A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants and reward response

作者：Macare, Christine; Ducci, Francesca; Zhang, Yuning; Ruggeri, Barbara; Jia, Tianye; Kaakinen, Marika; Kalsi, Gursharan; Charoen, Pimphen; Casoni, Filippo; Peters, Jan; Bromberg, Uli; Hil, Matthew; Buxton, Jessica; Blakemore, Alexandra; Veijola, Juha; Buchel, Christian; Banaschewski, Tobias; Bokde, Arun L. W.; Conrod, Patricia; Flor, Herta; Frouin, Vincent; Gallinat, Jurgen; Garavan, Hugh; Gowland, Penny A.; Heinz, Andreas; Itternnann, Bernd; Lathrop, Mark; Martinot, Jean-Luc; Paus, Tomas

来源：European Neuropsychopharmacology, 2018, 28(10): 1103-1114.

DOI：10.1016/j.euroneuro.2018.07.101

• fMRI
• Genetics
• IMAGEN-ALSPAC-NFBC
• Meta-analysis
• Risk taking
• Smoking

The TTC12-ANKK1-DRD2 gene-cluster has been implicated in adult smoking. Here, we investigated the contribution of individual genes in the TTC12-ANKK1-DRD2 cluster in smoking and their association with smoking-associated reward processing in adolescence. A meta-analysis of TTC12-ANKK1-DRD2 variants and self-reported smoking behaviours was performed in four European adolescent cohorts (N = 14,084). The minor G-allele of rs2236709, mapping TTC12, was associated with self-reported smoking (p = 5.0 x 10(-4)) and higher plasma cotinine levels (p = 7.0 x 10(-5)). This risk allele was linked to an increased ventral-striatal blood-oxygen level-dependent (BOLD) response during reward anticipation (n = 1,263) and with higher DRD2 gene expression in the striatum (p = 0.013), but not with TTC12 or ANKK gene expression. These data suggest a role for the TTC12-ANKK1-DRD2 gene-cluster in adolescent smoking behaviours, provide evidence for the involvement of DRD2 in the early stages of addiction and support the notion that genetically-driven inter-individual differences in dopaminergic transmission mediate reward sensitivity and risk to smoking.

• 出版日期2018-10
• 单位复旦大学; 上海市精神卫生中心; McGill