title: The possible role of maternal bonding style and CHRNB2 gene polymorphisms in nicotine dependence and related depressive phenotype.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Clinical and Theoretical Mental Health, Semmelweis University, Budapest, Hungary; Institute of Behavioral Sciences, Semmelweis University, Budapest, Hungary.
authors: Iren
authors: I
authors: Csala
authors: Department of Clinical and Theoretical Mental Health, Semmelweis University, Budapest, Hungary.
authors: Luca
authors: L
authors: Egervari
authors: Department of Clinical and Theoretical Mental Health, Semmelweis University, Budapest, Hungary; National Institute of Psychiatry and Addiction, Budapest, Hungary.
authors: Peter
authors: P
authors: Dome
authors: Department of Clinical and Theoretical Mental Health, Semmelweis University, Budapest, Hungary.
authors: Gabor
authors: G
authors: Faludi
authors: Department of Tumor Biology, National Koranyi Institute of Pulmonology, Budapest, Hungary; Department of Thoracic Surgery, Medical University of Vienna, Austria; Department of Thoracic Surgery, National Institute of Oncology and Semmelweis University, Budapest, Hungary; Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Austria.
authors: Balazs
authors: B
authors: Dome
authors: Department of Clinical and Theoretical Mental Health, Semmelweis University, Budapest, Hungary. Electronic address: lazaryjudit@gmail.com.
authors: Judit
authors: J
authors: Lazary
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D003863:Depression / Q000209:etiology / Q000235:genetics / Q000523:psychology; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009034:Mother-Child Relations / Q000523:psychology*; D009769:Object Attachment; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000209:etiology / Q000235:genetics / Q000523:psychology
chemical_list: D011978:Receptors, Nicotinic
keywords: Gene–environment interaction; Nicotine dependence; Parental bonding style; Suicidal ideation; α4β2 nAChRs