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Biomedical subjects

Alan C Swann

Publications and source records attributed to Alan C Swann.

At least 19 recordsLinked to original sources
PubMed2006

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 animal's 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.

Adolescent↗
PubMed2006

Impulsivity and BOLD fMRI activation in MDMA users and healthy control subjects.

The correlation between scores on the Barratt Impulsiveness Scale (BIS) and activation measured by functional magnetic resonance imaging in a dorsolateral prefrontal cortical (DLPFC) activating task was examined in 15 MDMA-using subjects and 19 controls. A significant correlation between BIS scores and DLPFC activation was found, supporting a role for the DLPFC in BIS-measured impulsivity.

Adult↗
PubMed2006

Chronic methylphenidate modulates locomotor activity and sensory evoked responses in the VTA and NAc of freely behaving rats.

Repeated exposure to psychostimulants leads to behavioral sensitization. The mode of action of brain circuitry responsible for behavioral sensitization is not well understood. There is some evidence that psychostimulants, such as amphetamine and cocaine, activate the ventral tegmental area (VTA) and nucleus accumbens (NAc). However, little is known about the effect of methylphenidate (MPD) on the electrophysiological properties of VTA and NAc neurons. The study was designed to investigate the chronic effects of MPD administration on sensory evoked field potentials of VTA and NAc in freely behaving rats previously implanted with permanent electrodes. On experimental day 1, locomotor behavior was recorded for 2 h post-saline injection followed by sensory evoked field potential recordings after saline and three different escalating (0.6, 2.5, and 10.0 mg/kg) MPD doses. After completion of the last recording, the rat was returned to its home cage. To induce behavioral sensitization, animals were injected for five days with 2.5 mg/kg MPD. Following a rechallenge with saline and identical MPD doses as those given on experimental day 1, locomotor recording of the rat was also performed on experimental days 2, 6 and 11. Results showed that repeated administration of MPD increased locomotion in dose-response manner and elicited behavioral sensitization, while the amplitude of the sensory evoked field responses of the VTA and NAc exhibited dose-response attenuation on both recording days (days 1 and 10). In addition, repeated administration of MPD resulted in attenuating the baseline amplitudes of sensory input on experimental day 10, while MPD administration on experimental day 10 elicited further attenuation of the VTA and NAc sensory evoked responses. Such further attenuation can be interpreted as electrophysiological sensitization.

Age Factors↗
PubMed2006

Sensory-evoked potentials recordings from the ventral tegmental area, nucleus accumbens, prefrontal cortex, and caudate nucleus and locomotor activity are modulated in dose-response characteristics by methylphenidate.

Most of the studies investigating the effects of methylphenidate (MPD) are using behavioral and biochemical approaches. There are some electrophysiological studies about the effects of MPD on spontaneous electrical activity; however, there is none about the effects of MPD on sensory inputs. The objectives of the present study were to investigate the MPD dose-response characteristics on locomotor activity and sensory inputs using acoustic stimuli. Freely behaving rats previously implanted with semi-microelectrodes were used to record from four brain areas known to be sites of psychostimulant action. For locomotor behavior assessment, rats received saline on experimental day 1 and an acute administration of MPD (0.6, 2.5, or 10.0 mg/kg, i.p.) on experimental day 2. Using an automated, computerized activity-monitoring system, locomotor behavior was recorded for 2-h postinjection on both days. For the electrophysiological experiments, animals were implanted with permanent electrodes in the ventral tegmental area (VTA), nucleus accumbens (NAc), prefrontal cortex (PFC), and caudate nucleus (CN) under general anesthesia. Five to seven days after electrode implantation, they were used to study the effects of three different MPD doses on the response to sensory inputs. The lowest dose of MPD (0.6 mg/kg, i.p.) failed to alter locomotor activity, while the two higher MPD doses (2.5 and 10.0 mg/kg) elicited increase in locomotion, with the 10.0 mg/kg dose increased at least twice as much as the 2.5 mg/kg dose. However, the same three MPD doses elicited significant attenuation of sensory inputs in dose-response characteristics, i.e., as MPD dose increased, evoked sensory inputs decreased. These opposite effects (motor activation and sensory input suppression) were further discussed.

Acoustic Stimulation↗
PubMed2006

Dose-response characteristics of methylphenidate on locomotor behavior and on sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats.

