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The “must-be-known” neurobiology of alcohol use disorders

The new topic of the month on our Resource Centre is neurobiology of alcohol use disorders. Continuous progress in technology has resulted in imaging techniques which enable us to visualize brain structure and function, measure neurotransmitters and their receptors, and electrical activity and changes in blood flow in the brain. Techniques like CT, MRI, DTI, PET, SPECT and MEG are yielding unprecedented images and show us what happens to and in the brain for instance when it is activated by emotional stimuli or when exposed to drugs of abuse or pharmacological agents. Advances in neurobiology paralleled by those made in genetics give us a better understanding of alcohol use disorders and the underlying mechanisms, increasing the body of evidence from which to design new drugs, optimize existing treatment options and identify which patients will respond best to which treatment. To learn more, see the video presentations by David Nutt on visualizing the alcohol dependent brain, and by Philip Gorwood on the genetics of alcohol dependence, and find a selection of articles on the topic on our articles page.


  • Readiness to change and brain damage in patients with chronic alcoholism

    Anne-Pascale Le Berre, Géraldine Rauchs, Renaud La Joie, Shailendra Segobin, Florence Mézenge, Céline Boudehent, François Vabret, Fausto Viader, Francis Eustache, Anne-Lise Pitel, Hélène Beaunieux

    Psychiatry Research 2013, Volume 213, pages 202–209

    Editor's comment:
    The main objective of this study was to gain a better understanding of the potential contribution of macrostructural brain abnormalities to why some alcoholic patients have difficulty changing their drinking behavior even when they are inpatients at clinical treatment entry. Taken as a group, the alcoholic inpatients participating in the study were found to have widespread gray matter abnormalities on MRI. The study results suggest that as a consequence of their brain volume deficits and associated impairment of critical abilities such as decision making, executive functions and social cognition skills, some alcohol dependent patients may not be able to attend a regular treatment in an addiction department. It may be relevant to favour brain recovery of patients with lower motivation by extending the period they spend without alcohol before being admitted to an Addiction department.

  • Recent binge drinking predicts smaller cerebellar volumes in adolescents

    Krista M. Lisdahl, Rachel Thayer, Lindsay M. Squeglia, Tim M. McQueeny, Susan F. Tapert

    Psychiatry Research 2013; Volume 211, pages 17–23

    Editor's comment:
    In this study, the authors found that increased binge drinks during the past 3 months significantly predicted smaller bilateral cerebellar gray matter and left hemisphere cerebellar white matter volumes, and marginally predicted smaller right hemisphere white matter cerebellar volume as assessed by high-resolution MRI in a sample of 106 normally developing 16- to 19-year olds. Gender did not moderate these effects. Given the high rates of binge drinking in teens and emerging adults, these findings highlight an important public health concern. Interventions geared towards lowering damaging patterns of binge alcohol use in teens and young adults that have shown evidence of efficacy need to be implemented more aggressively to prevent long-term neuronal damage, and to ensure optimal brain health and cognitive functioning in youth.

  • Effect of the TaqIA polymorphism on ethanol response in the brain

    Edythe D. London, Steven M. Berman, Parvenah Mohammadian, Terrie Ritchie, Mark A. Mandelkern, Mary K.W. Susselman, Florian Schlagenhauf, Ernest P. Noble

    Psychiatry Research: Neuroimaging 2009, Volume174, pages 163–170

    Editor's comment:
    Positron emission tomography with [F-18] fluorodeoxyglucose (FDG) was used in this study to assess regional cerebral glucose metabolism as a measure of relative brain activity while the study participants performed a vigilance task. The study participants, six A1+ and six A1− men, drank ethanol (0.75 ml/kg) or placebo beverages on each of two days. The study results showed lower anxiety and fatigue after ethanol in A1+ men, compared with higher anxiety and fatigue in A1− men, which strongly supports the hypothesis that ethanol is more reinforcing in A1 carriers. Alcohol-induced negative reinforcement may explain the greater risk for alcoholism associated with the A1 allele.

  • Abnormal white matter integrity and decision-making deficits in alcohol dependence

    Nabi Zorlu, Fazil Gelal, Ali Kuserli, Ebuzer Cenik, Ercan Durmaz, Aybala Saricicek, Seref Gulseren

    Psychiatry Research: Neuroimaging 2013, Volume 214, pages 382–388

    Editor's comment:
    The authors of this study used Tract Based Spatial Statistics (TBSS) to assess white matter changes in 17 inpatient alcohol dependent patients (ADP) who had been abstinent for at least 2 weeks before testing and diffusion tensor imaging scanning compared with 16 healthy controls. To measure decision-making in the study participants the Iowa Gambling Task (IGT) was used. Four significant clusters were found in which fractional anisotropy was significantly lower in ADP than in control subjects, including the corpus callosum and parietal, occipital and frontal regions. The authors found significant correlations between the widespread disruption of white matter integrity and impaired IGT performance. These results might help to explain observed decision making deficits in ADP.

  • AMPA receptors in post-mortem brains of Cloninger type 1 and 2 alcoholics: A whole-hemisphere autoradiography study

    Olli Kärkkäinen, Jukka Kupila, Merja Häkkinen, Virpi Laukkanen, Erkki Tupala, Hannu Kautiainen, Jari Tiihonen, Markus Storvik

    Psychiatry Research: Neuroimaging 2013, Volume 214, pages 429–434

    Editor's comment:
    The authors examined densities of AMPA receptors from human post-mortem brain regions in Cloninger type 1 and 2 alcoholics and non-alcoholic controls by whole-hemi-sphere autoradiography. [3H] AMPA binding was found to be significantly increased in type 2 alcoholics in the anterior cingulate cortex (ACC) when compared to controls. The study results support the idea that in type 2 alcoholics, some altered function in the ACC reflects a dysfunction in optimal-decision making and reward-related learning processes; such a dysfunction could be one of the neural changes leading to the addiction and impulsive behaviour already seen with type 2 alcoholics at an early age.

  • Resting state functional connectivity of the nucleus accumbens in youth with a family history of alcoholism

    Anita Cservenka, Kaitlyn Casimo, Damien A. Fair, Bonnie J. Nagel

    Psychiatry Research: Neuroimaging 2014, Volume 221, pages 210–219

    Editor's comment:
    In this study, resting state functional magnetic resonance imaging was used to examine the intrinsic connectivity of the nucleus accumbens (NAcc) in 47 adolescents with a family history of alcoholism (FHP) and 50 family history negative adolescents (FHN) aged 10−16 years, who had not used alcohol or other substances heavily. Findings from the rs-fcMRI included that, compared to FHN youth in the study, FHP youth had significantly weaker segregation of the NAcc and cortical executive control regions, suggesting poorer dissociation of appetitive and cognitive systems. FHP youth also had weaker synchrony between the NAcc and the orbitofrontal cortex, indicating poorer integration of the reward network. The aberrant pattern of NAcc connectivity observed may represent a risk factor in FHP adolescents for developing alcohol use disorders, as it could lead to improper reward learning and interference with cognitive control. Study results like these resting state fMRI findings may help guide prevention strategies aimed specifically at intergenerational transmission of alcohol use disorders.

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