Acute effects of low-dose flumazenil in panic disorder.
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Adult↗
Biomedical subjects
R J Maddock
Publications and source records attributed to R J Maddock.
Role of feedback in formation of acute tolerance to alcohol.
OBJECTIVE: The contributions of feedback to formation of acute ethanol tolerance were studied during performance of a task that allowed practice in the absence of feedback about performance accuracy. METHOD: The perceptual instability of the seen environment during head movement (apparent concomitant motion, ACM) and the vestibulo-ocular reflex (VOR) were measured before and after alcohol ingestion. In separate conditions, eight (six female) subjects were either deprived or not deprived of normal vision of the laboratory during the portion of the experiment following onset of alcohol ingestion. RESULTS: Alcohol caused ACM in the direction opposite head rotation to increase in both sessions. The degree of ACM increase was greater during sessions in which visual feedback was prevented than in sessions in which subjects could see the surroundings. The increase in ACM was accompanied by a decrease in gain of the VOR which was relatively larger in the no-feedback condition. In addition, ACM returned to normal (pre-alcohol ingestion) values more rapidly during sessions in which subjects received visual feedback. CONCLUSIONS: The results suggest that feedback is an important component in forming acute tolerance to alcohol, independent of task practice.
Adult↗
Activation of left posterior cingulate gyrus by the auditory presentation of threat-related words: an fMRI study.
This study investigated the cortical response to hearing threat-related and neutral words using functional magnetic resonance imaging (fMRI) in 16 coronal planes. Right-handed volunteers listened to (i) neutral words alternating with no words as the control condition, and (ii) neutral words alternating with threat-related words as the experimental condition. Threat-related words compared to neutral words activated left posterior cingulate gyrus in eight of 10 subjects with activation most prominent in the retrosplenial region. Patterns of activation produced by neutral words compared to no words included bilateral temporal and frontal regions but not posterior cingulate. The retrosplenial cingulate region has recently been implicated in episodic memory processes. We discuss the possible role of the posterior cingulate cortex in processes involving emotion and memory and in anxiety disorders.
Adult↗
Noise suppression digital filter for functional magnetic resonance imaging based on image reference data.
The central decision in every functional magnetic resonance imaging (fMRI) experiment is whether pixels in brain tissues are showing activation in response to neural stimulus or as a result of noise. Images are degraded not only by random (e.g., thermal) noise, but also by structured noise due to MR system characteristics, cardiac and respiratory pulsations, and patient motion. A novel digital filter has been developed to suppress cardiac and respiratory structured noise in fMRI images, using estimates of structured and random noise power spectra obtained directly from the images. It is an adaptive filter based on stationary noise statistics, and is equivalent in form to a Wiener filter. A mathematical model of the filtering process was developed to understand how the strength and distribution of structured and random noise power influenced filter performance. The filter was tested using images from an auditory activation study in ten subjects. In subjects whose structured noise power was localized to a relatively narrow frequency range, a strong relationship was found, both experimentally (R = 0.975, P < 0.0004 for H0: R = 0) and using the model, between filter performance and the level of structured noise power contaminating the experiment frequency. The filter significantly reduced the rate of false-positive activations in the subset of subjects whose experiment frequency was relatively heavily contaminated by structured noise. Notch filters, that simply eliminate unwanted frequencies, performed poorly in all subjects. Unlike the proposed Wiener filter, these filters did not suppress structured noise power at the experiment frequency that contributes to false-positive activations.
Brain↗
Explained and unexplained medical symptoms in generalized anxiety and panic disorder: relationship to the somatoform disorders.
We have examined the numbers and types of symptoms in a sample of 90 patients with generalized anxiety disorder (GAD) and 77 patients with panic disorder (PD) collected from six different sites during the conduct of a multicenter clinical trial. This information was obtained utilizing the Health Questionnaire, a 47-item self-report list of medical symptoms, patterned after the Somatization Disorder section of the Diagnostic Interview Schedule. Although the patients in this sample had a wide variety of medically explained and unexplained physical symptoms, none of them qualified for a diagnosis of somatization disorder by DSM-III-R criteria. GAD and PD patients reported remarkably similar numbers of explained and unexplained medical symptoms. The panoply of somatic symptoms presented by these patients presents a formidable diagnostic challenge for clinicians. These findings suggest that the pattern of overutilization of medical services that is well documented for PD patients may also be found for GAD patients.
Adult↗
Effects of lorazepam on the distribution of spatial attention.
