Search PubMed⌕ Search

Biomedical subjects

Alan C Swann

Publications and source records attributed to Alan C Swann.

At least 37 records · Page 2Linked to original sources

A multivantaged behavioural method for measuring onset and sequence of the clinical actions of antidepressants.

An aim in development of new antidepressants (ADs) now includes increasing speed of action. New drugs are tested primarily in outpatients who are less severely depressed than the patients treated in earlier trials of the tricyclic drugs. To determine early efficacy requires measures sensitive to initial changes in components of the illness as well as in the severity of the entire syndrome of depression. This paper describes the development of a brief 'multivantaged' (MV) method for assessing the major behavioural and affective components of depression. The revised Brief MV was significantly reduced from the original to make it more feasible to apply in outpatient studies. In this study we determined the Brief MV's (1) reliability and comparability to the original and (2) its ability to detect the onset of specific behavioural effects in outpatients treated with paroxetine for 6 wk. The latter is compared to the ability of the Hamilton Depression Scale (HAMD) to detect changes in global severity. The constructs derived from the Brief MV were found to be highly similar to those of the original version and as reliable. In depressed patients who responded to paroxetine, the HAMD and MV detected onset of improvement after 7 d of treatment. The Brief MV revealed that the improvement in global severity was due to the drug's action at this time on behaviours such as anxiety and distressed expression, as well as on a severity dimension of anxiety-agitation-somatization. Thus, the Brief MV, in uncovering underlying behavioural actions, represents an important addition to the current unidimensional HAMD approach in drug research.

Adolescent↗

Involvement in physical activity and risk for nearly lethal suicide attempts.

BACKGROUND: Although substantial research suggests that involvement in physical activity is associated with mental health benefits, relatively little is known about the association between physical activity and suicidal behavior. This study compared reports of recent physical activity among those surviving a nearly lethal suicide attempt to reports from community controls. METHODS: Analyses were conducted on data collected between November 1992 and July 1995 for a population-based, case-control study of nearly lethal suicide attempts among people aged 13 to 34 years. Logistic regression analyses were used to test the association between suicide attempts and physical activity, including the intensity, frequency, and duration of activity, while controlling for demographic factors and potential explanatory variables, such as depression, alcoholism, and the presence of a serious medical condition. RESULTS: Suicide attempters were far less likely than controls to report involvement in physical activity in the past month (48% vs 85%, respectively). Intensity, frequency, and duration of activity did not affect this association. The association persisted after adjusting for demographics and potential explanatory variables. CONCLUSIONS: Additional research is needed to explain the process through which the association occurs. The strong protective association observed is consistent with other research on the mental health benefits of physical activity and recommendations of involvement in regular physical activity.

Adolescent↗

Differential locomotor responses in male rats from three strains to acute methylphenidate.

Genetic variability is an important consideration in the study of the effect of drugs on humans and animals. Specifically, the effect of drugs on behavior varies from one rat strain to another. Methylphenidate (MPI), commonly known as Ritalin, is a psychostimulant with a pharmacological profile similar to amphetamine and cocaine, and is widely used in the treatment of attention deficit/hyperactivity disorder (ADHD). The purpose of this study was to examine the acute dose-response characteristics of MPD on three different male rat strains: spontaneously hypertensive/hyperactive rats (SHR), Wistar-Kyoto (WKY) rats, and Sprague-Dawley (SD) rats. Results showed clear differences in the pattern of behavioral response to the various MPD doses among the three rat strains. The 0.6 mg/kg MPD dose had no effect on any of the strains. At the dose of 2.5 mg/kg MPD, WKY rats reached peak locomotor activity within the initial 10 min, whereas SHR and SD rats reached peak activity in approximately 30 min. Furthermore, the effects on locomotor activity of SHR were longer in duration and higher in locomotor activity, whereas the effects on SD rats were shorter in duration and amplitude. Following the 10.0 mg/kg MPD, WKY, and SD mats reached their peak locomotor activity within 80 min post-injection, whereas SHR reached their peak locomotor activity within the initial 10 min post-injection. In addition, the SHR strain exhibited increased behavioral sensitivity to MPD as expressed by the latency, duration, and amplitude of their response. In conclusion, the dose-response experiment on the acute effects of MPD demonstrated that there are genetic differences in the responses to MPD.

