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Biomedical subjects

T W Uhde

Publications and source records attributed to T W Uhde.

At least 19 recordsLinked to original sources

Heart rate and plasma norepinephrine responsivity to orthostatic challenge in anxiety disorders. Comparison of patients with panic disorder and social phobia and normal control subjects.

Heart rate and plasma norepinephrine responsivity to a physiologic challenge, ie, orthostasis, were measured in 20 patients with panic disorder (PD) and 20 age- and sex-matched normal control subjects. While the two groups exhibited similar supine heart rates, patients with PD had a significantly greater heart rate response to orthostatic challenge. Plasma norepinephrine responses did not differ between patients with PD and normal control subjects. In a matched subgroup of 14 patients with PD, 14 normal control subjects, and 14 patients with social phobia, the patients with social phobia exhibited supine and upright plasma norepinephrine levels that were significantly higher than those of the other two diagnostic groups. Taken together, and in the context of findings from other studies, these preliminary observations suggest that the anxiety disorders may demonstrate differing patterns of autonomic dysfunction.

Adult

Fearful behavior, body size, and serum IGF-I levels in nervous and normal pointer dogs.

Panic disorder in adult humans is associated with disturbances in hypothalamic-growth hormone (GH) function and children with emotional deprivation or severe anxiety develop growth retardation. Nervous pointer dogs, a genetic animal model of panic disorder or severe anxiety, are characterized by extreme fearfulness and avoidance of novel stimuli. This experiment investigated indices of body stature, weight, and insulin-like growth factor I (IGF-I) levels in a colony of purebred nervous and purebred normal pointer dogs. The genetic line of nervous dogs had significantly greater scores of fearfulness, lower total body weights, lower weight/height ratio, and lower serum IGF-I levels than the normal line of pointer dogs. There was an inverse relationship between degree of fearfulness and total body weight in female, but not male, dogs. Stepwise logistic regression analysis indicated that the severity of fear behaviors, height, and weight were significantly associated with IGF-I levels. The best predictor of IGF-I levels in the dogs, however, was the severity of fearful behaviors elicited by exposure to novel stimuli and humans. These observations suggest that the neurobiological substrates of alarm, arousal, and fear influence hypothalamic-GH-somatomedin-mediated effects on weight and, to a lesser extent, height. Findings are discussed in terms of their relevance to future research in humans with anxiety disorders.

Animals

Quantitative electroencephalographic effects of caffeine in panic disorder.

It has been demonstrated that patients with panic disorder are more sensitive than normal control subjects to the anxiogenic effects of caffeine. The underlying physiologic basis for this difference is unclear. We examined the electroencephalographic (EEG) activity of seven patients with panic disorder and seven normal control subjects during the randomized double-blind, placebo-controlled administration of oral caffeine (7 mg/kg). EEG data were collected on-line from 28 electrodes; artifact-free epochs were selected manually for off-line Fourier transformation. Caffeine was associated with a significant increase in peak occipital alpha frequency and significant decreases in occipital alpha amplitude, central beta amplitude, and central theta amplitude. Despite the observation that caffeine increased anxiety more in the patients with panic disorder than in the normal control subjects, the two groups did not differ in their EEG responses to caffeine.

Adult

Elective mutism as a variant of social phobia.

To examine the relationship between the syndromes of elective mutism and social phobia, a case of elective mutism associated with social phobia in a 12-year-old girl is presented, and the clinical literature regarding the syndrome of elective mutism is reviewed. Elective mutism or reluctance to speak in unfamiliar social situations may be a symptom of social phobia. Social anxiety is a nearly universal characteristic of children manifesting the syndrome of elective mutism. Elective mutism may respond to treatment with medications that also are effective in the treatment of social phobia. Elective mutism may be a manifestation of social phobia rather than a separate diagnostic syndrome. Pharmacologic treatment may be effective.

Child

The National Institute of Mental Health Panic Questionnaire. An instrument for assessing clinical characteristics of panic disorder.

This paper introduces a new self-report inventory, the NIMH Panic Questionnaire (NIMH PQ), for obtaining and quantifying comprehensive information about the clinical characteristics of panic disorder in patients with previously diagnosed or suspected illness. Fifty-two patients who met DSM-III-R criteria for panic disorder completed the NIMH PQ; their responses were compared with data derived from 16 similar or identical questions on the Schedule for Affective Disorders and Schizophrenia modified for anxiety disorders. There were no significant differences between the two instruments on 15 of the 16 (93.7%) items tested. The one exception revealed a greater proportion of patients versus physicians endorsing "spontaneous" panic, and a nonsignificant trend for physicians over patients endorsing anticipatory anxiety with greater frequency. The NIMH PQ offers a potentially useful clinical and research tool in the assessment of patients with known or suspected panic disorder.

