Abstract
Alcohol-dependence is associated with cognitive and biological alterations, and also with interpersonal impairments. Although overwhelming in clinical settings and involved in relapse, these social impairments have received little attention from researchers. Particularly, brain alterations related to social exclusion have not been explored in alcohol-dependence. Our primary purpose was to determine the neural correlates of social exclusion feelings in this population. In all, 44 participants (22 abstinent alcohol-dependent patients and 22 paired controls) played a virtual game (‘cyberball’) during fMRI recording. They were first included by other players, then excluded, and finally re-included. Brain areas involved in social exclusion were identified and the functional connectivity between these areas was explored using psycho-physiological interactions (PPI). Results showed that while both groups presented dorsal anterior cingulate cortex (dACC) activations during social exclusion, alcohol-dependent participants exhibited increased insula and reduced frontal activations (in ventrolateral prefrontal cortex) as compared with controls. Alcohol-dependence was also associated with persistent dACC and parahippocampal gyrus activations in re-inclusion. PPI analyses showed reduced frontocingulate connectivity during social exclusion in alcohol-dependence. Alcohol-dependence is thus linked with increased activation in areas eliciting social exclusion feelings (dACC–insula), and with impaired ability to inhibit these feelings (indexed by reduced frontal activations). Altered frontal regulation thus appears implied in the interpersonal alterations observed in alcohol-dependence, which seem reinforced by impaired frontocingulate connectivity. This first exploration of the neural correlates of interpersonal problems in alcohol-dependence could initiate the development of a social neuroscience of addictive states.
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References
Adolphs R (2010). Conceptual challenges and directions for social neuroscience. Neuron 65: 752–767.
Bijl RV, Ravelli A (2000). Psychiatric morbidity, service use, and need for care in the general population: results of The Netherlands Mental Health Survey and Incidence Study. Am J Public Health 90: 602–607.
Bjork JM, Smith AR, Hommer DW (2008). Striatal sensitivity to reward deliveries and omissions in substance dependent patients. NeuroImage 42: 1609–1621.
Bolling DZ, Pitskel NB, Deen B, Crowley MJ, McPartland JC, Kaiser MD et al (2011). Enhanced neural responses to rule violation in children with autism: a comparison to social exclusion. Dev Cogn Neurosci 1: 280–294.
Bolling DZ, Pitskel NB, Deen B, Crowley MJ, McPartland JC, Mayes LC et al (2010). Dissociable brain mechanisms for processing social exclusion and rule violation. NeuroImage 54: 2462–2471.
Brandon TH, Vidrine JI, Litvin EB (2007). Relapse and relapse prevention. Annu Rev Clin Psychol 3: 257–284.
Bühler M, Mann K (2011). Alcohol and the human brain: a systematic review of different neuroimaging methods. Alcohol Clin Exp Res 35: 1771–1793.
DeWall CN, Macdonald G, Webster GD, Masten CL, Baumeister RF, Powell C et al (2010). Acetaminophen reduces social pain: behavioral and neural evidence. Psychol Sci 21: 931–937.
Eisenberger NI, Lieberman MD (2004). Why rejection hurts. A common neural alarm system for physical and social pain. Trends Cogn Sci 8: 294–300.
Eisenberger NI, Lieberman MD, Williams KD (2003). Does rejection hurt? An fMRI study of social exclusion. Science 302: 290–292.
Friston KJ (2004). Functional and effective connectivity in neuroimaging: a synthesis. Hum Brain Mapp 2: 56–78.
Friston KJ, Buechel C, Fink GR, Morris J, Rolls E, Dolan RJ (1997). Psychophysiological and modulatory interactions in neuroimaging. NeuroImage 6: 218–229.
Gilman JM, Davis MB, Hommer DW (2010). Greater activation in left hemisphere language-related regions during simple judgment tasks among substance-dependent patients in treatment for alcoholism. Alcohol Clin Exp Res 34: 331–341.