BACKGROUND: Methylphenidate (MPD) is a psychostimulant commonly prescribed for attention deficit/hyperactivity disorder. The mode of action of the brain circuitry responsible for initiating the animals' behavior in response to psychostimulants is not well understood. There is some evidence that psychostimulants activate the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC). METHODS: The present study was designed to investigate the acute dose-response of MPD (0.6, 2.5, and 10.0 mg/kg) on locomotor behavior and sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats previously implanted with permanent electrodes. For locomotor behavior, adult male Wistar-Kyoto (WKY; n = 39) rats were given saline on experimental day 1 and either saline or an acute injection of MPD (0.6, 2.5, or 10.0 mg/kg, i.p.) on experimental day 2. Locomotor activity was recorded for 2-h post injection on both days using an automated, computerized activity monitoring system. Electrophysiological recordings were also performed in the adult male WKY rats (n = 10). Five to seven days after the rats had recovered from the implantation of electrodes, each rat was placed in a sound-insulated, electrophysiological test chamber where its sensory evoked field potentials were recorded before and after saline and 0.6, 2.5, and 10.0 mg/kg MPD injection. Time interval between injections was 90 min. RESULTS: Results showed an increase in locomotion with dose-response characteristics, while a dose-response decrease in amplitude of the components of sensory evoked field responses of the VTA, NAc, and PFC neurons. For example, the P3 component of the sensory evoked field response of the VTA decreased by 19.8% +/- 7.4% from baseline after treatment of 0.6 mg/kg MPD, 37.8% +/- 5.9% after 2.5 mg/kg MPD, and 56.5% +/- 3.9% after 10 mg/kg MPD. Greater attenuation from baseline was observed in the NAc and PFC. Differences in the intensity of MPD-induced attenuation were also found among these brain areas. CONCLUSION: These results suggest that an acute treatment of MPD produces electrophysiologically detectable alterations at the neuronal level, as well as observable, behavioral responses. The present study is the first to investigate the acute dose-response effects of MPD on behavior in terms of locomotor activity and in the brain involving the sensory inputs of VTA, NAc, and PFC neurons in intact, non-anesthetized, freely behaving rats previously implanted with permanent electrodes.

Journal Article↗
PubMed2006

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

BACKGROUND: The 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. METHODS: The 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. RESULTS: Acute 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. CONCLUSION: MDMA sensitized to its own locomotor activating effects but did not elicit any cross-sensitization with amphetamine or methylphenidate.

Journal Article↗
PubMed2006

A randomized, placebo-controlled, multicenter study of divalproex sodium extended release in the treatment of acute mania.

OBJECTIVE: The efficacy and safety of divalproex sodium extended release (divalproex ER) were evaluated in patients hospitalized for acute mania associated with bipolar I disorder, manic or mixed type (DSM-IV-TR criteria). METHOD: Following screening and washout of psychotropic medications, 377 patients were randomly assigned in a 1:1 ratio to 21 days of double-blind treatment with divalproex ER (N = 192) or placebo (N = 185). Daily dosage was initiated at 25 mg/kg, increased 500 mg on day 3, and adjusted to serum valproate concentrations of 85 to 125 microg/mL. The Mania Rating Scale (MRS) was used to assess efficacy. Patients remained hospitalized at least 15 days during blinded treatment. The study was conducted from April 2003 to May 2004. RESULTS: Improvement from baseline on the MRS was significantly greater among patients who received divalproex ER compared with placebo at the first on-treatment rating assessment, day 5, and all subsequent ratings through day 21 (p = .013). Furthermore, the proportion of patients achieving at least 50% improvement from baseline in MRS was significantly higher in patients receiving divalproex ER (48%) than in patients receiving placebo (34%) (p = .012). Five of the 11 MRS items improved significantly more in patients receiving divalproex ER than placebo: less need for sleep (p <or= .01), more energetic (p <or= .05), increased activity (p <or= .05), generalized motor hyperactivity (p <or= .05), and racing thoughts (p <or= .001). Side effects associated with divalproex ER included somnolence, dizziness, and gastrointestinal complaints. CONCLUSION: The results indicate that dival-proex ER is effective and safe for the treatment of mania episodes in bipolar I patients. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00060905.

Acute Disease↗
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

Reduced anterior corpus callosum white matter integrity is related to increased impulsivity and reduced discriminability in cocaine-dependent subjects: diffusion tensor imaging.

