Low platelet MAO activity associated with high dysfunctional impulsivity and antisocial behavior: evidence from drunk drivers

Rationale Low platelet monoamine oxidase (MAO) activity is associated with problem drinking and other deviant behaviors. Since the majority of alcohol abusers are smokers, and tobacco smoke has a direct inhibitory effect on the enzyme, these associations may not be meaningful.Objective The authors compared platelet MAO activity and impulsivity in police-referred subjects caught driving while intoxicated and in control subjects, controlling for smoking.Methods Platelet MAO activity was measured radioenzymatically and impulsivity scores obtained from questionnaires. Smoking status was self-reported.Results Subjects caught driving while intoxicated had significantly higher dysfunctional impulsivity and lower platelet MAO activity than control subjects. This difference in platelet MAO activity between the two groups was significant in non-smokers and ex-smokers.Conclusions These findings demonstrate that platelet MAO activity is lower in subjects with socially deviant behavior, and the association of low platelet MAO and problem drinking is not an artifact of smoking.     

Diazepam produces disinhibitory cognitive effects in male volunteers

Rationale Diazepam has well known amnestic and sedative effects but effects on fronto-executive function remain largely uninvestigated, especially on neuropsychologically validated tests of risk taking and orbitofrontal cortex function.Objectives We aimed to determine the impact of diazepam on a variety of executive tasks.Methods The effects of 5, 10 and 20 mg of diazepam on a battery of neuropsychological tests were investigated using a randomised, double blind, placebo-controlled design. Seventy-five adult men were recruited. The Rogers et al. (1999b) test of risk-taking was given along with tasks from the CANTAB battery.Results Diazepam impaired performance on the Tower of London test of planning, without influencing visual pattern recognition memory. Subjects who had taken diazepam made more risky choices on the risk-taking task. On two speeded reaction time tasks diazepam impaired discrimination sensitivity and increased the bias to respond.Conclusions In contrast to the well-known sedative effects of diazepam, we demonstrate disinhibitory effects on two speeded reaction time tasks. Our results show that diazepam can impair performance on reaction time tasks both by impairing sensitivity and by increasing the bias to respond. Furthermore diazepam impaired performance on tests of planning and risky decision making that depend predominantly on dorsolateral and orbitofrontal regions of the prefrontal cortex, respectively.     

Impulsivity and alcohol-related risk among college students: Examining urgency,sensation seeking and the moderating influence of beliefs about alcohol's role in the college experience

The personality trait of impulsivity is predictive of heavy drinking and consequences among college students. The current study examined how impulsivity—measured via positive urgency, negative urgency, and sensation seeking—and a person's beliefs about the role alcohol plays in the college experience relate to drinking and consequences in a sample of 470 college students (mean age = 19 years, 61.3% female, 59.8% White). In support of the hypotheses, sensation seeking independently predicted greater drinking, and both positive urgency and negative urgency predicted greater experience of alcohol-related negative consequences after controlling for consumption level. Moreover, alcohol beliefs moderated the relationship between impulsivity types and alcohol outcomes. Among students high (versus low) in sensation seeking, strong beliefs about alcohol's role in college life were related to significantly greater drinking, and among students high (versus low) in negative urgency, endorsing strong beliefs about alcohol's role in college life were related to greater levels of alcohol-related negative consequences. Overall, findings inform college prevention efforts by highlighting the need to distinguish unique facets of impulsivity and examine how they intersect with students' beliefs about alcohol in college.     

Impulsivity: Four ways five factors are not basic to addiction

Several impulsivity-related models have been applied to understanding the vulnerability to addiction. While there is a growing consensus that impulsivity is multifaceted, debate continues as to the precise number of facets and, more critically, which are most relevant to explaining the addiction-risk profile. In many ways, the current debate mirrors that which took place in the personality literature in the early 1990s (e.g., Eysenck's ‘Big Three’ versus Costa and McCrae's ‘Big Five’). Indeed, many elements of this debate are relevant to the current discussion of the role of impulsivity in addictive behavior. Specifically, 1) the use of factor analysis as an atheoretical ‘truth-grinding machine’; 2) whether additional facets add explanatory power over fewer; 3) the delineation of specific neurocognitive pathways from each facet to addictive behaviors, and; 4) the relative merit of ‘top-down’ versus ‘bottom-up’ approaches to the understanding of impulsivity. Ultimately, the utility of any model of impulsivity and addiction lies in its heuristic value and ability to integrate evidence from different levels of analysis. Here, we make the case that theoretically-driven, bottom-up models proposing two factors deliver the optimal balance of explanatory power, parsimony, and integration of evidence.     

