Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany.
Eur Neuropsychopharmacol. 2013 Aug;23(8):902-9. doi: 10.1016/j.euroneuro.2012.09.003. Epub 2012 Oct 9.
Recent studies have emphasized an important role for neurotrophins, such as brain-derived neurotrophic factor (BDNF), in regulating the plasticity of neural circuits involved in the pathophysiology of stress-related diseases. The aim of the present study was to examine the interplay of the BDNF Val⁶⁶Met and the serotonin transporter promoter (5-HTTLPR) polymorphisms in moderating the impact of early-life adversity on BDNF plasma concentration and depressive symptoms. Participants were taken from an epidemiological cohort study following the long-term outcome of early risk factors from birth into young adulthood. In 259 individuals (119 males, 140 females), genotyped for the BDNF Val⁶⁶Met and the 5-HTTLPR polymorphisms, plasma BDNF was assessed at the age of 19 years. In addition, participants completed the Beck Depression Inventory (BDI). Early adversity was determined according to a family adversity index assessed at 3 months of age. Results indicated that individuals homozygous for both the BDNF Val and the 5-HTTLPR L allele showed significantly reduced BDNF levels following exposure to high adversity. In contrast, BDNF levels appeared to be unaffected by early psychosocial adversity in carriers of the BDNF Met or the 5-HTTLPR S allele. While the former group appeared to be most susceptible to depressive symptoms, the impact of early adversity was less pronounced in the latter group. This is the first preliminary evidence indicating that early-life adverse experiences may have lasting sequelae for plasma BDNF levels in humans, highlighting that the susceptibility to this effect is moderated by BDNF Val⁶⁶Met and 5-HTTLPR genotype.
最近的研究强调了神经递质（如脑源性神经营养因子（BDNF））在调节与应激相关疾病的病理生理学有关的神经回路可塑性方面的重要作用。本研究旨在探讨 BDNF Val⁶⁶Met 和 5-羟色胺转运体启动子（5-HTTLPR）多态性在调节早期生活逆境对 BDNF 血浆浓度和抑郁症状的影响中的相互作用。参与者来自一项流行病学队列研究，该研究从出生到成年早期长期跟踪早期风险因素的长期结果。在 259 名（119 名男性，140 名女性）被基因分型为 BDNF Val⁶⁶Met 和 5-HTTLPR 多态性的个体中，在 19 岁时评估了 BDNF 血浆浓度。此外，参与者完成了贝克抑郁量表（BDI）。根据 3 个月大时评估的家庭逆境指数确定早期逆境。结果表明，在暴露于高逆境后，BDNF Val 和 5-HTTLPR L 等位基因纯合的个体的 BDNF 水平明显降低。相比之下，在 BDNF Met 或 5-HTTLPR S 等位基因携带者中，BDNF 水平似乎不受早期心理社会逆境的影响。虽然前一组似乎最容易出现抑郁症状，但后者组的早期逆境影响不太明显。这是第一个初步证据表明，早期生活逆境可能对人类 BDNF 血浆水平产生持久的后果，突出表明这种影响的易感性受 BDNF Val⁶⁶Met 和 5-HTTLPR 基因型调节。
