Changes of frontal cortical subregion volumes in alcohol dependent individuals during early abstinence: associations with treatment outcome
- 17 Downloads
We previously reported that at 1-and-4 weeks of sobriety, those who relapsed after treatment demonstrated significantly smaller total frontal cortical volume than individuals who maintained abstinence for at least 12 months post treatment. The segmentation method employed did not permit examination of frontal subregions that serve as nodes of the executive, salience and emotional regulation networks; structural abnormalities in these circuits are associated with relapse in those seeking treatment for alcohol use disorders (AUD). The primary goal of this study was to determine if frontal cortical subregion volume recovery during early abstinence is associated with long-term abstinence from alcohol. We compared bilateral components of the dorsal prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex and insula volumes, at 1 and 4 weeks of abstinence, between individuals who resumed drinking within 12 months of treatment (Relapsers) those who showed sustained abstinence over 12 months following treatment (Abstainers) and healthy Controls. At 1 and 4 weeks of sobriety, Relapsers demonstrated significantly smaller volumes than Controls in 15 of 20 regions of interest, while Abstainers only had smaller volumes than Controls in 5 of 20 regions. In Relapsers, increasing volumes over 1 month in multiple frontal subregions and the insula were associated with longer duration of abstinence after treatment. The persistent bilateral frontal and insula volume deficits in Relapsers over 4 weeks from last alcohol use may have implications for neurostimulation methods targeting anterior frontal/insula regions, and represent an endophenotype that differentiates those who respond more favorably to available psychosocial and pharmacological interventions.
KeywordsAlcohol use disorder Brain volumes Relapse Magnetic resonance imaging Neurostimulation
This study was supported by National Institutes of Health (AA10788 to DJM and DA24136 to TCD) and Department of Veterans Affairs (RX002303 to TCD) with resources and use of facilities at the San Francisco VA Medical Center and the VA Palo Alto Health Care System. We thank Dr. Ellen Herbst, Ricky Chen and colleagues of the San Francisco Veterans Administration Substance Abuse Day Hospital and Dr. David Pating and colleagues at the Kaiser Permanente Chemical Dependency Recovery Program in San Francisco for their valuable assistance in participant recruitment. We thank Drs. Stefan Gazdzinski and Anderson Mon for MRI data acquisition, Dr. Xiaowei Zou for longitudinal FreeSurfer data processing, and Mr. Thomas Schmidt for assistance with psychiatric assessments and cohort maintenance. We also extend our gratitude to our participants, who made this research possible.
National Institutes of Health (AA10788 to Dieter J. Meyerhoff and DA24136 to Timothy C. Durazzo) and Department of Veterans Affairs (RX002303 to Timothy C. Durazzo) with resources and use of facilities at the San Francisco VA Medical Center and the VA Palo Alto Health Care System.
Compliance with ethical standards
Conflict of interest
The Authors received funding from the National Institutes and Department of Veterans Affairs. The Authors have no conflicts of interest to report.
All procedures performed in this study involving human participants were in accordance with the ethical standards of institutional review boards of the University of California San Francisco and the San Francisco VA Medical Center and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Written informed consent was obtained from all participants included in the study prior to involvement in any research-related procedures.
- Beck, A., Wustenberg, T., Genauck, A., Wrase, J., Schlagenhauf, F., Smolka, M. N., . . . Heinz, A. (2012). Effect of brain structure, brain function, and brain connectivity on relapse in alcohol-dependent patients. Archives of General Psychiatry, 69(8), 842–852. https://doi.org/10.1001/archgenpsychiatry.2011.2026.
- Cardenas, V. A., Durazzo, T. C., Gazdzinski, S., Mon, A., Studholme, C., & Meyerhoff, D. J. (2011). Brain morphology at entry into treatment for alcohol dependence is related to relapse propensity. Biological Psychiatry, 70(6), 561–567. https://doi.org/10.1016/j.biopsych.2011.04.003.CrossRefGoogle Scholar
- Cohen, J. (1977). Statistical power analysis for the behavioral sciences (rev. ed.). New York: Academic Press.Google Scholar
- Durazzo, T. C., Gazdzinski, S., Yeh, P. H., & Meyerhoff, D. J. (2008). Combined neuroimaging, neurocognitive and psychiatric factors to predict alcohol consumption following treatment for alcohol dependence. Alcohol and Alcoholism, 43(6), 683–691. https://doi.org/10.1093/alcalc/agn078.CrossRefGoogle Scholar
- Durazzo, T. C., Tosun, D., Buckley, S., Gazdzinski, S., Mon, A., Fryer, S. L., & Meyerhoff, D. J. (2011). Cortical thickness, surface area, and volume of the brain reward system in alcohol dependence: Relationships to relapse and extended abstinence. Alcoholism, Clinical and Experimental Research, 35(6), 1187–1200. https://doi.org/10.1111/j.1530-0277.2011.01452.x.CrossRefGoogle Scholar
- Durazzo, T. C., Mon, A., Pennington, D., Abe, C., Gazdzinski, S., & Meyerhoff, D. J. (2014). Interactive effects of chronic cigarette smoking and age on brain volumes in controls and alcohol-dependent individuals in early abstinence. Addiction Biology, 19(1), 132–143. https://doi.org/10.1111/j.1369-1600.2012.00492.x.CrossRefGoogle Scholar
- Durazzo, T. C., Mon, A., Gazdzinski, S., Yeh, P. H., & Meyerhoff, D. J. (2015). Serial longitudinal magnetic resonance imaging data indicate non-linear regional gray matter volume recovery in abstinent alcohol-dependent individuals. Addiction Biology, 20(5), 956–967. https://doi.org/10.1111/adb.12180.CrossRefGoogle Scholar
- Fettes, P., Schulze, L., & Downar, J. (2017). Cortico-striatal-thalamic loop circuits of the orbitofrontal cortex: Promising therapeutic targets in psychiatric illness. Frontiers in Systems Neuroscience, 11, 25. https://doi.org/10.3389/fnsys.2017.00025.
