24-h monitoring of plasma norepinephrine, MHPG, cortisol, growth hormone and prolactin in depression

Depression is associated with alterations in hormone and catecholamine circadian rhythms. Analysis of these alterations has the potential to distinguish between three neurobiological models of depression, the catecholamine model, the phase advance model and the dysregulation model. Although a number of studies of 24-h rhythms have been reported, inconsistencies among the findings have complicated efforts to model the chronobiology of depression. The present study takes advantage of frequent plasma sampling over the 24-h period and a multioscillator cosinor model to fit the 24-h rhythms. Method: Plasma levels of norepinephrine, cortisol, prolacatin and growth hormone were sampled at 30-min intervals, and MHPG at 60-min intervals, over a 24-h period in 22 patients with major depressive disorder and 20 healthy control volunteers. Results: The depressed patients had phase advanced circadian rhythms for cortisol, norepinephrine and MHPG, phase advanced hemicircadian rhythms for cortisol and prolactin, and a phase advanced ultradian rhythm for prolactin compared to healthy control subjects. In addition, the rhythm-corrected 24-h mean value (mesor) of norepinephrine was lower in the depressed patients compared to the healthy controls. There also was a poorer goodness-of-fit for norepinephrine to the circadian oscillator in the depressed patients relative to the healthy controls. Conclusions: These findings provide partial support for the dysregulation model of depression and are consistent with those studies that have found phase advances in cortisol, norepinephrine and MHPG rhythms in depression. Published by Elsevier Ltd.