Val66Met脑源性神经营养因子多态性作为乳腺癌女性炎症相关抑郁症状的一个易患因素。
Val66Met BDNF polymorphism as a vulnerability factor for inflammation-associated depressive symptoms in women with breast cancer.
作者信息
Dooley Larissa N, Ganz Patricia A, Cole Steve W, Crespi Catherine M, Bower Julienne E
机构信息
Department of Psychology, University of California, Los Angeles, United States.
Department of Health Policy & Management, UCLA Fielding School of Public Health, Los Angeles, CA, United States; Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States; Division of Cancer Prevention and Control Research, Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, United States.
出版信息
J Affect Disord. 2016 Jun;197:43-50. doi: 10.1016/j.jad.2016.02.059. Epub 2016 Mar 2.
BACKGROUND
Inflammation contributes to the development of depression in a subset of individuals, but risk factors that render certain individuals particularly vulnerable to inflammation-associated depression are undetermined. Drawing from animal studies showing that reduced neuroplasticity mediates effects of inflammation on depression, we hypothesized that individuals genetically predisposed to lower levels of neuroplasticity would be more susceptible to inflammation-associated depression. The current study examined whether the Met allele of the BDNF Val66met polymorphism, which predisposes individuals to reduced levels of brain-derived neurotrophic factor (BDNF), a protein vital for neuroplasticity, moderates the association between inflammation and depressive symptoms.
METHODS
Our sample was 112 women with early-stage breast cancer who had recently completed cancer treatment, which can activate inflammation. Participants provided blood for genotyping and assessment of circulating inflammatory markers, and completed a questionnaire assessing depressive symptoms, including somatic, affective, and cognitive dimensions.
RESULTS
There was a significant interaction between C-reactive protein (CRP) and the BDNF Val66met polymorphism in predicting cognitive depressive symptoms (p=.004), such that higher CRP was related to more cognitive depressive symptoms among Met allele carriers, but not among Val/Val homozygotes. Post-hoc longitudinal analyses suggested that, for Met carriers, higher CRP at baseline predicted higher cognitive depressive symptoms across a one-year follow-up period (p<.001).
CONCLUSION
The BDNF Met allele may be a risk factor for inflammation-associated cognitive depressive symptoms among breast cancer survivors. Women with breast cancer who carry this genotype may benefit from early identification and treatment.
LIMITATION
BDNF genotype is an indirect measure of BDNF protein levels.
背景
炎症在一部分个体的抑郁症发展过程中起作用，但使某些个体特别易患炎症相关性抑郁症的风险因素尚未明确。基于动物研究表明神经可塑性降低介导了炎症对抑郁症的影响，我们推测，遗传上易患神经可塑性水平较低的个体更容易患炎症相关性抑郁症。本研究检验了脑源性神经营养因子（BDNF）Val66met多态性的Met等位基因是否会调节炎症与抑郁症状之间的关联，该等位基因会使个体的脑源性神经营养因子（BDNF）水平降低，而BDNF是一种对神经可塑性至关重要的蛋白质。
方法
我们的样本是112名患有早期乳腺癌且最近完成癌症治疗的女性，癌症治疗可激活炎症。参与者提供血液用于基因分型和循环炎症标志物评估，并完成一份评估抑郁症状的问卷，包括躯体、情感和认知维度。
结果
在预测认知性抑郁症状方面，C反应蛋白（CRP）与BDNF Val66met多态性之间存在显著交互作用（p = 0.004），即较高的CRP与Met等位基因携带者中更多的认知性抑郁症状相关，但在Val/Val纯合子中并非如此。事后纵向分析表明，对于Met携带者，基线时较高的CRP预测了在一年随访期内较高的认知性抑郁症状（p < 0.001）。
结论
BDNF Met等位基因可能是乳腺癌幸存者中炎症相关性认知性抑郁症状的一个风险因素。携带这种基因型的乳腺癌女性可能会从早期识别和治疗中受益。
局限性
BDNF基因型是BDNF蛋白水平的间接测量指标。
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