Application of the Stages of Change Scale in a clinical drug trial

The Stages of Change Scale (SOC: McConnaughy, Prochaska, & Velicer, 1983) was used to predict outcome among 131 outpatients with generalized anxiety disorder who were enrolled in a clinical drug trial. As predicted, subjects high on Precontemplation did not experience as much relief from anxiety as subjects low on Precontemplation, whereas subjects high on Contemplation or Action experienced more decrease in anxiety during the trial than subjects low on these stages. Contrary to our hypothesis, only Contemplation was related to illness severity changes, and scores on the Maintenance scale were not related to outcome. Of the four stage scores, only Maintenance was related to premature termination of treatment. There were no differences between drug (adinazolam) and placebo groups and only Action scores interacted with drug/placebo assignment in this study. Results suggest that the SOC may be useful in identifying individuals who are most likely to experience decreased anxiety while enrolled in a clinical drug trial.     

Reduced benzodiazepine sensitivity in patients with panic disorder: comparison with patients with obsessive-compulsive disorder and normal subjects

OBJECTIVE: The authors sought to replicate their previous finding of reduced response to diazepam in patients with panic disorder, to test whether this effect was specific for panic disorder, and to determine whether this reduced response was merely an artifact of resistance to sedation from anxiety-related overarousal. METHOD: The effects of four increasing intravenous doses of diazepam on saccadic eye movement velocity and accuracy (the latter being a saccadic variable that is unaffected by sedation), short-term memory, and self- and observer-rated sedation were assessed in 18 patients with panic disorder, 15 patients with obsessive-compulsive disorder, and 14 normal comparison subjects. The ratios of effect to blood level areas under the curve for both ascending and descending limbs of the effect/blood level curves were compared for each variable. RESULTS: Patients with panic disorder showed significantly less diazepam effect on saccadic velocity and accuracy for the ascending limb of the blood level curve than comparison subjects. Patients with obsessive-compulsive disorder showed similar differences from comparison subjects but only for saccadic velocity. There were no group differences in diazepam effects on memory and sedation. CONCLUSIONS: Patients with panic disorder are less sensitive than comparison subjects to diazepam. Although this difference is not an artifact of resistance to sedation, it may not be specific for panic disorder but rather may reflect a more nonspecific aspect of anxiety disorders.     

Mental disorders and disability among patients in a primary care group practice

OBJECTIVE: This article examines social and occupational disability associated with several DSM-IV mental disorders in a group of adult primary care outpatients. METHOD: The subjects were 1,001 primary care patients (aged 18-70 years) in a large health maintenance organization. Data on each patient's sociodemographic characteristics and functional disability, including scores on the Sheehan Disability Scale, were collected at the time of a medical visit. A structured diagnostic interview for current DSM-IV disorders was then completed by a mental health professional over the telephone within 4 days of the visit. RESULTS: The most prevalent disorders were phobias (7.7%), major depressive disorder (7.3%), alcohol use disorders (5.2%), generalized anxiety disorder (3.7%), and panic disorder (3.0%). A total of 8.3% of the patients met the criteria for more than one mental disorder. The proportion of patients with co-occurring mental disorders varied by index disorder from 50.0% (alcohol use disorder) to 89.2% (generalized anxiety disorder). Compared with patients who had a single mental disorder, patients with co-occurring disorders reported significantly more disability in social and occupational functioning. After adjustment for other mental disorders and demographic and general health factors, compared with patients with no mental disorder, only patients with major depressive disorder, bipolar disorder, phobias, and substance use disorders had significantly increased disability, as measured by the Sheehan Disability Scale. CONCLUSIONS: Primary care patients with more than one mental disorder are common and highly disabled. Individual mental disorders have distinct patterns of psychiatric comorbidity and disability.     

