Dysfunction of reward processing correlates with alcohol craving in detoxified alcoholics

Individuals family-history positive (FHP) for alcoholism have increased risk for the disorder, which may be mediated by intermediate behavioral traits such as impulsivity. Given the sex differences in the risk for and clinical presentation of addictive disorders, risk for addiction may be differentially mediated by impulsivity within FHP males and females. FHP (N ¼ 28) and family-history negative (FHN, N ¼ 31) healthy, non-substance-abusing adults completed an fMRI Go/No-Go task and were assessed on impulsivity and alcohol use. Effects of family history and sex were investigated as were associations between neural correlates of impulse control and out-ofscanner measures of impulsivity and alcohol use. FHP individuals showed greater activation in the left anterior insula and inferior frontal gyrus during successful inhibitions, an effect that was driven primarily by FHP males. Higher self-reported impulsivity and behavioral discounting impulsivity, but not alcohol use measures, were associated with greater BOLD signal in the region that differentiated the FHP and FHN groups. Impulsivity factors were associated with alcohol use measures across the FHP and FHN groups. These findings are consistent with increased risk for addiction among FHP individuals being conferred through disrupted function within neural systems important for impulse control. Keywords: impulsivity; family history of alcoholism; insula; inferior frontal gyrus (IFG); addiction; sex differences. INTRODUCTIONAlcohol use disorders (AUDs) are prevalent and associated with detrimental health and societal outcomes (Li, 2008). Individuals with a family history of alcoholism (familyhistory positive (FHP)) have increased risk for alcoholism driven by genetic and environmental factors (Lieb et al, 2002;Slutske et al, 2002). Healthy FHPs model addiction vulnerability without confounding effects of excess alcohol on cognition and brain function.Increased AUD risk among FHPs may be conferred via heritable impulsive tendencies (Dick et al, 2010;Tessner and Hill, 2010). Impulsivity is a multi-factorial construct, where distinct sub-components appear to have differential neural bases and relationships with addiction (de Wit, 2009;Lejuez et al, 2010;Rogers et al, 2010). Aspects of impulsivity may both predispose to and be exacerbated by addictive behaviors. Impulsivity predicts development of AUDs; is higher in FHPs with more alcohol-dependent relatives (ie higher family-history load); and partially mediates the relationship between FHP and alcohol and substance use disorder (for review, see de Wit, 2009;Dick et al, 2010;Lejuez et al, 2010;Verdejo-Garcia et al, 2008). Other less well-studied impulsivity-related constructs (eg, sensationseeking, risk-taking, compulsivity, behavioural activation/ inhibition, reward/punishment sensitivity) have been related to addiction vulnerability, and addictions therefore warrant consideration (eg, Meda et al, 2009).Sex differences are important to consider as they are observable for rates, clinical presentation, and health cons...

Section: Lack Of Family History Of Alcoholism Effects In Ventral-stricontrasting

confidence: 49%

Neural Correlates of Impulsivity in Healthy Males and Females with Family Histories of Alcoholism

DeVito

Meda

Jiantonio

et al. 2013

“…In contrast, an fMRI study of children of alcoholics did not detect a difference in VST activation for monetary rewards (Bjork et al, 2008), while another study of FHP subjects found reduced VST activation to monetary rewards compared with FHN subjects (Andrews et al, 2011). However, monetary and alcohol cues may not elicit the same brain activation patterns (Wrase et al, 2007). Whereas fMRI does not identify specific neurotransmitters, our current findings are specific to VST DA, with the data suggesting that familial alcoholism is associated with increased dopaminergic signaling to alcohol-related cues (although see Munro et al, 2006 for null results with amphetamine).…”

Section: Discussionmentioning

confidence: 83%

Beer Flavor Provokes Striatal Dopamine Release in Male Drinkers: Mediation by Family History of Alcoholism