大学生冲动性与心理健康水平的相关研究

目的调查大学生的冲动性水平及心理健康水平,并分析二者之间的关系。方法采用大学生一般调查表、Barratt冲动性量表第11版（BIS-11）、症状自评量表（SCL-90）为研究工具,对分层随机抽取的722名大一-大三的在校学生进行问卷调查。结果大学生的冲动性总分为（67.43±8.67）分;SCL-90的恐怖因子高于全国常模（P〈0.05）,强迫症状、人际关系敏感、抑郁、偏执、精神病性5个因子的得分低于全国常模（P〈0.05）;SCL-90的10个因子与冲动性存在正相关（P〈0.05）。精神病性（b=0.295,P=0.007）、敌对（b=0.334,P=0.004）、焦虑（b=0.574,P=0.001）、恐怖（b=0.496,P=0.000）对于冲动性具有预测作用。结论大学生冲动性水平总体处于中等水平,心理健康水平总体稍优于全国水平,心理健康状况对冲动性水平具有较强的影响作用。     

High-dose MDMA does not result in long-term changes in impulsivity in the rat

Rationale Evidence suggests that recreational users of (±)3,4-methylenedioxymethamphetamine HCl (MDMA, “ecstasy”) have cognitive and behavioral deficits and show increased impulsivity consistent with 5-hydroxytryptamine (5-HT) neurotoxicity. MDMA effects on impulsivity in users are difficult to establish being confounded by polydrug use and individual predisposition to impulsivity or behavioral inhibition.Objective We previously observed a long-term anxiolytic effect of a neurotoxic dose of MDMA on elevated plus maze behavior in Dark Agouti (DA) rats while other strains were reported to show anxiogenesis. We have now examined whether MDMA influences impulsivity producing disinhibited behavior interpretable as anxiolysis.Methods Impulsivity was measured using an operant visuospatial discrimination procedure. Male DA rats (n=24) were trained to lever press for food reward in response to a light-stimulus and subsequently required to withhold responding. Correct responses, premature responses, and response latencies were used as measures of accuracy and impulsivity. Trained rats were administered MDMA (5 mg/kg, i.p. at 3-h intervals to a total of three injections). Performance was measured at 3 h and 7, 27, 49, and 80 days posttreatment.Results There was a short-term effect of MDMA on the percentage of correct responses at 3 h and day 1 with recovery to control levels by days 7–8 and no significant long-term changes up to day 80. There was no effect of MDMA on premature responses on any of the days measured. MDMA reduced cortical 5-HT content (MDMA 363±14 ng/g and control 440±10 ng/g tissue).Conclusion These results suggest that impulsivity may not be directly altered by MDMA despite serotonergic neurotoxicity.     

Impulsivity and the role of smoking-related outcome expectancies among dependent college-aged cigarette smokers

The relationship between trait-impulsivity and smoking expectancies on smoking progression in undergraduate college students was examined over a 48-hour period of smoking abstinence. Participants were forty-nine college-aged dependent cigarette smokers who completed measures designed to assess impulsivity, nicotine dependence, and smoking expectancies. Using a series of multilevel models, impulsivity by time analyses indicated significant differences in positive reinforcement expectancies, [F (2, 94)=3.19, p<.05], but not in negative reinforcement expectancies, [F (2, 94)=0.49, p=.61]. Simple slopes analyses indicated that heightened trait-impulsivity predicted greater increases in positive reinforcement outcome expectancies at 48 h of abstinence. Level of impulsivity, however, was not related to changes in negative reinforcement expectancies. Results indicate that during an abstinence period, college students higher in trait-impulsivity may be more prone to relapse due to stronger beliefs about the positive effects from smoking a cigarette. These findings highlight the importance of understanding the interaction of personality and cognitive factors when working with young adult smokers wishing to quit this health-compromising behavior.     

