Cluster B personality disorders are associated with allelic variation of monoamine oxidase A activity.
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Genetic variants of the monoamine oxidase A (MAOA) have been associated with aggression-, anxiety-, and addiction-related behavior in several nonclinical and clinical populations. Here, we investigated the influence of allelic variation of MAOA activity on aggression-related personality traits and disease risk in patients with personality disorders. Personality disorders were diagnosed with the Structured Clinical Interview of DSM-IV and were allocated to cluster A, B, and C. Personality features were assessed by the revised NEO Personality Inventory and the Tridimensional Personality Questionnaire. The genotype of the MAOA gene-linked polymorphic region (MAOA-LPR) was determined in 566 patients with personality disorders and in 281 healthy controls. MAOA genotype was significantly associated with cluster B personality disorders (chi2=7.77, p=0.005, df=1) but not with cluster C personality disorders. In total, 26.0% of cluster B patients were hemi- or homozygous for the low-activity variant of the MAOA genotype, compared to 16.4% in the control group. Associations between MAOA variants and personality domains related to impulsivity and aggressiveness were inconsistent. Our findings further support the notion that allelic variation of MAOA activity contributes modestly to the balance of hyper- (impulsive-aggressive) and hyporeactive (anxious-depressive) traits. (+info)
Hippocampal lesions facilitate instrumental learning with delayed reinforcement but induce impulsive choice in rats.
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BACKGROUND: Animals must frequently act to influence the world even when the reinforcing outcomes of their actions are delayed. Learning with action-outcome delays is a complex problem, and little is known of the neural mechanisms that bridge such delays. When outcomes are delayed, they may be attributed to (or associated with) the action that caused them, or mistakenly attributed to other stimuli, such as the environmental context. Consequently, animals that are poor at forming context-outcome associations might learn action-outcome associations better with delayed reinforcement than normal animals. The hippocampus contributes to the representation of environmental context, being required for aspects of contextual conditioning. We therefore hypothesized that animals with hippocampal lesions would be better than normal animals at learning to act on the basis of delayed reinforcement. We tested the ability of hippocampal-lesioned rats to learn a free-operant instrumental response using delayed reinforcement, and what is potentially a related ability -- the ability to exhibit self-controlled choice, or to sacrifice an immediate, small reward in order to obtain a delayed but larger reward. RESULTS: Rats with sham or excitotoxic hippocampal lesions acquired an instrumental response with different delays (0, 10, or 20 s) between the response and reinforcer delivery. These delays retarded learning in normal rats. Hippocampal-lesioned rats responded slightly less than sham-operated controls in the absence of delays, but they became better at learning (relative to shams) as the delays increased; delays impaired learning less in hippocampal-lesioned rats than in shams. In contrast, lesioned rats exhibited impulsive choice, preferring an immediate, small reward to a delayed, larger reward, even though they preferred the large reward when it was not delayed. CONCLUSION: These results support the view that the hippocampus hinders action-outcome learning with delayed outcomes, perhaps because it promotes the formation of context-outcome associations instead. However, although lesioned rats were better at learning with delayed reinforcement, they were worse at choosing it, suggesting that self-controlled choice and learning with delayed reinforcement tax different psychological processes. (+info)
Behavioral assessment of impulsivity: a comparison of children with and without attention deficit hyperactivity disorder.
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We conducted a brief computer-based assessment involving choices of concurrently presented arithmetic problems associated with competing reinforcer dimensions to assess impulsivity (choices controlled primarily by reinforcer immediacy) as well as the relative influence of other dimensions (reinforcer rate, quality, and response effort), with 58 children. Results were compared for children with attention deficit hyperactivity disorder (ADHD) who were and were not receiving medication, and with typically developing children without ADHD. Within-subject and between-groups analyses of the ordinal influence of each of the reinforcer dimensions were conducted using both time- and response-allocation measures. In general, the choices of children with ADHD were most influenced by reinforcer immediacy and quality and least by rate and effort, suggesting impulsivity. The choices of children in the non-ADHD group were most influenced by reinforcer quality, and the influence of immediacy relative to the other dimensions was not statistically significant. Results are discussed with respect to the implications for assessment and treatment of ADHD. (+info)
Alcohol expectancies, conduct disorder and early-onset alcoholism: negative alcohol expectancies are associated with less drinking in non-impulsive versus impulsive subjects.
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AIMS: Research suggests that positive alcohol expectancies promote excessive alcohol use while negative alcohol expectancies discourage excessive alcohol use. Evidence suggests that disinhibitory characteristics, such as conduct disorder and impulsivity, are associated with a general neglect of long-term negative outcomes. This study assessed whether negative expectancies would be associated more strongly with lower levels of alcohol use for low- compared with high-impulsive individuals. DESIGN: Positive and negative alcohol expectancies, alcohol use and impulsivity were assessed in a sample of 99 young adults with alcohol dependence (AD) and conduct disorder (CD), 77 with AD and no CD and 124 controls. FINDINGS: AD/CD subjects had higher proximal (same day) and distal (next day) negative alcohol expectancies, even though they drank more alcohol, compared with AD-alone and control subjects. Distal negative expectancies were associated more strongly with lower levels of drinking for low-impulsive compared with high-impulsive subjects. Proximal negative expectancies were associated more strongly with higher alcohol consumption for high- versus low-impulsive subjects. CONCLUSIONS: Impulsivity and conduct disorder may be important factors in determining how much distal negative alcohol expectancies may discourage excessive alcohol consumption. (+info)
Can alcohol lead to inhibition or disinhibition? Applying alcohol myopia to animal experimentation.
