# Exploring the Relationship Between Brain-Derived Neurotrophic Factor Haplotype Variants, Personality, and Nicotine Usage in Women

## TL;DR

This study explores how BDNF gene variants, personality traits, and nicotine use are related in women, finding that personality traits like Agreeableness and Conscientiousness differ between smokers and non-smokers.

## Contribution

The study investigates understudied BDNF variants and their potential role in nicotine use, offering new insights into addiction-related phenotypes in women.

## Key findings

- Cigarette users scored significantly lower on Agreeableness and Conscientiousness compared to never-smokers.
- No significant differences in BDNF genotype or allele distribution were found between smokers and non-smokers.
- Strong linkage disequilibrium was observed between the three BDNF polymorphic variants, but no haplotype associations were significant.

## Abstract

Brain-derived neurotrophic factor (BDNF) is associated with nicotine use behaviours, the intensity of nicotine cravings, and the experience of withdrawal symptoms. Given the established influence of sex, brain-derived neurotrophic factor variants, personality traits and anxiety levels on nicotine use, this study aimed to conduct a comprehensive association analysis of these factors within a cohort of women who use nicotine. The study included 239 female participants: 112 cigarette users (mean age = 29.19, SD = 13.18) and 127 never-smokers (mean age = 28.1, SD =10.65). Study participants were examined using the NEO Five-Factor Inventory and the State–Trait Anxiety Inventory. Genotyping of rs6265, rs10767664, and rs2030323 was performed by real-time PCR using an oligonucleotide assay. We did not observe significant differences in the distribution of either genotype or allele of rs6265, rs10767664 and rs2030323 between groups. However, compared to the never-smokers, cigarette users scored significantly lower on the Agreeableness (5.446 vs. 6.315; p = 0.005767; dCohen’s = 0.363; η2 = 0.032) and the Conscientiousness (5.571 vs. 6.882; p = 0.000012; dCohen’s = 0.591; η2= 0.08) scales. There was significant linkage disequilibrium between all three analysed polymorphic variants—between rs6265 and rs10767664 (D′ = 0.9994962; p < 2.2204 × 10−16), between rs6265 and rs2030323 (D′ = 0.9994935; p < 2.2204 × 10−16) and between rs10767664 and rs20330323 (D′ = 0.9838157; p < 2.2204 × 10−16), but the haplotype association analysis revealed no significant differences. While our study did not reveal an association between the investigated brain-derived neurotrophic factor polymorphisms (rs6265, rs10767664 and rs2030323) and nicotine use, it is essential to acknowledge that nicotine dependence is a complex, multifactorial phenotype. Our study expands the current knowledge of BDNF ’s potential role in addictive behaviours by exploring the understudied variants (rs10767664 and rs2030323), offering a novel contribution to the field and paving the way for future research into their functional relevance in addiction-related phenotypes. The lower Agreeableness and Conscientiousness scores observed in women who use nicotine compared to never-smokers suggest that personality traits play a significant role in nicotine use in women. The observed relationship between personality traits and nicotine use lends support to the self-medication hypothesis, suggesting that some women may initiate or maintain nicotine use as a coping mechanism for stress and negative affect. Public health initiatives targeting women should consider personality and psychological risk factors in addition to biological risks.