Noradrenergic mechanisms in stress and anxiety: II. Clinical studies

Studies in animals have shown a relationship between alterations in noradrenergic brain system function and behaviors of anxiety and fear. These findings have generated the hypothesis that the symptoms seen in patients with anxiety disorders may be related to alterations in noradrenergic function. A number of clinical studies have tested this hypothesis, utilizing measures of catecholaminergic function such as heart rate and blood pressure, measurement of norepinephrine and its metabolites in urine and plasma and adrenergic receptor binding in platelets, as well as pharmacological challenge to the noradrenergic system. Acute stressors, such as public speaking, have been associated with an increase in heart rate, blood pressure, and norepinephrine and its metabolites in urine and plasma. Findings in patients with panic disorder at baseline related to heart rate, blood pressure, baseline norepinephrine and its metabolites, and platelet adrenergic receptors have been mixed, while the most consistent findings have been blunted growth hormone response to clonidine and increased 3-methoxy-4-hydroxy-phenylethylene-glucol (MHPG) and anxiety following stimulation of the noradrenergic system with yohimbine. Baseline measures of noradrenergic function in patients with posttraumatic stress disorder (PTSD) have also been mixed, while an increased heart, blood pressure and norepinephrine response to traumatic reminders, as well as increased behavioral (as well as different brain metabolic) response to yohimbine, have been found in PTSD. There are fewer studies of noradrenergic function in the other anxiety disorders, and the findings there have not been consistent. These studies provide evidence for increased noradrenergic responsiveness in panic disorder and PTSD, although there does not appear to be an alteration in baseline noradrenergic function in these patients.