的EAGBR功率与GABA/Glu、GABA/Cre和Glu/Cre比值之间的关联。收集简明精神病评定量表（BPRS）和总体功能：角色/社会（GF：角色/社会）量表。
GABA/Glu比值与EAGBR功率呈负相关（LH：ρ = -0.87；RH：ρ = -0.85）。LH的GABA/Glu比值也与BPRS评分呈负相关（ρ = -0.64），与GF：社会评分呈正相关（ρ = 0.64），而RH的EAGBR功率与BPRS评分呈正相关（ρ = 0.70）。逐步线性回归表明，这些关系主要由GABA浓度驱动。
FESz患者中GABA/Glu比值、临床评分和EAGBR功率之间存在关联，表明这种诱发的γ波段反应反映了听觉系统内的皮质兴奋性过高，这与疾病早期阶段的病情严重程度密切相关。这些数据凸显了通过7特斯拉MRSI合并高精度的体内神经化学检测和MEG生理测量以验证既定疾病细胞模型的潜力。
