White matter microstructural recovery with abstinence and decline with relapse in alcohol dependence interacts with normal ageing: a controlled longitudinal DTI study
Open accessAbstract
Background Alcohol dependence exacts a toll on brain white matter microstructure, which has the potential of repair with prolonged sobriety. Diffusion tensor imaging (DTI) enables in-vivo quantification of tissue constituents and localisation of tracts potentially affected in alcohol dependence and its recovery. We did an extended longitudinal study of alcoholism's trajectory of effect on selective fibre bundles with sustained sobriety or decline with relapse.Methods Participants were drawn from a longitudinal, 1·5T DTI database of 841 scans of individuals with various medical or neuropsychiatric conditions and normal ageing. Participants diagnosed with alcohol dependence had to meet the criteria from DSM-IV for alcohol dependence. Controls were screened and free of any DSM-IV axis I diagnosis, including being without history of alcohol or drug abuse or dependence. Tract-based spatial statistics (TBSS) quantified white matter integrity throughout the brain in 47 alcohol-dependent individuals and 56 controls examined 2-5 times over 1-8 year intervals. We identified regions showing group differences with a white matter atlas. For macrostructural comparison, we measured corpus callosum and centrum semiovale volumes on MRI.Findings This study took place in the USA, between June 23, 2000, and Sept 6, 2011. TBSS identified a large cluster (threshold p<0·001), where controls showed significant fractional anisotropy (FA) decrease with ageing and alcohol-dependent individuals had significantly lower FA than controls regardless of age. Over the examination interval, 27 (57%) alcohol-dependent individuals abstained, ten (21%) relapsed into light drinking, and ten (21%) relapsed into heavy drinking (>5 kg of alcohol/year). Despite abnormally low FA, age trajectories of the abstainers were positive and progressing toward normality, whereas those of the relapsers and controls were negative. Axial diffusivity (lower values indexing myelin integrity) was abnormally high in the total alcohol-dependent group; however, the abstainers' slopes paralleled those of controls, whereas the heavy-drinking relapsers' slopes showed accelerated ageing. Callosal genu and body microstructure but not macrostructure showed untoward alcohol-related effects. Affected projection and association tracts had an anterior and superior neuroanatomical distribution.Interpretation Return to heavy drinking resulted in accelerating microstructural white matter damage. Despite evidence for damage, alcohol-dependent individuals maintaining sobriety over extended periods showed improvement in brain fibre tract integrity reflective of fibre reorganisation and myelin restoration, indicative of a neural mechanism explaining recovery.Funding US National Institute on Alcohol Abuse and Alcoholism (AA012388, AA017168, AA005965, AA013521-INIA).
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Following prolonged abstinence, alcohol or opiate users can show white matter microstructure that is not significantly different from nonusers.
“Following prolonged abstinence, abusers of alcohol (Pfefferbaum et al., 2014) or opiates (Wang et al., 2011) have white matter microstructure that is not significantly different from nonusers.”
From Substance abuse and white matter: Findings, limitations, and future of diffusion tensor imaging research (2019) · cites this paper as Pfefferbaum et al., 2014
Alcohol abuse is associated with higher axial diffusivity in alcohol-abusing groups.
“alcohol was associated with higher AD in alcohol abusing groups (Pfefferbaum et al., 2014; Topiwala et al., 2017).”
From Substance abuse and white matter: Findings, limitations, and future of diffusion tensor imaging research (2019) · cites this paper as Pfefferbaum et al., 2014
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
SMITH, S., & NICHOLS, T. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2008.03.061 · Cited by 5,250 · see citing works
Structured Clinical Interview for DSM-IV Axis I Disorders
Spitzer, R. L., First, M. B., & Gibbon, M. (1997) · Medical Entomology and Zoology · Cited by 3,582 · see citing works
Demyelination increases radial diffusivity in corpus callosum of mouse brain
Song, S.-K., Yoshino, J., Le, T. Q., Lin, S.-J., Sun, S.-W., Cross, A. H., & Armstrong, R. C. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.01.028 · Cited by 1,658 · see citing works
The cerebral cortex is damaged in chronic alcoholics
Kril, J. J., Halliday, G. M., Svoboda, M. D., & Cartwright, H. (1997) · Neuroscience · doi:10.1016/s0306-4522(97)00083-3 · Cited by 501 · see citing works
The SRI24 multichannel atlas of normal adult human brain structure
Torsten Rohlfing, B., Zahr, N. M., Sullivan, E. V., & Pfefferbaum, A. (2009) · Human Brain Mapping · doi:10.1002/hbm.20906 · Cited by 477 · see citing works
