Alan C. Swann

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.

Impulsivity and phase of illness in bipolar disorder

BACKGROUND Impulsivity is prominent in bipolar disorder, but there is little quantitative information relating it to phase of illness. METHODS We measured impulsivity in patients with bipolar disorder who had not met episode criteria for at least 6 months, patients who were manic, and healthy control subjects. Impulsivity was measured using the Barratt Impulsiveness Scale (BIS) and performance on the computerized Immediate Memory-Remote Memory Task (IMT-DMT), based on the Continuous Performance Test, which has been shown to reflect risk of impulsivity in other populations. RESULTS BIS scores in euthymic and manic bipolar subjects were identical, and were significantly elevated compared to controls. Commission errors (impulsive responses) on the IMT-DMT were elevated in manic subjects but were identical to controls in euthymic subjects. Measures of impulsivity did not appear related to depressive symptoms. LIMITATIONS The number of subjects was too small for detailed investigation of the role of comorbidities; subjects were receiving pharmacological treatments. CONCLUSIONS Impulsivity has state- and trait-related aspects in bipolar disorder.

Increased trait-like impulsivity and course of illness in bipolar disorder

BACKGROUND Impulsivity as a trait characteristic is increased in bipolar disorder and may be a core factor of the illness. We have investigated relationships between trait-like impulsivity, measured by the Barratt Impulsiveness Scale (BIS-11), and demographic and illness-course characteristics of bipolar disorder. METHODS We studied 114 subjects with bipolar disorder and 71 healthy comparison subjects. Diagnoses were based on the Structured Clinical Interview for DSM-IV. In addition to impulsivity, we examined age, education, gender, psychiatric symptoms, and characteristics related to course of illness. We used general linear mixed model analysis to evaluate the manner in which the variables contributed to BIS-11 scores. RESULTS All BIS-11 subscale scores were higher in bipolar disorder than in comparison subjects. There were less consistent independent effects of education and age. Elevated BIS-11 scores were associated with early onset, more frequent episodes of illness, and a history of suicide attempts. These relationships persisted when age, gender, and education were taken into account. DISCUSSION These results show that, after accounting for common confounding factors, trait-like impulsivity was substantially higher in subjects with bipolar disorder than in nonbipolar comparison subjects, regardless of symptoms. Within subjects with bipolar disorder, high trait impulsivity was associated with a more severe course of illness.

Sensitization to locomotor effects of methylphenidate in the rat

A computerized activity monitoring system was used to investigate whether repeated exposure to methylphenidate (MPD) could produce sensitization to its locomotor effects in the rat. Male Sprague-Dawley rats were housed in test cages and activity was recorded continuously for 16 days as follows: Baseline activity (Day 1-2), recording following saline injection (Day 3), MPD Challenge Doses--either 0.6, 2.5, or 10 mg/kg of MPD (Day 4); five days of a repeated dose of 2.5 mg/kg (Day 5-9), five additional recording days of no treatment (Days 10-14), and MPD Re-Challenge (Day 15). Each group was re-challenged with the same doses as on day 4. Recording was resumed for an additional post-treatment day (Day 16). All injections were at 14:00. Horizontal activity, total distance, vertical activity, stereotypic activity, and number of stereotypic movements were recorded and analyzed. An augmented response (i.e., sensitization) was observed only to the lower MPD doses of 0.6 and 2.5 mg/kg. The sensitized response was more pronounced for forward ambulation than for rearing, with a complete lack of sensitization to the stereotypic effects of MPD.

Chronic exposure to MDMA (Ecstasy) elicits behavioral sensitization in rats but fails to induce cross-sensitization to other psychostimulants

BackgroundThe recreational use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) among adolescents and young adults has become increasingly prevalent in recent years. While evidence suggests that the long-term consequences of MDMA use include neurodegeneration to serotonergic and, possibly, dopaminergic pathways, little is known about susceptibility, such as behavioral sensitization, to MDMA.MethodsThe objectives of this study were to examine the dose-response characteristics of acute and chronic MDMA administration in rats and to determine whether MDMA elicits behavioral sensitization and whether it cross-sensitizes with amphetamine and methylphenidate. Adult male Sprague-Dawley rats were randomly divided into three MDMA dosage groups (2.5 mg/kg, 5.0 mg/kg, and 10.0 mg/kg) and a saline control group (N = 9/group). All three MDMA groups were treated for six consecutive days, followed by a 5-day washout, and subsequently re-challenged with their respective doses of MDMA (day 13). Rats were then given an additional 25-day washout period, and re-challenged (day 38) with similar MDMA doses as before followed by either 0.6 mg/kg amphetamine or 2.5 mg/kg methylphenidate on the next day (day 39). Open-field locomotor activity was recorded using a computerized automated activity monitoring system.ResultsAcute injection of 2.5 mg/kg MDMA showed no significant difference in locomotor activity from rats given saline (control group), while animals receiving acute 5.0 mg/kg or 10.0 mg/kg MDMA showed significant increases in locomotor activity. Rats treated chronically with 5.0 mg/kg and 10.0 mg/kg MDMA doses exhibited an augmented response, i.e., behavioral sensitization, on experimental day 13 in at least one locomotor index. On experimental day 38, all three MDMA groups demonstrated sensitization to MDMA in at least one locomotor index. Amphetamine and methylphenidate administration to MDMA-sensitized animals did not elicit any significant change in locomotor activity compared to control animals.ConclusionMDMA sensitized to its own locomotor activating effects but did not elicit any cross-sensitization with amphetamine or methylphenidate.

