Cerebral Structural And Metabolic Correlates Of Aggressive Or Addictive Behavior

我们收集了完整的，体积的T-1加权磁共振图像，使用1.5 T扫描仪测量颅内体积350酗酒者（248名男性和112名女性）和163名健康，非酒精对照组（82名男性和81名女性）。使用自动分割程序将颅内内容物分为CSF、灰质和白色物质（Human Brain Mapping，5：194-205，1997）。当我们测量大脑体积时，我们测量的是两个过程的综合效果：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，并且由于ICV在整个生命过程中保持恒定，因此脑退化可以通过脑体积或灰质或白色物质体积与颅内内容物的剩余部分的比率来测量。酗酒者比不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更容易受到影响。酗酒者在20多岁到30多岁的时候，大脑萎缩的程度也比对照组大得多。此外，酗酒者的颅内体积比对照组小，这表明发病前大脑大小的差异可能会导致酗酒的风险。尽管大脑颅内容量存在显著差异，但与大脑生长相比，变性对酗酒者和对照组之间的脑容量差异有更大的影响。同样，是否存在共病精神障碍或其他物质滥用不会影响酗酒者的大脑萎缩。在过去的几年里，我们在自动测量脑容量方面取得了一些方法上的进步。开发并验证了一种将大脑分为左右半球的自动化方法。此外，我们还开发了一种自动化的方法来测量内侧和眶额叶皮质的体积，以及整个纹状体。 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。 有酗酒风险的儿童和青少年的纹状体（包括脑髓核）似乎比没有酗酒风险的儿童要小得多。 此外，我们还研究了酗酒家族史（FH）如何影响早发性和晚发性酗酒者的脑萎缩（通过脑体积与颅内体积的比值测量）以及最大脑生长（通过ICV测量）。FH阳性酒精中毒患者的ICV明显小于FH阴性患者，这表明父亲或母亲酗酒的酒精中毒患者发病前脑生长较小。脑萎缩不受FH的影响。晚发性酗酒者FH阳性和FH阴性患者的ICV比早发性酗酒者的差异更大。晚发型FH阳性患者的IQ评分也显著低于晚发型FH阴性患者，且IQ评分与ICV相关。 这些数据提供的证据表明，父母大量饮酒可能会增加后代酗酒的风险，部分原因是遗传和/或环境影响导致大脑发育减少。 我们还开始了对酗酒者和对照组额叶体积的具体调查。 酗酒者的额叶体积似乎比对照组小。 这种额叶体积的减少仅限于右额叶的侧面，并且继发于更大的脑萎缩，而不是在大量饮酒开始之前脑生长的差异。 我们还发现，在健康受试者中，延迟奖励（延迟折扣）被认为是衡量冲动性的一个很好的实验室指标，其贬值趋势与额叶侧面的萎缩有关。 在功能成像中，外侧额叶与延迟折扣任务中被激活的区域相同。因此，我们的研究结果与人类冲动性的功能神经解剖学是一致的，并且可能对理解与药物滥用发展风险相关的大脑差异很重要。

We have 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 few years 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. We have also begun specific investigations of frontal lobe volume in alcoholics and controls. Alcoholics appear to have smaller frontal lobe volumes than controls. This reduction in frontal volume is restricted to the lateral surface of the right frontal lobe and is secondary to greater brain shrinkage and not to differences in brain growth prior to the onset of heavy drinking. We have also found that among healthy subjects that the tendency to devalue delayed rewards (delay discounting), which is considered an excellent laboratory measure of impulsivity, is associated with shrinkage of the lateral surface of the frontal lobes. The lateral frontal lobe is the same region that has been shown to be activated during delayed discounting tasks during functional imaging. Thus our results are consistent with the functional neuroanatomy of human impulsivity and may be important in understanding brain differences associated with risk for the development of substance abuse.