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Family history of alcoholism interacts with alcohol to affect brain regions involved in behavioral inhibition.

ABSTRACT: RATIONALE:Impulsive behavior is associated with both alcohol use disorders and a family history of alcoholism (FHA). One operational definition of impulsive behavior is the stop-signal task (SST) which measures the time needed to stop a ballistic hand movement. OBJECTIVE:Employ functional magnetic resonance imaging (fMRI) to study right frontal responses to stop signals in heavy drinking subjects with and without FHA, and as a function of alcohol exposure. METHODS:Twenty-two family history-positive (FHP; age?=?22.7 years, SD?=?1.9) and 18 family history-negative (FHN; age?=?23.7, SD?=?1.8) subjects performed the SST in fMRI in two randomized visits: once during intravenous infusion of alcohol, clamped at a steady-state breath alcohol (BrAC) concentration of 60 mg/dL, and once during infusion of placebo saline. An independent reference group (n?=?13, age?=?23.7, SD?=?1.8) was used to identify a priori right prefrontal regions activated by successful inhibition (Inh) trials, relative to "Go" trials that carried no need for inhibition [Inh?>?Go]. RESULTS:FHA interacted with alcohol exposure in right prefrontal cortex, where alcohol reduced [Inh?>?Go] activation in FHN subjects but not in FHP subjects. Within this right frontal cortical region, stop-signal reaction time also correlated negatively with [Inh?>?Go] activation, suggesting that the [Inh?>?Go] activity was related to inhibitory behavior. CONCLUSIONS:The results are consistent with the low level of response theory (Schuckit, J Stud Alcohol 55:149-158, 1980; Quinn and Fromme, Alcohol Clin Exp Res 35:1759-1770, 2011), with FHP being less sensitive to alcohol's effects.

SUBMITTER: Kareken DA

PROVIDER: S-EPMC3695053 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Family history of alcoholism interacts with alcohol to affect brain regions involved in behavioral inhibition.

Kareken David A DA Dzemidzic Mario M Wetherill Leah L Eiler William W Oberlin Brandon G BG Harezlak Jaroslaw J Wang Yang Y O'Connor Sean J SJ

Psychopharmacology 20130307 2

<h4>Rationale</h4>Impulsive behavior is associated with both alcohol use disorders and a family history of alcoholism (FHA). One operational definition of impulsive behavior is the stop-signal task (SST) which measures the time needed to stop a ballistic hand movement.<h4>Objective</h4>Employ functional magnetic resonance imaging (fMRI) to study right frontal responses to stop signals in heavy drinking subjects with and without FHA, and as a function of alcohol exposure.<h4>Methods</h4>Twenty-tw ...[more]

PMID: 23468100

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Project description:RATIONALE:Compared to the general population, adult Attention-Deficit / Hyperactivity Disorder (ADHD) is more prevalent in patients with Alcohol Use Disorder (AUD). Impaired behavioral inhibition is a common characteristic in both ADHD and AUD. Relapse risk is increased in patients with AUD and comorbid, untreated ADHD and in AUD patients with increased neural cue-reactivity. OBJECTIVES:In this study, we examined the interaction between neural correlates of behavioral inhibition and alcohol cue-reactivity with a hybrid imaging task. METHODS:Out of 69 adult study participants, we included n?=?49 in our final analyses: Individuals had a diagnosis of either AUD (n?=?13), ADHD (n?=?14) or both (n?=?5), or were healthy controls (HC; n?=?17). The functional magnetic resonance imaging paradigm aimed to examine the combined effects of both an interference-inhibition task ("Simon-task") and an alcohol cue-reactivity task. Instead of segregating by diagnostic group, we pursued a dimensional approach in which we compared measures of AUD and ADHD severity, as well as the interaction of both, using multiple regression analyses. RESULTS:The four groups did not differ on the behavioral level on either the inhibition task or the alcohol cue-reactivity task. However, brain activation in frontal control and reward-related regions during completion of the combined tasks were related to ADHD and AUD severity (symptom load). During presentation of both alcohol cues and the inhibition task, participants with higher AUD and ADHD symptom load exhibited greater BOLD (blood oxygen level dependent) responses in subcortical reward-related regions. CONCLUSIONS:Our findings support the hypothesis that ADHD additionally diminishes inhibition ability in individuals with AUD. This may increase relapse risk when confronted with alcohol cues. Further, it is crucial for patients with comorbid AUD and ADHD to take into account not only reduced cognitive control over behavioral inhibition but also simultaneously heightened alcohol cue-reactivity.

Project description:BackgroundExtensive research indicates that having a positive family history of alcohol use disorder (FHP) and impulsivity are 2 risk factors for problem drinking. To our knowledge, no study has investigated which facets of impulsivity interact with family history to increase risk for problem drinking. The goal of this study was to: (i) examine whether FHP individuals with higher levels of impulsivity are more likely to engage in problematic drinking, and (ii) identify which facets of impulsivity interact with FHP to increase risk for problems.MethodsThe data consisted of a combined sample of 757 participants (50% female, 73% White, mean age = 32.85, SD = 11.31) drawn from the Transdisciplinary Tobacco Use Research Center and the Center for the Translational Neuroscience of Alcohol. Analyses of covariance and cumulative logistic regression models investigated the association of family history and impulsivity-related traits with drinking quantity, frequency, and alcohol-related problems. Models were adjusted for age, sex, race, ethnic group, education level, and data source.ResultsSignificant interactions between impulsivity and family history were found for measures of alcohol-related problems. Specifically, there was a stronger positive association of Barratt Impulsiveness Scale (BIS) poor self-regulation with interpersonal, F(1, 504) = 6.27, p = 0.01, and impulse control alcohol-related problems, F(1, 504) = 6.00, p = 0.01, among FHP compared to FHN individuals. Main effects of family history and impulsivity on alcohol quantity and frequency of use and problems were also found.ConclusionsThese findings suggest that having both a family history of AUD and high BIS poor self-regulation is more strongly associated with alcohol-related consequences in the interpersonal and impulse control domains. Given the heterogeneity of impulsivity, these findings highlight the need for additional research to examine which facets of impulsivity are associated with which alcohol outcomes to narrow phenotypic risk for alcohol misuse.

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Family history of alcoholism interacts with alcohol to affect brain regions involved in behavioral inhibition.

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Family history of alcoholism interacts with alcohol to affect brain regions involved in behavioral inhibition.

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