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Rationale Pathological gambling (PG) has recently been considered as a “behavioral” or nonsubstance addiction. A comparison of the characteristics of PG and substance use disorders (SUDs) has clinical ramifications and could help advance future research on these conditions. Specific relationships with impulsivity and compulsivity may be central to understanding PG and SUDs. Objectives This review was conducted to compare and contrast research findings in PG and SUDs pertaining to neurocognitive tasks, brain function, and neurochemistry, with a focus on impulsivity and compulsivity. Results Multiple similarities were found between PG and SUDs, including poor performance on neurocognitive tasks, specifically with respect to impulsive choice and response tendencies and compulsive features (e.g., response perseveration and action with diminished relationship to goals or reward). Findings suggest dysfunction involving similar brain regions, including the ventromedial prefrontal cortex and striatum and similar neurotransmitter systems, including dopaminergic and serotonergic. Unique features exist which may in part reflect influences of acute or chronic exposures to specific substances. Conclusions Both similarities and differences exist between PG and SUDs. Understanding these similarities more precisely may facilitate treatment development across addictions, whereas understanding differences may provide insight into treatment development for specific disorders. Individual differences in features of impulsivity and compulsivity may represent important endophenotypic targets for prevention and treatment strategies.

Impulsivity and compulsivity represent useful conceptualizations that involve dissociable cognitive functions, which are mediated by neuroanatomically and neurochemically distinct components of cortico-subcortical circuitry. The constructs were historically viewed as diametrically opposed, with impulsivity being associated with risk-seeking and compulsivity with harm-avoidance. However, they are increasingly recognized to be linked by shared neuropsychological mechanisms involving dysfunctional inhibition of thoughts and behaviors. In this article, we selectively review new developments in the investigation of the neurocognition of impulsivity and compulsivity in humans, in order to advance our understanding of the pathophysiology of impulsive, compulsive, and addictive disorders and indicate new directions for research.

Women diagnosed with premenstrual dysphoric disorder (PMDD) report significant symptom relief when treated with selective serotonin reuptake inhibitors, but few studies have addressed the possibility of capturing this effect in behavioral, laboratory-based tests. This study examined the effects of intermittent treatment with escitalopram (vs. placebo) on a behavioral measure of impulsivity and inattentiveness in women reporting high levels of premenstrual irritability and anger. Participants (  = 27) rated cardinal PMDD mood symptoms over three menstrual cycles using Visual Analogue Scales. In Cycles 2 and 3, participants displaying cyclicity with respect to the irritability/anger item received escitalopram (20 mg) or placebo in a randomized, single-blind, crossover design. The participants completed the Conners Continuous Performance Test (CPT 3) in the luteal phase of the intervention cycles. Additionally, they filled out the UPPS Impulsive Behavior Scale, once in the luteal phase and once in the follicular phase of the placebo cycle. In line with previous reports, escitalopram caused a significant reduction in self-rated irritability and anger in the luteal phase. When on escitalopram, the participants demonstrated a lower frequency of anticipatory responses and greater consistency in response speed in the CPT 3. With respect to self-reported impulsivity, participants reported higher levels of urgency and lower levels of sensation seeking in the luteal placebo phase versus the follicular phase. The finding that escitalopram impacted the outcome of the CPT 3 test in women with premenstrual irritability highlights the possible role of impulsivity in this condition.

Research has indicated a major role of dopamine in decision-making processes, but the underlying mechanisms remain largely unknown due to inconsistency in effects of dopaminergic drugs. To clarify the impact of dopamine on impulsive choice, we administered 150 mg L-DOPA to 87 healthy adults in a randomized, placebo-controlled, double-blind, crossover study, evaluating performance in four value-based decision-making tasks. We predicted that baseline impulsivity would moderate L-DOPA effects. In support of our hypothesis, L-DOPA had no main effect on impulsive choice, but reduced risk-seeking for gains in more-impulsive subjects. Because L-DOPA effects may be influenced by body weight, we repeated our analyses on data from half of the sample (n = 44) with lower weight, anticipating a stronger effect. In addition to the effect on risk-seeking for gains, low-weight participants also exhibited baseline-dependent effects of L-DOPA on loss aversion and delay discounting. Our results are consistent with the hypothesis of an inverted U-shaped dopamine function in which both low and high extremes of dopamine signaling are associated with high-impulsive choice. Consideration of differential baseline impulsivity and body weight may resolve previous seemingly paradoxical pharmacological results and might deepen our understanding of dopaminergic mechanisms underlying impulsivity.

