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（由申请人提供）：童年虐待（即父母、同龄人或兄弟姐妹的身体、性或情感虐待，身体和情感忽视）对药物滥用和依赖的风险有巨大影响。不良童年经历研究报告称，64% 的人口归因于药物滥用风险，其中与虐待相关的逆境经历过。了解这种关联对于我们预防、预防或治疗药物滥用的努力可能至关重要。在上一个资助期间，我们进行了一系列研究，以更好地了解儿童虐待与药物滥用之间的关联。我们在横断面研究中发现，与情感虐待相比，身体虐待是导致高水平吸毒和酗酒的更重要的危险因素，并且身体虐待（但不是情感虐待）与上行多巴胺系统主要组成部分的 T2 松弛时间（通过 MRI 评估脑血容量的间接测量）的显着变化相关。两个部分（背外侧前额叶和前扣带皮层）的 T2 松弛时间与药物和酒精使用程度相关。此外，我们发现受到身体虐待的受试者小脑蚓部第一小叶（小舌）的大小与物质使用程度之间存在很强的统计关系。我们还发现，受虐待者的药物使用量在 20 至 21 岁之间激增。拟议研究的主要目的是在前瞻性研究中测试背外侧前额叶和前扣带皮层的 T2 松弛时间以及大舌叶大小是否可以预测受虐待个体的药物和酒精使用程度。此外，我们将检验以下假设：遭受虐待的类型和时间很重要，并且存在敏感时期，在这些敏感时期，遭受特定类型的虐待最有可能影响这些大脑区域的发育，并增加药物滥用的风险。这些信息将从发育神经科学的角度审视这一现象，为我们对虐待和药物滥用之间关系的理解提供新的线索。这些研究可能提供必要的关键见解，以设计在最脆弱时期保护儿童的计划，并制定先发制人的策略，在暴露的个人的脆弱性变得明显之前帮助他们。