Animals↗

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↗

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↗

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↗

Psychosis in mania: specificity of its role in severity and treatment response.

BACKGROUND: Psychosis is a prominent characteristic of manic episodes. We investigated relationships between the presence of psychotic features, the severity of the manic syndrome, and syndrome severity's response to treatment. METHOD: 179 subjects meeting Research Diagnostic Criteria for a manic episode of bipolar I disorder were hospitalized for acute manic episodes and treated in a randomized trial of lithium, divalproex sodium, or placebo. Factor and cluster analyses were carried out using the clinician-rated Schedule for Affective Disorders and Schizophrenia, Change version (SADS-C) and the nurse-rated Affective Disorder Rating Scale (ADRS). RESULTS: Subjects with psychotic features had significantly (p < .005) greater overall impairment (lower Global Assessment Scale [GAS] scores) but did not differ in severity of mania scores compared with those without psychotic features. Psychosis factor scores correlated significantly (p < .000001) with GAS scores but not with mania scores. Baseline psychosis factor scores did not correlate with subsequent treatment-associated change in mania scores, but change in mania scores during treatment correlated significantly (p < .000001) with change in the psychosis factor. Changes in psychosis factor scores correlated significantly with changes in mania rating scale scores regardless of treatment. CONCLUSIONS: Psychotic features as a component of manic episodes contribute substantially to overall impairment. Treatments that successfully treat mania also reduce psychosis scores.

Anticonvulsants↗

Chronic pretreatment with methylphenidate induces cross-sensitization with amphetamine.

Consequence of the long-term use of psychostimulants as treatment for attention deficit/hyperactivity disorder (ADHD) is unknown, particularly whether treatment with psychostimulants at an early age increases an individual's potential for cross-sensitization to other stimulants exposed at a later age. Cross-sensitization occurs when pretreatment with one stimulant leads to greater sensitivity to another stimulant. The aims of this study were to investigate whether chronic treatment with methylphenidate (MPD; Ritalin) in both juvenile and adult rats induced cross-sensitization to amphetamine at a later time and whether this cross-sensitization to amphetamine was age-dependent. Male Sprague-Dawley rats were randomly divided into four treatment groups: (1) group treated intraperitoneally (i.p.) with saline as juveniles and adults, (2) group treated with 0.6 mg/kg amphetamine, i.p., as juveniles and adults, (3) group treated with 2.5 mg/kg MPD, i.p., as juveniles and adults, and (4) group treated with saline, i.p., as juveniles and 2.5 mg/kg MPD, i.p., as adults. All of the animals received an amphetamine (0.6 mg/kg, i.p.) challenge on the last experimental day. We examined the effects of chronic MPD treatment in juvenile and adult rats on their locomotor response to an acute amphetamine exposure. Three different locomotor indices were studied using an automated activity monitoring system. Changes in the locomotor responses to amphetamine of these animals were compared to those of control rats that were pretreated with saline as juveniles and as adults. It was found that prior chronic treatment with MPD produced cross-sensitization to the locomotor response to amphetamine as observed in the horizontal activity and total distance traveled. It also appears that this cross-sensitization to amphetamine may not be dependent on the age of the subjects, i.e., whether subjects were juvenile or adult rats when they received drugs, but rather it depended on the behavioral index examined.

Aging↗

Maintenance efficacy of divalproex in the prevention of bipolar depression.

Breakthrough depression is a common problem in the treatment of bipolar disorder. Only one, recently published, double-blind, placebo-controlled trial has examined the efficacy of divalproex in the prevention of depressive episodes in bipolar patients. This report describes, in further detail, the findings from that trial of the effect of divalproex on multiple dimensions of depressive morbidity in bipolar disorder. A randomized, double-blind, parallel-group, multicenter study was conducted over a 52-week maintenance period. Bipolar I patients, who may have been treated with open-label lithium or divalproex and who met recovery criteria within 3 months of onset of an index manic episode, were randomized to maintenance treatment with divalproex, lithium, or placebo in a 2 : 1 : 1 ratio. Adjunctive paroxetine or sertraline for breakthrough depression was allowed in maintenance phase. Outcome measures were the rate of early discontinuation for depression, time to depressive relapse, proportion of patients with depressive relapse, mean change in Depressive Syndrome Scale score, proportion of patients receiving antidepressants, and time in the study. Among patients taking an antidepressant, a higher percentage of patients on placebo than divalproex discontinued early for depression. Patients who were previously hospitalized for affective episodes or took divalproex in the open period relapsed later on divalproex than on lithium during the maintenance period. Divalproex-treated patients had less worsening of depressive symptoms than lithium-treated patients during maintenance. Indices of severity of prestudy illness course predicted worse outcome in all treatment groups. Divalproex improved several dimensions of depressive morbidity and reduced the probability of depressive relapse in bipolar disorder, particularly in patients who had responded to divalproex when manic, and among patients with a more severe course of illness.