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AIMS: Animal experimentation often demonstrates that alcohol leads to disinhibited behaviour, such as increased aggression, increased social behaviour, or increased impulsivity. However, human experimentation demonstrates that alcohol can have either disinhibiting or inhibiting effects on behaviour, depending on salient environmental cues. Our aim was to illustrate how alcohol myopia theory could be applied to the literature assessing the effects of alcohol on behaviour in animals. METHODS: The effects of alcohol on animal behaviour were reviewed in several domains, including aggression, social behaviours, and impulsivity. Suggestions for testing alcohol myopia with animal research paradigms were provided. RESULTS: Current animal research paradigms are often designed in such a way that alcohol myopia cannot be tested. To test alcohol myopia, we recommend manipulating the salience of both impelling and inhibiting environmental cues. CONCLUSIONS: Disinhibition alone cannot explain alcohol's effects on behaviour. We contend that alcohol myopia theory helps to explain some contradictory findings in the human and animal literature. We encourage animal researchers to develop research paradigms to provide tests of alcohol myopia. (+info)
Blunted hormone responses to Ipsapirone are associated with trait impulsivity in personality disorder patients.
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Impulsive aggression is associated with central serotonergic dysfunction. Animal models particularly implicate the 5-HT(1A) receptor in this behavior. We tested the hypothesis that central 5-HT(1A) receptor function is impaired in impulsive aggressive personality disorder patients. A total of 52 individuals with DSM-III-R personality disorders, all medically healthy adult outpatients without concurrent psychiatric medication treatment, underwent serial plasma cortisol, prolactin, and temperature measurements before and after ipsapirone 20 mg oral administration. Subjects completed self-report measures of impulsivity, hostility, depression and anxiety, and childhood maltreatment. Stepwise regression analysis revealed impulsivity alone among symptom measures to be associated with significantly decreased peak cortisol and prolactin responses. Diagnoses of borderline personality disorder (BPD) and intermittent explosive disorder-revised (IED-R) were associated with significantly increased and decreased cortisol responses, respectively. However, post hoc analyses indicated that impulsivity was significantly negatively correlated with cortisol responses in the BPD group, and may mediate the association of both BPD and IED-R with altered cortisol responses. Temperature response was associated with neither diagnostic nor symptom measures. Neither diagnostic nor dimensional measures of depression or anxiety, nor severity of childhood maltreatment, were significantly associated with cortisol, prolactin, or temperature responses. Impulsivity is related to impaired function at (or downstream to) postsynaptic 5-HT(1A) receptors, and this relationship may be partly responsible for the association of impaired serotonergic function with diagnoses such as BPD and IED-R. In addition, D(2) receptor dysfunction may play a role in impulsivity, whereas 5-HT(1A) cell-body autoreceptor function may be spared in these disorders. (+info)
Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on behavioral measures of impulsivity: alone and in combination with alcohol.
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The use of 3,4-methylenedioxymethamphetamine (MDMA) has frequently been associated with increased levels of impulsivity during abstinence. The effects of MDMA on measures of impulsivity, however, have not yet been studied during intoxication. The present study was designed to assess the acute effects of MDMA and alcohol, alone and in combination, on behavioral measures of impulsivity and risk-taking behavior. A total of 18 recreational users of MDMA entered a double-blind placebo-controlled six-way crossover study. The treatments consisted of MDMA 0, 75, and 100 mg with and without alcohol. Alcohol dosing was designed to achieve a peak blood alcohol concentration (BAC) of about 0.06 g/dl during laboratory testing. Laboratory tests of impulsivity were conducted between 1.5 and 2 h post-MDMA and included a stop-signal task, a go/no-go task, and the Iowa gambling task. MDMA decreased stop reaction time in the stop-signal task indicating increased impulse control. Alcohol increased the proportion of commission errors in the stop-signal task and the go/no-go task. Signal detection analyses of alcohol-induced commission errors indicated that this effect may reflect impairment of perceptual or attentive processing rather than an increase of motor impulsivity per se. Performance in the Iowa gambling task was not affected by MDMA and alcohol, but there was a nonsignificant tendency towards improvement following alcohol intake. None of the behavioral measures of impulsivity showed a MDMA x alcohol interaction effect. The lack of interaction indicated that the CNS stimulant effects of MDMA were never sufficient to overcome alcohol-induced impairment of impulse control or risk-taking behavior. (+info)
Neuropsychological function in ecstasy users: a study controlling for polydrug use.
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RATIONALE: A number of studies have compared ecstasy users to control groups on various measures of neuropsychological function in order to determine whether ecstasy use results in lasting cognitive deficits. However, few of those studies controlled adequately for non-ecstasy illicit drug use. OBJECTIVE: The aim of this study was to investigate neuropsychological function in chronic ecstasy users while controlling for polydrug use. METHODS: Neuropsychological function was assessed in four groups-30 current 3,4-methylenedioxymethamphetamine (MDMA) users with a little history of illicit drug use other than ecstasy and cannabis, 30 polydrug controls, 30 drug-naive controls and 20 ex-MDMA users-using a battery of well-validated, computerized neuropsychological tests. The battery focused on memory, executive function, impulsivity and risk-taking. RESULTS: Few differences were apparent between the groups, and on no measure were the current MDMA users impaired significantly relative to the polydrug controls. However, within the current MDMA users, questionnaire-measured impulsivity correlated with performance on a number of tests-a relationship that was not apparent in the controls. CONCLUSIONS: These data highlight the complexity in understanding the current ecstasy literature and suggest that some individuals may be particularly vulnerable to cognitive impairment following chronic use. Although no differences were identified between the current MDMA users and the controls, trait impulsiveness was significantly correlated with impairment on a number of neuropsychological outcome measures in the MDMA users, but not in the controls. These data suggest that impulsive individuals may be those most at risk for the development of cognitive impairment following chronic ecstasy use. (+info)