Scott D. Lane

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.

Relationships among laboratory and psychometric measures of impulsivity: Implications in substance abuse and dependence.

Objectives Problems with impulsive behavior are a key feature in substance use disorders. Many studies have examined this relationship, but methods used to measure impulsivity have varied greatly. The present study used a multimethod approach to determine relationships using both laboratory and psychometric measures of impulsivity commonly employed in the behavioral and health sciences. Methods Thirty-two adult male subjects participated for 5 days, completing psychometric instruments on day 1 and behavioral tests in counterbalanced order on days 2–5. Results Correlations between the behavioral and psychometric measures were uniformly low. Correlations within the psychometric instruments were consistently high. Principal components analysis revealed that the behavioral measures loaded into separate factors of response inhibition tasks and delay of reward tasks. Psychometric measures loaded into a single factor. Conclusions Results are discussed in terms of how studies of impulsivity might be interpreted based upon the tasks used, and how these interpretations may subsequently guide theory and measurement in substance abuse and dependence.

Selective activation of the nucleus accumbens during risk-taking decision making

This study implemented a risk-taking task during fMRI to probe the brain circuitry involved in risk-taking decision-making in 12 healthy control subjects. Partially supporting the initial hypotheses, deliberation prior to selection of safe relative to risky responses generated greater activation in the inferior frontal cortex, superior temporal gyrus, and middle temporal gyrus; and deliberation prior to selection of risky relative to safe responses generated greater activation in medial frontal cortex, occipital cortex, nucleus accumbens and caudate. Additionally, accumbens activation correlated positively with the harm avoidance subscale of the Temperament and Character Inventory (TCI) 125. These findings may provide target neural systems to study in subjects who exhibit problematic risk-taking behaviors and may partially explain why certain risky behaviors occur.

Acute marijuana effects on human risk taking.

Previous studies have established a relationship between marijuana use and risky behavior in natural settings. A limited number of laboratory investigations of marijuana effects on human risk taking have been conducted. The present study was designed to examine the acute effects of smoked marijuana on human risk taking, and to identify behavioral mechanisms that may be involved in drug-induced changes in the probability of risky behavior. Using a laboratory measure of risk taking designed to address acute drug effects, 10 adults were administered placebo cigarettes and three doses of active marijuana cigarettes (half placebo and half 1.77%; 1.77%; and 3.58% Δ9-THC) in a within-subject repeated-measures experimental design. The risk-taking task presented subjects with a choice between two response options operationally defined as risky and nonrisky. Data analyses examined cardiovascular and subjective effects, response rates, distribution of choices between the risky and nonrisky option, and first-order transition probabilities of trial-by-trial data. The 3.58% THC dose increased selection of the risky response option, and uniquely shifted response probabilities following both winning and losing outcomes following selection of the risky option. Acute marijuana administration thereby produced measurable changes in risky decision making under laboratory conditions. Consistent with previous risk-taking studies, shifts in trial-by-trial response probabilities at the highest dose suggested a change in sensitivity to both reinforced and losing risky outcomes. Altered sensitivity to consequences may be a mechanism in drug-induced changes in risk taking. Possible neurobiological sites of action related to THC are discussed.

P50, N100, and P200 sensory gating: Relationships with behavioral inhibition, attention, and working memory

P50, N100, and P200 auditory sensory gating could reflect mechanisms involved in protecting higher-order cognitive functions, suggesting relationships between sensory gating and cognition. This hypothesis was tested in 56 healthy adults who were administered the paired-click paradigm and two adaptations of the continuous performance test (Immediate/Delayed Memory Task, IMT/DMT). Stronger P50 gating correlated with fewer commission errors and prolonged reaction times on the DMT. Stronger N100 and P200 gating correlated with better discriminability on the DMT. Finally, prolonged P200 latency related to better discriminability on the IMT. These findings suggest that P50, N100, and P200 gating could be involved in protecting cognition by affecting response bias, behavioral inhibition, working memory, or attention.

