[Maternal bonding style, cholinergic receptor gene polymorphisms in association with smoking-related depressive...

Backgorund: There is accumulating evidence on the association between the cholinergic system and nicotine dependence (ND) in the literature and the bidirectional relationship of ND and depression. However, the molecular background of the development of ND and related affective phenotype is not clear.

We recruited 255 tretament-seeking smokers into our study. For phenotyping assessments we used the Fagerstrom Nicotine Dependence Test; The Minnessotta Nicotine Withdrawal Scale; the Zung Self-Rating Depression Scale and the Parental Bonding Instrument. DNA was isolated from buccal mucosa sample and CHRNA4 and CHRNB2 gene SNPs were genotyped with MassArray Sequenom techniques. For statistical analyses ANOVA test, Mann-Whitney U test, linear regression, two-step cluster analyses and hapscore tests were performed.

Two-step cluster analysis revealed 3 well-differentiated subgroups among smokers based on phenotypic characteristics. One subgroup was associated with the highest withdrawal and depressive scores. Frequency of the risk haplotype of CHRNA4 was significantly higher in this subgroup (p=0.019). Further, lifetime prevalence of major depression was also significantly higher in this subgroup. Besides, CHRNB2 gén variants showed a significant interacting effect with maternal bonding style on suicide thoughts (p=0.005).

Our results confirmed the genetic effect of CHRNA4 and CHRNB2 on smoking-related depression. These findings suggest that a genetically vulnerable subgroup can be distinguished among smokers and this subphenotype is more prone to withdrawal and depressive symptoms. Our data suggest that suicidal risk depends on both CHRNB2 gene variants and maternal bonding style. Pharmacogenetic concerns of CHRNA4 and CHRNB2 genes might be significant considering suicide as side effect of quitting therapy. Further pharmacogenetic investigations are requierd to clarify this possibility.