Peptides and anxiety: a dose-response evaluation of pentagastrin in healthy volunteers

A large body of data suggest that brain cholecystokinin (CCK) systems are involved in the regulation of anxiety, and numerous studies have demonstrated that CCK-4, a CCKB agonist, reliably induces panic attacks in patients with panic disorder. Recently, pentagastrin, a commercially available CCKB agonist, has been reported to have similar anxiogenic properties. To further explore the utility of pentagastrin as a challenge agent and to determine whether its effects are dose-related, a dose-response study was conducted in ten healthy volunteers. Pentagastrin (0.2 microgram/kg, 0.6 microgram/kg and 1.0 microgram/kg) and inactive placebo were infused over one minute on four separate challenge days in a double-blind fashion. Subjects received pentagastrin while participating in a structured social interaction task. Repeated measures of anxiety, blood pressure, pulse, ACTH, and cortisol were taken at baseline and postinfusion. Pentagastrin administration led to increases in anxiety, pulse, ACTH, cortisol and physical symptoms of panic, in a dose-related manner. Participation in the social interaction task led to increases in measures of anxiety as well as increases in pulse and blood pressure. Few differences were found between the 0.2 microgram/kg dose of pentagastrin and placebo, or between the 0.6 microgram/kg and the 1.0 microgram/kg doses of pentagastrin. These findings support the notion that CCK systems are involved in the regulation of anxiety, and suggest that the 0.6 microgram/kg dose may be optimal for increasing symptoms of anxiety while minimizing unpleasant side effects. The powerful anxiogenic effects of the social interaction task underscore the importance of contextual variables in challenge studies.     

The effect of exercise training on the severity and duration of a viral upper respiratory illness

OBJECTIVE: The purpose of this study was to assess whether joint hypermobility syndrome is more frequent in patients with panic disorder, agoraphobia, or both than in control subjects and, if so, to determine whether mitral valve prolapse modifies or accounts in part for the association. METHOD: A case-control study was conducted in a general teaching hospital outpatient clinic. Subjects were 99 patients, newly diagnosed and untreated, with panic disorder, agoraphobia, or both and two groups of age- and sex-matched control subjects: 99 psychiatric patients and 64 medical patients who had never suffered from any anxiety disorder. Measures consisted of the Structured Clinical Interview for DSM-III-R, Beighton's criteria for joint hypermobility syndrome, and two-dimensional and M-mode echocardiogram. The presence of mitral valve prolapse and joint hypermobility syndrome was explored by raters who were blind to subjects' psychiatric status. RESULTS: Joint hypermobility syndrome was found in 67.7% of patients with anxiety disorder but in only 10.1% of psychiatric and 12.5% of medical control subjects. On the basis of statistical analysis, patients with anxiety disorder were over 16 times more likely than control subjects to have joint laxity. These findings were not altered after the presence of mitral valve prolapse was taken into account. Of the patients with anxiety disorder, those who had joint hypermobility syndrome were younger and more often women and had an earlier onset of the disorder than those without joint hypermobility syndrome. CONCLUSIONS: Joint laxity is highly prevalent in patients with panic disorder, agoraphobia, or both and may reflect a constitutional disposition to suffer from anxiety. Mitral valve prolapse plays a secondary role in the association between joint hypermobility and anxiety.     

Prevalence of personality disorders among patients with anxiety disorders

Outpatients with a principal diagnosis of an anxiety disorder (n = 347) were administered the Structured Clinical Interview for DSM-III-R/Axis II Disorders (SCID-II) during their intake evaluation. At least one personality disorder was found in 35% of these patients. Patients with social phobia (61%) and generalized anxiety disorder (49%) were most often diagnosed with a personality disorder. Patients with simple phobia were rarely diagnosed with a personality disorder (12%). The most commonly diagnosed personality disorders were from the "anxious/fearful" cluster (27% received at least one diagnosis from cluster C), most notably avoidant and obsessive-compulsive personality. Our findings suggest that personality disorders, in general, are less prevalent among anxious patients than among depressive patients.     

A 1-year prospective study of panic attacks: Clinical course and factors associated with maintenance.

A prospective naturalistic l-year follow-up study of 39 patients with current panic disorder, 17 remitted panic patients, 46 infrequent panickers, 22 patients with simple phobias, and 45 controls assessed clinical course and variables related to the maintenance of panic attacks. Nearly all panic disorder patients (92%) continued to experience panic attacks, and 41% of the initially remitted patients relapsed. No significant effects of treatments delivered in the community were found. Infrequent panickers tended to be more likely to develop panic disorder (15%) than controls (2%). Maintenance/relapse was most consistently linked with good heartbeat perception, anxiety sensitivity, and avoidance in the different subsamples. Patients with simple phobias or normal controls who experienced their first panic attack during follow-up had shown higher anxiety sensitivity at initial assessment than nonpanickers. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of the 5-HT3 antagonist, ondansetron, on the behavioral and physiological effects of pentagastrin in patients with panic disorder and social phobia