We argue that impulsiveness is characterized by compromised timing functions such as premature motor timing, decreased tolerance to delays, poor temporal foresight and steeper temporal discounting. A model illustration for the association between impulsiveness and timing deficits is the impulsiveness disorder of attention-deficit hyperactivity disorder (ADHD). Children with ADHD have deficits in timing processes of several temporal domains and the neural substrates of these compromised timing functions are strikingly similar to the neuropathology of ADHD. We review our published and present novel functional magnetic resonance imaging data to demonstrate that ADHD children show dysfunctions in key timing regions of prefrontal, cingulate, striatal and cerebellar location during temporal processes of several time domains including time discrimination of milliseconds, motor timing to seconds and temporal discounting of longer time intervals. Given that impulsiveness, timing abnormalities and more specifically ADHD have been related to dopamine dysregulation, we tested for and demonstrated a normalization effect of all brain dysfunctions in ADHD children during time discrimination with the dopamine agonist and treatment of choice, methylphenidate. This review together with the new empirical findings demonstrates that neurocognitive dysfunctions in temporal processes are crucial to the impulsiveness disorder of ADHD and provides first evidence for normalization with a dopamine reuptake inhibitor.

RationaleIndividuals suffering from alcohol use disorder (AUD) demonstrate difficulty with decision-making and impulsivity that may be associated with impaired frontal cortical function. Therapeutics that enhance frontal dopamine tone could decrease impulsivity and in turn reduce alcohol consumption in individuals with AUD.ObjectivesTo determine if the catechol-O-methyltransferase (COMT) inhibitor tolcapone can attenuate alcohol consumption in individuals with AUD and whether this attenuation correlates with tolcapone-induced changes in laboratory-based decision-making tasks.MethodsWe used daily self-report and a novel group laboratory bar task to assess the effects of randomized double-blind crossover administration of tolcapone (100 mg TID for 5 days) on alcohol consumption and laboratory tasks assessing impulsivity in 55 non-treatment-seeking subjects with AUD.ResultsTolcapone significantly reduced self-reported alcohol consumption (t (54) = 2.05, p = 0.045). The effects of tolcapone on drinking significantly correlated with changes in impulsive decision-making, such that subjects with the greatest decrease in impulsive choice on tolcapone also reported the greatest decrease in alcohol consumption (r (45) = 0.40, p = 0.0053). We did not see effects of tolcapone on laboratory bar consumption. Adverse event (AE) reporting was low, with no significant difference in frequency or severity of AEs on tolcapone versus placebo.ConclusionsThese data demonstrate that COMT inhibitors such as tolcapone may be useful therapeutics for AUD.Trial registrationClinicalTrials.gov Identifier: NCT 02740582

The concepts of impulsivity and compulsivity are commonly used in psychiatry. Little is known about whether different manifest measures of impulsivity and compulsivity (behavior, personality, and cognition) map onto underlying latent traits; and if so, their inter-relationship. A total of 576 adults were recruited using media advertisements. Psychopathological, personality, and cognitive measures of impulsivity and compulsivity were completed. Confirmatory factor analysis was used to identify the optimal model. The data were best explained by a two-factor model, corresponding to latent traits of impulsivity and compulsivity, respectively, which were positively correlated with each other. This model was statistically superior to the alternative models of their being one underlying factor ('disinhibition') or two anticorrelated factors. Higher scores on the impulsive and compulsive latent factors were each significantly associated with worse quality of life (both p < 0.0001). This study supports the existence of latent functionally impairing dimensional forms of impulsivity and compulsivity, which are positively correlated. Future work should examine the neurobiological and neurochemical underpinnings of these latent traits; and explore whether they can be used as candidate treatment targets. The findings have implications for diagnostic classification systems, suggesting that combining categorical and dimensional approaches may be valuable and clinically relevant.