Gunther-Moor B, Güroğlu B, Op de Macks ZA, Rombouts SA, Van der Molen MW, Crone EA (2012). Social exclusion and punishment of excluders: neural correlates and developmental trajectories. NeuroImage 59: 708–717.
Heinz A, Wrase J, Kahnt T, Beck A, Bromand Z, Grüsser SM et al (2007). Brain activation elicited by affectively positive stimuli is associated with a lower risk of relapse in detoxified alcoholic subjects. Alcohol Clin Exp Res 31: 1138–1147.
Johnson B, Ruiz P, Galanter M (2003). Handbook of Clinical Alcoholism Treatment, 1st edn. Lippincott Williams & Wilkins: Philadelphia, PA.
Krill A, Platek SM (2009). In-group and out-group membership mediates anterior cingulate activation to social exclusion. Front Evol Neurosci 1: 1–7.
Kross E, Egner T, Ochsner K, Hirsch J, Downey G (2007). Neural dynamics of rejection sensitivity. J Cogn Neurosci 19: 945–956.
Lieberman MD (2007). Social cognitive neuroscience: a review of core processes. Annu Rev Psychol 58: 259–289.
Maisto SA, Zywiak WH, Connors GJ (2006). Course of functioning 1 year following admission for treatment of alcohol use disorders. Addict Behav 31: 69–79.
Masten CL, Colich NL, Rudie JD, Bookheimer SY, Eisenberger NI, Dapretto M (2011). An fMRI investigation of responses to peer rejection in adolescents with autism spectrum disorders. Dev Cogn Neurosci 1: 260–270.
Moselhy HF, Georgiou G, Kahn A (2001). Frontal lobe changes in alcoholism: a review of the literature. Alcohol Alcohol 36: 357–368.
Nutt DJ, King LA, Phillips LD, Independent Scientific Committee on Drugs (2010). Drug harms in the UK: a multicriteria decision analysis. Lancet 376: 1558–1565.
Onoda K, Okamoto Y, Nakashima K, Nittono H, Yoshimura S, Yamawaki S et al (2010). Does low self-esteem enhance social pain? The relationship between trait self-esteem and anterior cingulate cortex activation induced by ostracism. Soc Cogn Affect Neurosci 5: 385–391.
Perry Y, Henry JD, Sethi N, Grisham JR (2011). The pain persists: how social exclusion affects individuals with schizophrenia. Br J Clin Psychol 50: 339–349.
Pescosolido BA, Martin JK, Long JS, Medina TR, Phelan JC, Link BG (2010). ‘A disease like any other’? A decade of change in public reactions to schizophrenia, depression, and alcohol dependence. Am J Psychiatry 167: 1321–1330.
Pfefferbaum A, Sullivan EV (2005). Disruption of brain white matter microstructure by excessive intracellular and extracellular fluid in alcoholism: evidence from diffusion tensor imaging. Neuropsychopharmacology 30: 423–432.
Phan KL, Wager T, Taylor SF, Liberzon I (2002). Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI. NeuroImage 16: 331–348.
Poldrack RA, Mumford JA (2009). Independence in ROI analysis: where is the voodoo? Soc Cogn Affect Neurosci 4: 208–213.
Rando K, Hong KI, Bhagwagar Z, Ray Li CS, Bergquist K, Guarnaccia J et al (2011). Association of frontal and posterior cortical gray matter volume with time to alcohol relapse: a prospective study. Am J Psychiatry 168: 183–192.
Ross S, Peselow E (2009). Pharmacotherapy of addictive disorders. Clin Neuropharmacol 32: 277–289.
Saunders SM, Zygowicz KM, D’Angelo BR (2006). Person-related and treatment-related barriers to alcohol treatment. J Subst Abuse Treat 30: 261–270.
Schomerus G, Lucht M, Holzinger A, Matschinger H, Carta MG, Angermeyer MC (2011). The stigma of alcohol dependence compared with other mental disorders: a review of population studies. Alcohol Alcohol 46: 105–112.
