New studies and perspectives on the noradrenergic receptor system in depression: effects of the alpha 2-adrenergic agonist clonidine.
In an attempt to understand the dynamics of noradrenergic function in depression, we evaluated neuroendocrine, biochemical, cardiovascular, and behavioral responses to the acute intravenous administration of the alpha 2-adrenergic agonist, clonidine, in depressed patients and normal controls. Significantly more variance was observed in the depressed patients than the controls for most indices of basal noradrenergic output including plasma norepinephrine (NE) and 3-methoxy-4-hydroxyphenylglycol (MHPG). Growth hormone, plasma MHPG, and heart rate responses to clonidine were reduced in the depressed patients compared to the controls, all suggesting reduced responsiveness of alpha 2-adrenergic receptors in depression. Baseline levels of cortisol were elevated in the depressed patients compared to the controls. Clonidine decreased cortisol to normal levels in the depressed patients but had little effect in the controls. Thus the depressed patients manifested a significantly increased cortisol response to clonidine. These data raise the possibility that the hypercortisolemia of depression may be related to noradrenergic dysfunction. Clonidine also significantly reduced anxiety in the depressed patients, particularly those with elevated basal plasma MHPG, but not in controls. These results suggest that diminished alpha 2-adrenergic responsiveness as documented by decreased endocrine, biochemical, and physiological responses to clonidine may be related to the depressive and anxiety symptoms as well as the neuroendocrine disturbances characteristic of many depressed patients.
D000328:Adult; D001007:Anxiety / Q000188:drug therapy; D001794:Blood Pressure; D003000:Clonidine / Q000494:pharmacology*; D003866:Depressive Disorder / Q000378:metabolism*; D005260:Female; D013006:Growth Hormone / Q000378:metabolism; D006339:Heart Rate; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000097:blood; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011941:Receptors, Adrenergic / Q000187:drug effects*
D011941:Receptors, Adrenergic; D008734:Methoxyhydroxyphenylglycol; D013006:Growth Hormone; D003000:Clonidine; D006854:Hydrocortisone; D009638:Norepinephrine