the effect of alcohol on the hippocampus. The hippocampus is
the area with the greatest increase in lipofuscin deposition in
neurons as a result of chronic alcohol consumption.
the fatty acid ethyl esters produced in the brain from ethanol
are known to be particularly damaging to the hippocampus.
Our data are further consistent with the previous findings on
involvement of frontal cortical areas in the brain of patients
with alcohol addiction. Numerous neuropsychological studies
demonstrated substantial deficits in frontal executive functions
in patients with alcohol dependence.
Our results suggest
substantial volume reduction in the middle frontal gyrus and
precentral gyrus, although no changes were detected in other
frontal regions. These findings support previous reports on
decreased glucose metabolic rates in middle frontal regions in
patients with alcohol addiction
and a reduction of c
aminobutyric acid A/benzodiazepine receptors in superior
medial parts of the frontal lobes.
A significant decrease in WM volumes in the pons and
cerebellum in the our study is consistent with the previous results
that have shown the alcohol-associated degeneration of pontine
and cerebellar WM in patients with alcohol addiction,
whereas in healthy subjects these regions have been shown to
remain stable across the entire age span in both men and
The significant decrease in periventricular WM found in
our study is also consistent with previous data; however, the
analysis and interpretation of these changes in VBM studies is
difficult because of the possible bias due to partial volume effects.
Even low-to-moderate consumption of alcohol was associated
with brain atrophy in a study of middle-aged men.
increase the release of arachidonic acid from cell membranes and
cause oxidative stress in the brain by increased cyclo-oxygenase
activity. Furthermore, hydroxyethyl free radicals derived directly
from ethanol are nearly as damaging as hydroxyl radicals.
is also evidence from animal studies that alcohol causes cell
death. Rats fed a liquid diet containing moderate amounts of
ethanol for 6 weeks had a 66.3% decrease in the number of new
neurons and a 227–279% increase in cell death in the dentate
gyrus as compared with rats fed an alcohol-free diet.
In general, our data support the previous assumption that the
regional reduction of GM volumes may result from alcohol-
induced neuronal loss, whereas global brain shrinkage might be
caused by loss of WM.
Furthermore, our results support
previous findings on alteration of selected regions of the frontal
cortex and cerebellum in patients with alcohol addiction and
suggest the involvement of the anterior thalamus, posterior
hippocampus, insular cortex and periventricular WM in
alcohol-associated brain damage. A causal relationship between
alcohol consumption and regional brain atrophy still demands
further research, whereas VBM seems to represent a tool of
choice for in vivo detection of the brain areas predisposed to
Sergei Mechtcheriakov, Josef Marksteiner, Department of General
Psychiatry, Medical University Innsbruck, Innsbruck, Austria
Christian Brenneis, Department of Neurology, Medical University
Innsbruck, Innsbruck, Austria
Karl Egger, Michael Schocke, Department of Radiology I, Medical
University Innsbruck, Innsbruck, Austria
Florian Koppelstaetter, Department of Radiology II, Medical University
Competing interests: None declared.
1 Harper C. The neuropathology of alcohol-specific brain damage, or does alcohol
damage the brain? J Neuropathol Exp Neurol 1998;57:101–10.
2 Pfefferbaum A, Rosenbloom M, Deshmukh A, et al. Sex differences in the effects
of alcohol on brain structure. Am J Psychiatry 2001;158:188–97.
3 Pfefferbaum A, Sullivan EV, Mathalon DH, et al. Frontal lobe volume loss
observed with magnetic resonance imaging in older chronic alcoholics. Alcohol
Clin Exp Res 1997;21:521–9.
4 Visser PJ, Krabbendam L, Verhey FR, et al. Brain correlates of memory dysfunction in
alcoholic Korsakoff’s syndrome. J Neurol Neurosurg Psychiatry 1999;67:774–8.
5 Ding J, Eigenbrodt ML, Mosley TH Jr, et al. Alcohol intake and cerebral
abnormalities on magnetic resonance imaging in a community-based population
of middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study.
6 Moselhy HF, Georgiou G, Kahn A. Frontal lobe changes in alcoholism: a review
of the literature. Alcohol Alcohol 2001;36:357–68.
7 Sullivan EV, Pfefferbaum A. Magnetic resonance relaxometry reveals central
pontine abnormalities in clinically asymptomatic alcoholic men. Alcohol Clin Exp
8 Kril JJ, Halliday GM. Brain shrinkage in alcoholics: a decade on and what have
we learned? Prog Neurobiol 1999;58:381–7.
9 Cullen KM, Halliday GM, Caine D, et al. The nucleus basalis (Ch4) in the
alcoholic Wernicke-Korsakoff syndrome: reduced cell number in both amnesic
and non-amnesic patients. J Neurol Neurosurg Psychiatry 1997;63:315–20.
10 Harding A, Halliday G, Caine D, et al. Degeneration of anterior thalamic nuclei
differentiates alcoholics with amnesia. Brain 2000;123(Pt 1):141–54.
11 Harding AJ, Wong A, Svoboda M, et al. Chronic alcohol consumption does not
cause hippocampal neuron loss in humans. Hippocampus 1997;7:78–87.
12 Mann K, Widmann U. The neurobiology of alcoholism. Neuropathology and
CT/NMR findings. Fortschr Neurol Psychiatr 1995;63:238–47.
13 Bloomer CW, Langleben DD, Meyerhoff DJ. Magnetic resonance detects brainstem
changes in chronic, active heavy drinkers. Psychiatry Res 2004;132:209–18.
14 Ashburner J, Friston KJ. Voxel-based morphometry—the methods. Neuroimage
15 Kubicki M, Shenton ME, Salisbury DF, et al. Voxel-based morphometric analysis
of gray matter in first episode schizophrenia. Neuroimage 2002;17:1711–19.
16 Abell F, Krams M, Ashburner J, et al. The neuroanatomy of autism: a voxel-
based whole brain analysis of structural scans. Neuroreport 1999;10:1647–51.
17 Karas GB, Scheltens P, Rombouts SA, et al. Global and local gray matter loss in
mild cognitive impairment and Alzheimer’s disease. Neuroimage
18 Brenneis C, Wenning GK, Egger KE, et al. Basal forebrain atrophy is a distinctive
pattern in dementia with Lewy bodies. Neuroreport 2004;15:1711–14.
19 Caine D, Halliday GM, Kril JJ, et al. Operational criteria for the classification of
chronic alcoholics: identification of Wernicke’s encephalopathy. J Neurol
Neurosurg Psychiatry 1997;62:51–60.
20 Good CD, Johnsrude IS, Ashburner J, et al. A voxel-based morphometric study of
ageing in 465 normal adult human brains. Neuroimage 2001;14:21–36.
21 George MS, Anton RF, Bloomer C, et al. Activation of prefrontal cortex and
anterior thalamus in alcoholic subjects on exposure to alcohol-specific cues. Arch
Gen Psychiatry 2001;58:345–52.
Table 2 Reduced white matter volumes in patients with alcohol addiction: anatomical
locations, Brodmann areas, z scores and p values (false discovery rate corrected for multiple
comparisons across the entire volume)
Peak coordinates (mm)
z Value p Valuexy z
Pons 2 235 248 5.11 ,0.001
Right 6 57 27 34 6.21 ,0.001
Left 6 257 211 31 5.13 ,0.001
BA, Brodmann areas; MNI, Montreal Neurological Institute.
Peak coordinates are given in MNI space (http://www.bic.mni.mcgill.ca).
Patterns of cerebral atrophy in alcohol addiction 613