Stress and inflammation reduce brain-derived neurotrophic factor expression in first-episode psychosis: a pathway to smaller hippocampal volume.
Stress and inflammation reduce brain-derived neurotrophic factor expression in first-episode psychosis: a pathway to smaller hippocampal volume.
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DOI：
10.4088/jcp.10m06745
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发表时间：
2011-12
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影响因子：
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通讯作者：
Pariante CM
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作者：
Mondelli V;Cattaneo A;Murri MB;Di Forti M;Handley R;Hepgul N;Miorelli A;Navari S;Papadopoulos AS;Aitchison KJ;Morgan C;Murray RM;Dazzan P;Pariante CM
据报道，精神病患者的血清和血浆中脑源性神经营养因子（BDNF）水平降低。本研究的目的是通过检查BDNF水平与首发精神病患者的应激、炎症和海马体积之间的关系，研究这些患者BDNF表达减少的潜在原因和后果。在2006年1月至2008年12月期间招募的49名首发精神病患者（DSM-IV标准）和30名健康对照者的白细胞中测定了BDNF、白细胞介素（IL）-6和肿瘤坏死因子（TNF）α mRNA水平。在相同的受试者中，我们测量了唾液皮质醇水平，并收集了有关心理社会压力的信息（童年创伤的数量，最近的压力源的数量和感知压力）。最后，海马体积进行了测量，使用脑MRI，在一个子样本的19名患者。与对照组相比，患者的BDNF基因表达水平降低（效应量d=1.3，p<0.001），IL-6基因表达水平升高（效应量d=1.1，p<0.001），TNF-α基因表达水平升高（效应量d=1.7，p<0.001），以及心理社会压力水平升高。对患者的线性回归分析显示，童年创伤史和近期高水平的压力源通过炎症介导的途径预测较低的BDNF表达（校正R平方=0.23，p=0.009）。反过来，较低的BDNF表达、增加的IL-6表达和增加的皮质醇水平，都显著且独立地预测了较小的左侧海马体积（校正R平方=0.71，p<0.001）。应激激活的生物学变化是影响首发精神病患者脑结构和功能的一个重要因素，通过对BDNF的影响。
Reduced brain-derived neurotrophic factor (BDNF) levels have been reported in the serum and plasma of patients with psychosis. The aim of this study was to investigate potential causes and consequences of reduced BDNF expression in these patients, by examining the association between BDNF levels and measures of stress, inflammation and hippocampal volume in first-episode psychosis. BDNF, interleukin (IL)-6, and tumour-necrosis-factor (TNF) alpha mRNA levels were measured in leukocytes of 49 first-episode psychosis patients (DSM-IV criteria) and 30 healthy controls, recruited between January 2006 and December 2008. In the same subjects, we measured salivary cortisol levels, and collected information about psychosocial stressors (number of childhood trauma, number of recent stressors, and perceived stress). Finally, hippocampal volume was measured, using brain MRI, in a subsample of 19 patients. Patients had reduced BDNF (effect size d=1.3, p<0.001) and increased IL-6 (effect size d=1.1, p<0.001) and TNF-alpha (effect size d=1.7, p<0.001) gene expression levels, when compared with controls, as well as higher levels of psychosocial stressors. A linear regression analysis in patients showed that a history of childhood trauma and high levels of recent stressors predicted lower BDNF expression through an inflammation-mediated pathway (adjusted R square=0.23, p=0.009). In turn, lower BDNF expression, increased IL-6 expression, and increased cortisol levels, all significantly and independently predicted a smaller left hippocampal volume (adjusted R square=0.71, p<0.001). Biological changes activated by stress represent a significant factor influencing brain structure and function in first-episode psychosis, through an effect on BDNF.