Adult

Viscosity and social cohesion in temporal lobe epilepsy.

Clinical case reports suggest that viscosity, the behavioural tendency to talk repetitively and circumstantially about a restricted range of topics, is common in patients with temporal lobe epilepsy (TLE). Such patients are also reported to exhibit heightened levels of social cohesion, the tendency to become interpersonally "clingy". This "sticky" interpersonal style may be particularly common in TLE patients with a left sided temporal lobe seizure focus. To test this hypothesis, self-report and observer rating scales were developed to assess both viscosity and social cohesion. Subjects consisted of patients with right, left, or bilateral temporal lobe seizure foci, absence or primary generalised tonic-clonic seizures, psychiatric controls (panic disorder patients), and normal controls. Elevations on the viscosity scale were observed primarily in TLE patients with left or bilateral seizure foci. Viscosity scores also correlated with seizure duration and left handedness. No group differences were observed on the social cohesion scale. These findings are consistent with the hypothesis that viscosity results from subtle interictal language disturbances, although other pathogenetic mechanisms are discussed.

Anomia

Diurnal rhythms and symptom severity in panic disorder. A preliminary study of 24-hour changes in panic attacks, generalised anxiety, and avoidance behaviour.

Diurnal changes in the frequency of panic attacks and symptoms of generalised anxiety, phobic anxiety and phobic avoidance in 34 panic-disorder patients and 40 normal controls were evaluated. The panic-disorder patients had significant diurnal changes in generalised and phobic anxiety, but not phobic avoidance. Increased severity of symptoms and prominent diurnal changes were most evident in the panic-disorder patients with a history of depression. Although panic attacks were distributed throughout the 24-hour period, patients with a current episode or history of depression tended to have more frequent panic attacks in the morning or early afternoon. These observations challenge the traditional belief that 'anxious neurotic' patients are relatively asymptomatic upon awakening in the morning and then develop more severe symptoms of anxiety later in the day.

Adult

Evidence for hypothalamo-growth hormone dysfunction in panic disorder: profile of growth hormone (GH) responses to clonidine, yohimbine, caffeine, glucose, GRF and TRH in panic disorder patients versus healthy volunteers.

Given the abrupt and time-limited nature of daytime-awake and nocturnal-sleep panic attacks, several chemical and neuroendocrine challenge tests have been employed to investigate the neurobiology of "spontaneous" panic attacks. Previously we demonstrated that panic disorder patients have blunted growth hormone (GH) responses to clonidine, an alpha 2-adrenergic agonist. However, the mechanism of this blunted response and the role of hypothalamic-GH dysfunction, if any, remains unclear. To further delineate the status of hypothalamic-GH function in panic disorder, we review the literature and present original data on the GH responses to a number of different chemical and neuroendocrine challenge paradigms. Although stress-mediated increases in GH are thought to be a common correlate of stress in humans, our findings indicate that panic disorder patients have significantly blunted GH responses to clonidine, yohimbine, growth-hormone releasing factor, and caffeine compared to normal control subjects. A similar trend was noted in the delayed rise in GH after glucose challenge. There was no difference in the rate of abnormal GH responses to thyrotropin-releasing hormone in panic disorder compared to normal control subjects. No drug or neuroendocrine challenge, even if associated with marked increases in anxiety, produced a significantly enhanced GH response compared to normal control subjects. These findings provide support for a hyporesponsive hypothalamic-GH system in panic disorder. These observations, combined with preliminary observations from our clinic of short stature in several cases of prepubescent children with anxiety disorders, also underscore the need for assessing early growth patterns in individuals with panic disorder. Strategies for investigating the site(s) of possible neurotransmitter or hypothalamic-GH-somatomedin dysfunction are discussed.

Caffeine

An examination of syndromal validity and diagnostic subtypes in social phobia and panic disorder.

BACKGROUND: We investigated whether patients with DSM-III-R panic disorder and patients with social phobia could be distinguished on the basis of selected demographic variables and by several commonly used anxiety and phobia rating scales. METHOD: Sixty-six patients with social phobia and 60 patients with panic disorder (42 with and 18 without agoraphobia) were studied. Subjects completed a battery of self-report measures that assessed phobic fears, avoidance, and related problems. RESULTS: Social phobic patients showed an earlier age at onset than the panic disorder group, and there was a trend for more social phobics to have never married. Social phobics reported significantly greater levels of social phobic avoidance and distress, fear of negative evaluation, and avoidance of social situations than the panic disorder patients who reported more overall anxiety and rated themselves as significantly more avoidant of situations involving exposure to public places and to blood or injury. Discriminant function analyses showed that social phobic and panic disorder patients can be reliably discriminated on these scales. CONCLUSION: The results of this study lend further support for the validity of the DSM-III-R nosologic distinctions between social phobia and panic disorder. Furthermore, generalized social phobia appears to be remarkably different from discrete social phobia on these measures. This study provides less support for considering panic disorder with agoraphobia to be distinct from panic disorder without agoraphobia.

