Two models of impulsivity: relationship to personality traits and psychopathology.

BACKGROUND: Impulsivity is prominent in psychiatric disorders. Two dominant models of impulsivity are the reward-discounting model, where impulsivity is defined as inability to wait for a larger reward, and the rapid-response model, where impulsivity is defined as responding without adequate assessment of context. We have compared the role of these models of impulsivity in human psychopathology, based on the hypothesis that rapid-response impulsivity would be more strongly related to other aspects of psychopathology and to impulsivity as described by questionnaires.METHODS: We investigated relationships between personality and laboratory measures of impulsivity, and between these measures and clinical characteristics, in parents of adolescent subjects with disruptive behavioral disorders (DBDs) and matched control subjects. Diagnoses were rendered using the Structured Interview for DSM-IV. The Barratt Impulsiveness Scale (BIS) was used as a trait measure of impulsivity. Rapid-response impulsivity was assessed using a form of the Continuous Performance Test, the Immediate Memory-Delayed Memory Task (IMT/DMT). Reward-delay impulsivity was measured using two tasks where subjects could choose between smaller immediate or larger delayed rewards.RESULTS: Rapid-response, but not reward-delay impulsivity, was significantly higher in subjects with lifetime Axis I or Axis II diagnoses. Scores on the BIS were elevated in subjects with Axis I diagnoses and correlated significantly with both rapid-response and reward-delay tests, but more strongly with the former. Multiple regression showed that rapid-response, but not reward-delay performance or intelligence quotient, contributed significantly to BIS scores. Correlations were similar in parents of control subjects and of DBD subjects.CONCLUSIONS: These data suggest that measures of rapid-response impulsivity and of reward-delay impulsivity are both related to impulsivity as a personality characteristic. The relationship appears stronger, however, for rapid-response impulsivity, as measured by the IMT/DMT. Laboratory and personality measures of impulsivity appear to be related to risk of psychopathology.     

线索诱发海洛因依赖者心理渴求及相关因素分析

目的　了解环境线索对海洛因依赖者心理渴求的影响及其相关因素。方法　380名戒断 期海洛因依赖者暴露于海洛因相关环境线索,测量暴露前后血压、心率、瞳孔,Likert分级法记录暴露前 后的渴求程度,完成自编诱发后戒断反应问卷及自编毒品使用情况和一般社会学资料。采用配对t检 验,比较暴露前后渴求程度及心率、血压等生理指标的变化,运用逐步回归分析与线索诱发渴求相关的 指标。结果　暴露后渴求、心率、血压及瞳孔均明显高于暴露前,差别有极显著意义(分别为t= -15.02,-14.23,-8.12,-5.03,-14.65,P<0.01)。诱发渴求与毒品依赖自评分值、诱发后心率及 主观戒断反应呈正相关,与成瘾时间呈成负相关。结论　环境线索可以使戒断期海洛因依赖者心理渴 求明显增加,依赖自评分值、诱发后心率、主观戒断反应及成瘾时间均与诱发渴求程度相关。     

Early environmental experience alters baseline and ethanol-induced cognitive impulsivity: relationship to forebrain 5-HT1A receptor binding

The relationship between impulsivity and drug abuse is poorly understood despite evidence that impulsive behaviour both predicts, and is a consequence of, drug use. Moreover, although there are clear individual differences in the propensity to addiction, this relationship has not been investigated with respect to impulsive behaviour. We tested whether early environmental experience would influence behavioural measures of impulsivity, and further, whether this experience would alter impulsive choice following ethanol intoxication. Thirty-six male, Long-Evans rats were reared in either isolated (1 rat/cage), standard (2 rats/cage), or enriched (group housed with toys) conditions. After a 3-month rearing period, animals were tested in two operant tasks measuring either motor (go/no-go) or cognitive (delay-to-reinforcement) impulsivity. Rats were then re-tested following 0, 0.3, 0.6, 0.9, and 1.2 g/kg ethanol. Forebrain 5-HT1A binding was assessed post-mortem using in vitro receptor autoradiography with the agonist [3H]8-OH-DPAT (3H-8-hydroxy-2-[di-n-propylamino]tetralin). Rearing condition did not influence baseline motor impulsivity, but isolation rearing led to decreased baseline cognitive impulsivity. Ethanol did not affect motor impulsivity, but dose-dependently increased impulsive choice in the delay-to-reinforcement task. Enriched rats were more impulsive overall, and isolation-reared rats only showed a shift in impulsive behaviour after 1.2 g/kg. Isolation rearing decreased, and enrichment rearing increased 5-HT1A binding in the frontal pole of the cortex following experience in the delay-to-reinforcement task. Isolation-reared rats also showed a significant decrease in 5-HT1A binding in the dentate gyrus of the ventral hippocampus following experience in the delay-to-reinforcement relative to the go/no-go task. These data indicate that differential rearing has a significant influence on cognitive impulsivity, and that altered serotonergic function may underlie these differences.     