Reaction time (RT) to stimulus events was assessed for 2 tasks with different spatial attention demands before and after receiving either a placebo or lorazepam (1 mg). In 1 task (onset), 12 participants responded to the onset of 1 of 5 potential dot targets contained within either a small or large area. In the other task (offset), all 5 targets were illuminated and 12 participants responded to the offset of 1 of them. In the onset task, lorazepam slowed RT equally for both the large and small display areas. In the offset task, substantial impairment was found with the large but not the small display area. Results are consistent with the hypothesis that lorazepam interferes with the processes involved in the movement of spatial attention. The possibility that lorazepam selectively impairs the disengage component of attentional movement is discussed.
Adult↗
An effect of alcohol on the distribution of spatial attention.
OBJECTIVE: Previous research on the effects of alcohol on visual performance led us to the prediction that alcohol should interfere with the distribution of visual spatial attention. This prediction was examined in two experiments that measured the effect of alcohol on reaction time (RT) for tasks that differed in visual spatial attention requirements. METHOD: In the first experiment, 48 adult volunteers (33 female) responded to either the onset or offset of one of five potential targets without alcohol to determine the relative demands on attention of stimulus onset and offset. The spatial extent of the five-target display was also varied. In the second experiment, the effect of alcohol was determined for both the onset and the offset tasks in 12 adult volunteers (nine female). RESULTS: The offset task was found to place greater demands on spatial attention as the increase in display area result in relatively greater increases in RT. Alcohol increased RT in the offset task for the larger, but not the smaller, display, and there were no significant effects of alcohol for the onset task. CONCLUSIONS: The results indicate that alcohol impairs performance on tasks that place greater demands on visual spatial attention and likely disrupts the ability to shift attention from one spatial locus to another during serial search.
Adolescent↗
Adinazolam-SR in panic disorder with agoraphobia: relationship of daily dose to efficacy.
BACKGROUND: We report the results from a multicenter, double-blind, randomized, fixed-dose study designed to evaluate the relationship between daily dose and efficacy of adinazolam-SR in patients with panic disorder with agoraphobia. METHOD: Patients (N = 315) were randomized to one of four treatment groups (placebo, N = 83; 30-mg group, N = 79; 60-mg group, N = 81; and 90-mg group, N = 72) and then treated twice daily for 4 weeks. All treatment groups were comparable demographically. Primary efficacy measures included total number of panic attacks, global improvement score using the Clinical Global Impressions (CGI) scale, phobic anxiety dimension of the Symptom Checklist-90 phobic cluster, overall phobia state using the Phobia Scale, and severity of illness on the CGI. RESULTS: The 60- and 90-mg/day adinazolam-SR treatment groups showed superior results when compared with the placebo group at Week 4 while the 30-mg group did not. Treatment with adinazolam-SR was well tolerated, with sedation the only treatment-emergent symptom that occurred more frequently in patients treated with adinazolam-SR than placebo. CONCLUSION: These results suggest that adinazolam-SR at doses of 60-mg/day or greater administered twice daily is a safe and effective treatment in selected patients with panic disorder with agoraphobia.
Adolescent↗
Patient Stage of Change predicts outcome in a panic disorder medication trial.
OBJECTIVE: The authors test the hypothesis that patient readiness to change predicts outcome in a placebo-controlled medication trial. METHOD: Out-patients with panic disorder and agoraphobia completed the Stages of Change (SOC) questionnaire, a measure of readiness to change, before being randomly assigned either sustained release (SR) adinazolam or placebo in a 4 week double-blind trial. RESULTS: In the "intent to treat" analysis, for the 202 subjects who made at least one visit after baseline, adinazolam SR was significantly more effective than placebo on most major outcome measures. Of the 126 subjects who completed the SOC questionnaire, regression analyses showed significant correlations between SOC scores and all 5 outcome measures. In a second analysis, cluster membership based on SOC scores was predictive of outcome on 3 of 5 measures. In each statistical analysis, subjects who were not predisposed to change as measured by the SOC were significantly less likely to change. CONCLUSIONS: Patient readiness to change was strongly correlated with outcome in a placebo-controlled panic disorder trial with an effective medication. In this study, the SOC category, Precontemplation (i.e., those subjects who reported the belief that they had no problem) were less likely to change compared to those who believed that they had a problem.
Agoraphobia↗
Adinazolam sustained-release treatment of panic disorder: a double-blind study.
