Gene-Environment Interations Underlying Alcoholism Vulnerability Disorders

酒精中毒脆弱性疾病背后的基因-环境相互作用

• 批准号: 7591938
• 负责人: David Goldman
• 金额: $ 9.1万
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7591938
• 关键词: Adult; Age; Alcohol abuse; Alcoholism; Anxiety; Attention deficit hyperactivity disorder; Behavior; Birth; COMT gene; Catechol O-Methyltransferase; Caucasians; Caucasoid Race; Child; Childhood; DNA; Data; Development; Disease; Environment; Equilibrium; Event; Exhibits; Exposure to; General Population; Genes; Genetic Polymorphism; Genotype; Hyperactive behavior; Life; Long-Term Effects; Longitudinal Studies; Manuscripts; Mental Depression; Monoamine Oxidase A; Mothers; Parents; Patient Self-Report; Pregnancy; Preventive Intervention; Psychopathology; Publications; Questionnaires; Recruitment Activity; Research; Risk; Risk Factors; Sampling; Stress; Subgroup; Time; Writing; aged; anti social; boys; cohort; experience; externalizing behavior; gene environment interaction; girls; maltreatment; maternal depression; resilience; serotonin transporter; sex; stressor; teacher

Childhood adversity often pre-dates externalizing behaviors such as antisocial behavior and internalizing behaviors such as depression, both of which are risk factors for problem drinking and alcoholism. We have used data derived from parental and teacher self-report questionnaires in a birth cohort of approximately 7000 Caucasian girls and boys from the Avon Longitudinal Study of Parents and Children (ALSPAC), U.K. Mothers were recruited in early pregnancy and data is available on their children up to age 8 years. We have genotyped the children's DNA for functional polymorphisms in three genes: monoamine oxidase A (MAOA-LPR), serotonin transporter (5-HTTLPR) and catechol-O-methyltransferase (COMT Val158Met). We have found that in both sexes: (a) the maximum impact of nearly all stressors was at ages 0 to 2 years; (b) stress soon after birth predicted antisocial behavior (conduct disturbances, hyperactivity and ADHD) detectable as early as age 4 and persisting until at least age 8 years; (c) maternal anxiety / depression had the greatest influence (d) stressful life events experienced during the same time frame has the same, although less powerful, influence; (e) There was an interaction between MAOA-LPR and life events on behavior, particularly hyperactivity, in both sexes, with the effects strongest in girls. Our results have shown that mild stressors can have long-term effects on behavior predictive of adult psychopathology. Maternal psychopathology is the most important negative influence on young childrens behavior in the general population. Timing is important: exposure to adversity soon after birth has a maximal effect therefore early preventive intervention is critical. MAOA-LPR genotype influences the risk-resilience balance in the general population and not only in subgroups exposed to severe maltreatment. Our studies have also shown that maternal depression and stressful life events were associated with increased emotionality in children aged 6 to 7 years. There was an interaction between stressful life events and 5-HTTLPR genotype in girls: those girls with low and intermediate expression of the serotonin transporter exhibited increased emotionality when exposed to stress whereas the girls with high expression genotypes were resilient to the effects of stress. There was no main or interactive effect of COMT genotype on childhood emotionality. The results of the studies described above have been written up in three manuscripts that have been submitted for publication.

童年的逆境往往早于反社会行为等外化行为和抑郁等内化行为，这两种行为都是饮酒问题和酗酒的危险因素。我们使用了来自父母和教师自我报告问卷的数据，这些数据来自英国雅芳父母和儿童纵向研究（ALSPAC）中大约7000名白人女孩和男孩的出生队列，这些母亲在怀孕早期被招募，他们的孩子直到8岁。我们对儿童DNA进行了三个基因的功能多态性基因分型：单胺氧化酶A (MAOA-LPR)， 5-羟色胺转运蛋白（5-HTTLPR）和儿茶酚- o -甲基转移酶（COMT Val158Met）。