Methamphetamine-induced psychosis is associated with DNA hypomethylation and increased expression of AKT1 and key dopaminergic genes.
Methamphetamine-induced psychosis is associated with DNA hypomethylation and increased expression of AKT1 and key dopaminergic genes.
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DOI：
10.1002/ajmg.b.32506
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发表时间：
2016-12
期刊：
影响因子：
--
通讯作者：
Abdolmaleky HM
中科院分区：
文献类型：
--
作者：
Nohesara S;Ghadirivasfi M;Barati M;Ghasemzadeh MR;Narimani S;Mousavi-Behbahani Z;Joghataei M;Soleimani M;Taban M;Mehrabi S;Thiagalingam S;Abdolmaleky HM
甲基苯丙胺是世界上使用最频繁的非法药物之一，可在很大一部分滥用者中诱发精神病，它正成为卫生保健机构的一个主要问题。有一些证据表明，遗传和表观遗传因素可能在甲基苯丙胺精神病中发挥作用。在这项研究中，我们研究了甲基苯丙胺诱导的表观遗传和表达的变化，涉及精神病的几个关键基因。分别使用qRT-PCR和q-MSP分析了从甲基苯丙胺依赖伴和不伴精神病的患者以及对照受试者（每组25名）的唾液样本中提取的RNA和DNA的DRD 1、DRD 2、DRD 3、DRD 4、MB-COMT、GAD 1和AKT 1的表达和启动子DNA甲基化状态。我们发现DRD 3基因启动子区的DNA低甲基化具有统计学意义，（P=0.032），DRD 4（P=0.05），MB-COMT（P=0.009）和AKT 1（P=0.0008）与甲基苯丙胺精神病患者相应基因表达增加相关（分别为P=0.022、P=0.034、P=0.035、P=0.038），与对照组相比，非精神病患者中某些候选基因的表达程度较低。一般来说，甲基苯丙胺依赖与DNA甲基化降低和参与精神障碍发病机制的几个关键基因表达的相应增加有关。虽然这些表观遗传变化可以是甲基苯丙胺滥用者精神病的有用诊断生物标志物，但它也与使用富含甲基的饮食预防或抑制这些患者的精神病一致。这需要在未来的研究中得到证实。
Methamphetamine, one of the most frequently used illicit drugs worldwide, can induce psychosis in a large fraction of abusers and it is becoming a major problem for the health care institutions. There is some evidence that genetic and epigenetic factors may play roles in methamphetamine psychosis. In this study, we examined methamphetamine-induced epigenetic and expression changes of several key genes involved in psychosis. RNA and DNA extracted from the saliva samples of patients with methamphetamine dependency with and without psychosis as well as control subjects (each group 25) were analyzed for expression and promoter DNA methylation status of DRD1, DRD2, DRD3, DRD4, MB-COMT, GAD1, and AKT1 using qRT-PCR and q-MSP, respectively. We found statistically significant DNA hypomethylation of the promoter regions of DRD3 (P=0.032), DRD4 (P=0.05), MB-COMT (P=0.009), and AKT1 (P=0.0008) associated with increased expression of the corresponding genes in patients with methamphetamine psychosis (P=0.022, P=0.034, P=0.035, P=0.038, respectively), and to a lesser degree in some of the candidate genes in nonpsychotic patients versus the control subjects. In general, methamphetamine dependency is associated with reduced DNA methylation and corresponding increase in expression of several key genes involved in the pathogenesis of psychotic disorders. While these epigenetic changes can be useful diagnostic biomarkers for psychosis in methamphetamine abusers, it is also consistent with the use of methyl rich diet for prevention or suppression of psychosis in these patients. However, this needs to be confirmed in future studies.
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影响因子：
3.5
作者：
Dempster EL;Pidsley R;Schalkwyk LC;Owens S;Georgiades A;Kane F;Kalidindi S;Picchioni M;Kravariti E;Toulopoulou T;Murray RM;Mill J
通讯作者：
Mill J
影响因子：
5
作者：
Jiang, Wenda;Li, Ji;Wang, Zhejian
通讯作者：
Wang, Zhejian
DOI：
10.1002/ajmg.b.31192
发表时间：
2011-07-01
影响因子：
2.8
作者：
Ghadirivasfi, Mohammad;Nohesara, Shabnam;Abdolmaleky, Hamid Mostafavi
通讯作者：
Abdolmaleky, Hamid Mostafavi
影响因子：
3.3
作者：
Hong, CJ;Cheng, CY;Tsai, SJ
通讯作者：
Tsai, SJ
幼稚的精神分裂症患者中5-羟色胺转运蛋白基因启动子的DNA高甲基化。
影响因子：
4.5
作者：
Abdolmaleky HM;Nohesara S;Ghadirivasfi M;Lambert AW;Ahmadkhaniha H;Ozturk S;Wong CK;Shafa R;Mostafavi A;Thiagalingam S
通讯作者：
Thiagalingam S