Pentagastrin, a cholecystokinin (CCK) agonist, produces anxiety and panic in patients with panic disorder and social phobia. Preclinical data suggests that pentagastrin-induced anxiogenesis may be mediated via 5-HT3 receptors. In the present study, 14 patients with panic disorder or social phobia underwent pharmacological challenge in three conditions: (1) pretreatment with saline followed by pentagastrin infusion; (2) pretreatment with ondansetron followed by pentagastrin infusion; and (3) pretreatment with saline followed by saline infusion. As expected, pentagastrin administration led to increased anxiety, physical symptoms of panic attacks, pulse, plasma adrenocorticotropic hormone (ACTH), and cortisol. Pentagastrin's behavioral effects were not blocked by ondansetron, and in fact, tended to be exaggerated. Ondansetron pretreatment did not alter the pentagastrin-induced cortisol increase but significantly prolonged the pentagastrin-induced increase in ACTH. These findings suggest that pentagastrin's behavioral effects are not mediated by 5HT3 receptors. Mechanisms by which peripherally administered CCK agonists lead to anxiety remain to be elucidated.     

Generalized social phobia. Reliability and validity

OBJECTIVE: To investigate the reliability and validity of DSM-III-R "generalized" social phobia by examining interrater agreement and comparing patients with generalized and "nongeneralized" social phobia on demographic characteristics, clinical variables, and familial social phobia. DESIGN: Two senior clinicians classified 129 patients attending an anxiety clinic as having DSM-III-R social phobia that is generalized (fears most social situations) or nongeneralized (less than most) based on independent narrative review. RESULTS: Good reliability was achieved (kappa = 0.69). Patients with generalized social phobia were more often single, had earlier onsets of social phobia, had more interactional fears, and had higher rates of atypical depression and alcoholism. Familial social phobia was more common among patients with generalized social phobia than patients with nongeneralized social phobia and controls, with no difference between the latter two groups. CONCLUSIONS: Generalized social phobia (1) can be distinguished reliably from nongeneralized social phobia, (2) is a valid subtype, and (3) may characterize a familial form of the disorder.     

Relationship of genetically transmitted alpha EEG traits to anxiety disorders and alcoholism

We tested the hypothesis that a heritable EEG trait, the low voltage alpha (LV), is associated with psychiatric disorders. Modest to moderate evidence for genetic linkage of both panic disorder and the low voltage alpha trait to the same region of chromosome 20q has recently been reported, raising the issue of whether there is a phenotypic correlation between these traits. A total of 124 subjects including 50 unrelated index subjects and 74 relatives were studied. Alpha EEG power was measured and EEG phenotypes were impressionistically classified. Subjects were psychiatrically interviewed using the SADS-L and blind-rated by RDC criteria. Alcoholics were four times more likely to be LV (including so-called borderline low voltage alpha) than were nonalcoholic, nonanxious subjects. Alcoholics with anxiety disorder are 10 times more likely to be LV. However, alcoholics without anxiety disorder were similar to nonalcoholics in alpha power. An anxiety disorder (panic disorder, phobia, or generalized anxiety) was found in 14/17 LV subjects as compared to 34/101 of the rest of the sample (P < 0.01). Support for these observations was found in the unrelated index subjects in whom no traits would be shared by familial clustering. Lower alpha power in anxiety disorders was not state-dependent, as indicated by the Spielberger Anxiety Scale. Familial covariance of alpha power was 0.25 (P < 0.01). These findings indicate there may be a shared factor underlying the transmissible low voltage alpha EEG variant and vulnerability to anxiety disorders with associated alcoholism. This factor is apparently not rare, because LV was found in approximately 10% of unrelated index subjects and 5% of subjects free of alcoholism and anxiety disorders.     

