Department of Nuclear Medicine, West China Hospital of Sichuan University, No. 37 Guo Xue Alley, 610041, Chengdu, Sichuan, China.
Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, No. 37 Guo Xue Alley, 610041, Chengdu, Sichuan, China.
Cereb Cortex. 2024 Jul 3;34(7). doi: 10.1093/cercor/bhae298.
Behavioral addiction (BA) is a conceptually new addictive phenotype characterized by compulsive reward-seeking behaviors despite adverse consequences. Currently, its underlying neurogenetic mechanism remains unclear. Here, this study aimed to investigate the association between cortical thickness (CTh) and genetic phenotypes in BA. We conducted a systematic search in five databases and extracted gene expression data from the Allen Human Brain Atlas. Meta-analysis of 10 studies (343 addicted individuals and 355 controls) revealed that the BA group showed thinner CTh in the precuneus, postcentral gyrus, orbital-frontal cortex, and dorsolateral prefrontal cortex (P < 0.005). Meta-regression showed that the CTh in the precuneus and postcentral gyrus were negatively associated with the addiction severity (P < 0.0005). More importantly, the CTh phenotype of BA was spatially correlated with the expression of 12 genes (false discovery rate [FDR] < 0.05), and the dopamine D2 receptor had the highest correlation (rho = 0.55). Gene enrichment analysis further revealed that the 12 genes were involved in the biological processes of behavior regulation and response to stimulus (FDR < 0.05). In conclusion, our findings demonstrated the thinner CTh in cognitive control-related brain areas in BA, which could be associated with the expression of genes involving dopamine metabolism and behavior regulation.
行为成瘾(BA)是一种概念新颖的成瘾表型,其特征是尽管存在不良后果,但仍存在强迫性寻求奖励的行为。目前,其潜在的神经遗传机制尚不清楚。本研究旨在探讨皮质厚度(CTh)与 BA 中遗传表型的关联。我们在五个数据库中进行了系统搜索,并从 Allen 人类大脑图谱中提取了基因表达数据。对 10 项研究(343 名成瘾者和 355 名对照者)进行的荟萃分析显示,BA 组在前扣带回、中央后回、眶额皮质和背外侧前额叶皮质的 CTh 较薄(P<0.005)。元回归显示,前扣带回和中央后回的 CTh 与成瘾严重程度呈负相关(P<0.0005)。更重要的是,BA 的 CTh 表型与 12 个基因的表达呈空间相关(错误发现率[FDR]<0.05),多巴胺 D2 受体相关性最高(rho=0.55)。基因富集分析进一步表明,这 12 个基因参与了行为调节和对刺激的反应等生物学过程(FDR<0.05)。总之,我们的研究结果表明,BA 患者与认知控制相关的大脑区域的 CTh 变薄,这可能与涉及多巴胺代谢和行为调节的基因表达有关。