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J Douglas Bremner Meena Vythilingam Eric Vermetten George Anderson John W Newcomer Dennis S Charney 《Neuropsychopharmacology》2004,55(8):811-815
BACKGROUND: Major depression has been associated with hypercortisolemia in a subset of patients with depression. Administration of exogenous cortisol and other glucocorticoids to healthy human subjects has been observed to result in a transient impairment in verbal declarative memory function. The purpose of this study was to assess the effects of the glucocorticoid, dexamethasone, on verbal declarative memory function in patients with untreated unipolar major depressive disorder (MDD). METHODS: Fifty two men and women with (n = 28) and without (n = 24) MDD received placebo or dexamethasone (1 mg and 2 mg on 2 successive days) in a double-blind, randomized fashion. Declarative memory was assessed with paragraph recall at baseline (day 1) and day 3. RESULTS: There was a significant interaction between diagnosis and drug (dexamethasone vs. placebo) on paragraph recall. In the healthy subjects, memory improved from baseline to day 3 with placebo and was unchanged with dexamethasone, whereas in MDD patients memory function showed a pattern of decreasing with placebo and improving with dexamethasone from baseline to day 3. CONCLUSIONS: These findings are consistent with an altered sensitivity of declarative memory function in MDD to regulation by glucocorticoids. Possible explanations of the findings include alterations in glucocorticoid receptors in the hippocampus or other brain regions mediating declarative memory, or differential sensitivity to dexamethasone-induced reductions in cortisol, in patients with MDD. 相似文献
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The role of growth factors and cytokines in the impaired healing of chronic leg ulcers remains uncertain. The aim of this study was to determine whether changes in the amount and location of cytokines and growth factors may be associated with impaired healing in chronic leg ulcers. Biopsies from leg ulcers of 21 patients and from normal skin of nine healthy volunteers were examined immunohistochemically for selected growth factors and cytokines. Greater staining intensity was found in keratinocytes at the edges of ulcers compared to normal skin, or skin adjacent to the ulcers. Staining at the ulcer edge was more intense in nonhealing ulcers for only vascular endothelial growth factor and platelet-derived growth factor, whereas staining in the adjacent skin was more intense for all factors in the nonhealing phase. For all factors staining was cytoplasmic, suggesting production in these areas. This study shows up-regulation of the production of cytokines and growth factors in keratinocytes of chronic leg ulcers that is greater when the ulcers are nonhealing. 相似文献
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Situational panic attacks. Behavioral, physiologic, and biochemical characterization 总被引:2,自引:0,他引:2
S W Woods D S Charney C A McPherson A H Gradman G R Heninger 《Archives of general psychiatry》1987,44(4):365-375
To investigate the pathophysiology of nonpharmacologically induced panic attacks, 18 drug-free agoraphobic patients and 13 matched healthy subjects underwent structured exposure to phobic situations. Heart rate, blood pressure, and plasma free 3-methoxy-4-hydroxyphenylglycol (MHPG), cortisol, growth hormone, and prolactin levels were measured before, during, and after exposure. Fifteen patients experienced situational panic attacks during exposure. Panicking patients displayed significantly greater increases in heart rate but not blood pressure or plasma free MHPG or cortisol in comparison with the healthy subjects. Growth hormone and prolactin responses tended to be smaller in the patients. If brain noradrenergic hyperactivity occurs during situational panic attacks, it may be too brief or too restricted in regional localization to affect MHPG levels in plasma. Chronically recurrent attacks may cause an adaptation of neuroendocrine mechanisms activated by anxiety or stress. 相似文献
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Mitchel A Kling Salvatore Alesci Gyorgy Csako Rene Costello David A Luckenbaugh Omer Bonne Roman Duncko Wayne C Drevets Husseini K Manji Dennis S Charney Philip W Gold Alexander Neumeister 《Neuropsychopharmacology》2007,62(4):309-313
BACKGROUND: Major depressive disorder (MDD) shows increased coronary artery disease (CAD) risk of unknown mechanism(s). MDD is more common in women than men; CAD diagnosis can be difficult in women. Elevations of the inflammatory markers C-reactive protein (CRP) and serum amyloid A (SAA) predict increased CAD risk in populations; few data on these markers exist in MDD, particularly in remitted patients. METHODS: We measured fasting am serum CRP (high sensitivity, CRP(hs)) and SAA in 18 unmedicated, remitted women with MDD (mean age 41 +/- (SD)12, body mass index (BMI) 25.2 +/- 4.1 kg/m(2)) and 18 BMI-matched healthy control subjects (age 36 +/- 10, BMI 25.3 +/- 3.8 kg/m(2)) on 2 separate occasions, > or = 6 days apart. RESULTS: Repeat SAA and CRP(hs) measurements strongly correlated across study days (SAA: r = .83, p < .001; CRP(hs): r = .94, p < .001). Both SAA (5.30 +/- 3.39 vs. 2.84 +/- 1.87 mg/L, p < .005) and CRP(hs) (3.23 +/- 3.17 vs. 1.12 +/- 1.45 mg/L; p < .01) were significantly elevated in MDD women versus controls. CONCLUSIONS: Elevated SAA and CRP(hs) in remitted, unmedicated women with MDD indicate a pro-inflammatory state unrelated to current depressive symptoms or pharmacotherapy. These findings suggest that inflammatory mechanisms may in part underlie findings of increased CAD risk in MDD. 相似文献
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