APOE genotype influences P3b amplitude and response to smoking abstinence in young adults

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.