Conceptualizing impulsivity and risk taking in bipolar disorder: importance of history of alcohol abuse

Background:  Elevated levels of impulsivity and increased risk taking are thought to be core features of both bipolar disorder (BD) and addictive disorders. Given the high rates of comorbid alcohol abuse in BD, alcohol addiction may exacerbate impulsive behavior and risk-taking propensity in BD. Here we examine multiple dimensions of impulsivity and risk taking, using cognitive tasks and self-report measures, in BD patients with and without a history of alcohol abuse.
Methods:  Thirty-one BD subjects with a prior history of alcohol abuse or dependence (BD-A), 24 BD subjects with no history of alcohol abuse/dependence (BD-N), and 25 healthy control subjects (HC) were assessed with the Barratt Impulsiveness Scale (BIS) and the computerized Balloon Analogue Risk Task (BART).
Results:  Both BD groups scored significantly higher than controls on the BIS. In contrast, only the BD-A group showed impaired performance on the BART. BD-A subjects popped significantly more balloons than the BD-N and HC groups. In addition, subjects in the BD-A group failed to adjust their performance after popping balloons. Severity of mood symptomatology was not associated with performance on either task.
Discussion:  The current study supports a primary role of prior alcohol abuse in risk-taking propensity among patients with bipolar disorder. In addition, findings suggest that impulsivity and risky behavior, as operationalized by self-report and experimental cognitive probes, respectively, are separable constructs that tap distinct aspects of the bipolar phenotype.     

Impulsivity in patients with panic disorder-agoraphobia: The role of cyclothymia

The relationship between Panic Disorder (PD) and impulsivity is not well explored. The present investigation aims to compare impulsivity, measured by different rating tools, in PD patients vs. healthy controls and to explore the influence of co-morbid Cyclothymic Disorder (CD) on the relationship between PD and impulsivity. Sixty-four subjects with PD and 44 matched controls underwent a diagnostic and symptomatological evaluations by the Mini Neuropsychiatric Interview (M.I.N.I) Plus 5.0; the Bech-Rafaelsen Depression and Mania Scale (BRDMS), the State-Trait Anxiety Inventory (STAI), the Hypomania Check List (HCL-32) and the Clinical Global Impression (CGI); the Questionnaire for the Affective and Anxious Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Modified (TEMPS-M), the Separation Anxiety Sensitivity Index (SASI), the Interpersonal Sensitivity Symptoms Inventory (ISSI). Finally, psychometric and neurocognitive evaluations of impulsivity was carried out using the Barratt Impulsiveness Scale (BIS-11) and the Immediate and Delayed Memory Task (IMT/DMT). Subjects with PD were more impulsive than the controls in all the explored measures, reporting higher scores in symptomatological and temperamental scales. The comparison between PD patients with (Cyclo+) and without (Cyclo−) comorbid CD and controls showed that Cyclo+ are the most impulsive subjects in all the investigated measures and are characterized by the greatest symptomatological impairment, the highest scores in temperamental scales, and the highest levels of interpersonal sensitivity and separation anxiety. In our patients with PD, without lifetime comorbidity with major mood episodes, trait and state impulsivity may be related to the presence of comorbid cyclothymic mood instability.     