- Fischl, B., van der Kouwe, A., Destrieux, C., Halgren, E., Segonne, F., Salat, D.H., Busa, E., Seidman, L.J., Goldstein, J., Kennedy, D., Caviness, V., Makris, N., Rosen, B., Dale, A.M. (2004). Automatically parcellating the human cerebral cortex. Cerebral cortex, 14, 11–22Google Scholar
- George, M. S., Bohning, D. E., Lorberbaum, J. P., Nahas, Z., Anderson, B., Borckardt, J. J., Molnar, C., Kose, S., Ricci, R., & Rostogi, K. (2007). Overview of transcranial magnetic stimulation: History mechanisms physics and safety. In M. S. George & R. H. Belmaker (Eds.), Transcranial magnetic stimulation in clinical psychiatry (pp. 1–38). Washington, DC; London: American Psychiatric Publishing, Inc..Google Scholar
- Grant, B. F., Goldstein, R. B., Saha, T. D., Chou, S. P., Jung, J., Zhang, H., . . . Hasin, D. S. (2015). Epidemiology of DSM-5 alcohol use disorder: Results from the National Epidemiologic Survey on alcohol and related conditions III. JAMA Psychiatry, 72(8), 757–766. https://doi.org/10.1001/jamapsychiatry.2015.0584.
- Mon, A., Durazzo, T. C., Gazdzinski, S., Hutchison, K. E., Pennington, D., & Meyerhoff, D. J. (2013). Brain-derived neurotrophic factor (BDNF) genotype is associated with lobar gray and white matter volume recovery in abstinent alcohol dependent individuals. Genes, Brain, and Behavior, 12(1), 98–107. https://doi.org/10.1111/j.1601-183X.2012.00854.x.CrossRefGoogle Scholar
- Paulus, M. P. (2007). Neural basis of reward and craving--a homeostatic point of view. Dialogues in Clinical Neuroscience, 9(4), 379–387.Google Scholar
- Rando, K., Hong, K. I., Bhagwagar, Z., Li, C. S., Bergquist, K., Guarnaccia, J., & Sinha, R. (2011). Association of frontal and posterior cortical gray matter volume with time to alcohol relapse: A prospective study. The American Journal of Psychiatry, 168(2), 183–192. https://doi.org/10.1176/appi.ajp.2010.10020233.CrossRefGoogle Scholar
- Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., . . . Greicius, M. D. (2007). Dissociable intrinsic connectivity networks for salience processing and executive control. The Journal of Neuroscience, 27(9), 2349–2356. https://doi.org/10.1523/jneurosci.5587-06.2007.
- Seo, D., & Sinha, R. (2014). The neurobiology of alcohol craving and relapse. Handbook of Clinical Neurology, 125, 355–368. https://doi.org/10.1016/b978-0-444-62619-6.00021-5.CrossRefGoogle Scholar
- Seo, D., & Sinha, R. (2015). Neuroplasticity and predictors of alcohol recovery. Alcohol Research: Current Reviews, 37(1), 143–152.Google Scholar
- Sobell, L. C., Sobell, M. B., Maisto, S. A., & Cooper, A. M. (1985). Time-line follow-back assessment method. NIAAA treatment handbook series (Vol. 2, pp. 85–1380).Google Scholar
- Sobell, L. C., Sobell, M. B., Riley, D. M., Schuller, R., Pavan, D. S., Cancilla, A., . . . Leo, G. I. (1988). The reliability of alcohol abusers' self-reports of drinking and life events that occurred in the distant past. Journal of Studies on Alcohol, 49(3), 225–232.Google Scholar
- Stokes, M. G., Chambers, C. D., Gould, I. C., Henderson, T. R., Janko, N. E., Allen, N. B., & Mattingley, J. B. (2005). Simple metric for scaling motor threshold based on scalp-cortex distance: Application to studies using transcranial magnetic stimulation. Journal of Neurophysiology, 94(6), 4520–4527. https://doi.org/10.1152/jn.00067.2005.CrossRefGoogle Scholar
- Stokes, M. G., Chambers, C. D., Gould, I. C., English, T., McNaught, E., McDonald, O., & Mattingley, J. B. (2007). Distance-adjusted motor threshold for transcranial magnetic stimulation. Clinical Neurophysiology, 118(7), 1617–1625. https://doi.org/10.1016/j.clinph.2007.04.004.CrossRefGoogle Scholar
- Volkow, N. D., & Baler, R. D. (2014). Addiction science: Uncovering neurobiological complexity. Neuropharmacology, 76 Pt B, 235–249. https://doi.org/10.1016/j.neuropharm.2013.05.007.