The demographic data for the current group of patients are shown in . All patients currently met criteria for MDD; 16 of the 28 were recurrent and 16 of the 28 were melancholic. None were psychotic. In two subjects, dysthymia preceded the onset of major depression. Four patients had a history of anxiety disorders on the SCID (PTSD in two (both female); social anxiety disorder in three (all female); two with panic disorder (one male, one female)). In addition, five patients had a past history of alcohol abuse which resolved 2, 8, 10, 17 and 18 years earlier.
Baseline Description of Patients and Controls (Mean ±SD)
Our previous report addressed overall mean ACTH secretion and found lower circadian driven peak ACTH secretion in depressed men compared to either control men or depressed women. In contrast, depressed women showed no difference in mean or peak 24H ACTH secretion compared to age matched control women. (Young and Ribeiro, 2006
and show example graphs of the ACTH profiles and deconvolution output for one depressed patients () and one normal control (). The mean data for cortisol over the 24H as well as each of the 12H blocks is shown in . As can be seen, metyrapone blocked cortisol production to a mean of around 2μg/dl, confirming adequate blockade of cortisol production. The mean 24H cortisol in control men was 2.4±0.3 (SD) and for depressed men it was 2.3±0.7. The mean data for pulse parameters for patients and controls are shown in . Overall, there were no group differences between patients and controls in pulse number. However, there was a significant group by sex interaction (F=4.5, df=1/52, p=0.04). Post-hoc testing showed a greater number of ACTH pulses in depressed men than control men (p=0.02, paired t test), whereas there was no significant difference between depressed women and control women (p=.773). As would be expected by changes in pulse number over 24 hours, there was also significant group by sex interaction in interpulse interval, with control men showing a longer interval between pulses than control women (p=0.02) and female patients (p=0.039) but not male patients (p=.138, paired t). Interpulse interval did not differ between depressed women and control women (p=.773). Pulse height did not differ between patients and controls (F=0.22, df=1, p=0.6). There was a significant sex difference in pulse AUC (F=7.36. df=1/52, p=.009), with men showing a smaller ACTH AUC than women. However, no difference in AUC were found between controls and patients (F=0.9, df=1,p=0.35). Finally, the calculated half-life of ACTH pulse did not differ between patients and controls (F=0.02, df=1, p=.884).
Mean Cortisol Under Metyrapone Blockade in μg/dl (Mean ± SD)
Parameters of ACTH secretion (Mean ±SD)
While deconvolution was able to identify ACTH pulses, in general the pulses did not occur until approximately 12 hours into the study, following the onset of overnight ACTH secretory drive (see and as examples). The difficulty in characterizing pulses during the quiescent period may be a reflection of the presence of low plasma ACTH levels, which were sometimes below the detection limit of our assay. To assure that levels of ACTH below the detection level found in first 12H did not affect our findings with men, we examined pulse number in the last 12H, when all samples were above the detection limit. We found significantly increased pulses, 22±3.7 (SD), in depressed men and 16.7±4.3 (SD) in control men (p=.0074, t-test)