Department of Psychiatry and Imaging Research Center, University of California, Davis, Davis, California 95817, USA.
J Neurosci. 2010 Mar 10;30(10):3777-81. doi: 10.1523/JNEUROSCI.6158-09.2010.
The neural mechanisms underlying cognitive deficits in schizophrenia remain essentially unknown. The GABA hypothesis proposes that reduced neuronal GABA concentration and neurotransmission results in cognitive impairments in schizophrenia. However, few in vivo studies have directly examined this hypothesis. We used magnetic resonance spectroscopy (MRS) at high field to measure visual cortical GABA levels in 13 subjects with schizophrenia and 13 demographically matched healthy control subjects. We found that the schizophrenia group had an approximately 10% reduction in GABA concentration. We further tested the GABA hypothesis by examining the relationship between visual cortical GABA levels and orientation-specific surround suppression (OSSS), a behavioral measure of visual inhibition thought to be dependent on GABAergic synaptic transmission. Previous work has shown that subjects with schizophrenia exhibit reduced OSSS of contrast discrimination (Yoon et al., 2009). For subjects with both MRS and OSSS data (n = 16), we found a highly significant positive correlation (r = 0.76) between these variables. GABA concentration was not correlated with overall contrast discrimination performance for stimuli without a surround (r = -0.10). These results suggest that a neocortical GABA deficit in subjects with schizophrenia leads to impaired cortical inhibition and that GABAergic synaptic transmission in visual cortex plays a critical role in OSSS.
精神分裂症认知缺陷的神经机制尚不清楚。γ-氨基丁酸假说提出,神经元 GABA 浓度和神经传递的减少导致精神分裂症的认知障碍。然而,很少有体内研究直接检验这一假说。我们使用高磁场磁共振波谱(MRS)测量了 13 名精神分裂症患者和 13 名年龄匹配的健康对照组的视觉皮质 GABA 水平。我们发现精神分裂症组的 GABA 浓度降低了约 10%。我们通过检查视觉皮质 GABA 水平与定向特异性环绕抑制(OSSS)之间的关系进一步检验了 GABA 假说,OSSS 是一种被认为依赖 GABA 能突触传递的视觉抑制的行为测量。先前的工作表明,精神分裂症患者的对比度辨别 OSSS 减少(Yoon 等人,2009)。对于既有 MRS 又有 OSSS 数据的受试者(n = 16),我们发现这些变量之间存在高度显著的正相关(r = 0.76)。GABA 浓度与没有环绕的刺激的整体对比度辨别性能不相关(r = -0.10)。这些结果表明,精神分裂症患者的新皮质 GABA 缺乏导致皮质抑制受损,而视觉皮层中的 GABA 能突触传递在 OSSS 中起着关键作用。