Reduced glial and neuronal packing density in the orbitofrontal cortex in alcohol dependence and its relationship with suicide and duration of alcohol dependence

Background: 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. Methods: 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. Results: 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. Conclusions: 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.