Individuals family history positive for alcoholism show functional magnetic resonance imaging differences in reward sensitivity that are related to impulsivity factors

Melissa M. Andrews, Shashwath A. Meda, Andre D. Thomas, Marc N. Potenza, John H. Krystal, Patrick Worhunsky, Michael C. Stevens, Stephanie O'Malley, Gregory A. Book, Brady Reynolds, Godfrey D. Pearlson

Research output: Contribution to journalArticlepeer-review

139 Scopus citations


Background: Substance-abusing individuals tend to display abnormal reward processing and a vulnerability to being impulsive. Detoxified alcoholics show differences in regional brain activation during a monetary incentive delay task. However, there is limited information on whether this uncharacteristic behavior represents a biological predisposition toward alcohol abuse, a consequence of chronic alcohol use, or both. Methods: We investigated proposed neural correlates of substance disorder risk by examining reward system activity during a monetary incentive delay task with separate reward prospect, reward anticipation, and reward outcome phases in 30 individuals with and 19 without family histories of alcoholism. All subjects were healthy, lacked DSM-IV past or current alcohol or substance abuse histories, and were free of illegal substances as verified by a urine toxicology screening at the time of scanning. Additionally, we explored specific correlations between task-related nucleus accumbens (NAcc) activation and distinct factor analysis-derived domains of behavioral impulsivity. Results: During reward anticipation, functional magnetic resonance imaging data confirmed blunted NAcc activation in family history positive subjects. In addition, we found atypical activation in additional reward-associated brain regions during additional task phases. We further found a significant negative correlation between NAcc activation during reward anticipation and an impulsivity construct. Conclusions: Overall, results demonstrate that sensitivity of the reward circuit, including NAcc, is functionally different in alcoholism family history positive individuals in multiple regards.

Original languageEnglish
Pages (from-to)675-683
Number of pages9
JournalBiological Psychiatry
Issue number7
StatePublished - Apr 1 2011

Bibliographical note

Funding Information:
Dr. Potenza consults for and is an adviser to Boehringer Ingelheim; has consulted for and has financial interests in Somaxon; has received research support from the National Institutes of Health, Veteran's Administration, Mohegan Sun Casino, the National Center for Responsible Gaming and its affiliated Institute for Research on Gambling Disorders, and GlaxoSmithKline, Forest Laboratories, Ortho-McNeil, and Oy-Control/Biotie pharmaceuticals; has participated in surveys, mailings, or telephone consultations related to drug addiction, impulse control disorders, or other health topics; has consulted for law offices and the federal public defender's office in issues related to impulse control disorders; has performed grant reviews for the National Institutes of Health and other agencies; has given academic lectures in grand rounds, continuing medical education events, and other clinical or scientific venues; has edited for academic journals; has generated books or book chapters for publishers of mental health texts; and has provided clinical care in the Connecticut Department of Mental Health and Addiction Services Problem Gambling Services Program. Dr. Krystal's conflicts of interest are as follows: 1) Consultant for AstraZeneca Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceuticals, Merz Pharmaceuticals, Pfizer Pharmaceuticals, and Teva Pharmaceutical Industries, Ltd.; 2) Scientific advisory board/consultant for Abbott Laboratories, Bristol-Myers Squibb, Eli Lilly and Co., Forest Laboratories, Lohocla Research Corporation, SK Holdings Co. Ltd., Takeda Industries, and Transcept Pharmaceuticals; 3) Exercizable warrant options for Tetragenex Pharmaceuticals (value less than $100); 4) Research support to Department of Veterans Affairs for Janssen Research Foundation (provided drug and some study support to the Department of Veterans Affairs); 5) Derives income greater than $10,000 as the Editor of Biological Psychiatry; 6) Board Of Directors for American College of Neuropsychopharmacology; and 7) has the following Patents and Inventions: Seibyl JP, Krystal JH, Charney DS. Dopamine and noradrenergic reuptake inhibitors in treatment of schizophrenia. Patent #:5,447,948. September 5, 1995; co-inventor with Dr. Gerard Sanacora on a filed patent application by Yale University related to targeting the glutamatergic system for the treatment of neuropsychiatric disorders (PCTWO06 108055A 1); and Intranasal Administration of ketamine to Treat Depression (pending). Dr. Stephanie O'Malley is a member of American College of Neuropsychopharmacology work group sponsored by Johnson and Johnson, the Alcohol Clinical Trial Initiative, sponsored by Eli Lilly, Janssen, Schering Plough, Lundbeck, GlaxoSmithKline, and Alkermes; partner, Applied Behavioral Research; contract, Nabi Biopharmaceuticals; Advisory Board, Gilead Pharmaceuticals; consultant, GlaxoSmithKline; and Scientific Panel of Advisors, Hazelden. All other authors report no biomedical financial interests or potential conflicts of interest.

Funding Information:
The project was funded by the following sources: Veterans Affairs Alcohol Research Center , National Center for Posttraumatic Stress Disorder (JHK); National Institute on Alcohol Abuse and Alcoholism (NIAAA) Grant number 5 P50 AA012870 (JHK); Project 4 (GDP) and K05 AA-14906-01 (JHK); National Institute on Drug Abuse Grant number R01 DA020709 and NIAAA number R01AA016599 (GDP); NIAAA Grant number R01 AA017539 (MNP); and National Institute on Drug Abuse Grant number R01 DA020908 (MNP).


  • Alcoholism
  • anticipation
  • fMRI
  • family history
  • impulsivity
  • incentive
  • nucleus accumbens
  • reward
  • ventral striatum

ASJC Scopus subject areas

  • Biological Psychiatry


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