Biomedical subjects

F Gerard Moeller

Publications and source records attributed to F Gerard Moeller.

17 recordsLinked to original sources

PubMed2006

Safety, tolerability and efficacy of levodopa-carbidopa treatment for cocaine dependence: two double-blind, randomized, clinical trials.

RATIONALE: The role of dopamine in cocaine abuse has been long recognized. Cocaine use can profoundly alter dopaminergic functioning through depletion of this monoamine and changes in receptor functioning. Based on these facts, levodopa (L-dopa) pharmacotherapy may be helpful in reducing or abolishing cocaine use. OBJECTIVE: The current studies sought to evaluate the safety, tolerability and efficacy of L-dopa as a treatment for cocaine dependence. METHODS: In Study 1, 67 cocaine-dependent subjects were randomized in a 5-week, double-blind, placebo-controlled safety trial. Subjects received either placebo, or 400 mg L-dopa plus 100 mg of the peripheral decarboxylase inhibitor, carbidopa, in a sustained-release preparation (Sinemet CR). In Study 2, 122 cocaine-dependent subjects were enrolled in a 9-week, randomized, double-blind, placebo-controlled trial to compare placebo to 400/100 mg and 800/200 mg L-dopa/carbidopa treatments. Placebo or L-dopa were administered twice daily in both studies. RESULTS: L-dopa was well tolerated with similar retention and medication adherence rates compared to placebo. Only two side effects occurred more often in L-dopa-treated patients: nausea and dizziness. L-dopa lowered diastolic blood pressure in a dose-dependent fashion. In these trials, L-dopa had no effect on cocaine use, cocaine craving, or mood. CONCLUSION: These two studies demonstrate the safety and tolerability of L-dopa pharmacotherapy in cocaine-dependent patients. No evidence for greater efficacy of L-dopa compared to placebo was observed. The possibility of enhancing treatment effects by combining L-dopa with other behavioral or pharmacological interventions is discussed.

Adult↗

PubMed2005

Acute yohimbine increases laboratory-measured impulsivity in normal subjects.

BACKGROUND: State-dependent changes in impulsivity may be related to norepinephrine. To examine possible relationships between norepinephrine and acute changes in impulsivity, we measured effects of yohimbine, which increases norepinephrine release by blocking alpha-2 noradrenergic receptors, on laboratory-measured impulsivity in healthy subjects without psychiatric or substance-use disorders. METHODS: Impulsivity was assessed using the Immediate and Delayed Memory Tasks (IMT-DMT), derived from the Continuous Performance Test, before and after placebo or two doses of yohimbine, given 4 days apart. Blood pressure was monitored, and psychiatric symptoms were measured using self-rated visual analog scales. RESULTS: Yohimbine was associated with a dose-related increase in impulsive IMT commission errors, with an increase of > 50% relative to baseline at the higher dose. The activation factor of the Internal State Scale was increased at the same dose. CONCLUSIONS: These results are consistent with increased impulsivity in normal subjects given yohimbine, possibly related to increased norepinephrine.

Adrenergic alpha-Antagonists↗

PubMed2005

Increased impulsivity associated with severity of suicide attempt history in patients with bipolar disorder.

BACKGROUND: Impulsivity is a prominent and measurable characteristic of bipolar disorder that can contribute to risk for suicidal behavior. The purpose of this study was to investigate the relationship between impulsivity and severity of past suicidal behavior, a potential predictor of eventual suicide, in patients with bipolar disorder. METHOD: In bipolar disorder subjects with either a definite history of attempted suicide or no such history, impulsivity was assessed with both a questionnaire (Barratt Impulsiveness Scale) and behavioral laboratory performance measures (immediate memory/delayed memory tasks). Diagnosis was determined with the Structured Clinical Interview for DSM-IV. Interviews of patients and review of records were used to determine the number of past suicide attempts and the medical severity of the most severe attempt. RESULTS: Subjects with a history of suicide attempts had more impulsive errors on the immediate memory task and had shorter response latencies, especially for impulsive responses. Impulsivity was highest in subjects with the most medically severe suicide attempts. Effects were not accounted for by presence of depression or mania at the time of testing. Barratt Impulsiveness Scale scores were numerically, but not significantly, higher in subjects with suicide attempts. A history of alcohol abuse was associated with greater probability of a suicide attempt. Multivariate analysis showed that ethanol abuse history and clinical state at the time of testing did not have a significant effect after impulsivity was taken into account. DISCUSSION: These results suggest that a history of severe suicidal behavior in patients with bipolar disorder is associated with impulsivity, manifested as a tendency toward rapid, unplanned responses.

