Cerebral Structural And Metabolic Correlates Of Aggressi

攻击性的大脑结构和代谢相关性

• 批准号: 7317632
• 负责人: Daniel W Hommer
• 金额: --
• 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/7317632
• 关键词: Cerebral; Structural; Metabolic; Correlates; Aggressi

This research is designed to determine neuroanatomical and neurochemical correlates of addictive and aggressive/impulsive behavior in human subjects. The principal focus of these studies is the measurement and correlation of regional cerebral glucose metabolic activity, using positron emission tomography (PET), brain volumes using magnetic resonance imaging (MRI), cerebrospinal fluid metabolites, and measures of impulsive/aggressive behavior and excessive alcohol consumption. We collected full, volumetric T-1 weighted MR images using a 1.5 T scanner to measure intracranial volumes in 350 alcoholics (248 males and 112 females) and 163 healthy, non-alcoholic comparison subjects (82 males and 81 females). An automated segmentation program was used to divide the intracranial contents into CSF, gray and white matter (Human Brain Mapping, 5:194-205, 1997). When we measure brain volume we are measuring the combined effect of two processes: growth and degeneration. Growth determines maximum brain size achieved during life. Maximal brain growth can be estimated by intracranial volume (ICV) and since ICV remains constant throughout life, brain In additiondegeneration can be measured by the ratio of cerebral volume or gray matter or white matter volume to the remainder of the intracranial contents. Alcoholics show greater brain degeneration than non-alcoholics. Alcoholic women are more affected than alcoholic men. Alcoholics also show significantly greater brain shrinkage than controls by their mid to late twenties. In addition, alcoholics have smaller intracranial volumes than controls suggesting that pre-morbid differences in brain size may contribute to the risk for alcoholism. Despite the significant difference in intracranial volume brain, degeneration accounts for a greater amount of the difference in brain volume between alcoholics and controls than brain growth does. Similarly, presence or absence of co-morbid psychiatric disorder or other substance abuse does not affect brain shrinkage among alcoholics. Over the past year we have made several methodological advances in the automated measurement of brain volumes. An automated method for dividing the brain into right and left hemispheres was developed and validated. In addition, we have developed an automated method for measuring the volume of mesial and orbital frontal cortex, as well as the entire striatum. These regions are known to be involved in motivation and social behavior. We have begun to investigate the normal and pathological development of the striatum. It appears that children and adolescents at risk for the development of alcoholism have significantly smaller striatums, including nucleus accumbens, than child not at high risk for the development of alcoholism. In addition, we have also examined how a family history (FH) of heavy drinking affects both brain shrinkage as measured by the ratio of brain volumes to intracranial volume as well as maximal brain growth as measured by ICV in early-onset and late-onset alcoholics. FH positive alcoholic patients have significantly smaller ICVs than FH negative patients, suggesting smaller premorbid brain growth among alcoholics with a heavy drinking motr or father. Brain shrinkage was not affected by FH. Late-onset alcoholics show a greater difference in ICV between FH positive and FH negative patients than early-onset alcoholics. Late-onset FH positive patients also have significantly lower IQ scores than late-onset FH negative patients, and IQ scores are correlated with ICV. These data provide evidence that heavy parental alcohol use may increase risk for alcoholism in offspring in part by a genetic and/or environmental effect resulting in reduced brain growth.

本研究旨在确定人类受试者上瘾和攻击/冲动行为的神经解剖学和神经化学相关性。这些研究的主要焦点是区域脑葡萄糖代谢活动的测量和相关性，使用正电子发射断层扫描（PET），使用磁共振成像（MRI）的脑容量，脑脊液代谢物，以及冲动/攻击行为和过度饮酒的测量。我们使用1.5 T扫描仪收集了350名酗酒者（248名男性和112名女性）和163名健康非酗酒者（82名男性和81名女性）的完整体积T-1加权MR图像，以测量颅内体积。使用自动分割程序将颅内内容物分为脑脊液、灰质和白质（Human Brain Mapping, 5:194- 205,1997）。当我们测量脑容量时，我们测量的是两个过程的综合效应：生长和退化。生长决定了一生中大脑的最大尺寸。最大脑生长可以通过颅内体积（ICV）来估计，由于ICV在一生中保持不变，脑退化可以通过脑体积或灰质或白质体积与颅内剩余内容物的比例来衡量。酗酒者比非酗酒者表现出更严重的大脑退化。酗酒的女性比酗酒的男性受影响更大。在他们二十五六岁的时候，酗酒者的大脑萎缩程度也明显高于对照组。此外，酗酒者的颅内容量比对照组小，这表明发病前大脑大小的差异可能会增加酗酒的风险。尽管脑内容量存在显著差异，但酗酒者和对照组之间脑容量差异的主要原因是脑退化，而不是脑发育。同样，是否存在共病性精神障碍或其他药物滥用并不影响酗酒者的脑萎缩。在过去的一年里，我们在脑容量的自动测量方面取得了一些方法上的进步。一种将大脑分为左右半球的自动方法被开发和验证。此外，我们还开发了一种自动测量内侧和眶额叶皮质以及整个纹状体体积的方法。这些区域被认为与动机和社会行为有关。我们已经开始研究纹状体的正常和病理发育。似乎有酗酒风险的儿童和青少年的纹状体，包括伏隔核，明显小于没有酗酒风险的儿童。