Negative Urgency Mediates the Relation Between Genetically Influenced Serotonin Functioning and Alcohol Problems

Wang, Frances L.; Chassin, Laurie

doi:10.1177/2167702617733817

Cited by 17 publications

(11 citation statements)

References 69 publications

(111 reference statements)

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“…Neurochemically, negative urgency may reflect deficient 5-hydroxytryptamine (5-HT) and lower dopamine activity in the OFC and vmPFC (Floresco and Tse, 2007; Cyders and Smith, 2008), leading to less inhibition of both basal ganglia- and extended amygdala-subserved impulses. Accordingly, a composite polygenic 5-HT score predicted alcohol problems via an increase in negative urgency and not via other measures of impulsivity (Carver et al, 2011; Wang and Chassin, 2018). Evidence of lower 5-HT activity and responsiveness is likewise seen in bulimia nervosa with regard to the presence and severity of binge symptoms (Cyders and Smith, 2008).…”

Section: Neurocircuitry Implicated In Negative Urgency and Addictionmentioning

confidence: 99%

Impulsivity Derived From the Dark Side: Neurocircuits That Contribute to Negative Urgency

Zorrilla

Koob

2019

Front. Behav. Neurosci.

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Negative urgency is a unique dimension of impulsivity that involves acting rashly when in extreme distress and impairments in inhibitory control. It has been hypothesized to derive from stress that is related to negative emotional states that are experienced during the withdrawal/negative affect stage of the addiction cycle. Classically, a transition to compulsive drug use prevents or relieves negative emotional states that result from abstinence or stressful environmental circumstances. Recent work suggests that this shift to the “dark side” is also implicated in impulsive use that derives from negative urgency. Stress and anxious, depressed, and irritable mood have high comorbidity with addiction. They may trigger bouts of drug seeking in humans via both negative reinforcement and negative urgency. The neurocircuitry that has been identified in the “dark side” of addiction involves key neuropeptides in the central extended amygdala, including corticotropin-releasing factor. The present review article summarizes empirical and conceptual advances in the field to understand the role of the “dark side” in driving the risky and detrimental substance use that is associated with negative urgency in addiction.

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Section: Neurocircuitry Implicated In Negative Urgency and Addictionmentioning

confidence: 99%

Impulsivity Derived From the Dark Side: Neurocircuits That Contribute to Negative Urgency

Zorrilla

Koob

2019

Front. Behav. Neurosci.

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“…55 and 5-HT has been implicated in fly ethanol sedation. 59 Furthermore, there is a large literature linking 5-HT to alcohol problems in humans (eg, [60][61][62][63][64] ). These findings collectively suggested that there could be mechanistic connections between serotonergic neurons and the effect of dietary yeast on ethanol sedation.…”

Section: Resultsmentioning

confidence: 99%

“…Dietary yeast influences brain 5-HT content in flies 55 ; 5-HT likely plays a role in fly ethanol sedation, 59 and 5-HT is connected to problematic alcohol consumption in humans (eg, [60][61][62][63][64] ). Additionally, serotonergic neurons and serotonin signaling are important for hunger/satiety and feeding behavior in both larval and adult flies.…”

Section: Discussionmentioning

confidence: 99%

“…In flies, for example, dietary yeast influences brain 5-HT levels, 55 serotonergic neurons regulate feeding, [56][57][58] the 5-HT2A receptor impacts dietary protein consumption, 55 and 5-HT is implicated in ethanol sedation. 59 Additionally, there is a large literature linking 5-HT to alcohol problems in humans (eg, [60][61][62][63][64] ). Despite the insights of the studies summarized here, the possibility that 5-HT signaling underlies diet-induced changes in behavioral responses has not been formally addressed.…”

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confidence: 99%

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Dietary yeast influences ethanol sedation in Drosophila via serotonergic neuron function

et al. 2019

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Abuse of alcohol is a major clinical problem with far‐reaching health consequences. Understanding the environmental and genetic factors that contribute to alcohol‐related behaviors is a potential gateway for developing novel therapeutic approaches for patients that abuse the drug. To this end, we have used Drosophila melanogaster as a model to investigate the effect of diet, an environmental factor, on ethanol sedation. Providing flies with diets high in yeast, a routinely used component of fly media, increased their resistance to ethanol sedation. The yeast‐induced resistance to ethanol sedation occurred in several different genetic backgrounds, was observed in males and females, was elicited by yeast from different sources, was readily reversible, and was associated with increased nutrient intake as well as decreased internal ethanol levels. Inhibition of serotonergic neuron function using multiple independent genetic manipulations blocked the effect of yeast supplementation on ethanol sedation, nutrient intake, and internal ethanol levels. Our results demonstrate that yeast is a critical dietary component that influences ethanol sedation in flies and that serotonergic signaling is required for the effect of dietary yeast on nutrient intake, ethanol uptake/elimination, and ethanol sedation. Our studies establish the fly as a model for diet‐induced changes in ethanol sedation and raise the possibility that serotonin might mediate the effect of diet on alcohol‐related behavior in other species.

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“…There are numerous lines of evidence indicating that decreased levels of 5HT are strongly associated with increased alcohol consumption and risk for future alcohol problems (145–147). One recent study reported that negative urgency (as measured by UPPS-P) mediated the relationship between alcohol abuse and genetically driven decreases in 5HT availability (148). In this study, higher polygenic 5HT scores (indicating lower 5HT function) were positively correlated with higher self-reported negative urgency and greater levels of alcohol consumption.…”

Section: Neural and Genetic Correlates Of Negative Urgency And Potentmentioning

confidence: 99%

Integrating Preclinical and Clinical Models of Negative Urgency

2019

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Overwhelming evidence suggests that negative urgency is robustly associated with rash, ill-advised behavior, and this trait may hamper attempts to treat patients with substance use disorder. Research applying negative urgency to clinical treatment settings has been limited, in part, due to the absence of an objective, behavioral, and translational model of negative urgency. We suggest that development of such a model will allow for determination of prime neurological and physiological treatment targets, the testing of treatment effectiveness in the preclinical and the clinical laboratory, and, ultimately, improvement in negative-urgency-related treatment response and effectiveness. In the current paper, we review the literature on measurement of negative urgency and discuss limitations of current attempts to assess this trait in human models. Then, we review the limited research on animal models of negative urgency and make suggestions for some promising models that could lead to a translational measurement model. Finally, we discuss the importance of applying objective, behavioral, and translational models of negative urgency, especially those that are easily administered in both animals and humans, to treatment development and testing and make suggestions on necessary future work in this field. Given that negative urgency is a transdiagnostic risk factor that impedes treatment success, the impact of this work could be large in reducing client suffering and societal costs.

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Negative Urgency Mediates the Relation Between Genetically Influenced Serotonin Functioning and Alcohol Problems

Cited by 17 publications

References 69 publications

Impulsivity Derived From the Dark Side: Neurocircuits That Contribute to Negative Urgency

Impulsivity Derived From the Dark Side: Neurocircuits That Contribute to Negative Urgency

Dietary yeast influences ethanol sedation in Drosophila via serotonergic neuron function

Integrating Preclinical and Clinical Models of Negative Urgency

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