Adolescent↗

Strain differences in the behavioral responses of male rats to chronically administered methylphenidate.

Genetic variability in the behavioral responses of experimental subjects to psychostimulants such as amphetamine and cocaine have been reported. However, genetic differences in the locomotor responses of rat strains to methylphenidate (MPD), a commonly used psychostimulant in the treatment of attention deficit/hyperactivity disorder, have not been extensively investigated. Research using genetically defined rodent strains can enhance our understanding of the role genetic factors play in drug-related behaviors and the development of animal models for drug-sensitive diseases or behaviors. The objective of the present study was to investigate strain differences in the locomotor responses to MPD among three rat strains: Sprague-Dawley (SD), Wistar-Kyoto (WKY), and spontaneously hypertensive rats (SHR). Eight-week-old adult, male SD, WKY, and SHR were given a regimen of daily MPD administration (0.6, 2.5, or 10 mg/kg, i.p.) for 6 consecutive days followed by 3 days of washout and a day of MPD re-challenge with similar dosages as previously used. An automated activity monitoring system recorded their horizontal activity, total distance traveled, rearing, stereotypic movements, and number of discrete movements. Repeated administration of 0.6 mg/kg MPD produced no significant effect on locomotor activity compared with saline in all three strains. However, there were strain differences in the locomotor activity of SD, SHR, and WKY rats to repeated 2.5- and 10-mg/kg MPD treatment. Repeated administration of 2.5 mg/kg MPD elicited locomotor sensitization in SD and WKY rats but not in SHR. Repeated administration of 10 mg/kg MPD induced locomotor tolerance in SD and WKY rats, while SHR had variable locomotor responses to this MPD dose. In conclusion, rat strains play a significant role in the response to acute and chronic administration of MPD.

Animals↗

Divalproex in the treatment of impulsive aggression: efficacy in cluster B personality disorders.

Impulsive aggressive behavior is common in psychiatric disorders and accounts for significant morbidity and mortality. However, little systematic treatment data exist from placebo-controlled trials for this symptom domain. This was a multicenter, randomized, double-blind, placebo-controlled study in which outpatients with a score of > or =15 on the Aggression scale of the Overt Aggression Scale-Modified (OAS-M) and who fulfilled DSM-IV criteria for Cluster B personality disorder (n=96), intermittent explosive disorder (n=116), or post-traumatic stress disorder (n=34) were randomized to divalproex sodium or placebo for 12 weeks duration. Based on average OAS-M Aggression scores over the last 4 weeks of treatment, a treatment effect was not observed in the intent-to-treat data set (combined across the three psychiatric disorders), but was observed in both intent-to-treat and evaluable data sets for patients with Cluster B personality disorders. In the Cluster B evaluable data set, statistically significant treatment differences favoring divalproex were also observed for component items of the OAS-M Aggression score, including verbal assault and assault against objects, as well as OAS-M Irritability score, and Clinical Global Impression (CGI)-Severity at multiple time points throughout the study. No treatment group difference was noted for overall premature discontinuation rate; however, across psychiatric diagnoses, 21 (17%) patients in the divalproex group prematurely discontinued because of an adverse event, as compared to 4 (3%) patients in the placebo group (p <0.001). While a treatment effect was not observed when all diagnostic groups were combined, in a large subgroup of patients with Cluster B disorders, divalproex was superior to placebo in the treatment of impulsive aggression, irritability, and global severity.

Adult↗

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↗

Cognitive-behavioral treatment of late-life generalized anxiety disorder.

