Manafzadeh Fatemeh, Baradaran Behzad, Noor Azar Seyed Gholamreza, Javidi Aghdam Kamran, Dabbaghipour Reza, Shayannia Asghar, Ghafouri-Fard Soudeh
Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Ann Gen Psychiatry. 2025 Jan 13;24(1):4. doi: 10.1186/s12991-025-00545-1.
Schizophrenia is one of the most debilitating mental illnesses affecting any age group. The mechanism and etiology of schizophrenia are extremely complex and multiple signaling pathways recruit genes implicated in the etiology of this disease. While the role of Wnt/β-catenin signaling in this disorder has been verified, the impact of long noncoding RNAs (lncRNAs) associated with this pathway has not been studied in schizophrenia. The objective of this study was to examine the expression levels of Wnt/β-catenin-related lncRNAs, namely CCAT2, SNHG5, PTCSC3, and DANCR, as well as the CTNNB1 gene encoding beta-catenin protein in two groups of schizophrenia patients (drug-naïve and medicated) compared with healthy individuals. This study included 50 medicated patients in the remission phase of the disease, 25 drug-naive patients in the acute phase, and 50 control subjects. There was no significant difference in CTNNB1 gene expression in the medicated patients compared to controls (P value = 0.9754). However, the expression of this gene was significantly decreased in drug-naïve first-episode patients compared with controls (P value < 0.001). In contrast, expression of DANCR, PTCSC3, SNHG5, and CCAT2 genes was significantly higher in medicated (P values < 0.001, < 0.001, = 0.01, < 0.001, respectively) and drug-naive first-episode patients (P value < 0.001) compared to control subjects. ROC curve analysis revealed that DANCR, PTCSC3, SNHG5, and CCAT2 genes had diagnostic power with specificity and sensitivity of 80% and above in separation between study subgroups. In brief, our data demonstrated dysregulation of Wnt/β pathway related genes and lncRNAs in the peripheral blood of patients with schizophrenia and their potential as biomarkers for this disorder.
精神分裂症是影响任何年龄组的最使人衰弱的精神疾病之一。精神分裂症的机制和病因极其复杂，多种信号通路招募了与该疾病病因相关的基因。虽然Wnt/β-连环蛋白信号通路在这种疾病中的作用已得到证实，但与该通路相关的长链非编码RNA（lncRNA）在精神分裂症中的影响尚未得到研究。本研究的目的是检测两组精神分裂症患者（未用药和已用药）与健康个体相比，Wnt/β-连环蛋白相关lncRNA，即CCAT2、SNHG5、PTCSC3和DANCR，以及编码β-连环蛋白的CTNNB1基因的表达水平。本研究纳入了50例处于疾病缓解期的已用药患者、25例急性期未用药患者和50例对照受试者。与对照组相比，已用药患者的CTNNB1基因表达无显著差异（P值 = 0.9754）。然而，与对照组相比，未用药的首发患者中该基因的表达显著降低（P值 < 0.001）。相反，与对照受试者相比，DANCR、PTCSC3、SNHG5和CCAT2基因的表达在已用药患者（P值分别 < 0.001、< 0.001、= 0.01、< 0.001）和未用药的首发患者中显著更高（P值 < 0.001）。ROC曲线分析显示，DANCR、PTCSC3、SNHG5和CCAT2基因具有诊断能力，在区分研究亚组时特异性和敏感性均在80%及以上。简而言之，我们的数据表明精神分裂症患者外周血中Wnt/β通路相关基因和lncRNA失调，以及它们作为该疾病生物标志物的潜力。
