Early Stress, Sensitive Periods and the Neurobiology of Addiction

早期压力、敏感期和成瘾的神经生物学

• 批准号: 8449186
• 负责人: MARTIN H TEICHER
• 金额: $ 70.43万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-15 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8449186
• 关键词: 19 year old; 21 year old; Accounting; Affect; Age; Alcohol consumption; Alcohol or Other Drugs use; Alcohols; Anger; Anterior; Blood; Blood Volume; Brain; Brain region; Cerebellar vermis structure; Cerebellum; Cerebrum; Child; Child Abuse and Neglect; Childhood; Cross-Sectional Studies; Data Set; Development; Dopamine; Drug Addiction; Drug Exposure; Drug abuse; Drug usage; Drug user; Emotional; Evaluation; Exposure to; Funding; Goals; Hostility; Image; Individual; Light; Lingula (genus); Link; Lobule; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mental Depression; Neurobiology; Neurosciences; Parents; Pathway interactions; Pattern; Pharmaceutical Preparations; Population Attributable Risks; Post-Traumatic Stress Disorders; Prefrontal Cortex; Prevention; Prospective Studies; Punishment; Recovery; Recruitment Activity; Relative (related person); Relaxation; Reporting; Risk; Risk Factors; Sampling; Series; Sexual abuse; Siblings; Stress; Substance Addiction; Substance abuse problem; Symptoms; Testing; Time; addiction; base; cingulate cortex; design; dopamine system; emotional abuse; emotional neglect; experience; high risk; innovation; insight; maltreatment; novel; peer; physical abuse; physical neglect; preempt; prevent; programs; prospective; sensory system; young adult

DESCRIPTION (provided by applicant): Childhood maltreatment (i.e., physical, sexual or emotional abuse by parents, peers or siblings, physical and emotional neglect) has an enormous impact on risk for substance abuse and dependence. The Adverse Childhood Experience Study reported that exposure to maltreatment-related adversity accounted for 64% of the population attributable risk for substance abuse. Understanding this association may be crucial to our efforts to prevent, preempt or treat drug abuse. During the previous funding period we conducted a series of studies to better understand the association between childhood maltreatment and substance use. We found in cross-sectional studies that exposure to physical maltreatment was a more significant risk factor for high levels of drug and alcohol use than emotional maltreatment, and that physical maltreatment (but not emotional maltreatment) was associated with marked alterations in T2-relaxation time (an indirect measures of cerebral blood volume assessed by MRI) in major components of the ascending dopamine system. T2-relaxation time in two components (dorsolateral prefrontal and anterior cingulate cortex) correlated with degree of drug and alcohol use. Further we found a strong statistical relationship between the size of the first lobule (lingula) of the cerebellar vermis in physically maltreated subjects and degree of substance use. We also found that substance use by maltreated individuals spiked at 20-21 years of age. The key aims of the proposed study are to test in a prospective study whether T2-relaxation time in dorsolateral prefrontal and anterior cingulate cortex, and large lingula size can predict degree of drug and alcohol use by maltreated individuals. Moreover, we will test the hypothesis that type and timing of exposure to maltreatment matters, and that there are sensitive periods when exposure to specific types of maltreatment are most likely to effect the development of these brain regions¿ and to increase risk for drug abuse. This information will shed new light on our understanding of the relationship between maltreatment and drug abuse by examining the phenomenon from a developmental neuroscience perspective. These studies may provide the critical insights necessary to design programs to protect children during their most vulnerable periods, and to develop preemptive strategies to aid exposed individuals before their vulnerability becomes manifest.

描述（应用程序提供）：儿童虐待（即，父母，同龄人或兄弟姐妹的身体，性或情感虐待，身体和情感负面的虐待）对滥用药物和依赖的风险有增强的影响。不利的儿童经验研究报告说，与虐待相关的广告的接触占毒品滥用毒品的64％。了解这种关联可能对我们预防，抢先或治疗药物滥用的努力至关重要。在上一个资金期间，我们进行了一系列研究，以更好地了解儿童虐待与使用物质之间的关联。 We found in cross-sectional studies that exposure to physical maltreatment was a more significant risk factor for high levels of drug and alcohol use than emotional maltreatment, and that physical maltreatment (but not emotional maltreatment) was associated with marked alterations in T2-relaxation time (an indirect measurements of cerebral blood volume assessed by MRI) in major components of the ascending dopamine system. T2 - 释放时间在两个组成部分（形成前额叶和前扣带回皮层）中与药物和酒精的使用程度相关。此外，我们发现小脑vermis的第一个小叶（Lingula）的大小与物理性虐待受试者的大小（lingula）之间存在很强的统计关系。我们还发现，在20-21岁时，虐待的个体使用虐待的个体使用物质。拟议研究的主要目的是在一项前瞻性研究中测试T2 - 释放时间是否在背侧前额叶和前扣带回皮层中是否可以预测虐待的个体的药物和酒精使用程度。此外，我们将检验以下假设：暴露于虐待事项的类型和时机，并且在暴露于特定类型的虐待类型的敏感时期最有可能影响这些大脑区域的发展并增加药物滥用的风险。这些信息将通过从发展的神经科学的角度检查现象来了解我们对虐待与滥用药物滥用之间关系的理解。这些研究可能会为设计计划在最脆弱的时期设计计划提供必要的关键见解，并制定先发制人的策略，以帮助暴露的人在脆弱性变得明显之前。