Two hundred six outpatients with panic disorder and agoraphobia were randomly assigned to receive 4 weeks of treatment with placebo or sustained-release adinazolam under double-blind conditions. Eighty-eight percent of patients receiving drug and 85% of patients receiving placebo remained in the study at week 4. This report describes the "intent-to-treat" analysis of 202 patients who made at least one follow-up visit after randomization at baseline. On the basis of the Clinical Global Impressions-Improvement Scale, 69.7% of the adinazolam-treated patients were much or very much improved compared with 39.6% of the placebo-treated patients at week 4 or end-point (p = 0.0001). At week 4, panic attacks were completely blocked in 57.1% of adinazolam-treated patients and in 39.2% of the placebo-treated patients (p = 0.009). Adinazolam sustained-release treatment was statistically more effective than placebo treatment on measures of global improvement, number of panic attacks, SCL-90 phobia severity, main phobia severity, and anticipatory and general anxiety. No drug-placebo differences were found for overall self-rated phobia severity, unexpected or situational panic attacks, or for work, family, or social disability.
Adult↗
Decreased lymphocyte beta-adrenoreceptor function correlates with less agoraphobia and better outcome in panic disorder.
Previous studies have demonstrated reduced function of peripheral beta-adrenoreceptors in panic disorder with agoraphobia (PDA). We recently reported that decreased lymphocyte beta-receptor function was associated with milder agoraphobia and better treatment response in PDA. We now report on lymphocyte beta-receptor function in 12 additional patients with PDA. Lower cyclic AMP responses to isoproterenol were significantly correlated with milder agoraphobia and better response to naturalistic treatment. Lower beta-receptor density tended to correlate similarly with agoraphobia and treatment response. These findings further support the hypothesis that decreased peripheral beta-receptor function in PDA reflects an adaptive process associated with greater resistance to agoraphobia and greater capacity for recovery with treatment.
Adult↗
Benzodiazepine effects on flicker sensitivity: role of stimulus frequency and size.
1. Benzodiazepines (BZDs) impair sensitivity to temporally modulated visual stimuli (flicker). Critical flicker-fusion frequency (CFF) is commonly used as a measure of this effect, but it only measures sensitivity to a narrow range of frequencies, usually above 25 Hz. Are other frequencies more sensitive to the effects of BZDs? 2. Flicker sensitivity at 1, 2, 4, 8, 16, and 32 Hz was measured for 1 degrees and 5 degrees stimuli before and 50 to 100 minutes after triazolam (0.25 mg), lorazepam (1.0 mg) and placebo. Drug effects on CFF were also measured. 3. Both BZDs significantly impaired overall flicker sensitivity. Triazolam produced 50% more impairment than lorazepam. CFF was significantly impaired by triazolam. BZD effects did not vary with stimulus size. 4. Significantly greater BZD-induced impairment of flicker sensitivity occurred at 16 Hz than at 1, 2, 4, or 32 Hz. 5. The magnitude of BZD effects on flicker sensitivity vary with the temporal frequency of the stimulus. BZD effects are greatest for 8-16 Hz stimuli.
Adult↗
Evidence that decreased function of lymphocyte beta adrenoreceptors reflects regulatory and adaptive processes in panic disorder with agoraphobia.
OBJECTIVE: This study was designed to clarify the nature of the reduced function of the peripheral beta adrenoceptor system observed in panic disorder with agoraphobia. The authors hypothesized that this phenomenon reflected a regulatory and adaptive process. METHODS: Lymphocyte beta adrenoreceptor density and affinity, basal lymphocyte cAMP level, and isoproterenol-stimulated cAMP generation were measured in 27 untreated outpatients with panic disorder with agoraphobia and 24 healthy comparison subjects. Lymphocyte beta receptor attributes were again assessed in patients after 4 weeks of double-blind treatment with adinazolam (slow-release form) or placebo. Panic frequency, agoraphobic symptoms, overall anxiety, and improvement with treatment were assessed with standard rating instruments. RESULTS: Multivariate statistics revealed significantly lower beta receptor density and isoproterenol-stimulated cAMP generation in patients than in comparison subjects. beta receptor density tended to normalize after adinazolam but not after placebo. Pretreatment beta receptor density was lower in treatment responders than nonresponders. Patients with mild agoraphobia had lower cAMP responsivity than patients with moderate or severe agoraphobia. CONCLUSIONS: Decreased function of lymphocyte beta receptors in panic disorder with agoraphobia is expressed as both decreased density and decreased cAMP responsivity. This pattern of changes, and the tendency for receptor density to normalize with treatment, is consistent with an active, regulatory process rather than a structural deficit in the beta receptor system. Preliminary clinical findings suggest that these changes may reflect adaptive processes associated with a favorable clinical course in panic disorder with agoraphobia.