Discounting of delayed rewards in substance abusers: relationship to antisocial personality disorder

RATIONALE: Delay discounting is associated with impulsivity and drug abuse, and this study evaluated the relationship between discounting of delayed rewards and antisocial personality disorder (ASP). OBJECTIVES: To determine whether discounting is increased in substance abusers with ASP relative to those without; both groups were compared with non-substance-abusing controls. METHODS: Subjects ( n=166) chose between hypothetical monetary amounts available after various delays or immediately. Under one condition, a US $1000 reward was delayed at intervals ranging from 6 h to 25 years. At each delay interval, the immediately available rewards varied from US $1 to US $999 until choices reflected indifference between the smaller immediate and larger delayed rewards. Under a second condition, the delayed reward was US $100, and immediate rewards varied from US $0.10 to US $99.90. RESULTS: In all three groups, hyperbolic discounting functions provided a good fit of the data, and the smaller reward was discounted at a higher rate than the larger reward. Substance abusers discounted delayed rewards at significantly greater rates than controls, and substance abusers with ASP discounted delayed rewards at higher rates than their non-ASP substance-abusing counterparts. Discounting rates were correlated with impulsivity scores on a personality questionnaire. CONCLUSIONS: These results provide further evidence of more rapid discounting of delayed rewards in substance abusers, especially among substance abusers with a co-morbid diagnosis of ASP.     

The pharmacology of impulsive behaviour in rats VI: the effects of ethanol and selective serotonergic drugs on response choice with varying delays of reinforcement

Rationale: Tolerance to delay of reinforcement has been proposed as an important facet of self-control in both animals and man. Poor self-control, leading to impulsive behaviour, can be a major problem if it reaches pathological levels. Objectives: The effects of five serotonergic drugs were compared to those of ethanol on a procedure for measuring tolerance to delay of reinforcement in rats in order to elucidate further the role of the serotonin systems in the regulation of impulsive behaviour. Methods: Rats were trained to choose between a single food pellet (small reinforcer) delivered immediately or five food pellets (large reinforcer) delivered after programmed delays. At the start of each session, there was no delay between the response and delivery of the large reinforcer, but this was increased stepwise during the session to delays of 10, 20, 40 and 60 s. Results: The rats showed consistent preference for the larger reinforcer when it was not delayed but showed a shift in preference as the session continued, so that they preferred the small reinforcer when the large was delayed by 40 or 60 s. Ethanol at a dose of 1.0 g/kg produced a significance increase in preference for the small, immediate reinforcer throughout the session, although there were marked individual differences in the size of the effect. A similar, but somewhat smaller effect was seen with the 5-HT₂ agonist, DOI, at a dose of 1.0 mg/kg. In contrast, the 5-HT_1A agonist, 8-OH-DPAT (0.3 mg/kg) reduced preference for the large reinforcer at the start of the session, and reduced preference for the small reinforcer at the end of the session, i.e. produced a regression to indifference. Lower doses of these three drugs, and treatment with the 5-HT receptor subtype selective antagonists WAY-100635 (5-HT_1A: 0.01–0.1 mg/kg), ritanserin (5-HT₂: 0.1 and 0.3 mg/kg) and MDL-72222 (5-HT₃: 1.0 and 3.0 mg/kg) had no significant effects on reinforcer choice. Conclusion: These data show that ethanol and DOI increase preference for the immediate reinforcer, which can be construed as evidence of an increase in impulsive behaviour (reduction in self control), whereas selective blockade of the 5-HT_1A, 5-HT₂ or 5-HT₃ receptors using selective antagonists does not affect self-control. Received: 24 October 1998 / Final version: 16 February 1999     

Effects of d,l-fenfluramine on aggressive and impulsive responding in adult males with a history of conduct disorder

Rationale: The role of serotonin in aggression and impulsivity was examined by administering the serotonin-releasing drug, d,l-fenfluramine and measuring effects on aggressive and impulsive responding under controlled laboratory conditions. Methods: Ten male subjects with a history of conduct disorder and criminal behavior participated in experimental sessions, which measured aggressive and impulsive responses. Aggression was measured using the Point subtraction Aggression paradigm (PSAP), which provides subjects with an aggressive, escape and monetary reinforced response options. Impulsive responses were measured using a paradigm which provided subjects with choices between small rewards after short delays versus larger rewards have long delays. Results: Acute challenge doses (0.2,0.4 and 0.8 mg/kg) of d,l-fenfluramine produced significant dose-dependent decreases in aggressive and impulsive responses. Escape and monetary reinforced responses were not significantly changed. Decreases in aggressive responses were therefore selective, because escape responses were not affected, and could not be attributed to a non-specific sedative action because monetary reinforced responses were slightly increased. Conclusions: Release of serotonin and/or reuptake blockade by d,l-fenfluramine is the possible mechanism for reductions in aggression and impulsivity. These results are consistent with a large body of data linking reduced serotonin function and aggressive behavior and impulsivity. Received: 5 March 1999 / Final version: 2 June 1999