This study addressed the efficacy of cognitive-behavioral therapy (CBT), relative to minimal contact control (MCC), in a sample of 85 older adults (age 60 years and over) with generalized anxiety disorder (GAD). All participants completed measures of primary outcome (worry and anxiety), coexistent symptoms (depressive symptoms and specific fears), and quality of life. Results of both completer and intent-to-treat analyses revealed significant improvement in worry, anxiety, depression, and quality of life following CBT relative to MCC. Forty-five percent of patients in CBT were classified as responders, relative to 8% in MCC. Most gains for patients in CBT were maintained or enhanced over 1-year follow-up. However, posttreatment scores for patients in CBT failed to indicate return to normative functioning.

Age Factors↗

Differentiating anxiety and depression in older adults with generalized anxiety disorder.

To examine affect and cognition in differentiating anxiety and depression, 83 older participants with generalized anxiety disorder completed the Cognitive Checklist (CCL) and the Positive and Negative Affect Schedule (PANAS). A 3-factor solution was found for the PANAS: positive affect (PA), anxiety and anger (Negative Affect 1 [NA-1]), and guilt and shame (Negative Affect 2 [NA-2]). A 2-factor structure was noted for the CCL. Correlations with anxiety and depression measures suggested that the CCL Depression (CCL-D) subscale showed stronger correlations with depression, whereas the CCL Anxiety subscale did not uniquely correlate with anxiety. The NA-1 subscale correlated positively with measures of depression and anxiety, whereas the PA subscale showed negative correlations. Hierarchical regression suggested that the CCL-D subscale was a significant predictor of self-reported depression.

Affect↗

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↗

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↗

Divalproex sodium versus olanzapine in the treatment of acute mania in bipolar disorder: health-related quality of life and medical cost outcomes.

BACKGROUND: Divalproex sodium is a mood stabilizer used in the United States for the treatment of acute mania associated with bipolar disorder. Recently, olanzapine, an atypical antipsychotic, was approved for the treatment of acute mania. This study compares the clinical, health-related quality of life (HRQL), and economic outcomes of divalproex and olanzapine in the treatment of acute mania associated with bipolar disorder. METHOD: This 12-week, double-blind, double-dummy, randomized clinical trial included 120 subjects with DSM-IV bipolar disorder type I hospitalized for an acute manic episode recruited from 21 U.S. clinical centers. Subjects were randomly assigned to treatment with either divalproex or olanzapine and were followed in hospital for up to 21 days. If after 21 days clinical improvements (based on the Mania Rating Scale [MRS]) were not observed, subjects were discontinued. Subjects showing clinical improvement were treated for up to 12 weeks. HRQL was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) after hospital discharge (baseline) and at 6 and 12 weeks. Medical resource use and costs were collected over the 12-week study. RESULTS: A total of 120 subjects (N = 63 divalproex, N = 57 olanzapine) were randomized, and 78 (65%) were followed beyond 21 days. No statistically significant differences between the treatment groups for baseline-to-endpoint MRS or Q-LES-Q scores were observed. Total 12-week outpatient medical costs were significantly lower for the divalproex-treated group (541 US dollars) compared with the olanzapine-treated group (1080 US dollars) (p =.004). There was no significant difference in total medical costs between the 2 groups (divalproex = 13,703 US dollars; olanzapine = 15,180 US dollars; p =.88). CONCLUSION: Divalproex is associated with lower 12-week outpatient costs compared with olanzapine. Divalproex and olanzapine have similar short-term effects on clinical or HRQL outcomes in bipolar disorder subjects.

Acute Disease↗

Neuroreceptor mechanisms of aggression and its treatment.

Aggression results from the interaction of multiple systems. It can be classified as predatory, impulsive, or based on a medical condition. The likelihood of aggression is increased by environmental overstimulation or stress, transmitter balances favoring dopamine and excitatory amino acid transmission over serotonin and gamma-aminobutyric acid transmission, and the presence of problems related to impulsivity. Treatments for aggression are based on the underlying causes and generally should combine pharmacologic and environmental or psychotherapeutic measures. Useful pharmacologic agents include mood stabilizers and atypical antipsychotics that combine dopaminergic and serotonergic actions. Drugs acting on nicotine receptors may deserve further attention. Nonpharmacologic measures include behavioral techniques aimed at reducing impulsivity, relapse prevention techniques for substance abuse, and anger management techniques.

Aggression↗