Patients with pathological degrees of anxiety who meet DSM-III-R criteria for panic disorder, with or without agoraphobia; generalized anxiety disorder; or social phobia are evaluated using psychological, physiological, and biochemical methodologies. Patients with major affective illness, particularly those with a significant anxiety component, are also eligible for participation in the program. Particular attention is given to the role of the noradrenergic, dopaminergic, adenosinergic, and serotonergic neurotransmitter systems as assessed by: 1) measurement of the metabolites NE, MHPG, and HVA in plasma; 2) adrenergic receptor number and function in platelets; and 3) neuroendocrine and behavioral responses to the alpha-2 adrenergic agonist clonidine and antagonist yohimbine, the serotonin agonist m-chlorophenylpiperazine (MCPP), and the adenosine receptor antagonist, 1,3,7 trimethylxanthine. Research investigating the relationship of noradrenergic and adenosinergic function to other neurotransmitter systems and the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes also has been initiated. Caffeine and nifedipine challenges are administered to assess their behavioral and biochemical effects. Other approaches to understanding the pathophysiology of anxiety and its potential treatment with alprazolam, carbamazepine, clonidine, dipyridamole, imipramine and verapamil will be explored. An animal model using genetically """"""""nervous"""""""" and """"""""normal"""""""" pointer dogs has been developed and studied in relation to noradrenergic and adenosinergic function.
