Csala Iren, Egervari Luca, Dome Peter, Faludi Gabor, Dome Balazs, Lazary Judit
Department of Clinical and Theoretical Mental Health, Semmelweis University, Budapest, Hungary; Institute of Behavioral Sciences, Semmelweis University, Budapest, Hungary.
Department of Clinical and Theoretical Mental Health, Semmelweis University, Budapest, Hungary.
Prog Neuropsychopharmacol Biol Psychiatry. 2015 Jun 3;59:84-90. doi: 10.1016/j.pnpbp.2015.01.012. Epub 2015 Jan 29.
Neuronal nicotinic acetylcholinergic receptors (nAChR) and especially α4β2 nAChRs are the major targets for cessation medications and also for some promising antidepressant agents. Furthermore, depressive symptoms pose multifacet difficulties during cessation therapy. However, gene encoding for the β2 subunit of nAChRs has been poorly investigated in association with depression. Since both nicotine dependence (ND) and depressive phenotype are complex disorders, we investigated the effects of a significant early life experience, maternal bonding style (MB) and CHRNB2 gene SNPs on smoking-related depression.
We recruited two hundred and thirty-two treatment-seeking smokers in our study. Phenotypic variants were evaluated using the Fagerstrom Test for Nicotine Dependence (FTND), the Zung Self-Rating Depression Scale (ZSDS) and the Parental Bonding Instrument (PBI). Besides the total score (TS) of ZSDS, impulsivity (ZSDS-I) and suicidal ideation (ZSDS-S) were distinguished as phenotypic variable. DNAs were extracted from buccal mucosa samples and one SNP in promoter and two SNPs in 3' UTR of CHRNB2 gene were genotyped. GLM and ANOVA tests were performed for genotype associations and interaction analyses.
Maternal bonding had a significant impact on depressive phenotypes. Low care, high protection and affectionless control (ALC) were associated with ZSDS-TS and all subphenotypes of ZSDS. One SNP, the rs2072660 in 3' UTR, had a significant effect on the FTND score (p=0.010). Direct association of CHRNB2 variants and depressive phenotypes were not significant. However, in interaction with ALC, rs2072660 was significantly associated with ZSDS-S (p=0.005). MB had no significant effect on smoking-related phenotype.
Our results highlight the important role of 3' UTR in the CHRNB2 gene in the shared molecular background of ND and depressive phenotype. Parental bonding style can be suggested as a significant environmental factor in further GxE studies of depression. The presented significant GxE interaction on smoking-related suicidal subphenotype may help establish further investigations on development of more effective and safer smoking cessation and antidepressant agents.
神经元烟碱型乙酰胆碱能受体（nAChR），尤其是α4β2 nAChR，是戒烟药物以及一些有前景的抗抑郁药物的主要作用靶点。此外，抑郁症状在戒烟治疗过程中带来多方面困难。然而，与抑郁症相关的nAChR β2亚基的基因编码研究较少。由于尼古丁依赖（ND）和抑郁表型都是复杂的疾病，我们研究了重要的早期生活经历、母婴依恋模式（MB）和CHRNB2基因单核苷酸多态性（SNP）对吸烟相关抑郁的影响。
我们在研究中招募了232名寻求治疗的吸烟者。使用尼古丁依赖Fagerstrom测试（FTND）、zung自评抑郁量表（ZSDS）和父母养育方式问卷（PBI）评估表型变异。除了ZSDS总分（TS）外，冲动性（ZSDS-I）和自杀观念（ZSDS-S）被区分为表型变量。从口腔黏膜样本中提取DNA，并对CHRNB2基因启动子中的一个SNP和3'非翻译区中的两个SNP进行基因分型。进行广义线性模型（GLM）和方差分析（ANOVA）测试以进行基因型关联和相互作用分析。
母婴依恋对抑郁表型有显著影响。低关怀、高保护和冷漠控制（ALC）与ZSDS-TS以及ZSDS的所有亚表型相关。3'非翻译区中的一个SNP，即rs2072660，对FTND评分有显著影响（p = 0.010）。CHRNB2变异与抑郁表型的直接关联不显著。然而，与ALC相互作用时，rs2072660与ZSDS-S显著相关（p = 0.005）。MB对吸烟相关表型没有显著影响。
我们的结果突出了CHRNB2基因3'非翻译区在ND和抑郁表型共同分子背景中的重要作用。在抑郁症进一步的基因-环境（GxE）研究中，父母养育方式可被视为一个重要的环境因素。所呈现的吸烟相关自杀亚表型上显著的GxE相互作用可能有助于开展关于开发更有效、更安全的戒烟和抗抑郁药物的进一步研究。
