Progress in neuro-psychopharmacology & biological psychiatry
-
Prog. Neuropsychopharmacol. Biol. Psychiatry · Apr 2009
Distinct effects of acute and chronic sleep loss on DNA damage in rats.
The aim of this investigation was to evaluate genetic damage induced in male rats by experimental sleep loss for short-term (24 and 96 h) and long-term (21 days) intervals, as well as their respective recovery periods in peripheral blood, brain, liver and heart tissue by the single cell gel (comet) assay. Rats were paradoxically deprived of sleep (PSD) by the platform technique for 24 or 96 h, or chronically sleep-restricted (SR) for 21 days. We also sought to verify the time course of their recovery after 24 h of rebound sleep. ⋯ Corticosterone concentrations were increased after PSD (24 and 96 h) relative to control rats, whereas these levels were unaffected in the SR group. Collectively, these findings reveal that sleep loss was able to induce genetic damage in blood and brain cells, especially following acute exposure. Since DNA damage is an important step in events leading to genomic instability, this study represents a relevant contribution to the understanding of the potential health risks associated with sleep deprivation.
-
Prog. Neuropsychopharmacol. Biol. Psychiatry · Apr 2009
Clinical TrialAugmentation of antidepressants with perospirone for treatment-resistant major depressive disorder.
We examined the efficacy and tolerability of perospirone, a dopamine D2 and 5-HT2A receptor antagonist and a partial 5-HT1A receptor agonist, in the augmentation of antidepressant treatment of partially responding and nonresponding patients with major depressive disorder. Twelve patients with major depressive disorder and an incomplete or no response to different kinds of antidepressants (selective serotonin reuptake inhibitor, milnacipran, or sulpride) monotherapy or polytherapy for 8 weeks or more were treated with perospirone augmentation in an eight-week, open-label study. Data were gathered from July 2006 to March 2008. ⋯ The discontinuation rate after 8 weeks of treatment was zero. These findings suggest that perospirone may be an effective augmentation strategy for improving therapeutic response in patients with treatment-resistant major depressive disorder when administered in combination with standard antidepressant therapy. Based on this clinical evidence, a double-blind, placebo-controlled trial is warranted.
-
Prog. Neuropsychopharmacol. Biol. Psychiatry · Apr 2009
TPH2 -703G/T SNP may have important effect on susceptibility to suicidal behavior in major depression.
Serotonergic system-related genes can be good candidate genes for both major depressive disorder (MDD) and suicidal behavior. In this study, we aimed to investigate the association of serotonin 2A receptor gene -1438A/G SNP (HTR2A -1438A/G), tryptophan hydroxylase 2 gene -703G/T SNP (TPH2 -703G/T) and serotonin 1A receptor C-1019G (HTR1A C-1019G) with suicidal behavior. ⋯ Our results suggest that TPH2 -703G/T SNP may have an important effect on susceptibility to suicidal behavior. Furthermore, an increased frequency of G allele of TPH2 SNP may be associated with elevated suicidal behavior itself rather than with the diagnosis of major depression and may increase risk of suicidality, independent of diagnosis.