Translational Psychiatry:女性大麻成瘾者局部脑区体积更小

2021-05-14 MedSci原创 MedSci原创

与对照组相比,大麻使用者的选定ROI(即小脑白质和右侧OFC)体积更小。女性和存在大麻依赖可预测较小的ROI体积。这些结果表明,大麻依赖和女性是导致大麻使用者的微妙和区域性脑体积差异的驱动因素

大麻是地球上使用最广泛的非法物质,也是几乎全世界治疗服务中第一个关注的药物。性别差异在大麻使用和依赖的许多方面都很明显。例如,男性占大麻使用者的大多数,而且更有可能对大麻产生依赖性,但女性从娱乐性吸食发展到依赖性的速度更快,而且更经常复发。这种差异部分归因于潜在的神经生物学上的性别依赖。例如,大麻素1型受体(CB1Rs)与大麻的精神活性化合物(例如四氢大麻酚(THC))结合,其分布和亲和力受性激素的影响,男女各不相同。因此,在大麻使用的神经生物学相关方面可能存在性别差异。

性别差异在大麻使用者脑体积变化中的作用也没有得到充分的研究。在杏仁核(女性吸毒者>女性对照组)、PFC(女性吸毒者>女性对照,男性吸毒者<男性对照)和OFC(即女性成瘾吸毒者<女性对照)发现大麻性别效应,但在大脑的其它区域(如小脑、纹状体顶叶皮层)也没有发现这种现象。因此,大麻对男性和女性神经解剖学的不同影响仍然难以捉摸。迄今为止,大多数已发表的研究(即30项研究中有19项)存在男性抽样偏差,没有研究按性别分组的相互作用,或未能解释神经解剖学改变的驱动因素(如大麻依赖、酒精和烟草使用)。男性和女性表现出不同的大麻使用方式和相关的社会心理结果。但是,了解这种差异的神经解剖学基础知之甚少。

Valentina Lorenzetti等绘制了成瘾和娱乐性使用大麻的神经生物学性别差异(以大脑容量为指标)。并在Translational Psychiatry杂志发表文章。

比较了129名常规大麻使用者(其中70名是娱乐性使用者和59名大麻成瘾使用者)之间的先验目标区域(即杏仁核,海马体,伏隔核,伏隔,眶额皮质(OFC),前扣带回皮质和小脑)的体积)和从ENIGMA吸毒成瘾工作组中招募的114名对照,说明颅内体积,年龄,智商以及烟酒使用情况。依赖大麻的使用者,尤其是女性,与娱乐使用者和对照组相比,外侧OFC和小脑白质的体积(略有显着性)。在成瘾(但不是娱乐性的)大麻使用者中,女性与较小体积的小脑白质和OFC之间存在显着关联。还可以通过每月标准饮料量来预测OFC的量。没有其他大脑感兴趣区域出现显着影响。

大麻使用者(CB)的小脑白质(WM)和右外侧眶额皮质(OFC)的预测量。竖线和横线分别代表95%的置信区间和按性别分组的效应。

这项多部位MRI研究发现,与对照组相比,大麻使用者的一侧OFC和小脑白质出现了分组和分组的性别效应。这些影响有小到中等的影响规模,并没有通过FDR校正。然而,大麻使用者与对照组在杏仁核、海马体、脑岛、前扣带皮层、前扣带皮层和小脑灰质的体积上并没有表现出差异。最后,在娱乐性和依赖性大麻使用者中,发现一侧OFC和小脑白质体积可以通过性别和酒精剂量预测,但不能通过大麻使用测量

该研究的发现为将来进行多式联运研究提供了依据,这些研究将检验性别和大麻依赖性是否是大麻使用者神经生物学改变的特定关键驱动因素。反过来,这可以帮助确定特定于易受伤害的大麻使用者(例如,具有大麻依赖性的女性)的神经通路,并告知个体定制的神经生物学治疗靶标。

总之,与对照组相比,大麻使用者的选定ROI(即小脑白质和右侧OFC)体积更小。女性和存在大麻依赖可预测较小的ROI体积。这些结果表明,大麻依赖和女性是导致大麻使用者的微妙和区域性脑体积差异的驱动因素。随着男性和女性越来越容易获得大麻,有必要开展更多工作,以查明在进入和摆脱大麻依赖的轨迹中存在的性别差异和相关的社会心理问题的内在机制。这又将有助于为男性和女性经常使用和依赖大麻的人提供未来关于特定性别药物和行为干预的研究资料。

原文出处

Rossetti, M.G., Mackey, S., Patalay, P. et al. Sex and dependence related neuroanatomical differences in regular cannabis users: findings from the ENIGMA Addiction Working Group. Transl Psychiatry 11, 272 (2021). https://doi.org/10.1038/s41398-021-01382-y

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    2021-05-16 chg122

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