Comparison of prefrontal cell pathology between depression and alcohol dependence

Abstract

Chronic alcohol abuse is often co-morbid with depression symptoms and in many cases it appears to induce major depressive disorder. Structural and functional neuroimaging has provided evidence supporting some degree of neuropathological convergence of alcoholism and mood disorders. In order to understand the cellular neuropathology of alcohol dependence and mood disorders, postmortem morphometric studies have tested the possibility of alterations in the number and size of cells in the prefrontal cortex and other brain regions. The present review compares the cell pathology in the prefrontal cortex between alcohol dependence and depression, and reveals both similarities and differences. One of the most striking similarities is that, although pathology affects both neuronal and glial cells, effects on glia are more dramatic than on neurons in both alcohol dependence comorbid with depression and idiopathic depression. Moreover, prefrontal cortical regions are commonly affected in both depression and alcoholism. However, the cellular changes are more prominent and spread across cortical layers in alcohol dependent subjects than in subjects with mood disorders, and changes in glial nucleus size are opposite in alcoholism and depression. It could be argued that one defining factor in the manifestation of the depressive pathology is a reduction in the glial distribution in the dlPFC that is reflected in a reduced glial density. In alcoholism reduced glial nuclear size might be related to the cytotoxic effects of prolonged alcohol exposure, while in MDD, in the absence of alcohol abuse, other processes might be responsible for the increase in average size of glial nuclei. In either case abnormal function related to glial reduction would be associated with depression due to insufficient glial support to the surrounding neurons.

Fig. 1

High power micrograph of neurons and glial cells as they appear in the cortical layers of area 9 in coronal section through the prefrontal cortex stained with cresyl violet. Note that both the nucleus and cytoplasm are visible in neurons, while only the nucleus is visible in glial cells. The inset at the bottom right is a low power image of the cresyl violet-stained section containing the spot (black rectangle in area 9) where the high power micrograph was taken. High power: 40× objective; low power: 2× objective.

Fig. 2

Plots showing the distribution of individual values for packing density of glial cells in all layers combined of the dorsolateral prefrontal cortex in the four diagnostic groups of subjects: non-psychiatric controls (CONTROL), alcohol-dependent without depression (ALC. NON-DEPR), alcohol-dependent with depression (ALC. DEPR.), and subjects with major depressive disorder (MAJOR DEPR. DIS.). A horizontal bar indicates the median value. Note that a significant reduction in glial density is found in all three groups of patients as compared with the control group (ANOVA F=4.57, P<0.006) however, the most prominent reductions (P<0.006) are found in the group of subjects with comorbid alcohol dependence and depression. For further details see (Miguel-Hidalgo et al., 2002).

Fig. 3

Graph comparing the average size of glial cell nuclei in cortical layer III of the dorsolateral prefrontal cortex in the four diagnostic groups of subjects: non-psychiatric controls (CONTROL), alcohol-dependent without depression (ALC. NON-DEPR), alcohol-dependent with depression (ALC. DEPr.), and subjects with major depressive disorder (MAJORDEPR. DIS.). Error bars represent the standard error of the mean. Note that glial nuclei are larger in the group of subjects with major depressive disorder as compared to the group of alcohol-dependent without depression and alcohol dependent with depression. For further details see (Miguel-Hidalgo et al., 2002).