Sintov ND, Kendler KS, Young-Wolff KC, Walsh D, Patterson DG, Prescott CA (2010). Empirically defined subtypes of alcohol dependence in an Irish family sample. Drug Alcohol Depend 107: 230–236.
Sorg SF, Taylor MJ, Alhassoon OM, Gongvatana A, Theilmann RJ, Frank LR et al (2012). Frontal white matter integrity predictors of adult alcohol treatment outcome. Biol Psychiatry 71: 262–268.
Sugranyes G, Kyriakopoulos M, Corrigall R, Taylor E, Frangou S (2011). Autism spectrum disorders and schizophrenia: meta-analysis of the neural correlates of social cognition. PLoS One 6: e25322.
Swift R (2007). Emerging approaches to managing alcohol dependence. Am J Health Syst Pharm 64: 12–22.
Tracey I (2010). Getting the pain you expect: mechanisms of placebo, nocebo and reappraisal effects in humans. Nat Med 16: 1277–1283.
Trucco EM, Connery HS, Griffin ML, Greenfield SF (2007). The relationship of self-esteem and self-efficacy to treatment outcomes of alcohol-dependent men and women. Am J Addict 16: 85–92.
US Department of Health and Human Services (2000). 10th Special Report to the US Congress on Alcohol and Health, 1st edn. National Institute on Alcohol Abuse and Alcoholism: Bethesda, MD.
Uekermann J, Daum I (2008). Social cognition in alcoholism: a link to prefrontal cortex dysfunction? Addiction 103: 726–735.
Veltro F, Mazza M, Vendittelli N, Alberti M, Casacchia M, Roncone R (2011). A comparison of the effectiveness of problem solving training and of cognitive–emotional rehabilitation on neurocognition, social cognition and social functioning in people with schizophrenia. Clin Pract Epidemiol Ment Health 7: 123–132.
Vollstädt-Klein S, Hermann D, Rabinstein J, Wichert S, Klein O, Ende G et al (2010). Increased activation of the ACC during a spatial working memory task in alcohol-dependence versus heavy social drinking. Alcohol Clin Exp Res 34: 771–776.
Vul E, Harris C, Winkielman P, Pashler H (2009). Puzzlingly high correlations in fMRI studies of emotion, personality and social cognition. Perspect Psychol Sci 4: 274–290.
Williams KD (2007). Ostracism. Annu Rev Psychol 58: 425–452.
Williams KD, Jarvis B (2006). Cyberball: a program for use in research on interpersonal ostracism and acceptance. Behav Res Methods 38: 174–180.
Zadro L, Boland C, Richardson R (2006). How long does it last? The persistence of the effects of ostracism in the socially anxious. J Exp Soc Psychol 42: 692–697.
Zubieta JK, Bueller JA, Jackson LR, Scott DJ, Xu Y, Koeppe RA et al (2005). Placebo effects mediated by endogenous opioid activity on mu-opioid receptors. J Neurosci 25: 7754–7762.
Zywiak WH, Westerberg VS, Connors GJ, Maisto SA (2003). Exploratory findings from the reasons for drinking questionnaire. J Subst Abuse Treat 25: 287–292.
Acknowledgements
Pierre Maurage (Senior Research Fellow), Alexandre Heeren (Research Fellow), Nicolas Vermeulen (Research Associate), Olivier Corneille, Olivier Luminet (Senior Research Associate), and Philippe de Timary (Clinical Research Associate) are founded by the Belgian Fund for Scientific Research (FRS—FNRS, Belgium). This founding organization did not exert any role, editorial direction, or censorship in this experiment. We thank Professor Mauro Pesenti and Valérie Dormal for their help in data acquisition and analyses.
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Maurage, P., Joassin, F., Philippot, P. et al. Disrupted Regulation of Social Exclusion in Alcohol-Dependence: An fMRI Study. Neuropsychopharmacol 37, 2067–2075 (2012). https://doi.org/10.1038/npp.2012.54
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DOI: https://doi.org/10.1038/npp.2012.54
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