Personality traits in social phobia, II: Changes during drug treatment

BACKGROUND: Patients with social phobia often describe personality traits characterized by avoidant social behavior and more general depressive-anxious features. There is only sparse knowledge about the effects of drug treatment on these traits. METHOD: Fifty-seven patients with social phobia completed a 12-week double-blind, placebo-controlled trial with the reversible and selective monoamine oxidase A inhibitor brofaromine 150 mg/day. The Clinical Global Impressions-Improvement scale, Liebowitz Social Anxiety Scale, a questionnaire with 140 items regarding personality traits, and ratings on the presence or absence of diagnostic criteria for the DSM-III-R avoidant and dependent personality disorders were used for assessments at baseline and endpoint. Comparisons were made with a group of 58 healthy controls. RESULTS: Before treatment, there were no significant differences between the brofaromine and placebo groups in their ratings on situationally bound social anxiety or on personality traits that differed significantly from those of the controls. At endpoint, a marked normalization was noted in the brofaromine group. The changes that had occurred differed significantly from those in the placebo group. The normalization of traits seemed more marked than the normalization of anxiety in more specific social phobic situations. The number of brofaromine patients who fulfilled the criteria for avoidant personality disorder had diminished from 15 (60%) to 5 (20%). CONCLUSION: The results support the conclusion that the maladaptive personality traits characteristic of social phobia are at least as responsive to the monoamine oxidase inhibitor brofaromine as are the more circumscribed social anxiety responses.     

A comparison of alprazolam and behavior therapy in treatment of panic disorder.

The results of a clinical outcome study (N?=?57) comparing behavior therapy directed at panic disorder (panic control treatment [PCT]) with alprazolam were reported. These conditions were compared with a medication placebo and a waiting-list control group. Patterns of results on measures of panic attacks, generalized anxiety, and global clinical ratings reveal that PCT was significantly more effective than placebo and waiting-list conditions on most measures. The alprazolam group differed significantly from neither PCT nor placebo. The percentage of clients completing the study who were free of panic attacks following PCT was 87%, compared with 50% for alprazolam, 36% for placebo, and 33% for the waiting-list group. Since alprazolam may work more quickly than PCT but may also interfere with the effects of behavioral treatment, these data suggest a series of studies on the feasibility of integrating these treatments and on the precise patterns and mechanisms of action of various successful treatment approaches to panic disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Primary structure of apolipophorin-III from the greater wax moth, Galleria mellonella

BACKGROUND: Neurobiological research has implicated the dopamine and serotonin systems in the pathogenesis of autism. Open-label reports suggest that the serotonin2A-dopamine D2 antagonist risperidone may be safe and effective in reducing the interfering symptoms of patients with autism. METHODS: Thirty-one adults (age [mean+/-SD], 28.1+/-7.3 years) with autistic disorder (n=17) or pervasive developmental disorder not otherwise specified (n=14) participated in a 12-week double-blind, placebo-controlled trial of risperidone. Patients treated with placebo subsequently received a 12-week open-label trial of risperidone. RESULTS: For persons completing the study, 8 (57%) of 14 patients treated with risperidone were categorized as responders (daily dose [mean+/-SD], 2.9+/-1.4 mg) compared with none of 16 in the placebo group (P<.002). Risperidone was superior to placebo in reducing repetitive behavior (P<.001), aggression (P<.001), anxiety or nervousness (P<.02), depression (P<.03), irritability (P<.01), and the overall behavioral symptoms of autism (P<.02). Objective, measurable change in social behavior and language did not occur. Nine (60%) of 15 patients who received treatment with open-label risperidone following the double-blind placebo phase responded. Other than mild, transient sedation, risperidone was well tolerated, with no evidence of extrapyramidal effects, cardiac events, or seizures. CONCLUSION: Risperidone is more effective than placebo in the short-term treatment of symptoms of autism in adults.     

Evidence for the synthesis and secretion of a CBG-like serpin by human cumulus oophorus and fallopian tubes

BACKGROUND: The goal of the present study was to validate the French version of the Agoraphobic Cognitions Questionnaire (ACQ). METHODS: Subjects consisted of 115 patients with panic disorder and agoraphobia, 54 obsessive-compulsive patients and 72 normal controls. Patients were referred for outpatient treatment. They filled in the questionnaire before and after entering treatment. The control group consisted of people taken from the general population. It was matched with the clinical groups on age, sex and education. RESULTS: The ACQ appears to have a constant factor structure across US, Dutch and French samples. Results support the validity of the total score of the ACQ. Patients with panic disorder and agoraphobia scored significantly higher than obsessive-compulsive patients and control subjects. On the ACQ physical concerns subscale agoraphobic patients were significantly different from obsessive-compulsive patients and control subjects. On the social/behavioural subscale agoraphobic patients and obsessive-compulsive patients were significantly different from control subjects. The French translation of the ACQ was found to be stable over an interval of 15 days in the control group. The Cronbach coefficients of both subscales were also satisfactory. These results support the stability and the internal consistency of the questionnaire. In addition, the French translation of the ACQ was sensitive to changes with cognitive-behavioural therapy. CONCLUSIONS: These results support the findings of Chambless and Gracely [Cogn Ther Res 1989;13:9-20]. The ACQ physical concerns subscale is a specific feature for the anxiety status experienced by patients with panic disorder and agoraphobia. The ACQ social/behavioural subscale seems to be a more general feature of anxious patients.     

