Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Psychiatric Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Eur Neuropsychopharmacol. 2023 Jun;71:41-54. doi: 10.1016/j.euroneuro.2023.03.004. Epub 2023 Mar 25.
Cannabinoid 1 receptors coded by the CNR1 gene are implicated in mood disorders and addiction. Given the prevalence and negative correlates of cannabis use in bipolar disorder (BD), we examined CNR1 polymorphism rs1324072 in relation to resting-state functional connectivity (rsFC) in youth BD. Participants included 124 youth, ages 13-20 years: 17 BD G-carriers, 48 BD non-carriers, 16 healthy controls (HC) G-carriers, and 43 HC non-carriers. rsFC was obtained using 3T-MRI. General linear models examined main effects of diagnosis, gene, and diagnosis-by-gene interaction, controlling for age, sex, and race. Regions-of-interests in seed-to-voxel analyses included: bilateral amygdala, hippocampus, nucleus accumbens (NAc), and orbitofrontal cortex (OFC). Main effects of diagnosis were observed for rsFC between the right amygdala seed and right occipital pole, and between the left NAc seed and left superior parietal lobe. Interaction analyses identified 6 significant clusters. G-allele was associated with negative connectivity in BD and positive connectivity in HC for: left amygdala seed with right intracalcarine cortex; right NAc seed with left inferior frontal gyrus; and right hippocampal seed with bilateral cuneal cortex (all p<0.001). G-allele was associated with positive connectivity in BD and negative connectivity in HC for: right hippocampal seed with left central opercular cortex (p = 0.001), and left NAc seed with left middle temporal cortex (p = 0.002). In conclusion, CNR1 rs1324072 was differentially associated with rsFC in youth with BD in regions relevant to reward and emotion. Future studies powered to integrate CNR1 alongside cannabis use are warranted to examine the inter-relationship between rs1324072 G-allele, cannabis use, and BD.
大麻素 1 型受体由 CNR1 基因编码，与心境障碍和成瘾有关。鉴于双相情感障碍（BD）中大麻使用的普遍性和负面相关性，我们研究了 CNR1 多态性 rs1324072 与青少年 BD 的静息状态功能连接（rsFC）之间的关系。参与者包括 124 名年龄在 13-20 岁的年轻人：17 名 BD G 携带者、48 名 BD 非携带者、16 名健康对照（HC）G 携带者和 43 名 HC 非携带者。rsFC 是使用 3T-MRI 获得的。一般线性模型检查了诊断、基因和诊断-基因相互作用的主要影响，同时控制了年龄、性别和种族。种子到体素分析的感兴趣区域包括：双侧杏仁核、海马体、伏隔核（NAc）和眶额皮层（OFC）。在 rsFC 中观察到诊断的主要影响，包括右侧杏仁核种子与右侧距状裂皮质之间，以及左侧 NAc 种子与左侧顶下小叶之间。相互作用分析确定了 6 个显著簇。G 等位基因与 BD 的负连接和 HC 的正连接相关：左侧杏仁核种子与右侧内距状皮质；右侧 NAc 种子与左侧额下回；以及右侧海马体种子与双侧楔状皮质（均 p<0.001）。G 等位基因与 BD 的正连接和 HC 的负连接相关：右侧海马体种子与左侧中央脑回皮质（p=0.001），以及左侧 NAc 种子与左侧颞中皮质（p=0.002）。总之，CNR1 rs1324072 与青少年 BD 患者与奖励和情绪相关的 rsFC 区域存在差异相关。未来的研究需要整合 CNR1 与大麻使用情况，以研究 rs1324072 G 等位基因、大麻使用与 BD 之间的相互关系。
