Gene-environment interactions in COCCaINE Use Disorder: Collaborative Case-Control Initiative in Coccaine Addiction

可卡因使用障碍中的基因-环境相互作用：可卡因成瘾的协作病例控制计划

• 批准号: 10171828
• 负责人: Rodrigo Grassi-Oliveira
• 金额: $ 50.38万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10171828
• 关键词: Affect; Age; Aging; Area; Autopsy; Award; Bass; Behavioral; Bioinformatics; Biological; Brain region; Brazil; CD4 Lymphocyte Count; Chronic; Cocaine; Cocaine Dependence; Code; Collaborations; Consumption; Country; Criminal Justice; DNA; DNA Methylation; Databases; Development; Disease; Drug Use Disorder; Educational workshop; Environmental Impact; Epigenetic Process; Evaluation; Exposure to; Fellowship Program; Female; Future; Genes; Genetic; Goals; HIV; HIV Infections; Health; Healthcare; Heritability; Human Resources; Individual; Infrastructure; Latin America; Latin American; Life Stress; Mediating; Methylation; Modification; Molecular; Molecular Epidemiology; Needs Assessment; Network-based; North America; Oxidative Stress; Participant; Pathway Analysis; Patients; Physiological; Policies; Population; Population Database; Predisposing Factor; Prevalence; Psychostimulant dependence; Public Health; Quantitative Trait Loci; Race; Recording of previous events; Regulation; Research; Research Personnel; Research Project Grants; Research Training; Rewards; Risk Factors; Risk Marker; Role; Sampling; Scientist; Severities; Smoking History; Source; South America; Stress; Substance Use Disorder; System; Testing; Training; Training Activity; Training Programs; Trauma; Travel; Twin Studies; United States; Untranslated RNA; Variant; Work; addiction; base; biological adaptation to stress; biomarker development; case control; cocaine use; cohort; early life stress; early onset; effective therapy; environmental stressor; evidence base; gene environment interaction; genetic epidemiology; genetic makeup; genetic variant; genome wide association study; genome wide methylation; global health; individualized medicine; international center; male; methylation pattern; neurobehavioral; population based; research and development; response; sex; skills; stressor; trauma exposure; traumatic event; traumatic stress

ABSTRACT We propose to perform a population-based genetic epidemiological study of cocaine use disorder (CUD) in the region of Rio Grande Brazil to characterize the role of environmental stressors, both trauma exposure and HIV infection, on epigenetic signatures and gene-environment interactions in patients with CUD. Using already available DNA from 1000 CUD subjects and 1000 controls we will examine genome- wide associations and gene environment interactions (Aim 1), the relationship between traumatic stress and DNA methylation (Aim 2), and the additive effect of HIV infection as a biological stressor on DNA methylation (Aim 3). All molecular assessments will be correlated with behavioral and physiologic evaluations which are available from all individuals, to identify potential risk markers for CUD. These studies will examine the following hypotheses: 1) Genes involved in stress regulation will be associated with CUD, and CUD severity 2) Exposure to life stress and adversity (i.e., trauma) in genetically susceptible individuals represents a risk factor for development of CUD, and 3) HIV infection will have an additive effect on epigenetic modifications in genes related to stress regulation in subjects with CUD. The PI’s of this application have an established collaboration and history of research capacity building. The COllaborative Case-Control INitiativE in crack addiction (COCCaINE) project was initiated in 2014 as the result of needs assessment discussions between Drs. Grassi-Oliveira and Walss-Bass. This project forms the basis for the current application to the Fogarty International Center. As part of this application we will enhance research capacity and infrastructure (Aim 4) by implementing training programs in molecular epidemiology, bioinformatics, and management of substance use disorders and trauma for investigators in the area of Rio Grande Brazil. During the first year we will organize week-long theoretical and practical workshops taught by experts from UTHealth in Houston. During the second, third, fourth, and fifth years of the award we propose to create mini-fellowship programs for Brazilian investigators to travel to the United States for training. These training activities will be of great value for the research capacity building and development of qualified human resources in Brazil, and for successful implementation of the research goals. The proposed studies will lead to a better understanding of how changes in DNA methylation, as modulated by genetic make-up and in combination with exposure to environmental insults, impacts CUD severity and may serve as a biomarker for development of more tailored and targeted treatments for this chronic and global public health problem.

摘要

项目成果

Sex differences in brain regional homogeneity during acute abstinence in cocaine use disorder.

可卡因使用障碍急性戒酒期间大脑区域均匀性的性别差异。

• DOI: 10.1111/adb.13177
• 发表时间: 2022-05
• 期刊: Addiction biology
• 影响因子: 3.4

Association Between Recent Cannabis Consumption and Withdrawal-Related Symptoms During Early Abstinence Among Females With Smoked Cocaine Use Disorder.

患有吸食可卡因使用障碍的女性早期戒断期间近期大麻消费与戒断相关症状之间的关联。

• DOI: 10.1097/adm.0000000000000599
• 发表时间: 2020
• 期刊: Journal of addiction medicine
• 影响因子: 5.5
• 作者: Viola,ThiagoWendt;Sanvicente-Vieira,Breno;Kluwe-Schiavon,Bruno;Rothmann,LeonardoMelo;Mélo-Pereira,JoãoVítorNóbregaE;Bicca,Carla;OttoliaNiederauer,JoãoPaulo;Schmitz,Joy;Grassi-Oliveira,Rodrigo
• 通讯作者: Grassi-Oliveira,Rodrigo

Cingulate cortical thickness in cocaine use disorder: mediation effect between early life stress and cocaine consumption.

可卡因使用障碍中的扣带皮层厚度：早期生活压力与可卡因消费之间的中介作用。

• DOI: 10.1017/neu.2022.33
• 发表时间: 2024
• 期刊: Acta neuropsychiatrica
• 影响因子: 3.8
• 作者: Bittencourt,AugustoMartinsLucas;Silveira,BárbaraLuizaBelmonteda;Tondo,LuccaPizzato;Rothmann,LeonardoMelo;Franco,AlexandreRosa;Ferreira,PedroEugenioMazzucchiSantana;Viola,ThiagoWendt;Grassi-Oliveira,Rodrigo
• 通讯作者: Grassi-Oliveira,Rodrigo

White matter deficits in cocaine use disorder: convergent evidence from in vivo diffusion tensor imaging and ex vivo proteomic analysis.

• DOI: 10.1038/s41398-021-01367-x
• 发表时间: 2021-04-29
• 期刊: Translational psychiatry
• 影响因子: 6.8
• 作者: Tondo LP;Viola TW;Fries GR;Kluwe-Schiavon B;Rothmann LM;Cupertino R;Ferreira P;Franco AR;Lane SD;Stertz L;Zhao Z;Hu R;Meyer T;Schmitz JM;Walss-Bass C;Grassi-Oliveira R
• 通讯作者: Grassi-Oliveira R

Prenatal cocaine exposure and its influence on pediatric epigenetic clocks and epigenetic scores in humans.

• DOI: 10.1038/s41598-024-52433-5
• 发表时间: 2024-01-23
• 期刊: Scientific reports
• 影响因子: 4.6