Adult↗

PubMed2004

Suicidal behaviors and drug abuse: impulsivity and its assessment.

Impulsivity appears to play an important role in suicidal behaviors and drug abuse, which are two psychiatric problems that may interact with one another. Interpretation of the literature on impulsivity in these behaviors may be complicated by the variety of measurement techniques for the assessment of impulsivity. There are three general types of impulsivity assessment: self-report, biological, and laboratory behavioral. Because laboratory behavioral measures both meet an operational definition of impulsivity and are sensitive to state-dependent changes in impulsivity, this paper presents data that focuses on laboratory behavioral performance among samples emitting suicidal behaviors or substance abuse. To better account for influence of impulsivity in these psychiatric disturbances, no single source of measurement should be used without the consideration of other types of instruments.

Decision Making↗

PubMed2004

Functional MRI study of working memory in MDMA users.

RATIONALE: Methylene-dioxymethamphetamine (MDMA) is known to cause degeneration of serotonin nerve terminals after acute doses in animals. Similarly, behavioral studies in human MDMA users regularly find abnormalities in memory, mood, and impulse control. However, studies of brain function using brain imaging in MDMA users have been less consistent. OBJECTIVES: The purpose of this study was to determine, using functional magnetic resonance imaging (fMRI), whether individuals with a self-reported history of MDMA use would differ from non-MDMA using controls on activation while performing a working memory task. METHODS: Fifteen MDMA using subjects and 19 non-MDMA using controls underwent fMRI scanning while performing the immediate and delayed memory task (IMT/DMT). The study was based on a block design in which the delayed memory task (DMT) alternated with the immediate memory task (IMT), which served as a control condition. FMRI scans were acquired on a 1.5 T scanner, using a gradient echo echoplanar pulse sequence. RESULTS: Random effects SPM99 analysis showed significantly greater activation (whole volume corrected cluster P<0.05) during the DMT relative to the IMT in the MDMA subjects compared with the control subjects in the medial superior frontal gyrus, in the thalamus extending into putamen, and in the hippocampus. CONCLUSIONS: Although these effects could be due to other drugs used by MDMA users, these results are consistent with behavioral problems that are associated with MDMA use, and with animal studies on the effects of MDMA on brain function.

Adult↗

PubMed2004

Agonist-like or antagonist-like treatment for cocaine dependence with methadone for heroin dependence: two double-blind randomized clinical trials.

Concurrent abuse of cocaine and heroin is a common problem. Methadone is effective for opioid dependence. The question arises as to whether combining agonist-like or antagonist-like medication for cocaine with methadone for opioid dependence might be efficacious. Two parallel studies were conducted. One examined sustained release d-amphetamine and the other risperidone for cocaine dependence, each in combination with methadone. In total, 240 subjects (120/study) were recruited, who were both cocaine and heroin dependent and not currently receiving medication. All provided consent. Both studies were carried out for 26 weeks, randomized, double-blind and placebo controlled. Study I compared sustained release d-amphetamine (escalating 15-30 or 30-60 mg) and placebo. Study II examined risperidone (2 or 4 mg) and placebo. All subjects underwent methadone induction and were stabilized at 1.1 mg/kg. Subjects attended clinic twice/week, provided urine samples, obtained medication take-home doses for intervening days, and completed self-report measures. Each had one behavioral therapy session/week. In Study I, reduction in cocaine use was significant for the 30/60 mg dose compared to the 15/30 mg and placebo. Opioid use was reduced in all groups with a trend toward greater reduction in the 30/60 mg d-amphetamine group. In Study II, methadone reduced illicit opioid use but cocaine use did not change in the risperidone or placebo groups. There were no adverse medication interactions in either study. The results provide support for the agonist-like (d-amphetamine) model in cocaine dependence treatment but not for antagonist-like (risperidone) treatment. They coincide with our previous reports of amphetamine or risperidone administered singly in cocaine-dependent individuals.

