Molecular genetics of cocaine use disorders in humans.
Molecular genetics of cocaine use disorders in humans.
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DOI：
10.1038/s41380-021-01256-1
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发表时间：
2022-01
影响因子：
11
通讯作者：
Cormand B
中科院分区：
文献类型：
--
作者：
Fernàndez-Castillo N;Cabana-Domínguez J;Corominas R;Cormand B
药物成瘾是世界范围内的主要健康问题之一，其特征是药物摄入失控、渴望和戒断。在个人一级，滥用药物对健康产生严重后果，并对家庭环境、人际关系和工作关系产生负面影响。在更广泛的范围内，它们对社会经济和公共健康造成严重后果，并造成犯罪和公民不安全。可卡因是一种精神兴奋剂，是最常用的非法药物之一，特别是在美国，西欧和澳大利亚。滥用障碍（CUD）是由遗传和环境影响驱动的复杂的多因素条件。重要的是，并非所有使用可卡因的人都会发展成CUD，这至少部分是由于个体基因组中编码的生物因素。急性和重复使用可卡因会引起表观遗传和基因表达变化，导致神经元适应和脑回路重塑，从而导致从使用过渡到滥用或依赖。本综述的目的是描述这些因素，这最终应该有助于了解可卡因成瘾的易感性个体间的差异。CUD的遗传性估计值很高，可卡因成瘾的遗传风险因素已通过候选基因关联研究（CGAS）和全基因组关联研究（GWAS）进行了研究。此外，CUD和其他几种精神疾病之间存在的高共病性是众所周知的，包括精神分裂症，攻击性，反社会或冒险行为等表型。这些合并症与更糟糕的一生轨迹有关，在这里我们报告了可能导致这些合并症的共同遗传因素。基因表达的变化和表观遗传修饰引起的可卡因的使用和慢性滥用在人类中的神经元细胞和死后的大脑进行审查转录组学研究。我们报告了一些基因的表达被可卡因改变，也承担遗传风险变异的疾病。最后，我们对CUD治疗的药物遗传学进行了一瞥，仍处于早期阶段。更好地了解CUD的遗传基础将有助于寻找有效的治疗方法，并有助于向个性化医疗迈进。
Drug addiction, one of the major health problems worldwide, is characterized by the loss of control in drug intake, craving, and withdrawal. At the individual level, drugs of abuse produce serious consequences on health and have a negative impact on the family environment and on interpersonal and work relationships. At a wider scale, they have significant socio-economic and public health consequences and they cause delinquency and citizen insecurity. Cocaine, a psychostimulant substance, is one of the most used illicit drugs, especially in America, Western Europe, and Australia. Cocaine use disorders (CUD) are complex multifactorial conditions driven by both genetic and environmental influences. Importantly, not all people who use cocaine develop CUD, and this is due, at least in part, to biological factors that are encoded in the genome of individuals. Acute and repeated use of cocaine induces epigenetic and gene expression changes responsible for the neuronal adaptations and the remodeling of brain circuits that lead to the transition from use to abuse or dependence. The purpose of this review is to delineate such factors, which should eventually help to understand the inter-individual variability in the susceptibility to cocaine addiction. Heritability estimates for CUD are high and genetic risk factors for cocaine addiction have been investigated by candidate gene association studies (CGAS) and genome-wide association studies (GWAS), reviewed here. Also, the high comorbidity that exists between CUD and several other psychiatric disorders is well known and includes phenotypes like schizophrenia, aggression, antisocial or risk-taking behaviors. Such comorbidities are associated with a worse lifetime trajectory, and here we report shared genetic factors that may contribute to them. Gene expression changes and epigenetic modifications induced by cocaine use and chronic abuse in humans are addressed by reviewing transcriptomic studies performed on neuronal cells and on postmortem brains. We report some genes which expression is altered by cocaine that also bear genetic risk variants for the disorder. Finally, we have a glance to the pharmacogenetics of CUD treatments, still in early stages. A better understanding of the genetic underpinnings of CUD will foster the search of effective treatments and help to move forward to personalized medicine.
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影响因子：
4.2
作者：
Becker, Jill B.;McClellan, Michele L.;Reed, Beth Glover
通讯作者：
Reed, Beth Glover
影响因子：
2.1
作者：
Bauer IE;Graham DP;Soares JC;Nielsen DA
通讯作者：
Nielsen DA
DOI：
10.1002/ajmg.b.32552
发表时间：
2018-03
期刊：
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
影响因子：
--
作者：
Avramopoulos D
通讯作者：
Avramopoulos D
DOI：
10.1111/add.15242
发表时间：
2021-04
期刊：
Addiction (Abingdon, England)
影响因子：
--
作者：
Brandt L;Chao T;Comer SD;Levin FR
通讯作者：
Levin FR
影响因子：
4.6
作者：
Cabana-Domínguez J;Roncero C;Pineda-Cirera L;Palma-Álvarez RF;Ros-Cucurull E;Grau-López L;Esojo A;Casas M;Arenas C;Ramos-Quiroga JA;Ribasés M;Fernàndez-Castillo N;Cormand B
通讯作者：
Cormand B