精神分裂症患者代谢型谷氨酸受体 3 变体对前额叶脑活动的影响：使用多通道近红外光谱的影像遗传学研究。
Effect of metabotropic glutamate receptor-3 variants on prefrontal brain activity in schizophrenia: An imaging genetics study using multi-channel near-infrared spectroscopy.
机构信息
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan; MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London SE5 8AF, UK.
出版信息
Prog Neuropsychopharmacol Biol Psychiatry. 2015 Oct 1;62:14-21. doi: 10.1016/j.pnpbp.2015.04.006. Epub 2015 Apr 23.
BACKGROUND
The glutamatergic system is essential for learning and memory through its crucial role in neural development and synaptic plasticity. Genes associated with the glutamatergic system, including metabotropic glutamate receptor (mGluR or GRM) genes, have been implicated in the pathophysiology of schizophrenia. Few studies, however, have investigated a relationship between polymorphism of glutamate-related genes and cortical function in vivo in patients with schizophrenia. We thus explored an association between genetic variations in GRM3 and brain activation driven by a cognitive task in the prefrontal cortex in patients with schizophrenia.
MATERIALS AND METHODS
Thirty-one outpatients with schizophrenia and 48 healthy controls participated in this study. We measured four candidate single nucleotide polymorphisms (rs274622, rs2299225, rs1468412, and rs6465084) of GRM3, and activity in the prefrontal and temporal cortices during a category version of a verbal fluency task, using a 52-channel near-infrared spectroscopy instrument.
RESULTS AND DISCUSSION
The rs274622 C carriers with schizophrenia were associated with significantly smaller prefrontal activation than patients with TT genotype. This between-genotype difference tended to be confined to the patient group. GRM3 polymorphisms are associated with prefrontal activation during cognitive task in schizophrenia.
背景
谷氨酸能系统通过在神经发育和突触可塑性中发挥关键作用，对学习和记忆至关重要。与谷氨酸能系统相关的基因，包括代谢型谷氨酸受体（mGluR 或 GRM）基因，已被牵连到精神分裂症的病理生理学中。然而，很少有研究调查谷氨酸相关基因的多态性与精神分裂症患者体内皮质功能之间的关系。因此，我们探索了精神分裂症患者前额叶皮质认知任务驱动的脑激活与 GRM3 基因遗传变异之间的关联。
材料和方法
31 名精神分裂症门诊患者和 48 名健康对照者参与了这项研究。我们使用 52 通道近红外光谱仪，测量了 GRM3 的四个候选单核苷酸多态性（rs274622、rs2299225、rs1468412 和 rs6465084）和言语流畅性任务的前额叶和颞叶皮质的活动。
结果与讨论
携带 rs274622C 的精神分裂症患者的前额叶激活明显小于 TT 基因型患者。这种基因型间的差异似乎仅限于患者组。GRM3 多态性与精神分裂症认知任务期间的前额叶激活有关。
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