Brain imaging studies find evidence of prefrontal cortical dysfunction in cocaine-dependent subjects. Similarly, cocaine-dependent subjects have problems with behaviors related to executive function and impulsivity. Since prefrontal cortical axonal tracts cross between hemispheres in the corpus callosum, it is possible that white matter integrity in the corpus callosum could also be diminished in cocaine-dependent subjects. The purpose of this study was to compare corpus callosum white matter integrity as measured by the fractional anisotropy (FA) on diffusion tensor imaging (DTI) between 18 cocaine-dependent subjects and 18 healthy controls. The Barratt Impulsiveness Scale (BIS-11) and a continuous performance test: the Immediate and Delayed Memory Task (IMT/DMT) were also collected. Results of the DTI showed significantly reduced FA in the genu and rostral body of the anterior corpus callosum in cocaine-dependent subjects compared to controls. Cocaine-dependent subjects also had significantly higher BIS-11 scores, greater impulsive (commission) errors, and reduced ability to discriminate target from catch stimuli (discriminability) on the IMT/DMT. Within cocaine dependent subjects there was a significant negative correlation between FA in the anterior corpus callosum and behavioral laboratory measured impulsivity, and there was a positive correlation between FA and discriminability. The finding that reduced integrity of anterior corpus callosum white matter in cocaine users is related to impaired impulse control and reduced ability to discriminate between target and catch stimuli is consistent with prior theories regarding frontal cortical involvement in impaired inhibitory control in cocaine-dependent subjects.

Adult↗
PubMed2005

Relationship of mania symptomatology to maintenance treatment response with divalproex, lithium, or placebo.

Euphoric and mixed (dysphoric) manic symptoms have different response patterns to divalproex and lithium in acute mania treatment, but have not been studied in relationship to maintenance treatment outcomes. We examined the impact of initial euphoric or dysphoric manic symptomatology on maintenance outcome. Randomized maintenance treatment with divalproex, lithium, or placebo was provided for 372 bipolar I patients, who met improvement criteria during open phase treatment for an index manic episode. The current analysis grouped patients according to the index manic episode subtype (euphoric or dysphoric), and evaluated the impact on maintenance treatment outcome. The rate of early discontinuation due to intolerance during maintenance treatment was higher for initially dysphoric patients (N=249) than euphoric patients (N=123; 15.7 vs 7.3%, respectively; p=0.032). Both lithium (23.2%) and divalproex (17.1%) were associated with more premature discontinuations due to intolerance than placebo (4.8%; p=0.003 and 0.02, respectively) in the initially dysphoric patients. Among initially euphoric patients, treatment with lithium was associated with significantly more premature discontinuations due to intolerance compared to placebo (18.2 vs 0%; p=0.03), and divalproex was significantly (p=0.05) more effective than lithium, but not placebo in delaying time to a depressive episode. Initial euphoric mania appeared to predispose to better outcomes on indices of depression and overall function with divalproex maintenance than with either placebo or lithium. Dysphoric mania appeared to predispose patients to more side effects when treated with either divalproex or lithium during maintenance therapy.

Adult↗
PubMed2005

Impact of trait impulsivity and state aggression on divalproex versus placebo response in borderline personality disorder.

OBJECTIVE: The authors' goal was to determine whether specific pretreatment clinical characteristics differentially predict favorable treatment response to divalproex versus placebo for impulsive aggression in patients with borderline personality disorder. METHOD: Fifty-two outpatients with DSM-IV borderline personality disorder were randomly assigned to receive divalproex (N=20) or placebo (N=32), double-blind, for 12 weeks. Trait impulsivity symptoms were determined by using the Barratt Impulsiveness Scale, and state aggression symptoms were determined by using the Overt Aggression Scale modified for outpatients. Affective stability was determined by using the Young Mania Rating Scale and the Hamilton Depression Rating Scale. Analyses were performed to identify possible baseline symptom domains that predict treatment response. RESULTS: Divalproex was superior to placebo in reducing impulsive aggression in patients with borderline personality disorder. Divalproex-treated patients responded better than placebo-treated patients among those with higher baseline trait impulsivity symptoms and state aggression symptoms. The effects of baseline trait impulsivity and state aggression appear to be independent of one another. However, baseline affective instability did not influence differential treatment response. CONCLUSIONS: Both pretreatment trait impulsivity symptoms and state aggression symptoms predict a favorable response to divalproex relative to placebo for impulsive aggression in patients with borderline personality disorder.