Relationship between impulsivity and decision making in cocaine dependence

Impulsivity and decision making are associated on a theoretical level in that impaired planning is a component of both. However, few studies have examined the relationship between measures of decision making and impulsivity in clinical populations. The purpose of this study was to compare cocaine-dependent subjects to controls on a measure of decision making (the Iowa Gambling Task or IGT), a questionnaire measure of impulsivity (the Barratt Impulsiveness Scale or BIS-11) and a measure of behavioural inhibition (the immediate memory task or IMT), and to examine the interrelationship among these measures. Results of the study showed that cocaine-dependent subjects made more disadvantageous choices on the IGT, had higher scores on the BIS and more commission errors on the IMT. Cognitive model analysis showed that choice consistency factors on the IGT differed between cocaine-dependent subjects and controls. However, there was no significant correlation between IGT performance and the BIS total score or subscales or IMT commission errors. These results suggest that in cocaine-dependent subjects there is little overlap between decision making as measured by the IGT and impulsivity/behavioural inhibition as measured by the BIS and IMT.

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.

Performance of Cocaine Dependent Individuals and Controls on a Response Inhibition Task with Varying Levels of Difficulty

An assay in which groups perform at both similar and significantly different levels within the same test session may have experimental advantages both in understanding underlying behavioral-cognitive processes and in helping to resolve neuroimaging issues regarding functional significance vs. performance confounds. Here we report behavioral data from a response inhibition (Go/No-Go) task with two levels of No-Go difficulty (easy, hard). The sample included individuals with current cocaine dependence (N = 18) and controls (N = 15). Using signal detection methodology (d′ and Beta), significant main effects were observed for group and trial type on d′. Post-hoc analyses revealed the cocaine-dependent individuals performed significantly worse than controls on difficult, but not easy, trials. Differences on d′ but not Beta, and slower reaction times in cocaine subjects, suggest that response inhibition deficits were related to disruption in visual information processing rather than inhibition of motor activity.

Diffusion tensor imaging and decision making in cocaine dependence.

Background Chronic stimulant abuse is associated with both impairment in decision making and structural abnormalities in brain gray and white matter. Recent data suggest these structural abnormalities may be related to functional impairment in important behavioral processes. Methodology/Principal Findings In 15 cocaine-dependent and 18 control subjects, we examined relationships between decision-making performance on the Iowa Gambling Task (IGT) and white matter integrity as measured by diffusion tensor imaging (DTI). Whole brain voxelwise analyses showed that, relative to controls, the cocaine group had lower fractional anisotropy (FA) and higher mean of the second and third eigenvalues (λ⊥) in frontal and parietal white matter regions and the corpus callosum. Cocaine subjects showed worse performance on the IGT, notably over the last 40 trials. Importantly, FA and λ⊥ values in these regions showed a significant relationship with IGT performance on the last 40 trials. Conclusions Compromised white matter integrity in cocaine dependence may be related to functional impairments in decision making.

Severity of bipolar disorder is associated with impairment of response inhibition

BACKGROUND Pathological impulsivity in bipolar disorder could be related to deficiencies in mechanisms involved in attention or response inhibition. We investigated these mechanisms in subjects with bipolar disorder and examined relationships to severity of course of illness, use of medication, affective state, age, education, and gender. We measured two complementary aspects of response inhibition: attention-based and reward-based. METHODS Subjects with bipolar disorder (n=112) and healthy controls (n=71) were recruited from the community. Diagnoses were rendered using the SCID for DSMIV. Impulsivity-related measures included the Immediate Memory Task (IMT), a form of the Continuous Performance Task, and the Single Key Impulsivity Paradigm (SKIP), an operant procedure measuring ability to delay responding for a reward. RESULTS Subjects with bipolar disorder had fewer correct detections (Effect Size (ES)=0.5), prolonged reaction times (ES=0.88), and decreased discriminability (ES=0.57) on the IMT compared to controls. History of frequent episodes, substance use disorders, or suicide attempts predicted faster reaction times, especially to a commission error. Subjects with bipolar disorder who also met criteria for an Axis II disorder had fewer correct detections, more commission errors relative to correct detections, and poorer discriminability on the IMT than other subjects with bipolar disorder. Subjects with bipolar disorder made more responses on the SKIP than did controls (ES=0.5), with a shorter maximum delay (ES=0.62), consistent with inability to delay reward. Probit analysis showed that faster reaction time to a commission error on the IMT was associated with history of substance use disorder, suicide attempt, or many previous episodes. Effects of medication or affective state did not account for these differences. DISCUSSION Bipolar disorder was associated with impairment in attention and response inhibition, encompassing impaired inhibition of rapid responses and an inability to delay reward, and resulting in impulsivity. Response inhibition mechanisms are impaired further in subjects with more severe complications of illness.