Miguel-Hidalgo Jose J, Overholser James C, Meltzer Herbert Y, Stockmeier Craig A, Rajkowska Grazyna
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
Alcohol Clin Exp Res. 2006 Nov;30(11):1845-55. doi: 10.1111/j.1530-0277.2006.00221.x.
Reduced metabolism, blood flow, and tissue volume have been detected in the dorsolateral prefrontal cortex (dlPFC) of neurologically intact alcoholic subjects and these deficits are accompanied by lower density of neurons and glial cells. Another prefrontal region, the orbitofrontal cortex (ORB), functionally and structurally differentiated from the dlPFC, and heavily involved in decision-making processes, also shows functional alterations in alcoholic subjects. However, it is unknown whether changes in the packing density of neurons or glial cells also occur in the ORB and whether that density may be related to the increased suicide probability of alcoholic subjects or to the duration of alcohol dependence.
The present study used a 3-dimensional cell-counting method in postmortem brain tissue to determine the packing density of neurons and glial cells in the ORB (area 47) of 15 subjects with alcohol dependence (8 suicides, 7 nonsuicides) and 8 normal controls and to determine whether cell density is correlated with suicide and duration of alcohol dependence.
There was a significantly lower density of both neurons (by 27%) and glial cells (by 25%) in the ORB of alcoholic subjects compared with controls. Packing density of either neurons or glial cells was not significantly different in alcoholic suicides compared with alcoholic nonsuicides. Age was not correlated with neuronal or glial density in either group. However, the duration of alcohol dependence and the ratio of that duration to the length of life span were significantly and negatively correlated to the overall density of neurons.
The present results indicate that alcohol dependence is associated with a decrease in the packing density of neurons and glia in the ORB and that the reduction in neuronal but not glial density progresses with the duration of alcohol dependence.
在神经功能正常的酒精依赖者的背外侧前额叶皮质（dlPFC）中，已检测到代谢、血流和组织体积降低，并且这些缺陷伴随着神经元和胶质细胞密度降低。另一个前额叶区域，眶额皮质（ORB），在功能和结构上与dlPFC不同，并且大量参与决策过程，在酒精依赖者中也显示出功能改变。然而，尚不清楚ORB中神经元或胶质细胞的堆积密度是否也会发生变化，以及该密度是否可能与酒精依赖者自杀概率增加或酒精依赖持续时间有关。
本研究采用三维细胞计数法对死后脑组织进行检测，以确定15名酒精依赖者（8例自杀者，7例非自杀者）和8名正常对照者的ORB（47区）中神经元和胶质细胞的堆积密度，并确定细胞密度是否与自杀及酒精依赖持续时间相关。
与对照组相比，酒精依赖者的ORB中神经元密度（降低27%）和胶质细胞密度（降低25%）均显著降低。酒精依赖自杀者与非自杀者相比，神经元或胶质细胞的堆积密度无显著差异。两组中年龄均与神经元或胶质细胞密度无关。然而，酒精依赖持续时间及其与寿命长度的比值与神经元的总体密度显著负相关。
目前的结果表明，酒精依赖与ORB中神经元和胶质细胞的堆积密度降低有关，并且神经元密度的降低而非胶质细胞密度的降低随着酒精依赖持续时间的延长而加重。
