Cortisol secretion in endogenous depression. I. Basal plasma levels.
ABSTRACT Plasma levels of cortisol were sampled for 24 hours in 32 endogenously depressed (ED) patients and 72 normal controls who also underwent the dexamethasone suppression test. The ED patients had significantly higher mean 24-hour plasma levels of cortisol (means 24h PC). However, means 24h PC values of subjects in both groups were normally distributed, with a marked overlap between the two. Only seven ED patients had means 24h PC values higher than 2 SDs from the normal mean (greater than 10 micrograms/dL). An abnormal dexamethasone suppression test result was only partially related to basal cortisol levels. The mean plasma level of cortisol between 1 and 4 PM was found to be highly correlated with the means 24h PC value in ED patients, as has been previously reported in normal subjects and patients with various other diseases (in which it also powerfully discriminated between hypersecretors and normosecretors). This finding supports the use of mean cortisol levels between 1 and 4 PM as a reliable and convenient indication of cortisol secretion.
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ABSTRACT: Depression causes significant morbidity in the human population. The Diathesis-Stress/Two-Hit model of depression hypothesizes that stress interacts with underlying (probably genetic) predispositions to produce a central nervous system that is primed to express psychopathology when confronted with stressful experiences later in life. Nonhuman primate (NHP) studies have been extensively utilized to test this model. NHPs are especially useful for studying effects of early experience, because many aspects of NHP infancy are similar to humans, whereas development occurs at an accelerated rate and therefore allows for more rapid assessment of experimental variables. In addition, the ability to manipulate putative risk factors, including introducing experimental stress during development, allows inference of causality not possible with human studies. This manuscript reviews experimental paradigms that have been utilized to model early adverse experience in NHPs, including peer-rearing, maternal separation, and variable foraging. It also provides examples of how this model has been used to investigate the effects of early experience on later neurobiology, physiology, and behavior associated with depression. We conclude that the NHP offers an excellent model to research mechanisms contributing to the Diathesis-Stress/Two-Hit model of depression.ILAR journal / National Research Council, Institute of Laboratory Animal Resources 09/2014; 55(2):259-73. · 1.05 Impact Factor
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ABSTRACT: Emerging evidence indicates that stress hormone glucocorticoids (GC) are an important modulator of brain development and function. To investigate whether GCs modulate neurosteroid biosynthesis in neural cells, we studied the effects of GCs on steroidogenic gene expression in human glioma GI-1 cells. The GC dexamethasone (Dex) reduced steroidogenic acute regulatory protein (StAR), CYP11A1 and 3β-hydroxysteroid dehydrogenase gene expression in a dose- and GC receptor-dependent manner. In addition to its effects on steroidogenic gene expression, Dex also reduced de novo synthesis of progesterone (PROG). Furthermore, Dex inhibited all-trans retinoic acid (ATRA) and vitamin D3-induced steroidogenic gene expression and PROG production. This suggests that GC regulates steroidogenic gene expression in neural cells via cross-talk with the two fat-soluble vitamins, A and D. The relationship between the effects of GCs on neurosteroid biosynthesis and on cognitive behaviors and hippocampal neural activity is also discussed herein.Biological & Pharmaceutical Bulletin 01/2014; 37(7):1241-7. · 1.78 Impact Factor
- Frontiers in Neuroscience 09/2014; 8:247.