Activation of reward circuitry in human opiate addicts

The neurobiological mechanisms of opiate addictive behaviour in humans are unknown. A proposed model of addiction implicates ascending brainstem neuromodulatory systems, particularly dopamine. Using functional neuroimaging, we assessed the neural response to heroin and heroin-related cues in established opiate addicts. We show that the effect of both heroin and heroin-related visual cues are maximally expressed in the sites of origin of ascending midbrain neuromodulatory systems. These context-specific midbrain activations predict responses to salient visual cues in cortical and subcortical regions implicated in reward-related behaviour. These findings implicate common neurobiological processes underlying drug and drug-cue-related effects.     

Polyradiculoneuropathy associated with heroin abuse.

Neurological complications of heroin addiction have occurred only sporadically in the United Kingdom. We report the case of a young female patient who developed an acute polyradiculoneuropathy when she recommended intravenous heroin after four years abstinence. Another possible aetiological factor was a preceding flu-like illness but, after full investigations, we concluded that heroin abuse was the most likely cause of the neurological symptoms.     

Imaging the neurochemistry of alcohol and substance abuse

Animal models of abuse and dependence have long suggested that chronic drug and alcohol exposure is associated with marked changes in neurochemistry. The development of PET and SPECT imaging now allows investigation of the effects of addiction on the neurochemistry of the human brain. This article reviews the literature of radiochemical imaging in cocaine, alcohol, heroin, methamphetamine, MDMA, and ketamine abuse and dependence.     

Impulsivity: a link between bipolar disorder and substance abuse

Background:  Substance abuse is present in most patients with bipolar disorder and associated with poor treatment outcome and increased risk of suicide. Increased impulsivity may be a link between bipolar disorder and substance abuse.
Methods:  First, we compared impulsivity as a stable trait (Barratt Impulsiveness Scale, BIS) and as state-dependent behavioral laboratory performance (Immediate Memory–Delayed Memory task, derived from the Continuous Performance Task) in interepisode bipolar and non-bipolar subjects with and without substance abuse. Secondly, we compared impulsivity in interepisode and manic bipolar subjects with and without substance abuse.
Results:  The BIS scores were increased in interepisode bipolar disorder and in subjects with histories of substance abuse, and were increased further in interepisode bipolar subjects with substance abuse. Performance impulsivity was increased in subjects with substance abuse, regardless of whether they had bipolar disorder. Among subjects with bipolar disorder, after correction for age, BIS scores were increased in those with substance abuse. Performance impulsivity was increased in manic compared with interepisode subjects, regardless of substance abuse history, and was increased in interepisode subjects with substance abuse similarly to manic subjects without substance abuse. These differences could not be accounted for by age, gender, or course of illness.
Conclusions:  Trait impulsivity is increased additively in bipolar disorder and substance abuse. Performance impulsivity is increased in interepisode bipolar disorder only if a history of substance abuse is present. This increased predisposition to impulsivity when not manic may contribute to the decrement in treatment outcome and compliance, and increased risk for suicide and aggression, in bipolar disorder with substance abuse.     

Multidimensional assessments of impulsivity in subjects with history of suicidal attempts

Objective

This study aimed to examine whether subjects with history of suicidal attempts had higher impulsivity as measured by neurocognitive tests and self-report questionnaires. The interrelationships among different impulsivity measures were also explored.

Methods

Fifty-four nonpsychotic psychiatric inpatients, including 24 subjects with previous history of suicidal attempts and 30 comparison subjects without previous suicidal attempts, completed the self-report Barratt Impulsiveness Scale-11-Chinese version (BIS-11-CH) and 2 neuropsychologic tests of impulsivity: the immediate memory task/delayed memory task (IMT/DMT) and the single key impulsivity paradigm (SKIP).

Results

The results indicated that subjects with previous suicidal attempts exhibited higher BIS-11-CH factor 2 (lack of self-control/attentional impulsivity) subscore (P = .02) and more commission errors in IMT (P = .03). However, BIS-11-CH scores and performance indices of IMT/DMT and of SKIP did not correlate with each other.