Adult↗
Relationships between thyroid indices and symptoms of anxiety in depressed outpatients.
Scores on rating scales measuring symptoms of depression, panic anxiety, state anxiety, trait anxiety, and agoraphobic avoidance were correlated, using multivariate statistics, with total thyroxine- and thyrotropin-releasing hormone concentrations in outpatients with major depression. A significant inverse relationship was demonstrated between agoraphobic avoidance and total thyroxine concentrations in female patients. No other symptom ratings were significantly associated with these thyroid indices. The depressed patients scored in the clinically significant range for agoraphobic symptoms. Assessment of agoraphobic avoidance may help identify a clinically and biologically distinct subgroup of depressed patients.
Adult↗
Relationship of past depressive episodes to symptom severity and treatment response in panic disorder with agoraphobia.
BACKGROUND: Many investigators have reported that panic disorder (PD) patients with comorbid major depression (MD) have more severe symptoms and a poorer response to treatment than patients with PD alone. It is not known if this is due to a distinct and more serious underlying disorder in these patients or simply a result of the simultaneous presence of the two disorders. METHOD: Nondepressed patients presenting for treatment of panic disorder with agoraphobia (PDA) were studied before treatment (N = 180) and after 4 weeks of treatment with adinazolam sustained release (N = 89) or placebo (N = 91). Twenty-nine percent (N = 53) of the patients had a past history of MD. Symptom severity and treatment outcome were compared in patients with primary, secondary, single, recurrent, or no past MD. RESULTS: There were no consistent differences in symptom severity or treatment outcome in patients with a past history of primary, secondary, or single episode MD compared with patients with no history of MD. However, a small number of patients with history of recurrent MD exhibited consistently greater symptom severity and poorer response to treatment than patients with no history of MD. CONCLUSION: The greater severity and worse outcome of comorbid PD and MD observed in earlier studies are more likely due to the simultaneous presence of the two disorders than to a more serious and enduring underlying disorder. However, our results suggest that recurrent MD may indicate a more serious condition in patients with PDA. This possibility warrants further study.
Adult↗
Imipramine and alprazolam effects on stress test reactivity in panic disorder.
The reactivity of 40 panic disorder patients on mental arithmetic, cold pressor, and 5% CO2 inhalation stressors was tested before and after 8 weeks of treatment with imipramine, alprazolam, or placebo. Mean levels of subjective and physiological stress measures were compared during a baseline before any stressors were given, and at anticipation, stressor, and recovery periods for each stressor. After treatment, imipramine patients differed from the other two treatment groups on the prestressor baseline in showing higher systolic blood pressure (mean difference about 10 mmHg), higher diastolic blood pressure (10 mm Hg), higher heart rate (15 bpm), less respiratory sinus arrhythmia, shorter pulse transit time, and lower T-wave amplitude. Respiratory measures, electrodermal measures, body movement, and self-reported anxiety and excitement did not distinguish the groups. Reactivity to the stress tests was unaffected by the medications, but tonic differences present in the baseline persisted.
Adult↗
Stress test reactivity in panic disorder.
The psychological and physiological reactivity of 52 patients with panic disorder to mental arithmetic, cold pressor, and 5% carbon dioxide inhalation tests was compared with that of 26 age- and sex-matched normal subjects. In general, patients with panic disorder were neither more physiologically reactive to these stressors than normal subjects nor slower to recover from them, but they were tonically more anxious and much more likely to ask to stop carbon dioxide inhalation or to report panic attacks during this test. Patients who reported panic attacks (46%) had manifested greater anticipatory anxiety before the gas was delivered, accompanied with increased beta-adrenergic cardiac tone. Thus, anticipatory anxiety can be an important factor in panic provocation. Physiological measures varied greatly in their sensitivity to phasic or tonic anxiety. Carbon dioxide stimulated large increases in respiratory minute volume, but these increases were no greater for patients than for normal subjects.
Adult↗
Patterns of abnormal processing of emotional information in panic disorder and major depression.
Studies showing interference with color naming threat-related words in patients with anxiety disorders suggest a bias towards processing threatening material in these patients. We assessed the specificity of this finding to anxiety disorders and to threatening stimuli by administering Stroop cards with a variety of types of emotional stimuli to 24 panic disorder patients with no history of major depression, 30 patients with major depression and no history of panic attacks and 25 controls with no history of an axis I disorder. Our findings suggest that the abnormal information processing seen in panic disorder may be characterized by a more general bias towards processing emotional stimuli than previously thought. They also suggest that this more general bias may illustrate differences in information processing in panic disorder and major depression.
Adult↗