白细胞介素 1 β（IL1B）基因与重度抑郁症患者缓解失败和情绪处理受损有关。
The interleukin 1 beta (IL1B) gene is associated with failure to achieve remission and impaired emotion processing in major depression.
机构信息
Department of Psychiatry and Psychiatric Neuroscience, James Cook University, Queensland, Australia.
出版信息
Biol Psychiatry. 2010 Mar 15;67(6):543-9. doi: 10.1016/j.biopsych.2009.11.004. Epub 2009 Dec 30.
BACKGROUND
Accumulating evidence suggests the involvement of inflammatory processes and cytokines in particular in the pathophysiology of major depression (MDD) and resistance to antidepressant treatment. Furthermore, amygdala and anterior cingulate cortex (ACC) responsiveness to emotional stimuli has been suggested as a predictor of treatment response. This study investigated the association between genetic variants of the interleukin 1 beta (IL1B) gene and amygdala and ACC responsiveness to emotional stimuli and response to antidepressant treatment.
METHODS
In this analysis, 256 Caucasian patients with MDD (145 women, 111 men) were genotyped for variants rs16944, rs1143643, and rs1143634 in the IL1B gene (2q14). Response to antidepressant treatment over 6 weeks was defined as remission (< or = 7 on the Hamilton Rating Scale for Depression-21-question) and response (>50% decrease on Hamilton Rating Scale for Depression-21-question). Brain activity under visual presentation of emotional faces was assessed in a subsample of 32 depressed patients by means of functional magnetic resonance imaging at 3 T.
RESULTS
Pharmacogenetic analyses show significant associations of the GG genotypes of single nucleotide polymorphisms (SNPs) rs16944 (odds ratio = 1.74; 95% confidence interval 1.2-4.3) and rs1143643 (odds ratio = 3.1; 95% confidence interval 1.3-7.8) (compared with the AA genotype) with nonremission after 6 weeks. The imaging analyses show that the number of G-alleles in both SNPs (rs16944 and rs1143643) was associated with reduced responsiveness of the amygdala and ACC to emotional stimulation.
CONCLUSIONS
The present study suggests a negative effect of the IL1B gene on pharmacological response and amygdala and ACC function involving the same genotypes of two SNPs (rs16944, rs116343), which taken together increase the risk of nonremission over 6 weeks of antidepressant treatment in MDD.
背景
越来越多的证据表明，炎症过程和细胞因子，尤其是在重度抑郁症（MDD）的病理生理学和抗抑郁治疗的抵抗中发挥了作用。此外，杏仁核和前扣带皮层（ACC）对情绪刺激的反应能力已被认为是治疗反应的预测指标。本研究调查了白细胞介素 1β（IL1B）基因的遗传变异与杏仁核和 ACC 对情绪刺激的反应能力以及对抗抑郁治疗反应之间的关系。
方法
在这项分析中，256 名高加索裔 MDD 患者（145 名女性，111 名男性）的白细胞介素 1β基因（2q14）中的 rs16944、rs1143643 和 rs1143634 变体进行了基因分型。6 周抗抑郁治疗的反应定义为缓解（<或=7 分汉密尔顿抑郁量表-21 项）和反应（汉密尔顿抑郁量表-21 项评分下降>50%）。通过功能磁共振成像在 3T 下对 32 名抑郁患者的一个亚组进行了视觉呈现情绪面孔下的大脑活动评估。
结果
药物遗传学分析显示，单核苷酸多态性（SNP）rs16944（比值比=1.74；95%置信区间 1.2-4.3）和 rs1143643（比值比=3.1；95%置信区间 1.3-7.8）的 GG 基因型与 6 周后无缓解显著相关（与 AA 基因型相比）。成像分析表明，两个 SNP（rs16944 和 rs1143643）中的 G-等位基因数量与杏仁核和 ACC 对情绪刺激的反应性降低有关。
结论
本研究表明，白细胞介素 1β基因对药物反应和杏仁核和 ACC 功能有负面影响，涉及两个 SNP（rs16944、rs116343）的相同基因型，这些基因型共同增加了 MDD 患者抗抑郁治疗 6 周内无缓解的风险。
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