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

DeVito, Elise E.; Meda, Shashwath A.; Jiantonio, Rachel E.; Potenza, Marc N.; Krystal, John H.; Pearlson, Godfrey D.

doi:10.1038/npp.2013.92

Cited by 69 publications

(65 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Repeated cycles of alcohol intoxication and abstinence resulted in increased impulsivity (Irimia et al, 2013). On the other hand, high impulsivity has been found in families with alcoholism, suggesting a genetic link between alcoholism and impulsivity (Saunders et al, 2008; DeVito et al, 2013). Therefore, the high impulsivity of our alcoholic group could be regarded both as a state consequence of chronic alcohol consumption and as an inherited trait temperament.…”

Section: Discussionmentioning

confidence: 99%

Compromised frontocerebellar circuitry contributes to nonplanning impulsivity in recovering alcoholics

et al. 2014

View full text Add to dashboard Cite

Rationale Degradation of frontocerebellar circuitry is a principal neural mechanism of alcoholism-related executive dysfunctions affecting impulse control and cognitive planning. Objective We tested the hypothesis that alcoholic patients would demonstrate compromised dorsal anterior cingulate cortex (dACC)-cerebellar functional connectivity when adjusting their strategies to accommodate uncertain conditions and would recruit compensatory brain regions to overcome ineffective response patterns. Methods 26 alcoholics and 26 healthy participants underwent functional MRI in two sequential runs while performing a decision-making task. The first run required a response regardless of level of ambiguity of the stimuli; the second run allowed a PASS option (i.e., no response choice), which was useful on ambiguous trials. Results Healthy controls demonstrated strong synchronous activity between the dACC and cerebellum while planning and executing a behavioral strategy. By contrast, alcoholics showed synchronous activity between the dACC and the premotor cortex, perhaps enabling successful compensation for accuracy and reaction time in certain conditions; however, a negative outcome of this strategy was rigidity in modifying response strategy to accommodate uncertain conditions. Compared with the alcoholic group, the control group had lower nonplanning impulsiveness, which correlated with using the option PASS to respond in uncertain conditions. Conclusion These findings suggest that compromised dACC-cerebellar functional circuitry contributes to recruitment of an alternative network—dACC-premotor cortex—to perform well under low risk, unambiguous conditions. This compensatory network, however, was inadequate to enable the alcoholics to avert making poor choices in planning and executing an effective behavioral strategy in high-risk, uncertain conditions.

show abstract

Section: Discussionmentioning

confidence: 99%

Compromised frontocerebellar circuitry contributes to nonplanning impulsivity in recovering alcoholics

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Impaired impulsivity and altered brain responsiv ity in areas responsible for executive functioning and reward processing are risk factors for developing an AUD [120,121]. A recent preclinical study examined expression patterns of cortical genes and impulsive behavior in BXD strains of mice [122].…”

Section: Ras Signalingmentioning

confidence: 99%

Promising Pharmacogenetic Targets for Treating Alcohol Use Disorder: Evidence from Preclinical Models

Rinker

Mulholland

2017

Pharmacogenomics

View full text Add to dashboard Cite

Inherited genetic variants contribute to risk factors for developing an alcohol use disorder, and polymorphisms may inform precision medicine strategies for treating alcohol addiction. Targeting genetic mutations linked to alcohol phenotypes has provided promising initial evidence for reducing relapse rates in alcoholics. Although successful in some studies, there are conflicting findings and the reports of adverse effects may ultimately limit their clinical utility, suggesting that novel pharmacogenetic targets are necessary to advance precision medicine approaches. Here, we describe promising novel genetic variants derived from preclinical models of alcohol consumption and dependence that may uncover disease mechanisms that drive uncontrolled drinking and identify novel pharmacogenetic targets that facilitate therapeutic intervention for the treatment of alcohol use disorder. Alcohol use disorder (AUD) is a chronic neurological disorder characterized by an inability to regulate alcohol intake despite a host of serious and harmful health, soci etal and personal consequences [1]. The cur rent pharmacotherapies available for AUD treatment have been met with variable out comes that are modest at best and thus have not been widely embraced by the medical community. This gap in treatment options provides an opportunity to explore new avenues toward identifying novel pharmaco therapeutic targets. As with other addictive disorders, AUD is influenced, to a consid erable degree, by genetics, with heritability estimates upward of 60% [2,3]. Despite the comparatively large influence of genetics, the exact etiology of AUD is by no means simple or straightforward, which under scores the difficulty in effective treatment of this disorder. In this review, we provide an evaluation of our understanding of the genet ics of AUD in relation to current precision medicine approaches. Demonstrating the considerable heterogeneity that exists within the AUD population and understanding the contribution of genetic variation to treatment response provides a framework for promot ing a pharmacogenetic approach. Moreover, understanding the genetic variation among individuals with AUD in treatment response will provide valuable information that will allow for personalized treatment plans.A diagnosis of AUD is based strictly on a set of clinical diagnostic criteria, because as of yet, there are no reliable biomarkers to identify AUD or subpopulations that might be more or less responsive to certain medica tions. This means that, at best, we are treat ing AUD by trial and error on a, presumably, largely heterogeneous population. There are currently only three US FDA approved pharmaco therapies for treating AUD, nal trexone, acamprosate and disulfiram, all of

show abstract

“…Relatively increased activation was observed in the left anterior insula and inferior frontal gyrus during successful inhibitions in the family-history-positive group, and these same regions were implicated in greater impulsivity when scans were compared to out of scanner self-reported impulsivity (on the BIS-11) and greater discounting in an experiential discounting task [47]. Smokers show activation in similar regions when performing a monetary incentive GNG task, such as hyperactivation in the right insula, inferior and middle frontal gyri, dlPFC, and the inferior parietal lobe during inhibition [48].…”

Section: Underlying Neurocircuitry Of Impulsivitiesmentioning

confidence: 99%

Recent Insights into the Neurobiology of Impulsivity

Mitchell

Potenza

2014

Curr Addict Rep

View full text Add to dashboard Cite

Impulsivity is associated with various psychopathologies, and elevated impulsivity is typically disadvantageous. This manuscript reviews recent investigations into the neurobiology of impulsivity using human imaging techniques and animal models. Both human imaging and preclinical pharmacological manipulations have yielded important insights into the neurobiological underpinnings of impulsivity. A more thorough understanding of the complex neurobiology underlying aspects of impulsivity may provide insight into new treatment options that target elevated impulsivity and psychopathologies such as addictions.

show abstract

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

Cited by 69 publications

References 50 publications

Compromised frontocerebellar circuitry contributes to nonplanning impulsivity in recovering alcoholics

Compromised frontocerebellar circuitry contributes to nonplanning impulsivity in recovering alcoholics

Promising Pharmacogenetic Targets for Treating Alcohol Use Disorder: Evidence from Preclinical Models

Recent Insights into the Neurobiology of Impulsivity

Contact Info

Product

Resources

About