Dataset Information

Comparing the Rate of Nicotine Metabolism Among Smokers With Current or Past Major Depressive Disorder.

ABSTRACT:

Background and objectives

Persons with current or past major depressive disorder (MDD) vs those without have higher smoking rates. The nicotine metabolite ratio (NMR) represents variation in the rate of nicotine metabolism and has been associated with smoking behaviors and response to tobacco treatments. We compared NMR between smokers with current or past MDD (MDD+) vs smokers without MDD (MDD-). We also assessed correlates of NMR and compared withdrawal and craving between MDD+ and MDD- smokers.

Methods

Using baseline data from two clinical trials and propensity score weighting based on sex, race, body mass index, and smoking rate, we compared NMR between MDD+ (N = 279) and MDD- (N = 1575) smokers. We also compared groups on and nicotine withdrawal and craving.

Results

Mean NMR (β = -.02, 95% confidence interval [CI]: -0.05 to 0.01, P = .13) and the distribution of smokers across NMR quartiles (odds ratio [OR] = 0.76, 95% CI: 0.50 to 1.16, P = .21) were similar between MDD+ and MDD- samples. This relationship was not affected by antidepressant medication. In the MDD+ sample, African Americans had significantly lower mean NMR, while older smokers and smokers with lower education had higher mean NMR (Ps < .05). MDD+ smokers had significantly higher withdrawal and craving than MDD- smokers (Ps < .05).

Discussion and conclusions

While variability in NMR may not explain differences in smoking rates between MDD+ and MDD- smokers, MDD+ smokers report increased withdrawal and craving.

Scientific significance

In this first study to assess NMR among MDD+ smokers, the findings underscore the need to address withdrawal and craving within smoking cessation treatments for those with MDD. (Am J Addict 2021;00:00-00).

SUBMITTER: Schnoll R

PROVIDER: S-EPMC8243789 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.