Reward Processing in Alcohol-Dependent Patients and First-Degree Relatives: Functional Brain Activity During Anticipation of Monetary Gains and Losses

BACKGROUND: According to the reward deficiency syndrome and allostatic hypotheses, hyposensitivity of meso-corticolimbic regions to non-alcohol-related stimuli predisposes to dependence or is long-lastingly enhanced by chronic substance use. To date, no study has directly compared mesocorticolimbic brain activity during non-drug reward anticipation between alcohol-dependent, at risk, and healthy subjects. METHODS: Seventy-five abstinent alcohol-dependent human subjects (mean abstinence duration 957.66 days), 62 healthy first-degree relatives of alcohol-dependent individuals, and 76 healthy control subjects without family history of alcohol dependence performed a monetary incentive delay task. Functional magnetic resonance imaging data of the anticipation phase were analyzed, during which visual cues predicted that fast response to a target would result in monetary gain, avoidance of monetary loss, or a neutral outcome. RESULTS: During gain anticipation, there were no significant group differences. During loss anticipation, abstinent alcohol-dependent subjects showed lower activity in the left anterior insula compared with healthy control subjects without family history of alcohol dependence only (Montreal Neurological Institute [MNI] 225 19 -5; t206 = 4.17, familywise error corrected p = .009). However, this effect was no longer significant when age was included as a covariate. There were no group differences between abstinent alcohol-dependent subjects and healthy first-degree relatives or between healthy first-degree relatives and healthy control subjects during loss anticipation, respectively. CONCLUSIONS: Neither the neural reward deficiency syndrome nor the allostatic hypotheses are supported by the results. Future studies should investigate whether the incentive salience hypothesis allows for more accurate pre-dictions regarding mesocorticolimbic brain activity of subjects with alcohol dependence and healthy individuals during reward and loss anticipation and further examine the neural substrates underlying a predisposition to dependence.