Department of Psychiatry, Bakirkoy Prof Mazhar Osman Training and Research Hospital for Psychiatry, Neurology, and Neurosurgery, 34147, Istanbul, Turkey.
Department of Neuroscience, Medipol University, Istanbul, Turkey.
Mol Neurobiol. 2022 Dec;59(12):7413-7422. doi: 10.1007/s12035-022-03054-4. Epub 2022 Oct 3.
Schizophrenia (SZ) is a mental disorder with a strong genetic basis as well as epigenetic aspects. Siblings of patients with SZ can share certain endophenotypes with the patients, suggesting that siblings may be important for distinguishing between trait and state markers. In the current study, we aimed to characterize the balance between pro-BDNF/mature BDNF and its receptors p75NTR/TrkB, which are tPA-BDNF pathways proteins and are thought to play a role in synaptic pruning, as a possible endophenotype of schizophrenia. Forty drug-naïve patients with first-episode psychosis (FEP) matched for age, gender, and level of education, 40 unaffected siblings (UAS) of patients with FEP, and 67 healthy controls (HC) were included in the study. Blood samples were collected from all participants to determine BDNF, pro-BDNF, TrkB and p75NTR, PAI1, tPA, ACTH, and cortisol levels. We showed that levels of proteins of the tPA-BDNF pathway as well as the pro-BDNF/m-BDNF and p75NTR/TrkB ratios could successfully differentiate FEP and their siblings from the HCs by using ROC analysis. Plasma levels of m-BDNF were found to be the lowest in the healthy siblings and highest in the HCs with statistically significant differences between all 3 groups. The plasma level of pro-BDNF in the HC group was similar to the FEP patients, the same in the healthy siblings of the FEP patients. Our data support the hypothesis that imbalance between neurotrophic and apoptotic proteins might occur in SZ and this imbalance could be an endophenotype of the disease.
精神分裂症（SZ）是一种具有强烈遗传基础和表观遗传方面的精神障碍。SZ 患者的兄弟姐妹可能与患者共享某些表型，这表明兄弟姐妹可能对于区分特质和状态标志物很重要。在当前研究中，我们旨在描述前精神病发作（FEP）患者的未用药兄弟姐妹中促脑源性神经营养因子（pro-BDNF）/成熟脑源性神经营养因子（m-BDNF）与其受体 p75NTR/TrkB 之间的平衡，因为它们被认为在突触修剪中发挥作用，是精神分裂症的一种可能的表型。我们纳入了 40 名年龄、性别和教育程度匹配的首次发作精神病（FEP）患者、40 名 FEP 患者的未受影响的兄弟姐妹（UAS）和 67 名健康对照（HC）。从所有参与者中采集血液样本，以确定脑源性神经营养因子（BDNF）、pro-BDNF、TrkB 和 p75NTR、PAI1、tPA、ACTH 和皮质醇水平。我们通过 ROC 分析表明，tPA-BDNF 通路蛋白以及 pro-BDNF/m-BDNF 和 p75NTR/TrkB 比值水平可以成功区分 FEP 和他们的兄弟姐妹与 HC。发现 m-BDNF 的血浆水平在健康兄弟姐妹中最低，在 HC 中最高，3 组之间存在统计学差异。HC 组的 pro-BDNF 血浆水平与 FEP 患者相似，与 FEP 患者的健康兄弟姐妹相同。我们的数据支持这样的假设，即神经营养和凋亡蛋白之间的失衡可能发生在 SZ 中，这种失衡可能是疾病的一个表型。
