http://hdl.handle.net/2027.42/49477 Sat, 18 May 2013 14:55:56 GMT 2013-05-18T14:55:56Z http://deepblue.lib.umich.edu:80/bitstream/id/184577/mbnilogo.gif http://hdl.handle.net/2027.42/49477 http://hdl.handle.net/2027.42/51379 Anxious and Depressive Disorders and Their Comorbidity: Effect on Central Nervous System Noradrenergic Function Cameron, Oliver G.; Abelson, James L.; Young, Elizabeth A. Background: Although comorbidity of anxiety with depression is common, investigations of physiologic abnormalities related specifically to comorbidity are rare. This study examined relationships of DSM-IV-defined depression, anxiety, and their comorbidity to noradrenergic function measured by blunting of the growth hormone (GH) response to the alpha2 adrenoreceptor agonist (and imidazoline receptor agent) clonidine and by blood pressure and symptom responses. Methods: Fifteen subjects with pure social anxiety or panic disorder, 15 with pure major depression, and 18 with both depression and anxiety were compared with healthy control subjects matched for age and gender. Other factors known to affect GH (weight, menstrual status, prior antidepressant, or other drug exposure) were controlled. Results: Anxiety produced GH blunting, but depression was associated with normal GH responses. The comorbid state did not affect results beyond the impact of anxiety. Preclonidine stress-related GH elevations were observed, to the greatest degree in anxious subjects. Relevant symptom, but not blood pressure, changes were significantly associated with blunting. Conclusions: With use of pure depression and anxiety groups and careful control of other factors known to affect GH, these results demonstrate central nervous system noradrenergic dysfunction in anxiety disorders. In contrast to less rigorously controlled studies, noradrenergic function in depression was normal. Wed, 01 Dec 2004 00:00:00 GMT http://hdl.handle.net/2027.42/51379 2004-12-01T00:00:00Z http://hdl.handle.net/2027.42/51378 Cortisol and Catecholamines in Posttraumatic Stress Disorder Young, Elizabeth A.; Breslau, Naomi Background: Prior research has connected posttraumatic stress disorder (PTSD) to increased levels of catecholamines. However, studies of cortisol levels have produced mixed results. Objective: To examine urinary catecholamine and cortisol levels in individuals with PTSD in a community sample. Design: A representative cohort of young adult community residents, assessed periodically during a10-year period for exposure to trauma and PTSD, was used to select a subset for urine collection studies conducted in a sleep laboratory across 2 consecutive nights and the intermediate day. Setting: The sample of young adults was randomly selected from a large health maintenance organization and is representative of the geographic area except for the extremes of the socioeconomic status range. Participants: A subsample was selected from the 10-year follow-up cohort (n=913; 91.1% of the initial sample). Eligibility criteria were: (1) persons exposed to trauma during the preceding 5 years, (2) other individuals who met PTSD criteria, and (3) a random preselected subsample. Of 439 eligible individuals, 292 (66.5%) participated, including 69 with lifetime PTSD. Main Outcome Measures: Measures of cortisol and catecholamine levels in urine. Results: The lifetime PTSD group demonstrated significantly higher catecholamine levels than the group exposed to trauma without PTSD and the nonexposed group. Individuals exposed to trauma without PTSD demonstrated significantly lower urine catecholamine levels than the nonexposed and the PTSD groups. Mean cortisol levels did not differ across groups. When analyzed by comorbidity with major depressive disorder (MDD), the PTSD-only group did not differ in cortisol levels from the groups with neither PTSD nor MDD. Women withMDD plus PTSD demonstrated significantly higher cortisol levels than women with neither disorder or with either disorder alone. Conclusions: Trauma per se does not lead to sustained increases in cortisol or catecholamine levels. Posttraumatic stress disorder is associated with higher catecholamine levels. In contrast, persons with PTSD had neither an increase nor a decrease in mean urinary cortisol levels.Women with PTSD and comorbid MDD had higher cortisol levels. Thu, 01 Apr 2004 00:00:00 GMT http://hdl.handle.net/2027.42/51378 2004-04-01T00:00:00Z http://hdl.handle.net/2027.42/51374 Saliva Cortisol in Posttraumatic Stress Disorder: Young, Elizabeth A.; Breslau, Naomi Background: Stress activates the hypothalamic–pituitary–adrenal (HPA) axis, so it was expected that posttraumatic stress disorder (PTSD) would be associated with activation of this axis; however, studies have found both increased and decreased cortisol in PTSD. To address this question, we collected saliva cortisol at home in a subsample of a longitudinal epidemiologic sample. Methods: Six hundred eighty-four persons randomly selected from the total sample of 913 were requested to collect saliva samples upon awakening and in the early evening. Of these, 538 responded with samples, 516 of whom met inclusion criteria. These were 68 exposed to trauma with lifetime PTSD, 265 exposed to trauma with no PTSD, and 183 never exposed to trauma. Results: In a comparison of these three groups, lifetime PTSD revealed elevated evening saliva cortisol compared with exposed/no PTSD. When lifetime comorbidity with major depressive disorder (MDD) was included in the analysis, only persons with comorbid PTSD and MDD showed this evening elevation in cortisol. Persons with PTSD alone (never MDD) showed normal saliva cortisol levels, as did subjects with lifetime MDD alone. Conclusions: Neither exposure to trauma nor PTSD alone is associated with alterations in saliva cortisol; however, elevated cortisol is found in PTSD comorbid with lifetime MDD. Sun, 01 Aug 2004 00:00:00 GMT http://hdl.handle.net/2027.42/51374 2004-08-01T00:00:00Z http://hdl.handle.net/2027.42/51372 Interaction of Brain Noradrenergic System and the Hypothalamic-Pituitary-Adrenal (HPA) Axis in Man Young, Elizabeth A.; Abelson, James L.; Cameron, Oliver G. 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. Fri, 30 Sep 2005 00:00:00 GMT http://hdl.handle.net/2027.42/51372 2005-09-30T00:00:00Z