Peripheral catecholamine levels and the symptoms of anxiety: studies in patients with and without pheochromocytoma.

We studied the correlation of plasma and urinary epinephrine (E) and norepinephrine (NE) levels with anxiety symptoms in three patient groups: 1) pheochromocytoma (PH+) (n = 17); 2) hypertensives with elevated catecholamine levels shown not to have a PH (PH-) (n = 25); and 3) patients with panic disorder (PD) (n = 23). Structured interviews and four self-rated anxiety scales were used: the SCL-90R Anxiety and Phobic Anxiety scales, and the Spielberger State/Trait Anxiety Inventories. The SCL-90R Somatization scale (which measures 12 somatic symptoms) was also utilized. None of the PH+ patients met DSM-III criteria for PD. Two met criteria for generalized anxiety disorder (GAD). Of the PH- patients, two had PD, two had GAD, and three had both. Urinary and plasma E did not show significant positive correlations with any of the four anxiety scales in any of the three patient groups. In both the PH+ and PH- groups, E was significantly correlated with the SCL-90R Somatization scale. NE was not significantly correlated with any of the four anxiety scales in the PH+ group. In contrast, in the PH- group, plasma NE was significantly correlated with anxiety on all anxiety scales (r = +0.55 to +0.77, p less than 0.05). Furthermore, in the PH- group, plasma NE was significantly correlated with those items of the SCL-90R Anxiety scale measuring the cognitive rather than the noncognitive symptoms of anxiety. In the PD group as well, plasma NE showed a significant correlation with the SCL-90R Anxiety Scale (r = +0.67, p less than 0.05). Taken together, our observations suggest that: 1) the effects of catecholamines in the periphery derived from a source independent of nervous system control (such as a PH) are not sufficient to elicit an anxiety disorder meeting DSM-III criteria; and 2) in patients without an autonomous source of peripheral catecholamines, NE in the periphery results from sympathetic nervous system activation and probably reflects, rather than causes, anxiety.

Intravenous yohimbine. Selective enhancer of norepinephrine and cortisol secretion and systolic blood pressure in humans.

Yohimbine hydrochloride was administered intravenously to nine normal volunteers to assess alpha 2-adrenergic receptor function. Plasma catecholamines, cortisol, and psychophysiological parameters (blood pressure, pulse, somatic symptoms checklist, and visual analogue scales assessing mood) were used as dependent variables. Plasma norepinephrine and plasma cortisol increased significantly after yohimbine administration, while epinephrine remained unchanged. Systolic blood pressure and somatic symptoms were also significantly increased by yohimbine. These findings suggest that low-dose intravenous yohimbine is an effective probe for alpha 2-adrenergic receptors and the hypothalamic-pituitary-adrenal axis.

Serial dexamethasone suppression tests in depressed patients treated only with electroconvulsive therapy.

Several systematic studies have evaluated serial dexamethasone suppression tests (DST) in patients with major depression who were treated with antidepressant medications. DST changes were noted to parallel clinical improvement in most recovering patients. If serial DSTs are a valid state-related correlate of depressive pathophysiology, all types of effective antidepressant treatment should result in DST 'normalization'. However, no treatment modalities other than antidepressant medications have been studied serially with systematic assessments. To test whether serial DSTs reflect clinical progress in depressives treated solely with electroconvulsive therapy (ECT), we studied weekly DSTs and Hamilton Rating Scales for Depression (HRSD) in 22 drug-free depressed patients. We observed progressive DST 'normalization' in most patients and moderately high correlations between weekly DST and HRSD values throughout treatment. Most patients receiving ECT became DST suppressors. In most patients the DST appeared to reflect the severity of depressive pathophysiology, perhaps providing serial feedback to clinicians monitoring the progress of treatment with ECT.

Circadian fluctuation of plasma epinephrine in supine humans.

Previous studies have demonstrated circadian fluctuations of systemic catecholamines in man. However, methodological differences and conflicting results with epinephrine are apparent. In the present study, plasma and urinary epinephrine and norepinephrine and plasma cortisol were studied in healthy young adult males over 24 hr with 20 min plasma sampling and EEG monitoring of sleep. Plasma epinephrine did not have a circadian variation in supine subjects. Urinary epinephrine levels and small urinary circadian variations were increased by normal posture and activity. Sleep and sleep stage were not associated with different plasma epinephrine levels, and no ultradian fluctuation was observed. Levels of norepinephrine and cortisol were normal. Based on all studies to date, it appears that basal plasma epinephrine has either a very small amplitude or no circadian rhythm, but that changes in posture and activity or the rest/activity cycle may modify this pattern.

Anxiety in patients with pheochromocytomas.

Anxiety has been considered an important clinical feature of patients with pheochromocytomas. We studied 17 patients with active pheochromocytoma to determine whether they experienced anxiety that met criteria of the Diagnostic and Statistical Manual of Mental Disorders, third edition, for either panic disorder or generalized anxiety disorder. Fifty-two patients with primary anxiety disorders were used as a comparison group. Six patients with pheochromocytomas had norepinephrine-secreting tumors and 11 had mixed-secretion tumors, with elevated levels of both epinephrine and norepinephrine. None of the 17 patients described the severe apprehension or fear characteristic of panic attacks and none described agoraphobia. One patient received a diagnosis of possible panic disorder, two met criteria for generalized anxiety disorder, and two met criteria for major depressive episode. Thus, the elevated levels of catecholamines secreted by pheochromocytomas are not sufficient to elicit an anxiety disorder.