Rapid antidepressant effects of sleep deprivation therapy correlates with serum BDNF changes in major depression.
ABSTRACT Recent reports have suggested that brain-derived neurotrophic factor (BDNF) levels are reduced in individuals suffering major depressive disorder and these levels normalize following antidepressant treatment. Various antidepressants and electroconvulsive therapy are shown to have a positive effect on brain-derived neurotrophic factor levels in depressive patients. The aim of this study was to assess the effect of total sleep deprivation therapy on BDNF levels in major depressive patients. Patients were assigned to two treatment groups which consisted of 22 patients in the sertraline group and 19 patients in the total sleep deprivation plus sertraline group. Patients in the sleep deprivation group were treated with three total sleep deprivations in the first week of their treatment and received sertraline. Patients in sertraline group received only sertraline. BDNF levels were measured in the two treatment groups at baseline, 7th, 14th, and 42nd days. Patients were also evaluated using the Hamilton Rating Scale for Depression (HAM-D). A control group, consisting of 33 healthy volunteers had total sleep deprivation, BDNF levels and depression measured at baseline and after the total sleep deprivation. Results showed that serum BDNF levels were significantly lower at baseline in both treatment groups compared to controls. Decreased levels of BDNF were also negatively correlated with HAM-D scores. First single sleep deprivation and a series of three sleep deprivations accelerated the treatment response that significantly decreased HAM-D scores and increased BDNF levels. Total sleep deprivation and sertraline therapy is introduced to correlate with the rapid treatment response and BDNF changes in this study.
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ABSTRACT: Major depressive disorder is a leading debilitating disease known to occur at a two-fold higher rate in women than in men. The neurotrophic hypothesis of depression suggests that loss of brain-derived neurotrophic factor (BDNF) may increase susceptibility for depression-like behavior, although direct evidence is lacking. Using the chronic unpredictable stress (CUS) paradigm, we investigated whether male and female mice with inducible BDNF deletion in the forebrain were more susceptible to depression-related behavior. We demonstrate that in certain behavioral measures the loss of BDNF lowers the threshold for female mice studied at random throughout estrus to display anxiogenic and anhedonic behaviors after chronic stress compared with wild-type female mice. However, the loss of BDNF in forebrain does not increase the susceptibility to depression-like behavior in male mice. These gender differences suggest a role for BDNF in mediating some aspects of depression-related behavior in females.Biological psychiatry 05/2009; 66(1):84-90. · 8.93 Impact Factor
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ABSTRACT: Sleep is a restorative process and is essential for maintenance of mental and physical health. In an attempt to understand the complexity of sleep, multidisciplinary strategies, including genetic approaches, have been applied to sleep research. Although quantitative real time PCR has been used in previous sleep-related gene expression studies, proper validation of reference genes is currently lacking. Thus, we examined the effect of total or paradoxical sleep deprivation (TSD or PSD) on the expression stability of the following frequently used reference genes in brain and blood: beta-actin (b-actin), beta-2-microglobulin (B2M), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and hypoxanthine guanine phosphoribosyl transferase (HPRT). Neither TSD nor PSD affected the expression stability of all tested genes in both tissues indicating that b-actin, B2M, GAPDH and HPRT are appropriate reference genes for the sleep-related gene expression studies. In order to further verify these results, the relative expression of brain derived neurotrophic factor (BDNF) and glycerol-3-phosphate dehydrogenase1 (GPD1) was evaluated in brain and blood, respectively. The normalization with each of four reference genes produced similar pattern of expression in control and sleep deprived rats, but subtle differences in the magnitude of expression fold change were observed which might affect the statistical significance. This study demonstrated that sleep deprivation does not alter the expression stability of commonly used reference genes in brain and blood. Nonetheless, the use of multiple reference genes in quantitative RT-PCR is required for the accurate results.BMC Molecular Biology 02/2009; 10:45. · 2.80 Impact Factor
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ABSTRACT: Gastrointestinal peptides and hormones are known to penetrate through the utero-placental barrier and regulate fetal development. In the present study, we tested permeation of maternal brain-derived neurotrophic factor (BDNF) to fetuses, using BDNF-gene deficient mice and exogenous BDNF administration. At embryonic day 13.5 (E13.5)-14.5, BDNF protein concentrations in the fetal brain of BDNF homozygous null mutant (bdnf (-/-)) were comparable to the levels seen in wild-type fetuses. After E17.5, BDNF protein levels in bdnf (-/-) fetal brain were still detectable but its levels were significantly decreased below those in wild-type brain. When recombinant BDNF protein was injected into pregnant wild-type mice carrying E14.5 embryos, BDNF protein levels in fetal brain were elevated dose-dependently. These findings suggest that maternal BDNF reaches the fetal brain through utero-placental barrier and might contribute to its development.Neurochemistry International 01/2009; 54(2):95-8. · 2.66 Impact Factor