This study supports the hypothesis that chronic alcohol abuse affects different parts of the brain. In outpatients with chronic alcoholism lateral ventricles were enlarged more than 30% compared to control subjects. These results are in line with studies showing an enlargement of lateral ventricles of severely dependent alcohol patients compared to their non alcoholic twins [16
]. In the present study, after a period of convalescence a significant regress of about 5% of the ventricular enlargement could be shown. Other authors reported on a regeneration of the ventricular system as well [20
], however, objective of these studies was mainly the third ventricle.
The prefrontal lobe volume in alcohol patients was reduced for more than 10% compared to control subjects. This fits to the results of other studies reporting lesions of the prefrontal brain regions [26
]. Especially in older alcohol patients frontal deficits could be observed in these studies. In contrast to the ventricular enlargement, not even partially regeneration of the prefrontal lobes could be demonstrated after 6 months of convalescence for the present sample.
The results of our study suggest that excessive alcohol drinking causes brain volumetric deficits that could be partially reversible if patients reduce their alcohol consumption or stay abstinent. Probably, in the affected cortical regions the brain regeneration may take a longer time than needed for the ventricular system. However, it is unclear if a complete recovery of the brain damages is possible at all [23
It was shown that long-term abstinent alcoholics still present reduced gray matter density within the amygdala [14
], which may be the result of long-term alcohol abuse or dependence, but may also reflect a pre-existing factor that predisposes to severe alcoholism. Alcohol patients may also have a disposition for brain deficits such as ventricular enlargement or decrease of frontal lobes before beginning with excessive alcohol consumption. This assumption was supported by studies investigating high-risk subjects for alcohol dependence reporting significantly smaller volumes of superior frontal, cingulate and parahippocampal gyri, amygdyla, thalamus and cerebellum compared to matched low-risk subjects [2
Then, these brain deficits would be a possible cause of the disease and on the other hand the disease would deteriorate the brain deficits. Following this explanation, which is supported by the finding that in our study there were no significant correlations between duration of illness and brain structure volumes, it could not be expected that mean volumes of alcohol patients reach the level of control subjects, not even after long periods of abstinence. In contrast other studies could demonstrate an association of early age at first drinking and the extent of decreased gray matter volumes in the cerebellum, brainstem and frontal regions using voxel-based morphometry [11
Comparing baseline to follow-up, lateral ventricle enlargement only decreased in patients with treatment success. One plausible explanation for this finding is, that in patients showing no essential improvement of their drinking behavior and relapsing, chronic toxicity of alcohol on the brain still persists and therefore ventricular regeneration could not be expected. A recent study investigating recovering alcohol patients with deformation tensor morphometry, a new MRI processing method suggested to be more sensitive to focal effects on brain structure, showed significantly faster recovery in the frontal and temporal lobe in abstainers than in light drinkers [9
]. In abstainers compared to relapsing patients significantly greater recovery was observed in temporal lobe, thalamus, brainstem, cerebellum, corpus callosum, anterior cingulated, insula, and subcortical white matter [9
]. This underlines the effect of maintaining sobriety on the recovery of different brain structures and fits to our results, although there are relevant methodological differences between the studies.
Regeneration of the ventricular enlargement could only be observed in patients having not more than one detoxification in their disease course. This finding might be explained by the observation that the ventricular enlargement of subjects with only one detoxification was above average at baseline (T0), suggesting the first alcohol excess might have the strongest negative effect on the ventricular system, especially when the elevated alcohol consumption continues over many years. Patients with multiple detoxifications may have experienced certain periods of previous abstinence and recovery of the brain from alcohol toxic effects before entering the study.
We could observe a significant correlation between alcohol dependent changes of liver function (elevated gamma-GT) as well as blood chemistry (elevated MCV), and brain abnormalities (increased ventricular enlargement). Decreased gamma-GT and MCV at follow-up were associated with recovery of ventricular enlargement. Our findings were supported though the literature, e.g. one study reporting a correlation between lower red blood cell count, hemoglobin level, and hematocrit with higher ventricular volumes in alcoholic men [28
There is much evidence that lateral ventricles are enlarged in certain psychiatric diseases, e.g. schizophrenia [13
]. On this background it amazes that the lateral ventricles of alcohol patients without additional psychiatric ICD-10 diagnosis were increased compared to patients with personality or behavior disorder (ICD-10: F6). This might be a sample artifact. On the other hand persons with small ventricles might dispose to personality or behavior disorders.
The precise neurobiological pathophysiology of the volume recovery during abstinence is not known. Proposed explanations have been rehydration (vasopressin secretion may be suppressed during alcohol intoxication), regeneration (augmented dendritic growth) or changes in perfusion (vascularization) [34
]. The rehydration hypothesis has not been confirmed by the majority of investigators using post-mortem examination. It has been demonstrated that, during high-dose alcohol ingestion and acute withdrawal, there is a significant but transient reduction in perfusion of the brain as shown by single photon emission tomography (SPECT), PET and measures of regional cerebral blood flow using Xenon 133 (133Xe-rCBF) investigations [3
]. This reduction was thought to lead to atrophic brain changes, as it is known for other chronic hypoperfusion states. Therefore increased perfusion after sobriety could be responsible for the volume recovery. However, more recent studies reveal evidence for neuronal and white matter regeneration (glial and neuronal regrowth) in alcohol patients after abstinence [12
], e.g. using additionally proton MR spectroscopy in follow-up investigations and showing elevation of N
-acteyl-aspartate, a neuronal marker, in frontomesial regions and choline, a marker for myeline, in the cerebellum [1
There are some limitations of our study. One shortcoming of this study is the method of MRI-processing. A semi-computerized procedure would have been preferred to the manual delineation using hardcopies and overhead projection. In the latter method, which was used for this study, there are more sources of error probably being responsible for the weak reliability in brain structures that were difficult to delineate such as the amygdala-hippocampus-complex or the third ventricle. Unfortunately the technical requirements for computer supported MRI-processing were not available in this study. Nevertheless, for the analyzed regions the data show sufficient high reliability, comparable to the other cited studies. Another limitation of our study is that we did not evaluate the exactly amount of alcoholic drinks taken during the follow-up period. So, we could not estimate a dose-dependent influence of the target brain structures at follow-up.
However, there are some strengths of our study. We were able to follow a relatively large sample of patients and could perform brain imaging 6–9 months after baseline. There are not many studies available using the region of interest approach investigating large sample sizes during longer time periods. Most studies consist of small sample sizes and short time intervals for rescanning after obtaining sobriety.
In summary, our hypotheses of differences in key brain structures for the disease between alcoholic patients and healthy controls as well as the reversibility of ventricular enlargement after reducing drinking behavior were essentially confirmed. Further follow-up studies might be useful to answer the question if brain damages caused by alcohol abuse are completely reversible. However, such studies should be designed over a period of 10 years or more and because of a high expected rate of relapsing patients and drop-outs they would require a very large sample size at baseline.