Specificity of mixed affective states: clinical comparison of dysphoric mania and agitated depression

To investigate the clinical specificity of mixed affective states, we compared clinical characteristics of mixed (dysphoric) manics to those of agitated depressed patients. The subjects were inpatients studied in the NIMH Clinical Research Branch Collaborative Study on the Psychobiology of Depression, Biological Studies. Behavior and symptom ratings for depressive and manic symptoms were obtained during a 15-day placebo washout period. Patients with agitated depression were compared to those in acute manic episodes with and without prominent depressive symptoms. Mania ratings clearly distinguished agitated depressed from mixed manic patients. Concerning depression and general psychopathology, mixed manics had more severe agitation, hostility and cognitive impairment than did agitated depressed patients. Depressed mood and anxiety did not differ significantly between the two groups. Nurse ratings for depression and anxiety, based on ward behavior, were similar for mixed manics and agitated depressed patients, while physician-interview rated depression and anxiety were higher in agitated depressed patients. These data support the existence of superimposed depressive and manic syndromes in mixed manics.

Acute and chronic methylphenidate dose-response assessment on three adolescent male rat strains.

Methylphenidate (MPD), commonly known as Ritalin, is the most frequently prescribed drug to treat children and adults with attention deficit hyperactivity disorder (ADHD). Adolescence is a period of development involving numerous neuroplasticities throughout the central nervous system (CNS). Exposure to a psychostimulant such as MPD during this crucial period of neurodevelopment may cause transient or permanent changes in the CNS. Genetic variability may also influence these differences. Thus, the objective of the present study was to determine whether acute and chronic administration of MPD (0.6, 2.5, or 10.0mg/kg, i.p.) elicit effects among adolescent WKY, SHR, and SD rats and to compare whether there were strain differences. An automated, computerized, open-field activity monitoring system was used to study the dose-response characteristics of acute and repeated MPD administration throughout the 11-day experimental protocol. Results showed that all three adolescent rat groups exhibited dose-response characteristics following acute and chronic MPD administration, as well as strain differences. These strain differences depended on the MPD dose and locomotor index. Chronic treatment of MPD in these animals did not elicit behavioral sensitization, a phenomenon described in adult rats that is characterized by the progressive augmentation of the locomotor response to repeated administration of the drug. These results suggest that the animals age at time of drug treatment and strain/genetic variability play a crucial role in the acute and chronic effect of MPD and in the development of behavioral sensitization.

P300 event-related potential amplitude and impulsivity in cocaine-dependent subjects.

Previous studies report reduced amplitude of the P300 event-related potential in cocaine-dependent individuals. Cocaine dependence is also associated with increased impulsivity, possibly due to deficits in cognitive function that are associated with reduced P300 amplitude. In the current study, the relationship between cocaine dependence, impulsivity, and P300 amplitude were examined. An auditory oddball event-related potential task along with self-report (Barratt Impulsiveness Scale version 11) and behavioral laboratory (Immediate and Delayed Memory Task) measures of impulsivity were assessed in healthy controls (n = 14) and subjects who met DSM-IV criteria for current cocaine dependence (n = 17). P300 amplitude was reduced and self-reported and behavioral laboratory impulsivity scores were elevated among the cocaine-dependent group compared to controls. There was a positive correlation between the questionnaire and behavioral laboratory measures of impulsivity, and a negative correlation between impulsivity measures and P300 amplitude. The correlation between self-reported impulsivity scores and P300 amplitude remained after taking into account the number of childhood conduct disorder symptoms. This study supports the hypothesis that the basic neurophysiology responsible for the P300 amplitude in cocaine-dependent individuals is associated with impulsivity independent of a history of childhood conduct disorder symptoms.

A comparison of clinical features in Trichotillomania and obsessive-compulsive disorder

Trichotillomania (TM) recently has been conceptualized as a variant of obsessive-compulsive disorder (OCD). However, no systematic data have compared the clinical features of these two disorders. Here we report data from 8 TM and 13 OCD patients which suggest important clinical differences between groups. First, TM patients reported a significantly greater degree of pleasure during hair-pulling than OCD patients reported during performance of ritualistic behaviors. Second, TM was accompanied by significantly fewer associated obsessive-compulsive symptoms. Third, the groups differed with regard to other clinical features including anxiety, depression, and personality characteristics. We conclude that TM is not conceptualized best as a variant of OCD.

Lithium treatment of mania: Clinical characteristics, specify of symptom change, and outcome

The effects of lithium treatment and prediction of response in 18 manic patients were studied as part of the National Institute of Mental Health Collaborative Study of the Psychobiology of Depression. Patients were rated using the Mania Diagnostic and Severity Scale (MADS) and an additional battery of behavioral constructs developed for measurement of state and drug response in depressed patients. About 67% of the patients had good treatment outcome after 26 days of lithium treatment. Responders did not differ from nonresponders before treatment with respect to delusions, hallucinations, or irritable-paranoid symptoms. Nonresponders were rated as more anxious than responders before treatment and had higher scores on the Hamilton Rating Scale for Depression. Improvement on the MADS, however, did not correlate with pretreatment behavioral ratings. Patients with relatively high ratings for aspects of behavior not specific to mania tended to improve in these regardless of change in MADS score. Manic patients who were also depressed (44%) had higher mania ratings than manic patients who were not depressed. Patients with concomitant depression and mania had significantly worse overall treatment outcome, although their depression ratings improved during lithium treatment.