Yee Jie Yin, Nurjono Milawaty, Teo Stephanie Ruth, Lee Tih-Shih, Lee Jimmy
Research Division, Institute of Mental Health, Singapore, Singapore.
Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
PLoS One. 2017 Jan 25;12(1):e0170805. doi: 10.1371/journal.pone.0170805. eCollection 2017.
γ-Aminobutyric acid (GABA), the primary inhibitory neurotransmitter, has often been studied in relation to its role in the pathophysiology of schizophrenia. GABA is synthesized from glutamate by glutamic acid decarboxylase (GAD), derived from two genes, GAD1 and GAD2. GAD1 is expressed as both GAD67 and GAD25 mRNA transcripts with the former reported to have a lower expression level in schizophrenia compared to healthy controls and latter was reported to be predominantly expressed fetally, suggesting a role in developmental process. In this study, GAD67 and GAD25 mRNA levels were measured by quantitative PCR (qPCR) in peripheral blood of subjects with first-episode psychosis (FEP) and from healthy controls. We observed low GAD25 and GAD67 gene expression levels in human peripheral blood. There was no difference in GAD25 and GAD67 gene expression level, and GAD25/GAD67 ratio between patients with FEP and healthy controls. PANSS negative symptoms were associated with levels of GAD25 mRNA transcripts in patients with FEP. While the current study provides information on GAD25 and GAD67 mRNA transcript levels in whole blood of FEP patients, further correlation and validation work between brain regions, cerebrospinal fluid and peripheral blood expression profiling are required to provide a better understanding of GAD25 and GAD67.
γ-氨基丁酸（GABA）是主要的抑制性神经递质，人们经常研究它在精神分裂症病理生理学中的作用。GABA由谷氨酸通过谷氨酸脱羧酶（GAD）合成，GAD有两个基因，即GAD1和GAD2。GAD1表达为GAD67和GAD25 mRNA转录本，据报道，与健康对照相比，前者在精神分裂症中的表达水平较低，而后者据报道主要在胎儿期表达，提示其在发育过程中发挥作用。在本研究中，通过定量聚合酶链反应（qPCR）测量了首发精神病（FEP）患者和健康对照外周血中GAD67和GAD25 mRNA水平。我们观察到人类外周血中GAD25和GAD67基因表达水平较低。FEP患者与健康对照之间的GAD25和GAD67基因表达水平以及GAD25/GAD67比值没有差异。PANSS阴性症状与FEP患者的GAD25 mRNA转录本水平相关。虽然本研究提供了FEP患者全血中GAD25和GAD67 mRNA转录本水平的信息，但需要在脑区、脑脊液和外周血表达谱之间进行进一步的相关性和验证工作，以更好地了解GAD25和GAD67。