Oberlin

Džemidžić

Tran

et al. 2013

Striatal dopamine (DA) is increased by virtually all drugs of abuse, including alcohol. However, drug-associated cues are also known to provoke striatal DA transmission-a phenomenon linked to the motivated behaviors associated with addiction. To our knowledge, no one has tested if alcohol's classically conditioned flavor cues, in the absence of a significant pharmacologic effect, are capable of eliciting striatal DA release in humans. Employing positron emission tomography (PET), we hypothesized that beer's flavor alone can reduce the binding potential (BP) of [ 11 C]raclopride (RAC; a reflection of striatal DA release) in the ventral striatum, relative to an appetitive flavor control. Forty-nine men, ranging from social to heavy drinking, mean age 25, with a varied family history of alcoholism underwent two [ 11 C]RAC PET scans: one while tasting beer, and one while tasting Gatorade. Relative to the control flavor of Gatorade, beer flavor significantly increased self-reported desire to drink, and reduced [ 11 C]RAC BP, indicating that the alcohol-associated flavor cues induced DA release. BP reductions were strongest in subjects with first-degree alcoholic relatives. These results demonstrate that alcoholconditioned flavor cues can provoke ventral striatal DA release, absent significant pharmacologic effects, and that the response is strongest in subjects with a greater genetic risk for alcoholism. Striatal DA responses to salient alcohol cues may thus be an inherited risk factor for alcoholism.

“…For example, risk seeking was shown to be associated with increased risk for relapse (eg, Goto et al, 2009) and might be a vulnerability factor for substance abuse. In addition, previous studies reported a dysfunction in reward-related brain regions such as the ventral striatum in addiction, with decreased activation in response to non-drug rewards (eg, Wrase et al, 2007). However, the present data show that neither risk taking (explained variance ¼ 0.1%) nor activation in the ventral striatum in response to reward anticipation during the MID task (explained variance ¼ 0.1%) significantly contributed to alcohol use in adolescents, while the personality traits of novelty seeking (explained variance ¼ 13.2%) and impulsivity (7.4%) did.…”

Section: Discussionmentioning

confidence: 99%

“…Neurobiological factors such as deficient recruitment of motivational circuitry by non-drug rewards (Ratsma et al, 2002) and psychosocial factors such as adverse life events resulting from deviant and risky behavior (eg, Clark et al, 1997). Augmented impulsivity has been observed in a subfraction of alcoholic patients manifested by a dysfunctional preference of immediate vs delayed reward (Cloninger, 1987) and higher dispositional and behavioral impulsivity compared with healthy persons (Wrase et al, 2007). In drug and alcohol-dependent patients, increased inability to resist the temptation of a smaller immediate reward instead of receiving a larger reward at a later date has repeatedly been observed (de Wit, 2009).…”

Section: Introductionmentioning

confidence: 99%

Determinants of Early Alcohol Use In Healthy Adolescents: The Differential Contribution of Neuroimaging and Psychological Factors

Nees

Tzschoppe

Patrick

et al. 2011

Self Cite

126

Individual variation in reward sensitivity may have an important role in early substance use and subsequent development of substance abuse. This may be especially important during adolescence, a transition period marked by approach behavior and a propensity toward risk taking, novelty seeking and alteration of the social landscape. However, little is known about the relative contribution of personality, behavior, and brain responses for prediction of alcohol use in adolescents. In this study, we applied factor analyses and structural equation modeling to reward-related brain responses assessed by functional magnetic resonance imaging during a monetary incentive delay task. In addition, novelty seeking, sensation seeking, impulsivity, extraversion, and behavioral measures of risk taking were entered as predictors of early onset of drinking in a sample of 14-year-old healthy adolescents (N ¼ 324). Reward-associated behavior, personality, and brain responses all contributed to alcohol intake with personality explaining a higher proportion of the variance than behavior and brain responses. When only the ventral striatum was used, a small non-significant contribution to the prediction of early alcohol use was found. These data suggest that the role of reward-related brain activation may be more important in addiction than initiation of early drinking, where personality traits and reward-related behaviors were more significant. With up to 26% of explained variance, the interrelation of reward-related personality traits, behavior, and neural response patterns may convey risk for later alcohol abuse in adolescence, and thus may be identified as a vulnerability factor for the development of substance use disorders.