Conclusions

Our findings supported that subjects with previous suicidal attempts had higher impulsivity, which could be revealed by both self-report and neurocognitive measures. However, there is no correlation among self-report, IMT/DMT, and SKIP measures, indicating that they might be measuring different dimensions of impulsivity.     

Impact of contextual cues in the expression of the memory associated with diazepam withdrawal: involvement of hippocampal PKMζin vivo,and Arc expression and LTP in vitro

Hippocampal synaptic plasticity has been related to learning and adaptive processes developed during chronic drug administration, suggesting the existence of a common neurobiological mechanism mediating drug addiction and memory. Moreover, protein kinase M zeta (PKMζ) is critical for the maintenance of hippocampal long‐term potentiation (LTP) and spatial conditioned long‐term memories. Also, a link between activity‐regulated cytoskeleton‐associated protein (Arc), PKMζ and LTP has been proposed. Our previous results demonstrated that re‐exposure to the withdrawal environment was able to evoke the memory acquired when the anxiety measured as a diazepam (DZ) withdrawal sign was experienced. In the present work we evaluated if the memory associated with DZ withdrawal could be affected by changes in the contextual cues presented during withdrawal and by intrahippocampal administration of a PKMζ inhibitor. We found that the context was relevant for the expression of withdrawal signs as changes in contextual cues prevented the expression of the anxiety‐like behavior observed during plus‐maze (PM) re‐exposure, the associated enhanced synaptic plasticity and the increase in Arc expression. Furthermore, intrahippocampal administration of PKMζ inhibitor previous to re‐exposure to the PM test also impaired expression of anxiety‐like behavior and the facilitated LTP. These results support the relevance of the hippocampal synaptic plasticity in the maintenance of the memory trace during benzodiazepines withdrawal, adding new evidences for common mechanisms between memory and drug addiction that can be intervened for treatment or prevention of this pathology.     

PET imaging of dopamine D2 receptors in monkey models of cocaine abuse: genetic predisposition versus environmental modulation

OBJECTIVE: Animals self-administer many of the drugs that humans abuse, including cocaine. This article describes studies using preclinical animal models to differentiate the influences of neurobiological predisposition from environmental modulation of cocaine addiction, including studies from the authors' laboratory using nonhuman primates. METHOD: Addiction is described in terms of vulnerability, maintenance, and abstinence. This review focuses on dopamine receptor function, in particular that of the D2-like receptors, as measured by the noninvasive imaging procedure positron emission tomography. Findings from human studies of addiction and animal models are reviewed. RESULTS: There appears to be an inverse relationship between D2 receptor availability and vulnerability to the reinforcing effects of cocaine. Environmental variables can increase or decrease D2 receptor binding in an orderly fashion, and the resulting changes in D2 function influence the vulnerability to abuse cocaine. In maintenance, chronic cocaine exposure produces decreases in D2 receptor binding, which may be a mechanism that contributes to continued drug use. Finally, during abstinence there are individual differences in rates of recovery of D2 receptor availability. CONCLUSIONS: The goal of the preclinical research described in this review is to achieve a better understanding of individual differences in susceptibility and vulnerability to the reinforcing effects of cocaine. It is clear that the development of novel animal models will extend our understanding of the neurobiological basis of drug addiction to include a greater appreciation of the role of environmental factors in affecting predisposition, mediating continued drug use, and triggering relapse.     

Brief access to sweets protect against relapse to cocaine-seeking

The availability of alternative rewards can reduce acquisition and maintenance of cocaine self-administration in rats and humans. Once acquired, however, addiction is an intractable disease where relapse is elicited by exposure to drug-associated cues, the drug itself, or stress. The present study shows that both cocaine-seeking and drug-induced relapse are significantly reduced when drug-experienced, but abstinent, rats are given just 5 min daily prior access to a palatable glucose + saccharin mixture. The results suggest that presentation of an alternative reward may be useful as a therapeutic intervention for cocaine seeking and relapse.     

