Impulsivity and clinical symptoms among adolescents with non-suicidal self-injury with or without attempted suicide.

This study examined clinical characteristics and laboratory-measured impulsive behavior of adolescents engaging in either non-suicidal self-injury with (NSSI+SA; n=25) or without (NSSI-Only; n=31) suicide attempts. We hypothesized that adolescent with NSSI+SI would exhibit more severe clinical symptoms and higher levels of behavioral impulsivity compared to adolescents with NSSI-Only. Adolescents were recruited from an inpatient psychiatric hospital unit and the two groups were compared on demographic characteristics, psychopathology, self-reported clinical ratings, methods of non-suicidal self-injury, and two laboratory impulsivity measures. Primary evaluations were conducted during psychiatric hospitalization, and a subset of those tested during hospitalization was retested 4-6 weeks after discharge. During hospitalization, NSSI+SA patients reported worse depression, hopelessness, and impulsivity on standard clinical measures, and demonstrated elevated impulsivity on a reward-directed laboratory measure compared to NSSI-Only patients. In the follow-up analyses, depression, hopelessness, suicidal ideation, and laboratory impulsivity were improved for both groups, but the NSSI+SA group still exhibited significantly more depressive symptoms, hopelessness, and impulsivity than the NSSI-Only group. Risk assessments for adolescents with NSSI+SA should include consideration not only of the severity of clinical symptoms but of the current level impulsivity as well.

Distinctions in Behavioral Impulsivity: Implications for Substance Abuse Research.

OBJECTIVES: Researchers have clearly implicated impulsivity as having a key role in substance use disorders, and comparisons of self-report measures suggest there are measurably different components of impulsive behavior. However comparatively little research has been devoted to understanding the multidimensional nature of this construct using laboratory measures of impulsivity that may be more sensitive to tracking changes across time. Many studies have measured impulsivity, but this construct has been measured using methodologically different types of laboratory impulsivity paradigms that are often used in isolation. As a result, it is important to determine whether some of the most frequently used types of behavioral measures of impulsivity account for unique variance. METHODS: Here, we used factor analytical techniques in two studies to evaluate the independence of three of the most commonly used behavioral impulsivity paradigms. First, a factor analysis was conducted using previously collected data (n = 204), and second, data was gathered specifically to replicate and extend the results of our original analysis (n = 198). RESULTS: Both studies revealed three distinct factors, confirming our hypothesis of at least three components of impulsive behavior that can be measured by these methodological approaches. CONCLUSIONS: These findings suggest that researchers should carefully consider their selection of laboratory-behavioral impulsivity measures, and that the measure(s) selected should be related to the particular underlying processes relevant to substance use disorders and treatment success.

A test of alcohol dose effects on multiple behavioral measures of impulsivity.

BACKGROUND: Acute alcohol administration affects impulsive behavior, although these effects vary as a function of alcohol dose, assessment instrument, and time of measurement following administration. METHODS: We concurrently examined the dose-dependent effects of alcohol on three distinct types of impulsivity tasks (continuous performance [IMT], stop-signal [GoStop], and delay-discounting [SKIP] tasks). Ninety healthy alcohol drinkers were assigned to one of the three task groups (n=30 each), each group experienced placebo, 0.2, 0.4, 0.6, and 0.8 g/kg alcohol doses across 5 experimental days, and task performance was assessed at 0.5h before and 0.25, 1.0, and 2.0 h after alcohol administration. We hypothesized that impulsive responding on all tasks would be increased by acute alcohol administration both across time and during the peak BrAC, but the magnitude would depend on the task being tested. Analyses included the time course and the peak BrAC effects. Task comparisons of peak behavioral changes following each dose are illustrated using standardized scores. RESULTS: While alcohol consumption increased impulsive responding during all three tasks to some extent, our hypothesis was only partially supported. During the IMT, the 0.6 and 0.8 g/kg doses produced increased impulsive responding across time and at the peak BrAC. However, during the GoStop and SKIP, impulsivity increased across time regardless of the alcohol dose size, with no differences in impulsive responding among dose conditions at peak BrAC. CONCLUSIONS: This study demonstrated alcohol-induced changes in impulsivity are not uniformly affected by alcohol. These data, in conjunction with previous studies, further support that impulsivity is not a unitary construct.

Modulation of human risky decision making by flunitrazepam.

RATIONALE: GABA-modulating drugs produce disinhibitory effects that increase the probability of risk-taking behavior. Previous reports suggest that the misuse of the benzodiazepine flunitrazepam is associated with several forms of harmful risky behavior, including theft, violence, and intoxication-related auto accidents. OBJECTIVES: The present study examined the dose-response relationships between acute flunitrazepam administration and human decision making under conditions of risk. The analyses also examined flunitrazepam-mediated changes in decision-making processes using a computational modeling approach, the expectancy valence model (EVM). MATERIALS AND METHODS: Using a laboratory measure of risky decision making designed to address acute drug effects, 12 adults were administered placebo, 0.5, 1.0, and 2.0 mg/70 kg flunitrazepam in a within-subject, repeated measures counterbalanced design. Flunitrazepam was compounded and doses were administered in an 8-oz liquid solution. Primary data analyses examined subjective effects, response rates, distribution of choices between the risky and nonrisky option, and personality correlates related to peak drug effects. Individual-subject data were submitted to a computational modeling analysis (EVM) that provided parameter estimates corresponding to components of valence; updating expectancies about alternatives (learning/memory); and consistency between choices and expected outcomes (sensitivity to learned outcomes). RESULTS: Flunitrazepam produced dose-related changes in subjective effects and response rates, and increased selection of the risky response option. High doses significantly changed decision-making processes related to the learning/memory and consistency parameters. CONCLUSIONS: At sufficiently high doses, flunitrazepam can engender increases in risky decision making. Globally, these changes appear similar to previous effects we have observed after acute administration of alcohol and alprazolam. As suggested by the EVM outcomes, the mechanisms underlying the changes in risky decision making are more similar to alprazolam than alcohol.

