Noradrenergic mechanisms in stress and anxiety: II. Clinical studies

Abstract

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. © 1996 Wiley‐Liss, Inc.

Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities

“…Although further analyses are needed to clarify the causes and effects of the transmitter content abnormality, preclinical and clinical evidence suggests a relationship between increased noradrenergic neurotransmission and symptoms associated with stress and anxiety. 24,26 Considering the anxiety-like behavior in the Slitrk1-deficient mice, the altered noradrenergic transmission may be involved in the appearance of depression-like behavior.…”

“…[36][37][38][39] Clinical studies suggest a relationship between norepinephrine and behaviors of anxiety and fear, as well as alterations in noradrenergic function in patients with psychiatric disorders related to anxiety and stress, panic disorder and posttraumatic stress disorder. 26,40,41 Further analysis of Slitrk1-deficient mice will be beneficial for understanding the pathogenesis of TS and other related neuropsychiatric diseases. ) and entries into open arms in Slitrk1-deficient mice (U = 10.5, P < 0.05) (b), whereas the drug had no effect on locomotor activity (c).…”

Neurosteroids in the context of stress: Implications for depressive disorders

“…Both animal and human studies indicate that chronic or severe stress exposure, especially early in life (Coplan et al, 1996), can result in persistent alterations in neurobiological systems that are stress responsive (Bremner & Vermetten, 2001;Heim et al, 2001). There is particularly compelling evidence that such long-term adaptation to either early life stress or to chronic on-going stress occurs for HPA axis regulation (Lemieux & Coe, 1995;Resnick et al, 1995;Coplan et al, 1996;Ladd et al, 1996;Kaufman et al, 1997, Heim et al, 2001Szikszay & Benedek, 1989;D'Amore et al, 1993;Heim et al, 2002;Bennett et al, 2004), and there is also evidence that it occurs for noradrenergic regulation (Bremner et al, 1996;Young & Breslau, 2004).…”

Pharmacological Blockade of α2-Adrenoceptors Induces Reinstatement of Cocaine-Seeking Behavior in Squirrel Monkeys

“…There is, however, a growing body of literature linking activation of noradrenergic transmission to the behavioral and physiological consequences of stress (Stanford, 1995;Bremner et al, 1996). Recent findings using rodent models of reinstated drug seeking suggest a potentially important role for the noradrenergic system in stress-induced relapse (Stewart, 2000;Shaham et al, 2003).…”