Benedetti Francesco, Ambrée Oliver, Locatelli Clara, Lorenzi Cristina, Poletti Sara, Colombo Cristina, Arolt Volker
Division of Neuroscience, Scientific Institute Ospedale San Raffaele, Milano and University Vita-Salute San Raffaele, Milano, Italy.
Department of Psychiatry, University of Münster, Münster, Germany.
Neurosci Lett. 2017 Aug 24;656:177-181. doi: 10.1016/j.neulet.2017.07.043. Epub 2017 Jul 25.
In healthy humans, both childhood trauma and the short form of the serotonin promoter transporter genotype (5-HTTLPR) are associated with lower levels of brain-derived neurotrophic factor (BDNF). In subjects with bipolar disorder (BD), lower levels of BDNF and a higher degree of childhood trauma were observed compared with healthy controls. However, is still unknown if the functional 5-HTTLPR polymorphisms exerts an effect on both abnormalities. In 40 inpatients affected by a major depressive episode in the course of BD, we genotyped 5-HTTLPR, measured serum BDNF with ELISA, and assessed early adversities by the childhood trauma questionnaire (CTQ). Data were analyzed in the context of the general linear model correcting for age, sex, ongoing lithium treatment, severity of current depression, and CTQ minimization/denial scores to investigate the effect of 5-HTTLPR polymorphism and childhood trauma on BDNF levels. Early trauma were negatively associated with BDNF serum levels (higher CTQ scores, lower BDNF; p=0.0019). 5-HTTLPR l/l homozygotes showed significantly higher BDNF levels than 5-HTTLPRs carriers (30.57±6.13 vs 26.82±6.41; p=0.0309). A separate-slopes analysis showed that 5-HTTLPR significantly influenced the relationship between early trauma and adult BDNF (interaction of 5-HTTLPR with CTQ scores: p=0.0023), due to a significant relationship between trauma and BDNF in 5-HTTLPRs carriers, but not among l/l homozygotes. Putatively detrimental effects of childhood trauma exposure on adult BDNF serum levels are influenced by 5-HTTLPR genotype in patients affected by BD. Possible mechanisms include epigenetic modulation of BDNF gene expression, due to different reactivity to stressors in 5-HTTLPR genotype groups.
在健康人群中，童年创伤和血清素启动子转运体基因短型（5-HTTLPR）均与脑源性神经营养因子（BDNF）水平较低有关。在双相情感障碍（BD）患者中，与健康对照组相比，观察到BDNF水平较低且童年创伤程度较高。然而，功能性5-HTTLPR多态性是否对这两种异常情况都有影响仍不清楚。在40名患有BD过程中出现重度抑郁发作的住院患者中，我们对5-HTTLPR进行基因分型，用酶联免疫吸附测定法（ELISA）测量血清BDNF，并通过儿童创伤问卷（CTQ）评估早期逆境。在一般线性模型的背景下分析数据，校正年龄、性别、正在进行的锂治疗、当前抑郁的严重程度以及CTQ最小化/否认评分，以研究5-HTTLPR多态性和童年创伤对BDNF水平的影响。早期创伤与BDNF血清水平呈负相关（CTQ评分越高，BDNF越低；p = 0.0019）。5-HTTLPR l/l纯合子的BDNF水平显著高于5-HTTLPRs携带者（30.57±6.13 vs 26.82±6.41；p = 0.0309）。单独斜率分析表明，5-HTTLPR显著影响早期创伤与成人BDNF之间的关系（5-HTTLPR与CTQ评分的相互作用：p = 0.0023），这是因为在5-HTTLPRs携带者中创伤与BDNF之间存在显著关系，但在l/l纯合子中不存在。童年创伤暴露对成人BDNF血清水平的假定有害影响在BD患者中受5-HTTLPR基因型影响。可能的机制包括BDNF基因表达的表观遗传调控，这是由于5-HTTLPR基因型组对应激源的反应不同。
