Department of Child and Adolescent Psychiatry, Technische Universität Dresden, Faculty of Medicine, 01307, Dresden, Germany.
Technische Universität Chemnitz, Chair for Clinical Psychology and Psychotherapy, Chemnitz, Germany.
Transl Psychiatry. 2022 Aug 6;12(1):317. doi: 10.1038/s41398-022-02025-6.
The association between extent of chronic cannabis use (CCU-extent) and cognitive impairment among adolescents has been the subject of controversial debate. Linking DNA methylation to CCU-extent could help to understand cannabis associated changes in cognitive performance. We analyzed cognitive task performances, CpG methylation in peripheral whole-blood samples and self-reported past-year CCU-extent of n = 18 adolescents (n = 9 psychiatric outpatients with chronic cannabis use (CCU), n = 9 without) who were matched for age, gender and psychiatric disorders. Patients with CCU were at least 24 h abstinent when cognitive tasks were performed. A Principal Component Analysis (PCA) was carried out to identify group differences in whole genome DNA methylation. Mediation analyses were performed between CCU-extent associated CpG sites and CCU-extent associated variables of cognitive tasks. PCA results indicated large differences in whole genome DNA methylation levels between the groups that did not reach statistical significance. Six CpG sites revealed reduced methylation associated with CCU-extent. Furthermore, CCU-extent was associated with lower scores in verbal learning. All six CpG sites mediated the effects between CCU-extent and verbal learning free recall. Our results indicate that CCU is associated with certain patterns in the methylome. Furthermore, CCU-extent associated impairments in memory function are mediated via differential methylation of the six CCU-associated CpG sits. Six identified CpG are located in genes previously described in the context of neurodegeneration, hippocampus-dependent learning and neurogenesis. However, these results have to be carefully interpreted due to a small sample size. Replication studies are warranted.
慢性大麻使用（CCU-程度）与青少年认知障碍之间的关联一直是有争议的辩论主题。将 DNA 甲基化与 CCU-程度联系起来可以帮助理解与大麻相关的认知表现变化。我们分析了认知任务表现、外周全血样本中的 CpG 甲基化以及 n = 18 名青少年（n = 9 名慢性大麻使用（CCU）的精神科门诊患者，n = 9 名无 CCU）的自我报告过去一年 CCU-程度，这些患者在进行认知任务时至少 24 小时没有使用大麻。进行了主成分分析（PCA），以确定全基因组 DNA 甲基化的组间差异。在 CCU-程度相关的 CpG 位点和 CCU-程度相关的认知任务变量之间进行了中介分析。PCA 结果表明，两组之间的全基因组 DNA 甲基化水平存在很大差异，但未达到统计学意义。六个 CpG 位点显示与 CCU-程度相关的甲基化减少。此外，CCU-程度与言语学习的分数降低相关。所有六个 CpG 位点介导了 CCU-程度与言语学习自由回忆之间的效应。我们的结果表明，CCU 与甲基组的某些模式有关。此外，CCU-程度与记忆功能相关的损害是通过六个与 CCU 相关的 CpG 位点的差异甲基化介导的。六个确定的 CpG 位于先前在神经退行性变、海马依赖学习和神经发生背景下描述的基因中。然而，由于样本量小，这些结果必须谨慎解释。需要进行复制研究。