Eye movement impairment and schizotypal psychopathology

OBJECTIVE: Eye movement dysfunction in relation to a smooth pursuit task has been documented in schizophrenic patients and in patients with the related personality disorder, schizotypal personality disorder. To investigate which quantitative measures are associated with the eye movement dysfunction and whether the dysfunction is more related to the psychotic-like or the deficit-like symptoms of schizotypal personality disorder, ratings of eye movements in several groups of subjects were compared. METHOD: The study groups consisted of 26 patients with schizotypal personality disorder, 42 patients with other personality disorders (22 who also had two or more schizotypal personality traits and 20 who had fewer than two), and 37 normal comparison subjects. Smooth pursuit eye tracking of sinusoidal and constant velocity targets was recorded by an infrared eye tracking system. Two raters evaluated pursuit gain and large and small saccades in the direction of the target and in the direction opposite to that of the target (quantitative ratings) and constant velocity (qualitative rating). RESULTS: Patients with schizotypal personality disorder and patients with other personality disorders and two or more schizotypal traits, but not those with fewer than two schizotypal traits, had significantly poorer qualitative ratings of tracking than the normal comparison subjects. Neither gain nor any of the saccadic measures significantly differed between groups. The number of large saccades in the direction of the target was the only quantitative variable that predicted low qualitative ratings. Qualitatively poor tracking was associated with the deficit-like, but not the psychotic-like, symptoms of schizotypal personality disorder. CONCLUSIONS: Patients with schizotypal personality disorder demonstrate qualitatively poorer tracking than comparison groups, and the impaired tracking is associated with deficit-like symptoms.     

Increased cardiac awareness in panic disorder.

Investigated cardiac perception in panic disorder with both self-report and objective measures. In Study 1, 120 patients with panic disorder, 86 infrequent panickers, and 38 patients with other anxiety disorders reported greater cardiac and gastrointestinal awareness than 62 normal control Ss. Ss with panic attacks reported greater cardiac awareness, but not gastrointestinal awareness, than those with other anxiety disorders. Studies 2 and 3 included a test of heart rate perception in which Ss silently counted their heartbeats without taking their pulse. In Study 2, 65 panic disorder patients showed better performance than 50 infrequent panickers, 27 patients with simple phobias, and 46 normal control Ss. No group differences were found in ability to estimate time intervals. In Study 3, 13 patients with panic disorder and 15 with generalized anxiety disorder showed better heart rate perception than 16 depressed patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Psychopathology in the offspring of anxiety disorders patients.

Children of patients with an anxiety disorders diagnosis were assessed with a battery of self-report inventories and a semistructured interview schedule. The performance of these children was compared with that of children of patients with a diagnosis of dysthymic disorder, children of normal parents, and normal school children. Children of anxiety disorders patients were found to be more anxious and fearful; to report more school difficulties, more worries about family members and themselves, and more somatic complaints; and to spend more time engaged in solitary activities than children in either of the two normal groups. In addition, they were found to be more than 7 times as likely to meet criteria for an anxiety disorder than the two normal groups and to be twice as likely to have an anxiety disorder than the children of dysthymics. The resultant implications for familial factors in anxiety disorders are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sleep Deprivation in social phobia and generalized anxiety disorder

BACKGROUND: Sleep deprivation has been shown to improve depressive symptoms in some patients with major depressive disorder, but it has not been tested in patients with generalized anxiety disorder (GAD) or social phobia (SP). METHODS: To determine if sleep deprivation altered anxiety or depressive symptoms in patients with GAD (n = 7) or SP (n = 8), we sleep deprived patients and normal controls (n = 18) for one night. RESULTS: On one measure of anxiety, GAD patients improved compared with controls, but there were otherwise no significant change differences between controls and SP or GAD patients. CONCLUSIONS: The lack of benefit is consistent with previous findings that sleep deprivation provides no benefit to patients with other anxiety disorders. Sleep deprivation may be a biological intervention that distinguishes anxiety from affective disorders.