Department of Neuroscience and Addiction Study, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Psychosomatic Medicine, Imam Khomeini Hospital Complex (IKHC), School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
J Mol Neurosci. 2022 Aug;72(8):1670-1681. doi: 10.1007/s12031-021-01879-7. Epub 2022 May 27.
Schizophrenia (SCZ) is a debilitating, destructive, and chronic mental disorder and affects approximately one percent of the human population. Diagnosis in psychiatry is based on the patient's descriptions of his/her symptoms, interviewer's observations, history of disorder over time, and response to treatment. All of these data measure phenotype-based functions. But it appears that accurate diagnosis of such a complex disorder must be based on valid and reliable factors. In the present study, gene selection was based on the possible role of γ-aminobutyric acid (GABA) in psychopathology of SCZ and expression in blood. We evaluated the association of Na-K-Cl co-transporter 1 (NKCC1) and K-Cl co-transporter 2 (KCC2) genes' messenger ribonucleic acid (mRNA) levels, and also the NKCC1/KCC2 ratio with positive and negative syndrome scale (PANSS) and brief psychiatric rating scale (BPRS) scores in an SCZ group. By using real-time PCR (RT-PCR), the present study is the first attempt to explore levels of NKCC1 and KCC2 expression at mRNA level and their relative expression in human peripheral blood of patients with SCZ. Our results showed that the NKCC1 to KCC2 mRNA ratio is significantly increased (but based on the delta cycle of threshold [∆Ct] is significantly lower) in the total sample of cases rather than controls (p = 0.045) and also higher in male sample cases rather than male controls (p = 0.016). In female samples, we found a trend toward a significant effect between the case and control participants (p = 0.075). We also found statistically significant association between mRNA of NKCC1 and KCC2 genes and NKCC1/KCC2 mRNA ratio with the positive and negative syndrome scale (PANSS) and brief psychiatric rating scale (BPRS) scores.
精神分裂症（SCZ）是一种使人虚弱、具破坏性且慢性的精神障碍，影响了大约百分之一的人口。精神科的诊断基于患者对其症状的描述、访谈者的观察、疾病随时间的变化史以及对治疗的反应。所有这些数据都衡量基于表型的功能。但是，对于如此复杂的疾病，准确的诊断似乎必须基于有效和可靠的因素。在本研究中，基因选择基于γ-氨基丁酸（GABA）在 SCZ 精神病理学中的可能作用以及在血液中的表达。我们评估了钠-钾-氯共转运蛋白 1（NKCC1）和钾-氯共转运蛋白 2（KCC2）基因的信使核糖核酸（mRNA）水平与阳性和阴性综合征量表（PANSS）和简明精神病评定量表（BPRS）评分之间的关联，以及 SCZ 组的 NKCC1/KCC2 比值。通过实时 PCR（RT-PCR），本研究首次尝试探索 NKCC1 和 KCC2 在人类外周血中的 mRNA 水平表达及其相对表达，并探索其在人类外周血中的表达。我们的结果表明，NKCC1 与 KCC2 的 mRNA 比值在病例总样本中显著增加（但基于 ∆Ct 的 delta 循环明显降低），而不是对照（p = 0.045），在男性病例样本中也高于男性对照（p = 0.016）。在女性样本中，我们发现病例组和对照组参与者之间存在显著效应的趋势（p = 0.075）。我们还发现 NKCC1 和 KCC2 基因的 mRNA 与 NKCC1/KCC2 mRNA 比值与阳性和阴性综合征量表（PANSS）和简明精神病评定量表（BPRS）评分之间存在统计学显著关联。
