Low Smoking Exposure, the Adolescent Brain, and the Modulating Role of CHRNA5 Polymorphisms
Low Smoking Exposure, the Adolescent Brain, and the Modulating Role of CHRNA5 Polymorphisms
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DOI：
10.1016/j.bpsc.2019.02.006
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发表时间：
2019-07-01
影响因子：
5.9
通讯作者：
Tahmasebi, Amir
中科院分区：
文献类型：
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作者：
Chaarani, Bader;Kan, Kees-Jan;Tahmasebi, Amir
背景：研究青春期吸烟的神经后果，包括与早期轻度使用相关的神经后果，可能有助于揭示从最初使用烟草到成年期尼古丁依赖的转变机制。然而，针对青少年的研究很少，而且样本也很小。此外，将烟碱受体基因与青少年吸烟行为联系起来的神经机制（如果存在的话）仍不清楚。 方法：从大量 14 岁青少年样本中获取结构和扩散张量磁共振成像数据，这些青少年完成了一系列广泛的神经心理学、临床、人格和药物使用评估。在 16 岁时进行了额外的评估。 结果：青少年吸烟，即使是低剂量的吸烟，也与腹内侧前额叶皮质的体积变化和胼胝体神经元连接的改变有关。纵向分析强烈表明，这些影响并不是吸烟者原有的状况。遗传因素是，在携带 α 5 烟碱受体亚基基因 rs16969968 高风险基因型的吸烟者中，烟量减少的效应被放大。结论：这些发现深入了解了涉及基因、大脑结构和连通性的机制，这些机制是一些青少年发现尼古丁特别容易上瘾的原因。
BACKGROUND: Studying the neural consequences of tobacco smoking during adolescence, including those associated with early light use, may help expose the mechanisms that underlie the transition from initial use to nicotine dependence in adulthood. However, only a few studies in adolescents exist, and they include small samples. In addition, the neural mechanism, if one exists, that links nicotinic receptor genes to smoking behavior in adolescents is still unknown.METHODS: Structural and diffusion tensor magnetic resonance imaging data were acquired from a large sample of 14-year-old adolescents who completed an extensive battery of neuropsychological, clinical, personality, and druguse assessments. Additional assessments were conducted at 16 years of age.RESULTS: Exposure to smoking in adolescents, even at low doses, is linked to volume changes in the ventromedial prefrontal cortex and to altered neuronal connectivity in the corpus callosum. The longitudinal analyses strongly suggest that these effects are not preexisting conditions in those who progress to smoking. There was a genetic contribution wherein the volume reduction effects were magnified in smokers who were carriers of the high-risk genotype of the alpha 5 nicotinic receptor subunit gene, rs16969968.CONCLUSIONS: These findings give insight into a mechanism involving genes, brain structure, and connectivity underlying why some adolescents find nicotine especially addictive.