Prefrontal white matter impairment in substance users depends upon the catechol-o-methyl transferase (COMT) val158met polymorphism.
Prefrontal white matter impairment in substance users depends upon the catechol-o-methyl transferase (COMT) val158met polymorphism.
复制标题
物质使用者的前额白质损伤取决于儿茶酚邻甲基转移酶 (COMT) val158met 多态性。
DOI：
10.1016/j.neuroimage.2012.11.056
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发表时间：
2013
期刊：
影响因子：
5.7
通讯作者：
Stein,ElliotA
中科院分区：
文献类型：
--
作者：
Zhang,Xiaochu;Lee,MaryR;Salmeron,BettyJo;Stein,DanJ;Hong,LElliot;Geng,Xiujuan;Ross,ThomasJ;Li,Nan;Hodgkinson,Colin;Shen,Pei-Hong;Yang,Yihong;Goldman,David;Stein,ElliotA
对大多数化学物质成瘾的个体表现为多巴胺能系统功能减退以及前额叶白色物质结构改变。前额叶多巴胺能紧张度受遗传控制，并受下行皮质-纹状体多巴胺能通路的影响和调节，而下行皮质-纹状体多巴胺能通路反过来又调节纹状体多巴胺的释放。儿茶酚-O-甲基转移酶（COMT）基因在密码子108/158（rs 4680）处包含进化上最近的和常见的功能变体，其在调节前额叶多巴胺能张力中起重要作用。为了确定COMT val 158 met基因型是否影响白色物质完整性（即，部分各向异性（FA）），126名健康对照和146名物质使用者进行了基因分型和磁共振成像。采用全脑弥散张量成像（DTI）评估FA，采用两个受试者间因素（COMT基因型和成瘾状态）的一般线性模型。在左前额叶皮层中发现了显著的基因型×药物使用状态相互作用。事后分析显示，减少前额FA仅在Met/Met纯合子谁也吸毒者。这些数据表明，Met/Met纯合子个体，在成瘾的背景下，增加了对白色物质结构改变的易感性，这可能有助于先前确定的结构和功能性前额叶皮质缺陷成瘾。
Individuals addicted to most chemical substances present with hypoactive dopaminergic systems as well as altered prefrontal white matter structure. Prefrontal dopaminergic tone is under genetic control and is influenced by and modulates descending cortico-striatal glutamatergic pathways that in turn, regulate striatal dopamine release. The catechol-O-methyltransferase (COMT) gene contains an evolutionarily recent and common functional variant at codon 108/158 (rs4680) that plays an important role in modulating prefrontal dopaminergic tone. To determine if the COMT val158met genotype influences white matter integrity (i.e., fractional anisotropy (FA)) in substance users, 126 healthy controls and 146 substance users underwent genotyping and magnetic resonance imaging. A general linear model with two between-subjects factors (COMT genotype and addiction status) was performed using whole brain diffusion tensor imaging (DTI) to assess FA. A significant Genotype×Drug Use status interaction was found in the left prefrontal cortex. Post-hoc analysis showed reduced prefrontal FA only in Met/Met homozygotes who were also drug users. These data suggest that Met/Met homozygous individuals, in the context of addiction, have increased susceptibility to white matter structural alterations, which might contribute to previously identified structural and functional prefrontal cortical deficits in addiction.