Adolescent↗

PubMed2004

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.

Adult↗

PubMed2004

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.

Adult↗

PubMed2004

Laboratory measured behavioral impulsivity relates to suicide attempt history.

The purpose of this study was to examine the relationship between laboratory behavioral measured impulsivity (using the Immediate and Delayed Memory Tasks) and suicidal attempt histories. Three groups of adults were recruited, those with either: no previous suicide attempts (Control, n = 20), only a single suicide attempt (Single, n = 20), or multiple suicidal attempts (Multiple, n = 10). As hypothesized, impulsive responses increased with the number of suicide attempts (Control < Single < Multiple). This study helps to demonstrate how laboratory behavioral measures of impulsivity can be used to discriminate groups based on suicidal histories among samples not currently exhibiting significant suicidal behaviors.

Adult↗

PubMed2003

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.

Adult↗

PubMed2003

Familial transmission of Continuous Performance Test behavior: attentional and impulsive response characteristics.

Continuous Performance Tests (CPTs) provide information on attentional processing and impulsive behavior. The results of previous research that used self-report measures have provided evidence for familial transmission (through genetic and/or environmental influences) of impulsive characteristics. The authors of the present study examined whether the impulsive behavioral parameters that are measured by the CPT also share familial relationships. The researchers asked 26 healthy parent-adolescent pairs to complete the Immediate and Delayed Memory Tasks (IMT/DMT; D. M. Dougherty, 1999; D. M. Dougherty, D. M. Marsh, & C. W. Mathias, 2002), a modified CPT (B. A. Cornblatt, N. J. Risch, G. Faris, D. Friedman, & L. Erlenmeyer-Kimling, 1988; H. E. Rosvold, A. Mirsky, I. Sarason, E. D. Breansome, Jr., & L. H. Beck, 1956), and the Barratt Impulsiveness Scale (BIS; J. H. Patton, M. S. Stanford, & E. S. Barratt, 1995), a self-report measure. The main findings can be summarized as follows: (a) commission errors (but not correct detections) on the IMT and DMT were correlated between parents and their adolescent children, (b) adolescents emitted a higher proportion of commission errors than did their parents, and (c) self-reported impulsivity (i.e., BIS) was correlated with commission errors for parents, but not for adolescents. The findings of this study support the use of an objective behavioral measure of impulsivity to assess familial relationships of impulsivity.

Adolescent↗

PubMed2003

Behavioral impulsivity paradigms: a comparison in hospitalized adolescents with disruptive behavior disorders.

BACKGROUND: Behavioral impulsivity paradigms vary widely and studies using these measures have typically relied on a single measure used in isolation. As a result, comparisons between measures are difficult, with little consensus regarding which method may be most sensitive to individual impulsivity differences of different populations. METHOD: A single testing session of each of four different impulsivity tasks was completed by two groups of adolescents aged 13-17: hospitalized inpatients with disruptive behavior disorders (DBD; n = 22) and controls (n = 22). Tasks included two rapid-decision (IMT/DMT and GoStop) and two reward-directed (TC and SKIP) impulsivity paradigms. Behavioral testing took place within 3 days of hospitalization for the adolescents with DBD. RESULTS: Compared to controls, the DBD group exhibited higher commission error rates, lower inhibited response rates after a stop-signal, and twice as many reward-directed responses even after IQ differences between the groups were taken into account. When the four paradigms were compared, effect-size calculations indicated that the two rapid-decision paradigms were more sensitive to group differences than the reward-directed tasks. CONCLUSIONS: Despite the initiation of pharmacotherapy within the first 3 days of hospitalization, in contrast to the control group, the adolescents with DBD performed consistently with what has been operationally defined as impulsivity. Based on these results, these tasks appear to measure similar, but unique components of the impulsivity construct. With further study, laboratory behavioral paradigms may prove to be useful additions to current clinical diagnostic and treatment procedures in a variety of psychiatric populations.

