Laboratório de Neurociencias (LIM 27), Instituto de Psiquiatria, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR; Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBION), Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil.
Laboratório de Neurociencias (LIM 27), Instituto de Psiquiatria, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR.
Psychiatry Res. 2023 Sep;327:115402. doi: 10.1016/j.psychres.2023.115402. Epub 2023 Aug 1.
Neurotrophins (NTs) and their precursors (pro-NTs) are polypeptides with important roles in neuronal development, differentiation, growth, survival and plasticity, as well as apoptosis and neuronal death. Imbalance in NT levels were observed in schizophrenia spectrum disorders, but evidence in ultra-high risk for psychosis (UHR) samples is scarce.
A naturalistic sample of 87 non-help-seeking UHR subjects and 55 healthy controls was drawn from the general population. Blood samples were collected and NT-3, NT-4/5, BDNF, pro-BDNF, NGF, pro-NGF were analyzed through enzyme linked immunosorbent assay (ELISA). Information on cannabis and tobacco use was also collected. Logistic regression models and path analysis were used to control for confounders (tobacco, age, cannabis use).
NT-4/5 was significantly decreased, and pro-BDNF was significantly increased in UHR individuals compared to controls. Cannabis use and higher NGF levels were significantly related to transition to psychiatric disorders among UHR subjects. Increased pro-BDNF and decreased NT-4/5 influenced transition by the mediation of perceptual abnormalities.
Our study shows for the first time that NTs are altered in UHR compared to healthy control individuals, and that they can be a predictor of transition to psychiatric illnesses in this population. Future studies should employ larger naturalistic samples to confirm the findings.
神经营养因子（NTs）及其前体（pro-NTs）是在神经元发育、分化、生长、存活和可塑性以及细胞凋亡和神经元死亡中具有重要作用的多肽。在精神分裂症谱系障碍中观察到 NT 水平失衡，但在精神病超高危（UHR）样本中的证据很少。
从普通人群中抽取了 87 名未寻求帮助的 UHR 受试者和 55 名健康对照者的自然样本。通过酶联免疫吸附试验（ELISA）分析了血液样本中的 NT-3、NT-4/5、BDNF、pro-BDNF、NGF 和 pro-NGF。还收集了关于大麻和烟草使用的信息。使用逻辑回归模型和路径分析来控制混杂因素（烟草、年龄、大麻使用）。
与对照组相比，UHR 个体的 NT-4/5 显著降低，pro-BDNF 显著升高。大麻使用和较高的 NGF 水平与 UHR 受试者向精神障碍的转变显著相关。增加的 pro-BDNF 和减少的 NT-4/5 通过感知异常的中介作用影响了转变。
我们的研究首次表明，与健康对照组相比，UHR 中的 NTs 发生了改变，并且它们可能是该人群向精神疾病转变的预测因子。未来的研究应采用更大的自然样本来证实这些发现。