Trait impulsivity and response inhibition in antisocial personality disorder

Background

Impulsive behavior is a prominent characteristic of antisocial personality disorder. Impulsivity is a complex construct, however, representing distinct domains of cognition and action. Leading models refer to impulsivity as an inability to evaluate a stimulus fully before responding to it (rapid-response impulsivity), and as an inability to delay responding despite a larger reward (reward-delay impulsivity). We investigated these models in terms of the diagnosis and severity of antisocial personality disorder.

Methods

Thirty-four male subjects on probation/parole who met DSM-IV criteria for ASPD, and 30 male healthy comparison subjects, matched by ethnicity, were recruited from the community. The Barratt Impulsiveness Scale (BIS-11) provided an integrated measure of trait impulsivity. Rapid-response impulsivity was assessed using the Immediate Memory Task (IMT), a continuous performance test. Reward delay impulsivity was assessed using the Two-choice Impulsivity Paradigm (TCIP), where subjects had the choice of smaller-sooner or larger-delayed rewards, and the Single Key Impulsivity Paradigm (SKIP), a free-operant responding task.

Results

Compared to controls, subjects with ASPD had higher BIS-11 scores (Effect Size (E.S.) = 0.95). They had slower reaction times to IMT commission errors (E.S. = 0.45). Correct detections, a measure of attention, were identical to controls. On the SKIP, they had a shorter maximum delay for reward (E.S. = 0.76), but this was not significant after correction for age and education. The groups did not differ on impulsive choices on the TCIP (E.S. < 0.1). On probit analysis with age and education as additional independent variables, BIS-11 score, IMT reaction time to a commission error, and IMT positive response bias contributed significantly to diagnosis of ASPD; SKIP delay for reward did not. Severity of ASPD, assessed by the number of ASPD symptoms endorsed on the SCID-II, correlated significantly with commission errors (impulsive responses) on the IMT, and with liberal IMT response bias. This relationship persisted with correction for age and education.

Discussion

These results suggest that ASPD is characterized by increased rapid-response impulsivity. Aspects of impulsivity related to reward-delay or attention appear relatively intact.     

Maintenance treatment of opiate addicts

Maintenance treatment is now the most common treatment of opiate addicts in Germany. The principle of maintenance treatment is the administration of an opioid in order to suppress withdrawal symptoms and heroin craving. In this manner, maintenance treatment successfully reduces heroin abuse and directly associated risk behaviour. Only a minority of maintenance patients became opiate abstinent (including the maintenance drug). Racemic methadone is the most extensively evaluated maintenance drug. A differential indication between medical opioids has not been scientifically established. According to the German regulations psychosocial support is an obligatory part of maintenance treatment. Most opiate addicts suffer from comorbid mental and somatic diseases. Therefore psychiatric and somatic treatment is indicated and of proven value.     

Neurocognitive deficits associated with shoplifting in young adults

Objectives

Shoplifting is a relatively common behavior in young adults, but the demographic and neuropsychological correlates of shoplifting remain poorly characterized in this context.

Method

Non–treatment-seeking young adults (18-29 years) were recruited from the general community on the basis of having no Axis I disorders, no history of illicit substance use, and no history of conduct disorder or antisocial personality disorder. Participants were grouped according to presence or absence of shoplifting (at least 1 time over the past 12 months). Measures relating to impulsivity along with objective computerized neuropsychological measures were collected.

Results

Shoplifters (n = 14) and controls (n = 95) did not differ significantly in terms of salient demographic characteristics. Compared with controls, shoplifters endorsed higher impulsivity on the Barratt Impulsiveness Scale and Eysenck Impulsivity Questionnaire, gambled significantly more points on the Cambridge Gambling Task, and showed deficits on the hardest level of difficulty on the Spatial Working Memory task. Performance on executive planning, set-shifting, and response inhibition did not differ significantly between shoplifters and controls.

Conclusions

This study identified significant cognitive deficits in those with past-year shoplifting behavior even in the absence of Axis I disorders and a history of illicit drugs or alcohol. These preliminary findings inform our understanding of the neurocognitive sequelae of shoplifting and its relationship with other impulse control problems, subclinical and clinical. Future work should use longitudinal designs to examine the temporal relationship between these deficits, shoplifting behavior, other impulsive behavior, and functional impairment.     

