Monoamine receptor systems and anxiety disorders

Fear is an adaptive response of the organism to external threat and the physiologic and behavioral responses to stimuli that induce fear involves activation of the sympathetic nervous system. Drugs that alter the function of two of the major brain monoamine neurotransmitter systems involved in sympathetic nervous system regulation (NE and 5-HT) have been shown to alter levels of "fear and anxiety" in laboratory animals, healthy humans, and patients. The relative clinical efficacy in the treatment of anxiety disorders with many of these drugs also emphasizes the importance of these two systems in anxiety. Recent advances in neuropharmacology have led to an improved understanding of how drugs that interact at specific NE and 5-HT receptors alter the function of these two neurotransmitter systems, and a few of the drugs that selectively interact at NE and 5-HT receptors have been used in studies of patients with anxiety disorders. Stimulation of the 5-HT system does not produce marked abnormalities in patients, but stimulation of the NE system does produce abnormal changes in measures of anxiety, somatic symptoms, blood pressure, and a plasma NE metabolite and cortisol levels in patients with panic disorder but not in patients with generalized anxiety disorder, obsessive-compulsive disorder, depression, or schizophrenia. This indicates that some patients with panic disorder have an abnormality in the regulation of the NE system that could explain many of the clinical features of this syndrome. Progress in assessing neurochemistry in the brains of living patients through brain imaging and new advances in the molecular biology of neurotransmitter receptor proteins will offer important new methods to be used in the study of these possible abnormalities.