Li Juan, Yin Zhao, Yu Zeming, Li Jiannan, Yang Lu
Department of Anesthesiology, The Sixth Medical Center of People's Liberation Army (PLA) General Hospital, Beijing, CHN.
Department of Cardiology, People's Liberation Army (PLA) Strategic Support Force Characteristic Medical Center, Beijing, CHN.
Cureus. 2024 Aug 1;16(8):e65922. doi: 10.7759/cureus.65922. eCollection 2024 Aug.
Background Observational studies suggested that cannabis use was associated with alternation of brain structures; however, as subjected to confounding factors, they were difficult to make causal inferences and direction determinations. In this study, a two-sample Mendelian randomization (MR) analysis was employed to examine the potential causal association between cannabis use and brain structures. Methods The genome-wide association studies (GWAS) data for lifetime cannabis use (LCU), cannabis use disorder (CUD), and brain cortical and subcortical structures were utilized in this study. Cortical structures were divided into 34 distinct gyral-defined regions with surface area (SA) and thickness (TH) measured. Subcortical structures encompassed volumes from seven specified regions. The primary estimator used in our analysis was inverse-variance weighted (IVW), complemented by MR-Egger and weighted median methods to enhance the robustness of the results. The Cochran's Q test, funnel plots, and MR-Egger intercept tests were used to detect heterogeneity and pleiotropy. Results No causal relationship was detected between LCU and global cortical SA or TH. However, at the regional cortex level, LCU was associated with decreased TH in the fusiform (β = -0.0168 mm, SE = 0.00581, P = 0.0039) and lateral occipital (β = -0.0141 mm, SE = 0.00531, P = 0.0079) regions, while increasing TH in the postcentral region (β = 0.0093 mm, SE = 0.00445, P = 0.0374). At the subcortical level, LCU was found to increase the brainstem volume (β = 0.224 mm, SE = 0.09, P = 0.0128). CUD did not show any causal association with brain structure at either cortical or subcortical levels. Nonetheless, after applying multiple comparison corrections, the P values for the MR analysis of causal relationships between cannabis use and these brain structures did not meet the significance threshold. Conclusion The evidence for cannabis use causally influencing brain structures is insufficient.
背景 观察性研究表明，使用大麻与脑结构改变有关；然而，由于受到混杂因素的影响，这些研究难以进行因果推断和方向判定。在本研究中，采用两样本孟德尔随机化（MR）分析来检验使用大麻与脑结构之间的潜在因果关联。方法 本研究使用了终生大麻使用（LCU）、大麻使用障碍（CUD）以及脑皮质和皮质下结构的全基因组关联研究（GWAS）数据。皮质结构被划分为34个不同的脑回定义区域，并测量其表面积（SA）和厚度（TH）。皮质下结构包括7个特定区域的体积。我们分析中使用的主要估计方法是逆方差加权（IVW），并辅以MR-Egger和加权中位数方法以增强结果的稳健性。使用 Cochr an's Q检验、漏斗图和MR-Egger截距检验来检测异质性和多效性。结果 未检测到LCU与全皮质SA或TH之间存在因果关系。然而，在区域皮质水平，LCU与梭状回（β = -0.0168 mm，SE = 0.00581，P = 0.0039）和枕外侧回（β = -0.0141 mm，SE = 0.00531，P = 0.0079）的TH降低有关，而与中央后回的TH增加有关（β = 0.0093 mm，SE = 0.00445，P = 0.0374）。在皮质下水平，发现LCU会增加脑干体积（β = 0.224 mm，SE = 0.09，P = 0.0128）。CUD在皮质或皮质下水平均未显示与脑结构有任何因果关联。尽管如此，在应用多重比较校正后，大麻使用与这些脑结构之间因果关系的MR分析的P值未达到显著性阈值。结论 大麻使用对脑结构有因果影响的证据不足。
