We observed a positive correlation between cortisol levels and FKBP5 mRNA, but not genotype, which is consistent with previous reports.12 The correlation with cortisol levels was strongest when subjects were in nicotine withdrawal and disappeared after IV nicotine administration. Our findings are consistent with previous studies demonstrating the regulatory influence of FKBP5 on glucocorticoid receptors.17, 50 The acute and chronic effects of nicotine exposure on stress hormone levels are relevant to many clinical features of ND. For example, work by Cohen et al. suggests that cortisol level correlates with nicotine withdrawal severity after an acute withdrawal period,51 while others have reported correlations between cortisol and risk of relapse to smoking.24, 25 Additional investigations on the relationship of FKBP5 variation to cortisol levels and the behavioral correlates of FKBP5 mRNA levels in smokers are warranted.