Effects of acute tiagabine administration on aggressive responses of adult male parolees.

Experimental and clinical studies have supported a relationship between gamma-aminobutyric acid (GABA) and aggressive behavior in non-humans and humans. Tiagabine is a GABA uptake inhibitor that has been shown to produce acute behavioral effects in animals. In addition, tiagabine has been shown to decrease aggression in agitated patients when administered chronically. The present study was designed to investigate the effects of acute administration of tiagabine on aggressive responding on a laboratory task in adult humans. Ten adult males participated in experimental sessions on the Point Subtraction Aggression Paradigm (PSAP), which provided subjects with aggressive, escape, and monetary-reinforced response options. All subjects received four acute oral doses of Tiagabine (4, 8, 12 and 16 mg) separated by placebo sessions. Tiagabine decreased aggression at doses that either did not affect, or affected to a lesser extent, monetary-reinforced responding. The results are consistent with some prior research using the PSAP showing a possible unique role for GABA in the regulation of human aggression. A possible behavioral mechanism for the rate-decreasing effects on aggressive responding produced in the present study is that tiagabine may modify aggressive responding by suppressing reactions to aversive stimuli.

Human proactive aggression: association with personality disorders and psychopathy.

Aggressive behaviors can be divided into two categories: reactive and proactive. Reactive aggressive behaviors occur in response to a stimulus or provocation. Proactive aggressive behaviors occur without provocation and are goal directed. A number of findings have suggested that individuals displaying proactive aggression may be discerned from individuals not displaying proactive aggression on measures of personality, psychopathology and psychopathy as well as in aggressive histories and type and severity of aggressive behaviors committed. In this study, subjects were recruited from a large urban community and classified as proactive (n = 20), reactive-only (n = 20) or nonaggressive (n = 10) based on laboratory behavioral testing. Subjects were administered a battery of questionnaires and structured interviews pertaining to personality disorders and psychopathy. It was hypothesized that proactive aggressive subjects would show greater numbers of personality disorders and have greater psychopathy relative to reactive-only and nonaggressive subjects. These hypotheses were supported. These results suggest that proactive aggression may be identified in a laboratory-based task, and differences between proactive and reactive-only aggressors can be detected.

Individual differences in aggressive responding to intravenous flumazenil administration in adult male parolees.

Nonhuman and human studies have shown that benzodiazepine (BZD) receptor agonists can modify aggressive behaviour. However, it is unknown whether flumazenil, a BZD receptor antagonist, enhances or inhibits aggressive behaviour. The present study was designed to investigate the effects of acute administrations of flumazenil on aggressive responding in adult humans. Six adult males with histories of childhood conduct disorder (DSM IV R) participated in experimental sessions. Aggression was measured using the Point Subtraction Aggression Paradigm (PSAP; Cherek 1992), which provided subjects with aggressive and monetary-reinforced response options. Acute doses of flumazenil (2 and 3mg) did not produce statistically significant changes in either monetary-reinforced responding or aggressive responding. The analysis of individual subjects data revealed that aggressive responses varied across subjects. The results are discussed in terms of individual differences based on the previous history of BZD abuse. Additional laboratory research is needed to better clarify the behavioural mechanisms by which BZD receptor antagonists modify human aggressive responding.

Acute effects of alprazolam on risky decision making in humans.

RATIONALE: GABA-A receptor ligands, including benzodiapines, may induce disinhibitory effects that increase the probability of risky decision making. To date, few laboratory studies have examined the acute, dose-related effects of benzodiazepines on human risk-taking behavior. Recent data indicate that in the United States alprazolam is the benzodiazepine most frequently misused for recreational purposes. OBJECTIVES: The present study was designed to demonstrate a dose-response relationship between acute alprazolam administration and human risk taking. Furthermore, this investigation sought to examine: (1) the behavioral mechanisms that may be involved in changes in the probability of risky decision making related to alprazolam administration and (2) risk seeking-related personality variables that may predict drug effects on risk taking. METHODS: Using a laboratory measure of risk taking designed to address acute drug effects, 16 adults were administered placebo, 0.5, 1.0, and 2.0 mg alprazolam in a within-subject repeated-measures design. The risk-taking task presented subjects with a choice between two response options operationally defined as risky and nonrisky. Data analyses examined subjective effects, response rates, distribution of choices between the risky and nonrisky option, trial-by-trial response probabilities, and personality correlates related to drug effects at the 2.0-mg dose. RESULTS: Alprazolam administration produced dose-related changes in subjective effects, response rates, and, most importantly, dose-dependently increased selection of the risky response option. The 2.0-mg dose increased the probability of making consecutive risky responses following a gain on the risky response option. Increases at 2.0 mg were related to a combination of personality scales that included high venturesomeness and novelty seeking and low harm avoidance. CONCLUSIONS: Alprazolam administration produced increases in human risk taking under laboratory conditions. In union with previous studies, the observed shift in trial-by-trial response probabilities suggests that sensitivity to consequences (e.g., oversensitivity to recent rewards) may be an important mechanism in the psychopharmacology of risky decision making. Additionally, risk-seeking personality traits may be predictive of acute drug effects on risk-taking behavior.