The majority of drug abusers are incapable of sustaining abstinence over any length of time. Accumulating evidence has linked intense and involuntary craving, Impulsive decision-making and mood disturbances to risk for relapse. However, little is known about temporal changes of these neuropsychological functions in methamphetamine (METH)-dependent individuals. To investigate the effect of length of abstinence on decision-making, craving (baseline and cue-induced), and emotional state in METH-addicted individuals. In this cross-sectional study, 183 adult METH-dependent patients at an addiction rehabilitation center who were abstinent for 6 days (n = 37), 14 days (n = 33), 1 month (n = 31), 3 months (n = 30), 6 months (n = 26), or 1 year (n = 30) and 39 healthy subjects were administered the Iowa Gambling Task (IGT) to assess decision-making performance. Depression, anxiety, and impulsivity were also examined. One hundred thirty-nine METH abusers who were abstinent for the aforementioned times then underwent a cue session, and subjective and physiological measures were assessed. METH dependent individuals who were abstinent for longer periods of time exhibited better decision-making than those who were abstinent for shorter periods of time. And self-reported emotional symptoms improved with abstinence. METH abusers' ratings of craving decreased with the duration of abstinence, while cue-induced craving increased until 3 months of abstinence and decreased at 6 months and 1 year of abstinence. We present time-dependent alterations in decision-making, emotional state, and the incubation of cue-induced craving in METH-dependent individuals, which might have significant clinical implications for the prevention of relapse.

Background New psychoactive substances (NPS) are chemical analogues designed to mimic the effects of various classic recreational drugs of abuse including MDMA, LSD, and cannabis. NPS use is associated with concern about the acute and longer-term effects particular substances might have, with abuse and addiction as potential consequences. Impulsivity and sensitivity to the rewarding effects of drugs have been considered as risk factors for drug abuse. In light of the popularity of 4-fluoroamphetamine (4-FA), it is important to assess whether 4-FA can lead to subjective drug liking and wanting, and impulsive behavior, all factors contributing to the abuse likelihood of a substance. Methods A placebo-controlled 2-way crossover study in 12 healthy poly-drug using participants was conducted to test subjective and behavioral effects of 4-FA (100 mg). 4-FA concentrations were determined in serum up to 12 h after administration and two impulsivity tasks and two drug experience questionnaires assessing drug liking and wanting, and good and bad drug effect, were administered between 1 and 11 h post-administration. Results Findings showed that 4-FA did not affect impulsive behavior. Self-ratings of drug liking and wanting and good drug effect were increased 1 h after administration; this effect was absent 11 h after drug intake. Discussion and conclusion To conclude, 4-FA (single dose) increased self-rated liking and wanting , which is known to contribute to the abuse likelihood of a substance; however, it left another factor impulsive behavior unaffected. It has to be noted that the current picture is limited and might change with increased sample size, and/or different 4-FA doses. Clinical trial registration Trial acronym: 4-FA. URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6164 . Registration number: NTR6164 (Dutch clinical trial registry number).

Objective: It has been shown repeatedly that impulsivity, obesity and food intake are related; obese people are more impulsive than lean people and impulsive people eat more than less impulsive people. The relation between impulsivity and food intake might be state dependent; hunger motivates food seeking behaviour and food consumption, especially of high caloric food. Difficulties to overrule automatic behavioural tendencies might make impulsive people more susceptible to the effects of hunger on food selection. Therefore, they are expected to increase their intake more than low impulsive people when feeling hungry. Study 1: Fifty-seven female participants were randomly assigned to a hunger or sated condition. Response inhibition (a measure of impulsivity) and food intake were measured. Results show that impulsive participants ate significantly more, but only when feeling hungry. Study 2: Ninety-four undergraduate students participated. Hunger, response inhibition and the purchase of food in a virtual supermarket were measured. The same interaction was found: impulsive participants bought most calories, especially from snack food, but only when feeling hungry. Conclusion: Hunger and impulsivity interact in their influence on consumption. These data suggest that reducing hunger during calorie restricting diets is important for successful weight loss, particularly for the impulsive dieters.