Reduced grey matter in the posterior insula as a structural vulnerability or diathesis to addiction

A number of neuroimaging studies have shown that drug addiction is associated with morphological differences in several brain areas, including orbito-frontal and limbic structures. Most of these studies have investigated patients with addiction to cocaine. The neurobiological mechanisms which play a role in drug addiction are not fully understood, however, and the causal factors remain under investigation. The present study investigated morphological differences between patients with history of cocaine (N=14) and heroin (N=24) abuse and healthy matched controls (N=24). A 3D T1W MRI scan was acquired for all participants and the grey matter images of each patient group compared with those of controls. A direct comparison of the two addiction groups was also carried out. When compared with controls cocaine dependent patients had lower grey matter values in the left middle occipital gyrus, right putamen and insula, whereas heroin abusers had lower grey matter values in the right insula. The direct comparison between the two addiction groups showed that cocaine abusers had less grey matter in the right posterior cingulate, medio-temporal and cerebellar regions, whereas heroin abusers showed less grey matter in parietal regions on both sides, including postcentral gyrus and inferior parietal lobule. Reduced right posterior insular cortex was commonly found in both cocaine and heroin dependent patients. This morphological difference might represent a structural marker of addiction, which is independent of the discrete regional effects of each psychotropic substance of abuse, and might constitute a possible neurobiological vulnerability or diathesis to addiction. Equally, the discrete structural differences emerging from the direct comparison of cocaine and heroin abusers might reflect the effects of differential drug binding in the brain and/or express a form of neurobiological vulnerability which might explain individual drug choice.     

Behavioral sensitization to WIN55212.2 in rats pretreated with heroin

There is evidence of similarities and interactions between central opioid and cannabinoid system with reference to drug reinforcement and abuse. Here we demonstrate that repeated injection of heroin produces behavioral sensitization towards administration of the synthetic cannabinoid receptor agonist WIN55212.2 in the rat. These effects were blocked by both the cannabinoid antagonist SR141716A and the opioid antagonist naloxone. These findings suggest that repeated exposure to heroin produces neuroadaptative changes in brain circuits that contribute to mediate the behavioral consequences of acute administration of WIN55212.2. The present results expand our knowledge on the interactions between central opioid and cannabinoid systems with respect to drug abuse.     

GDNF and addiction

Biochemical adaptations to drugs of abuse and alcohol are especially profound in midbrain dopaminergic neurons. Long-lasting molecular and structural changes in mesolimbic dopaminergic neurons that result from chronic exposure to drugs of abuse and alcohol are thought to underlie adverse behaviors such as compulsive drug seeking and relapse. Recent studies suggest that a subset of these changes is prevented/reversed by activation of the glial cell line-derived neurotrophic factor (GDNF) signaling pathway. Behavioral effects of drugs of abuse such as cocaine and alcohol are also negatively regulated by GDNF: inhibition of the endogenous GDNF pathway enhances the activity of drugs of abuse, while administration of GDNF reduces the severity of the effects. In this review, we summarize the data implicating GDNF as a negative regulator of drug and alcohol addiction. We also provide evidence to suggest that therapies that activate GDNF signaling may be useful for the treatment of drug and alcohol addiction.     

The caudal part of the posterior insula of rats participates in the maintenance but not the acquisition of morphine conditioned place preference

The heterogeneous insular cortex plays an interoceptive role in drug addiction by signaling the availability of drugs of abuse. Here, we tested whether the caudal part of the multisensory posterior insula (PI) stores somatosensory‐associated rewarding memories. Using Sprague Dawley rats as subjects, we first established a morphine‐induced conditioned place preference (CPP) paradigm, mainly based on somatic cues. Secondly, an electrolytic lesion of the caudal portion of the PI was carried out before and after the establishment of CPP, respectively. Our data demonstrated that the caudal PI lesions disrupted the maintenance, but not the acquisition of morphine‐induced CPP. Lesion or subtle disruption of the PI had no major impact on locomotor activity. These findings indicate that the caudal portion of the PI might be involved in either the storage or the retrieval of morphine CPP memory.