BDNF and NGF Signalling in Early Phases of Psychosis: Relationship With Inflammation and Response to Antipsychotics After 1 Year.
BDNF and NGF Signalling in Early Phases of Psychosis: Relationship With Inflammation and Response to Antipsychotics After 1 Year.
复制标题
DOI：
10.1093/schbul/sbv078
复制
发表时间：
2016-01
影响因子：
6.6
通讯作者：
FLAMM-PEPs
中科院分区：
文献类型：
--
作者：
Martinez-Cengotitabengoa M;MacDowell KS;Alberich S;Diaz FJ;Garcia-Bueno B;Rodriguez-Jimenez R;Bioque M;Berrocoso E;Parellada M;Lobo A;Saiz PA;Matute C;Bernardo M;Gonzalez-Pinto A;Leza JC;FLAMM-PEPs
先前的研究表明，首发精神病 (FEP) 患者体内的促炎或抗炎平衡出现系统失调，这种失调会持续 12 个月。为了确定潜在的风险/保护因素以及与症状严重程度的关联，我们评估了外周血单核细胞 (PBMC) 中神经营养因子（脑源性神经营养因子 [BDNF] 和神经生长因子 [NGF]）及其受体血浆水平的可能变化。 FEP患者PBMC中2种形式的BDNF受体（活性TrkB-FL和非活性TrkB-T1）的表达随着时间的推移而变化，诊断后1年TrkB-FL表达增加，而TrkB-T1表达减少。仅非情感性精神病组的 TrkB-FL/TrkB-T1 比率（以下简称 FL/T1 比率）在随访期间增加，表明 FEP 患者亚组中存在不同的潜在病理生理机制。此外，随访期间患者中主要 NGF 受体 TrkA 的表达普遍增加。在调整潜在的混杂因素后，一氧化氮合酶、环氧合酶和核转录因子的诱导同工型的基线水平与 FL/T1 比率显着相关，表明更多的炎症与该比率的较高值相关。有趣的是，FL/T1 比率可能具有功能预测因子的作用，这是一种 1 年功能回归模型，表明基线 FL/T1 比率对 1 年功能的影响取决于患者是否接受抗精神病药物治疗。这些发现可能具有转化意义；具体来说，在 FEP 中开始抗精神病治疗之前评估 TrkB 受体同工型的表达可能有用。
Previous studies have indicated systemic deregulation of the proinflammatory or anti-inflammatory balance in individuals with first-episode psychosis (FEP) that persists 12 months later. To identify potential risk/protective factors and associations with symptom severity, we assessed possible changes in plasma levels of neurotrophins (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) and their receptors in peripheral blood mononuclear cells (PBMCs). Expression of the 2 forms of BDNF receptors (active TrkB-FL and inactiveTrkB-T1) in PBMCs of FEP patients changed over time, TrkB-FL expression increasing by 1 year after diagnosis, while TrkB-T1 expression decreased. The TrkB-FL/TrkB-T1 ratio (hereafter FL/T1 ratio) increased during follow-up in the nonaffective psychosis group only, suggesting different underlying pathophysiological mechanisms in subgroups of FEP patients. Further, the expression of the main NGF receptor, TrkA, generally increased in patients at follow-up. After adjusting for potential confounders, baseline levels of inducible isoforms of nitric oxide synthase, cyclooxygenase, and nuclear transcription factor were significantly associated with the FL/T1 ratio, suggesting that more inflammation is associated with higher values of this ratio. Interestingly, the FL/T1 ratio might have a role as a predictor of functioning, a regression model of functioning at 1 year suggesting that the effect of the FL/T1 ratio at baseline on functioning at 1 year depended on whether patients were treated with antipsychotics. These findings may have translational relevance; specifically, it might be useful to assess the expression of TrkB receptor isoforms before initiating antipsychotic treatment in FEPs.