Adult↗
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↗
PubMed2005

Extended-release carbamazepine capsules as monotherapy for acute mania in bipolar disorder: a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Although carbamazepine has long been used for the treatment of acute mania, only recently was its efficacy confirmed in a large, multicenter, parallel-group, placebo-controlled, randomized trial. In the present study, we further evaluated the efficacy and safety of monotherapy with beaded, extended-release carbamazepine capsules (ERC-CBZ) in patients with bipolar I disorder experiencing manic or mixed episodes. METHOD: Hospitalized bipolar I disorder (DSM-IV criteria) patients (N = 239) with manic or mixed episodes were randomly assigned on a double-blind basis to receive ERC-CBZ or placebo for 3 weeks, following a single-blind placebo lead-in. Treatment with ERC-CBZ was initiated at 200 mg twice daily, and investigators were encouraged to increase doses, as necessary and tolerated, by 200 mg/day up to 1600 mg/day. Efficacy was assessed weekly with the Young Mania Rating Scale (YMRS), Clinical Global Impressions scale (CGI), and Hamilton Rating Scale for Depression. The study was conducted from July 23, 2002, to April 1, 2003. RESULTS: 144 patients (60.3%) completed the study, with a significant number of placebo patients discontinuing due to lack of efficacy (p < .001). Extended-release carbamazepine treatment was associated with significant improvements in mean YMRS total and CGI total scores, using last-observation-carried-forward analyses, beginning at day 7 (p < .05). Adverse events occurring more frequently in the ERC-CBZ-treated group included dizziness (39.3%), somnolence (30.3%), and nausea (23.8%) [corrected] Patients taking ERC-CBZ experienced a significant increase in total cholesterol, composed of increases in both high-density and low-density lipoproteins. CONCLUSION: Extended-release carbamazepine monotherapy had significantly greater efficacy compared with placebo in the treatment of acute mania in this large, randomized, double-blind, placebo-controlled trial.

Acute Disease↗
PubMed2005

The Texas implementation of medication algorithms: update to the algorithms for treatment of bipolar I disorder.

BACKGROUND: A panel consisting of academic psychiatrists and pharmacist administrators of the Texas Department of State Health Services (formerly Texas Department of Mental Health and Mental Retardation), community mental health physicians, advocates, and consumers met in May 2004 to review new evidence in the pharmacologic treatment of bipolar I disorder (BDI). The goal of the consensus conference was to update and revise the current treatment algorithm for BDI as part of the Texas Implementation of Medication Algorithms, a statewide quality assurance program for the treatment of major psychiatric illness. The guidelines for evaluating possible medications, the criteria for selection and ranking, and the updated algorithms are described. METHOD: Principles from previous consensus conferences were reviewed and amended. Medication algorithms for the acute treatment of hypomanic/manic or mixed and depressive episodes in BDI were developed after examining recent efficacy and safety and tolerability data. Recommendations for maintenance treatments were developed. RESULTS: The panel updated the 2 primary algorithms (hypomanic/manic/mixed and depressive) based on clinical evidence for efficacy, tolerability, and safety developed since 2000. Expert consensus was utilized where clinical evidence was limited. Prevention of new episodes or prophylaxis treatment recommendations were developed based on recent data from longer-term trials. Maintenance recommendations are provided as levels versus a specified staged algorithm, as for acute treatment, due to the relatively limited database to inform treatment. CONCLUSIONS: These algorithms for the treatment of BDI represent the recommendations based on the most recent evidence available. These recommendations are meant to provide a framework for clinical decision making, not to replace clinical judgment. As with any algorithm, treatment practices will evolve beyond the recommendations of this consensus conference as new evidence and additional medications become available.

Algorithms↗
PubMed2005

Practical Clues to Early Recognition of Bipolar Disorder: A Primary Care Approach.

Early treatment can favorably impact the course of bipolar disorder, a lifelong illness. Because bipolar disorder can masquerade as various mental and physical illnesses-primarily major depressive disorder-patients with this condition frequently go unrecognized for years. During this recognition lag, such patients may present to their primary care physician on multiple occasions. Accordingly, primary care physicians would benefit from knowing the "clues" to early recognition of the disorder, because early recognition and management can reduce disability, improve social and employment stability, and result in improved functional outcomes. This review describes 3 pathways to the diagnosis of bipolar disorder relevant to the primary care setting: detection of mania or hypomania, differential diagnosis of recurrent depressive episodes, and identification of interepisode disorder and its comorbidities. We summarize these pathways in terms of a practical tool that a primary care physician can use to trigger further evaluation or referral.

Journal Article↗
PubMed2005

Long-term treatment in bipolar disorder.

Bipolar disorder is a lifelong illness with a course that is usually chronic or recurrent. Severity of complications is generally proportionate to the number of episodes, especially depression. In addition to potentially preventing episodes, effective treatment reduces mortality. This article reviews long-term treatment strategies for bipolar disorder, focusing on depressive episodes, and discusses treatment studies, including problems in design. Treatment effectiveness, including reduction of suicide risk, is enhanced if patients and physicians collaboratively recognize and treat prodromal symptoms, preventing the emergence of episodes. Strategies for treatment differ as one progresses from obtaining syndromal recovery in the acute episode, to functional recovery during continuation treatment, to stability during maintenance treatment. Successful long-term treatment of bipolar disorder requires integrated pharmacologic and nonpharmacologic treatments combined with a therapeutic alliance that facilitates a proactive, preventive approach to the illness.

Acute Disease↗
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↗