Abstract
Rationale
There is strong evidence that nicotine can enhance cognitive functions and growing evidence that this effect may be larger in young healthy APOE ε4 carriers. However, the moderating effects of the APOE ε4 allele on cognitive impairments caused by nicotine deprivation in chronic smokers have not yet been studied with brain indices.
Objective
We sought to determine whether young female carriers of the APOE ε4 allele, relative to noncarriers, would exhibit larger abstinence-induced decreases in P3b amplitude during a two-stimulus auditory oddball task.
Methods
We compared parietal P3bs in female chronic smokers with either APOE ε3/ε3 (n = 54) or ε3/ε4 (n = 20) genotype under nicotine-sated conditions and after 12–17-h nicotine deprivation.
Results
Nicotine deprivation significantly reduced P3b amplitudes in APOE ε4 carriers, but not in APOE-ε3/ε3 individuals, such that the difference seen prior to nicotine deprivation was eliminated.
Conclusions
The results suggest that subjects with the APOE ε4 allele are more sensitive to nicotine, which could influence smoking patterns, the risk for nicotine dependence, and the cognitive effects of nicotine use in these individuals.
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Data availability
DGG, NER, RC, and GMR had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
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Acknowledgments
We thank F. Joseph McClernon, Louisette C. Plath, Carmen L. Masson, Allison E. Anderson, and Kaye F. Sly for their help in the collection of this data and the dozens of undergraduate research assistants who helped conduct this study, without whom it would have been impossible to complete. We also greatly appreciate the contributions of John D. Lindt in helping prepare the manuscript for publication.
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The study was supported by NIH grant R01DA07572 awarded to David Gilbert and by the Center for Integrated Research in Cognitive & Neural Sciences, Southern Illinois University.
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The study was designed by DGG. The data were acquired by DGG and NER. The ERP and statistical analyses were conducted by RC and DGG. The genotyping was performed by JH, TH, and KW. The manuscript was drafted by GMR and DGG. Each author contributed to critical revisions and approval of the final version of the manuscript. Funding was obtained by DGG. Supervision of the study was done by DGG.
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David Gilbert ended grant funding and all other connections with or benefits from R. J. Reynolds Tobacco Company in 1997 and has not received funding from any source other than the National Institutes of Health and the Southern Illinois University Center for Integrated Research in Cognitive & Neural Sciences since that time. He received free nicotine and placebo patches from Glaxo-Smith Kline in 2003. He received a consultation fee from Pfizer in 2003 and co-authored two publications with them in 2004 and 2007. Norka Rabinovich worked with several grant projects from R. J. Reynolds prior to the termination of funding from RJR in 1997. The other authors have no conflicts of interest.
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Coppens, R., Rabinovich, N.E., Kanneganti, R. et al. APOE genotype influences P3b amplitude and response to smoking abstinence in young adults. Psychopharmacology 238, 1171–1181 (2021). https://doi.org/10.1007/s00213-021-05763-5
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DOI: https://doi.org/10.1007/s00213-021-05763-5