Adolescent↗

PubMed2003

Commission error rates on a continuous performance test are related to deficits measured by the Benton Visual Retention Test.

This study is one in a series investigating the relationship between impulsive behavior on a Continuous Performance Test (i.e., the Immediate and Delayed Memory Task) and other cognitive deficits measured by clinical instruments. Forty-two adolescents were selected for two groups, controls and hospitalized patients with disruptive behavior disorders. Each adolescent completed the Immediate and Delayed Memory Task and the Benton Visual Retention Test. Our main findings were that, even when controlling for IQ, the Immediate and Delayed Memory Task commission errors were associated with adverse Benton performance, but only in the patient group. These results may be explained by a shared association between processes of impulsivity and other deficits of executive control that may interfere with successful performance of the Benton.

Adolescent↗

PubMed2002

Increased impulsivity in cocaine dependent subjects independent of antisocial personality disorder and aggression.

Several previous studies show a relationship between impulsivity and substance abuse; however, it is unclear whether the increased impulsivity seen in substance dependent groups is specifically related to substance abuse, or if it is due to concomitant antisocial personality disorder (ASPD) or aggression. The issue of whether impulsivity is specifically related to substance abuse is important since it has a bearing on risk factors for development of substance abuse. To determine whether cocaine dependent subjects show increased impulsivity independent of ASPD, the Barratt impulsiveness scale (BIS-11), a delayed reward laboratory measure of impulsivity, and the life history of aggression scale were administered to 49 cocaine dependent subjects and 25 controls. Results showed that cocaine dependent subjects with ASPD were more impulsive and aggressive than controls, but cocaine dependent subjects without ASPD were also more impulsive compared to controls. Controlling for aggression history, cocaine dependent subjects without ASPD continued to have elevated impulsivity as measured by the BIS-11, but not the delayed reward task. This study supports the hypothesis that the increased impulsivity as measured by the BIS-11 in cocaine dependent individuals is not exclusively due to concomitant increases in aggression or ASPD.

Adult↗

PubMed2002

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.

Adult↗

PubMed2002

Serotonin 2a receptor T102C polymorphism and impaired impulse control.

Patients homozygous for the C allele of the T102C serotonin (5-HT) 2a receptor polymorphism have shown increased suicidal ideation or behavior in some reports, but not in others. We conducted a pilot investigation to determine whether this polymorphism might relate more specifically to a dimension of impaired impulse control, which may underlie only a portion of suicides. Rates of commission (impulsive) errors in a variant of the Continuous Performance Test (CPT) were compared across the genotypes of the T102C polymorphism in adults recruited from the community. The 102C/102C genotype was jointly associated with a greater incidence of past mood disorder or substance-use disorder, as well as significantly more commission errors compared to the 102T/102C and 102C/102C genotypes. These preliminary data suggest that the T102C 5-HT2a receptor polymorphism may be a marker for impaired behavior control-perhaps in the context of psychiatric disorder history.

Adult↗

PubMed2002

Laboratory-measured aggressive behavior of women: acute tryptophan depletion and augmentation.

Plasma L-tryptophan (Trp) reductions have been related to aggression increases in men. Impairment of serotonin synthesis and neurotransmission is one explanation. Using repeated-measures, this Trp manipulation study measured laboratory-induced aggression in 12 women after Trp augmentation (T+), depletion (T-), and food-restricted (fasting control) conditions. Participants were provoked with periodic subtraction of money from their task earnings by a (fictitious) partner. Aggression was defined as the number of point subtractions participants made from their fictitious partner. Participants completed five testing sessions under each condition. T+ decreased aggressive responses and T- increased aggressive responses. Post-hoc analyses showed changes in aggressive behavior were specific to women with higher fasting control plasma Trp, which is consistent with research demonstrating that men with higher levels of baseline Trp are more aggressive. These findings indicate that both T+ and T- can influence aggressive behavior and that certain subgroups of women may be more susceptible to serotonin manipulation.

Adolescent↗