Interaction of brain noradrenergic system and the hypothalamic-pituitary-adrenal (HPA) axis in man.
BACKGROUND
Numerous interactions between the brainstem locus coeruleus system and the HPA axis have been shown in experimental animals. This relationship is less well characterized in humans and little is known about the influence of psychiatric disorders, which disturb one of these systems, on this relationship.


METHODS
Untreated subjects with pure MDD (n = 13), MDD with comorbid anxiety disorders (n = 17), and pure anxiety disorders (n = 15) were recruited by advertising. Age and sex matched control subjects were recruited for each subject with a psychiatric diagnosis (n = 45). All subjects underwent a social stressor, the Trier Social Stress Test (TSST), and blood was collected for ACTH assay. These same subjects also underwent a clonidine challenge study for assessment of growth hormone release as a marker of tonic noradrenergic activation.


RESULTS
Examining log transformed area under the curve response for each hormone, a significant negative relationship (simple regression) was observed between systems in normal subjects. This relationship was preserved in anxiety subjects. However, both pure depressed and comorbid depressed and anxiety subjects demonstrated disruption of this relationship.


CONCLUSIONS
Under normal circumstances, noradrenergic systems can influence the magnitude of the HPA axis response to stress. However, in subjects with major depression, HPA axis activation appears autonomous of noradrenergic influence.
Young
Elizabeth A
EA
Department of Psychiatry, University of Michigan, Ann Arbor, 48109-0720, USA. eayoung@umich.edu
Abelson
James L
JL
Cameron
Oliver G
OG
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001008:Anxiety Disorders / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D019540:Area Under Curve; D003865:Major Depressive Disorder / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology*; D016014:Linear Models; D008125:Locus Coeruleus / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D016555:Matched-Pair Analysis; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D009638:Norepinephrine / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology*; D012016:Reference Values; D013315:Stress, Psychological / Q000097:blood / Q000503:physiopathology*
D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; D009638:Norepinephrine