Adolescent

Anxiogenic effects of m-CPP in patients with panic disorder: comparison to caffeine's anxiogenic effects.

The behavioral and neuroendocrine effects of meta-chlorophenylpiperazine (m-CPP), a serotonergic agonist, were compared with the effects of caffeine, an adenosine antagonist, in panic disorder patients. Patients with panic disorder were given single oral doses of 0.5 mg/kg m-CPP, 480 mg caffeine, and placebo on separate days under double-blind conditions. Both m-CPP and caffeine had significantly greater anxiogenic and panic-inducing effects than placebo, although caffeine produced nonsignificantly greater increases on all anxiety rating scales than m-CPP. Both m-CPP and caffeine produced significant equivalent increases in plasma cortisol concentrations, but only m-CPP produced plasma prolactin increases. These findings provide further evidence implicating both the serotonergic and adenosinergic receptor systems in the neurobiology of panic disorder.

Adult

The QKd interval in panic disorder: an assessment of end-organ thyroid hormone responsivity.

The QKd interval was utilized as a presumptive index of end-organ thyroid hormone effect to test the hypothesis that patients with panic disorder might have abnormal tissue-level responsivity to normal levels of peripherally circulating thyroid hormones. No significant differences in QKd intervals were found between 15 patients with panic disorder (230 +/- 50 msec) and 20 normal controls (224 +/- 29 msec) while drug-free. These findings suggest that patients with panic disorder have normal tissue-level responsivity to thyroid hormone.

Adult

Endocrine, cardiovascular, and behavioral effects of intravenous protirelin in patients with panic disorder.

The effects of protirelin administration on the anterior pituitary release of thyrotropin and prolactin were examined in 26 patients with panic disorder and 22 healthy volunteers. There were no differences observed in hormonal responses to protirelin between patients and controls. However, higher Beck Depression Inventory scores were associated with smaller baseline-corrected maximal changes in thyrotropin responses. Cardiovascular responses to protirelin did not differ between a subgroup of 15 patients with panic disorder and 15 age- and sex-matched healthy controls. Although protirelin produced robust increases in heart rate and blood pressure, only one patient with panic disorder experienced a panic attack during the infusion. The hormonal findings suggest that the presence of depressive symptoms may have a significant impact on various indexes of neuroendocrine responsivity and should be taken into consideration when looking at biologic measures in patients with panic disorder. The cardiovascular and behavioral findings do not support the hypothesis that all panic-producing stimuli are nonspecific and suggest that the induction of physical stimuli may be insufficient to produce panic attacks even in susceptible individuals.

Adult

Cognitive-behavioral and pharmacological treatments of social phobia. A controlled study.

Sixty-five patients with social phobia were treated in a study that compared a cognitive-behavioral group treatment program with pharmacotherapy with alprazolam, phenelzine sulfate, or pill-placebo plus instructions for self-directed exposure to phobic stimuli. Statistically significant repeated-measures effects were shown on all measures, indicating that the treatments studied were associated with substantial improvements in patients with severe and chronic social phobia. Patients who were treated with phenelzine were rated by clinicians as more improved on a measure of work and social disability than patients who were treated with alprazolam or placebo (patients in the cognitive-behavior therapy group were not rated on this measure). Subjects showed positive cognitive changes from before to after treatment, and there were no differences between treatment groups on the cognitive measure. We discuss the implications of these findings within the context of demographic and clinical predictors of response.

Adolescent

Phenomenology and neurobiology of social phobia: comparison with panic disorder.

Like panic disorder, social phobia is a common, frequently severe, anxiety disorder that can cause significant work and social impairment. Unlike panic disorder, social phobia has only recently begun to undergo neurobiologic study and to receive pharmacotherapeutic attention. There is a high comorbidity between social phobia and panic disorder; however, many differences exist--including age at onset, gender distribution, contextual framework of anxiety, help-seeking and help-avoidance behavior, quality of sleep and sleep patterns, caffeine and lactate sensitivity, and, most probably, pharmacologic responses. Social phobia can now be included among the growing number of anxiety disorders that respond to pharmacotherapy.

Adult