Impulsivity behaviors and white matter mediate the relationship between genetic risk for cannabis use disorder and early cannabis use in adolescents.

IF 5.2 1区医学 Q1 PSYCHIATRY

Addiction Pub Date : 2025-01-10 DOI:10.1111/add.16750

Renata Basso Cupertino, Sarah Elizabeth Medland, Jonatan Ottino-Gonzalez, Zhipeng Cao, Anthony Juliano, Devarshi Pancholi, Tobias Banaschewski, Arun L W Bokde, Sylvane Desrivières, Herta Flor, Antoine Grigis, Penny Gowland, Andreas Heinz, Rüdiger Brühl, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Eric Artiges, Frauke Nees, Dimitri Papadopoulos Orfanos, Herve Lemaitre, Tomáš Paus, Luise Poustka, Sarah Hohmann, Juliane H Fröhner, Michael N Smolka, Henrik Walter, Robert Whelan, Gunter Schumann, Patricia Conrod, Peter Callas, Hugh Garavan, Scott Mackey

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引用次数: 0

Abstract

Background and aim: Cannabis use disorder (CUD) is strongly influenced by genetic factors; however the mechanisms underpinning this association are not well understood. This study investigated whether a polygenic risk score (PRS) based on a genome-wide association study for CUD in adults predicts cannabis use in adolescents and whether the association can be explained by inter-individual variation in structural properties of brain white matter or risk-taking behaviors.

Design and setting: Longitudinal and cross-sectional analyses using data from the IMAGEN cohort, a European longitudinal study integrating genetic, neuroimaging and behavioral measures. We measured associations between PRS for CUD, novelty and sensation seeking traits and fractional anisotropy (FA) of white matter tracts. Mediation modeling explored whether novelty seeking and FA mediated the association between the PRS and cannabis use.

Participants: Participants were assessed at 14 (n = 1762), 19 (n = 1175) and 23 (n = 1139) years old.

Measurements: European School Survey Project on Alcohol and Other Drugs, substance use risk profile scale, Fagerstrom Test for Nicotine Dependence, temperament and character inventory, Kirby Monetary Questionnaire, diffusor tensor imaging and CUD-PRS.

Findings: CUD-PRS was associated with adolescent total cannabis exposure [P < 0.001, beta = 0.098 (95% confidence interval = 0.059, 0.137)] as well as with other substance use measures [alcohol P = 0.002, beta = 0.058 (0.020, 0.096); cigarettes smoked P < 0.001, beta = 0.086 (0.044, 0.128); fargestrom score P < 0.001, beta = 0.062 (0.028, 0.096); drug score P < 0.001, beta = 0.106 (0.065, 0.147)]. CUD-PRS was also associated with impulsivity, risk-taking behaviors [impulsivity P < 0.001, beta = 0.106 (0.060, 0.142); sensation seeking P < 0.001, beta = 0.094 (0.0523, 0.1357); novelty seeking P < 0.001, beta = 0.105 (0.064, 0.146); discounting task P < 0.001, beta = 0.051 (0.013, 0.089)] and average FA [P < 0.001, beta = -0.010 (-0.015, -0.005)]. Longitudinal mediation models showed that these behaviors and brain measures could mediate the association of PRS with cannabis use [overall indirect effect for novelty seeking P < 0.001, beta = 0.048 (0.028, 0.068); impulsivity P = 0.016, beta = 0.019 (0.004, 0.035); sensation seeking P < 0.001, beta = 0.034 (0.017, 0.05)].

Conclusions: The genetic risk of adult cannabis use disorder appears to be associated with substance use behavior and white matter structure as early as age 14. The observed mediation effect is consistent with the notion that genetic risk increases novelty seeking in a way that leads to more cannabis use in adolescents.

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冲动行为和白质介导大麻使用障碍遗传风险与青少年早期大麻使用的关系。

背景和目的：大麻使用障碍（CUD）受遗传因素的强烈影响；然而，支持这种联系的机制尚未得到很好的理解。本研究调查了基于成人CUD全基因组关联研究的多基因风险评分（PRS）是否可以预测青少年的大麻使用情况，以及这种关联是否可以通过脑白质结构特性的个体间差异或冒险行为来解释。设计和背景：纵向和横断面分析使用IMAGEN队列数据，IMAGEN队列是一项欧洲纵向研究，整合了遗传、神经成像和行为测量。我们测量了CUD、新颖性和感觉寻求特征的PRS与白质束分数各向异性（FA）之间的关系。中介模型探讨了寻求新奇和FA是否介导了PRS和大麻使用之间的关联。参与者：参与者被评估为14 (n = 1762), 19 （n = 1175）和23 （n = 1139）岁。测量方法：欧洲学校酒精和其他药物调查项目、物质使用风险概况量表、Fagerstrom尼古丁依赖测验、气质和性格量表、Kirby货币问卷、弥散张量成像和cudp - prs。结论：成人大麻使用障碍的遗传风险似乎早在14岁时就与物质使用行为和白质结构有关。观察到的中介效应与遗传风险增加寻求新奇事物的方式导致青少年更多使用大麻的概念是一致的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Addiction 医学-精神病学

CiteScore

10.80

自引率

6.70%

发文量

319

审稿时长

3 months

期刊介绍： Addiction publishes peer-reviewed research reports on pharmacological and behavioural addictions, bringing together research conducted within many different disciplines. Its goal is to serve international and interdisciplinary scientific and clinical communication, to strengthen links between science and policy, and to stimulate and enhance the quality of debate. We seek submissions that are not only technically competent but are also original and contain information or ideas of fresh interest to our international readership. We seek to serve low- and middle-income (LAMI) countries as well as more economically developed countries. Addiction’s scope spans human experimental, epidemiological, social science, historical, clinical and policy research relating to addiction, primarily but not exclusively in the areas of psychoactive substance use and/or gambling. In addition to original research, the journal features editorials, commentaries, reviews, letters, and book reviews.