Impulsivity behaviors and white matter mediate the relationship between genetic risk for cannabis use disorder and early cannabis use in adolescents.
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 ca...
| Publicado en: | Addiction Vol. 120; no. 5; pp. 984 - 997 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
May2025
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=184446041&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 184446041 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 09652140 AIO jtl: Addiction issn: 09652140 maglogo: Y pubinfo: dt: May2025 vid: 120 iid: 5 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 184446041 183800191 184446041 184446041 10.1111/add.16750 184446041 ppf: 984 ppct: 13 formats: fmt: – @attributes: type: T – @attributes: type: C – @attributes: type: P tig: atl: Impulsivity behaviors and white matter mediate the relationship between genetic risk for cannabis use disorder and early cannabis use in adolescents. aug: au: Cupertino, Renata Basso Medland, Sarah Elizabeth Ottino‐Gonzalez, Jonatan Cao, Zhipeng Juliano, Anthony Pancholi, Devarshi Banaschewski, Tobias Bokde, Arun L. W. Desrivières, Sylvane Flor, Herta Grigis, Antoine Gowland, Penny Heinz, Andreas Brühl, Rüdiger Martinot, Jean‐Luc Martinot, Marie‐Laure Paillère Artiges, Eric Nees, Frauke Orfanos, Dimitri Papadopoulos Lemaitre, Herve affil: Department of Psychiatry, University of California San Diego, San Diego California,, USA sug: subj: Substance Use Disorders Risk Factors Substance Use Disorders Prognosis Cannabis Impulsive Behavior Risk Taking Behavior White Matter Polymorphism, Genetic Genetic Risk Score Risk Assessment Funding Source Human Male Female Adolescence Young Adult Genome Wide Association Study Prospective Studies Cross Sectional Studies Mediation Analysis Smoking Delay Discounting Poisson Distribution Linear Regression P-Value Data Analysis Software Descriptive Statistics Scales Questionnaires Adolescent: 13-18 years Male Female ab: 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. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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