Self-citationPfefferbaum, A., Sullivan, E. V., Mathalon, D. H., Shear, P. K., Rosenbloom, M. J., & Lim, K. O. (1995) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1995.tb01598.x · Cited by 420 · see citing works
Self-citationHuman alcohol-related neuropathology
de la Monte, S. M., & Kril, J. J. (2014) · Acta Neuropathologica · doi:10.1007/s00401-013-1233-3 · Cited by 416 · see citing works
Pfefferbaum, A., Sullivan, E. V., Rosenbloom, M. J., Mathalon, D. H., & Lim, K. O. (1998) · Archives of General Psychiatry · doi:10.1001/archpsyc.55.10.905 · Cited by 396 · see citing works
Self-citationGene Expression in Human Alcoholism: Microarray Analysis of Frontal Cortex
Lewohl, J. M., Wang, L., Miles, M. F., Zhang, L., Dodd, P. R., & Harris, R. A. (2000) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2000.tb01993.x · Cited by 379 · see citing works
Patterns of gene expression are altered in the frontal and motor cortices of human alcoholics
Mayfield, R. D., Lewohl, J. M., Dodd, P. R., Herlihy, A. H., Liu, J., & Harris, R. A. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00860.x · Cited by 312 · see citing works
Liu, J., Lewohl, J. M., Harris, R. A., Iyer, V. R., Dodd, P. R., Randall, P. K., & Mayfield, R. D. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300947 · Cited by 254 · see citing works
Deformation-based morphometry of brain changes in alcohol dependence and abstinence
Cardenas, V. A., Studholme, C., Gazdzinski, S. P., Durazzo, T. C., & Meyerhoff, D. J. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2006.10.015 · Cited by 237 · see citing works
Pfefferbaum, A., Rosenbloom, M. J., Torsten Rohlfing, B., & Sullivan, E. V. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.10.039 · Cited by 220 · see citing works
Self-citationMicrostructural but Not Macrostructural Disruption of White Matter in Women with Chronic Alcoholism
Pfefferbaum, A., & Sullivan, E. V. (2002) · NeuroImage · doi:10.1006/nimg.2001.1018 · Cited by 220 · see citing works
Self-citationHarper, C. G., Dixon, G., Sheedy, D. L., & Garrick, T. M. (2003) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(03)00155-6 · Cited by 209 · see citing works
Factors underlying prefrontal and insula structural alterations in smokers
Zhang, X., Salmeron, B. J., Ross, T. J., Geng, X., Yang, Y., & Stein, E. A. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2010.08.008 · Cited by 188 · see citing works
White matter volume in alcohol use disorders: a meta‐analysis
Monnig, M. A., Tonigan, J. S., Yeo, R. A., Thoma, R. J., & McCrady, B. S. (2013) · Addiction Biology · doi:10.1111/j.1369-1600.2012.00441.x · Cited by 114 · see citing works
Is there remyelination during aging of the primate central nervous system?
Peters, A., & Sethares, C. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10639 · Cited by 112 · see citing works
Cerebral white matter recovery in abstinent alcoholics—a multimodality magnetic resonance study
Gazdzinski, S. P., Durazzo, T. C., Mon, A., Yeh, P., & Meyerhoff, D. J. (2010) · Brain · doi:10.1093/brain/awp343 · Cited by 100 · see citing works
Cigarette smoking and white matter microstructure
Hudkins, M., O’Neill, J., Tobias, M. C., Bartzokis, G., & London, E. D. (2012) · Psychopharmacology · doi:10.1007/s00213-011-2621-9 · Cited by 95 · see citing works
Rapid Partial Regeneration of Brain Volume During the First 14 Days of Abstinence from Alcohol
van Eijk, J., Demirakça, T., Frischknecht, U., Hermann, D., Mann, K. F., & Ende, G. (2012) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2012.01853.x · Cited by 86 · see citing works
Segobin, S. H., Chételat, G., Berre, A. L., Lannuzel, C., Boudehent, C., Vabret, F., Eustache, F., Beaunieux, H., & Pitel, A. (2014) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.12300 · Cited by 81 · see citing works
Pfefferbaum, A., Rosenbloom, M. J., Fama, R., Sassoon, S. A., & Sullivan, E. V. (2010) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2010.01197.x · Cited by 75 · see citing works
Self-citationAlhassoon, O. M., Sorg, S. F., Taylor, M. J., Stephan, R. A., Schweinsburg, B. C., Stricker, N. H., Gongvatana, A., & Grant, I. (2012) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2012.01808.x · Cited by 70 · see citing works
Drinking History Associations with Regional White Matter Volumes in Alcoholic Men and Women
Ruiz, S. M., Oscar‐Berman, M., Sawyer, K. S., Valmas, M. M., Urban, T., & Harris, G. J. (2012) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2012.01862.x · Cited by 68 · see citing works
THE EFFECTS OF ALCOHOL ON THE FEMALE BRAIN: A NEUROPATHOLOGICAL STUDY
Harper, C., SMITH, N. A., & Kril, J. J. (1990) · Alcohol and Alcoholism · doi:10.1093/oxfordjournals.alcalc.a045035 · Cited by 62 · see citing works
Bagga, D., Sharma, A., Kumari, A., Kaur, P., Bhattacharya, D., Garg, M. L., Khushu, S., & Singh, N. (2013) · Alcohol · doi:10.1016/j.alcohol.2013.10.009 · Cited by 48 · see citing works
Morphological changes in the corpus callosum in chronic alcoholism.
Tarnowska-Dziduszko, E., Bertrand, E., & Szpak, G. M. (1995) · PubMed · Cited by 42 · see citing works
Differential protein expression in the corpus callosum (genu) of human alcoholics
Kashem, M. A., Harper, C. G., & Matsumoto, I. (2008) · Neurochemistry International · doi:10.1016/j.neuint.2008.04.003 · Cited by 37 · see citing works
Restoring the balance between disease and repair in multiple sclerosis: insights from mouse models
Miller, R. H., & Fyffe-Maricich, S. L. (2010) · Disease Models & Mechanisms · doi:10.1242/dmm.001958 · Cited by 26 · see citing works
Remodeling of neuronal dendritic networks with aging and alcohol.
Pentney, R. J. (1991) · PubMed · Cited by 13 · see citing works
(1877) · The Lancet · doi:10.1016/s0140-6736(02)48232-3 · Cited by 2 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [26]Mori S Wakana S Nagae-Poetscher LM Van Zijl PMC An Atlas of Human White Matter 2005 Elsevier B.V. Amsterdam, the Netherlands
Cited by
Sorted by citations
Koch, M., Fitzpatrick, A. L., Rapp, S. R., Nahin, R. L., Williamson, J. D., Lopez, O. L., DeKosky, S. T., Kuller, L. H., Mackey, R. H., Mukamal, K. J., et al. (2019) · JAMA Network Open · doi:10.1001/jamanetworkopen.2019.10319 · Cited by 218 · see citing works
Burzynska, A. Z., Jiao, Y., Knecht, A. M., Fanning, J., Awick, E. A., Chen, T., Gothe, N., Voss, M. W., McAuley, E., & Kramer, A. F. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00059 · Cited by 150 · see citing works
Hampton, W. H., Hanik, I. M., & Olson, I. R. (2019) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2019.02.005 · Cited by 95 · see citing works
Henriques, J. F., Portugal, C. C., Canedo, T., Relvas, J. B., Summavielle, T., & Socodato, R. (2018) · Toxicology Letters · doi:10.1016/j.toxlet.2017.11.002 · Cited by 89 · see citing works
Longitudinal self-supervised learning
Zhao, Q., Liu, Z., Adeli, E., & Pohl, K. M. (2021) · Medical Image Analysis · doi:10.1016/j.media.2021.102051 · Cited by 71 · see citing works
Self-citationZhao, Q., Sullivan, E. V., Honnorat, N., Adeli, E., Podhajsky, S., De Bellis, M. D., Voyvodic, J., Nooner, K. B., Baker, F. C., Colrain, I. M., et al. (2021) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2020.4064 · Cited by 50 · see citing works
Self-citationImaging resilience and recovery in alcohol dependence
Charlet, K., Rosenthal, A., Lohoff, F. W., Heinz, A., & Beck, A. (2018) · Addiction · doi:10.1111/add.14259 · Cited by 29 · see citing works
- Authors
- Pfefferbaum, A., Rosenbloom, M. J., Chu, W., Sassoon, S. A., Rohlfing, T., Pohl, K. M., Zahr, N. M., & Sullivan, E. V.
- Affiliations
- SRI International (US)
- Stanford Medicine (US)
- Corresponding author
- Sullivan, Edith V
- Venue
- The Lancet Psychiatry
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 1
- Issue
- 3
- Pages
- 202-212
- ISSN
- 2215-0366 (ISSN-L)
- PMC
- PMC4750405
- OpenAlex
- W2133157289
- Cited by
- 115
- References
- 32
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 5 · 2023: 7 · 2022: 11 · 2021: 18 · 2020: 15 · 2019: 14 · 2018: 6 · 2017: 13 · 2016: 7 · 2015: 6 · 2014: 1
- FWCI
- 7.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Lancet Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- US National Institute on Alcohol Abuse and Alcoholism (AA012388, AA017168, AA005965, AA013521-INIA)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Neurology › Alcoholism and Thiamine Deficiency
- Keywords
- alcoholism, white matter microstructure, abstinence, relapse, aging, fractional anisotropy, axial diffusivity, corpus callosum, centrum semiovale, tract-based spatial statistics, heavy drinking, myelin integrity
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
