No association between the sigma receptor type 1 gene and schizophrenia: results of analysis and meta-analysis of case-control studies

BACKGROUND: Several lines of evidence have supported possible roles of the sigma receptors in the etiology of schizophrenia and mechanisms of antipsychotic efficacy. An association study provided genetic evidence that the sigma receptor type 1 gene (SIGMAR1) was a possible susceptibility factor for schizophrenia, however, it was not replicated by a subsequent study. It is necessary to evaluate further the possibility that the SIGMAR1 gene is associated with susceptibility to schizophrenia. METHODS: A case-control association study between two polymorphisms of the SIGMAR1 gene, G-241T/C-240T and Gln2Pro, and schizophrenia in Japanese population, and meta-analysis including present and previous studies. RESULTS: There was no significant association of any allele or genotype of the polymorphisms with schizophrenia. Neither significant association was observed with hebephrenic or paranoid subtype of schizophrenia. Furthermore, a meta-analysis including the present and previous studies comprising 779 controls and 636 schizophrenics also revealed no significant association between the SIGMAR1 gene and schizophrenia. CONCLUSION: In view of this evidence, it is likely that the SIGMAR1 gene does not confer susceptibility to schizophrenia

Effects of haloperidol on serum brain-derived neurotrophic factor (BDNF) levels in schizophrenic patients

BACKGROUND: Previous studies had reported that serum brain derived neurotrophic factor (BDNF) levels were decreased in chronic schizophrenic patients [Toyooka et al., 2002]. Recent evidence suggests that BDNF might be involved in antipsychotic action in the central nervous system, and some researchers have reported that prolonged treatment with haloperidol significantly down-regulates hippocampal BDNF protein level. However, it is unknown whether this antipsychotic drug has the similar effect on the peripheral system. In this study, we attempted to investigate the potential effect of haloperidol on patient’s serum BDNF level. METHODS: A case control study was performed on 22 chronic schizophrenic patients, under haloperidol treatment, and 22 normal controls, age and sex matched. BDNF level was measured by two site enzyme immunoassay (ELISA) method. No differences were found in the BDNF level between patients (41.46F10.72 ng/ml) and controls (38.41F7.55 ng/ml). CONCLUSION: Further research is under way to more fully understand the effect of drug treatment on serum BDNF levels and whether drug treatment normalizes serum BDNF levels

Differential effect of chronic corticosterone and antidepressant treatment on amygdale cell proliferation and depression-like behavior

In this paper the Elastodynamic Finite Integration Technique (EFIT) [1] is applied to an isotropic, inhomogeneous, three media acoustic-elastic problem. We consider three media: an acoustic medium, air, above an elastic layer of acrylic, and another layer of air below the elastic layer. Numerical integration results are presented for various values of the simulation parameters. We generate simulated data by variation of the transducer angle and the presence of planar defects in the acrylic. We compare and discuss the results for both the wavefront images and simulated A-scan data from a second transducer located in the lower acoustic medium

The modulation of paroxetine to the suppressive effect of corticosteroid on adult hippocampal neurogenesis

Program no. 552.3Background: Clinical experience and previous research showed that cognitive deficiency or emotional changes might occur with chronic treatment of glucocorticoids. Results from animal studies, suggested that this might be caused by the suppressive effect of glucocorticoid on hippocampal neurogenesis. Paroxetine is a specific and potent serotonin uptake inhibitor antidepressant (SSRI) commonly used in psychiatry. Here, we investigated whether the long term use of Paroxetine 1) increases adult hippocampal neurogenesis and 2) reverses the reduced neurogenesis induced by corticosteroid. Methods: Adult male SD rats were given daily injection of vehicle, corticosteroid, Paroxetine, or both corticosteroid and Paroxetine for 14 days. Cell proliferation in the dentate gyrus was quantified by using BrdU immunohistochemistry, and the number of BrdU positive cells was evaluated. Results: Our results showed that corticosteroids suppressed hippocampal neurogenesis. Chronic Paroxetine treatment alone resulted in the increase of adult hippocampal neurogenesis. More importantly, this treatment could reverse the suppressive effect of corticosteroid on hippocampal neurogenesis. Conclusion: These data demonstrate that chronic treatment with paroxetine can protect the hippocampus from the potentially deleterious effects of corticosteroid on neurogenesis which provides a clue to prevent hippocampal damage during the chronic use of glucocorticoids in the clinic. Corresponding authors: KF So and SW Tang

Corticosteroid decreases subventricular zone cell proliferation, which could be reversed by paroxetine

Purpose: Major depressive disorder is often associated with elevated glucocorticoid levels, which in turn suppress cell proliferation and neurogenesis in the hippocampus. Increasing evidence supports that antidepressants induce hippocampal neurogenesis and this induces speculation that decrease in hippocampal neurogenesis has causal relationship with depression. There is, however, a lack of information about neurogenic effects of antidepressants on the subventricular zone, which is another CNS region with continuous neurogenesis throughout adulthood. In the present study, we investigated whether corticosterone and the SSRI paroxetine, have effects on SVZ cell proliferation. Methods: Rats were treated with the corresponding drugs for 14 days and the proliferating cells were labeled with bromodeoxyuridine (BrdU). BrdU labeled cells in the SVZ were quantified and analyzed. Results: In the corticosterone-treatment group, cell proliferation was decreased by 18% compared to vehicle-treatment group. Paroxetine-treatment group, in contrast, shows a 34% increase in cell proliferation. The decreased cell proliferation caused by corticosterone was prevented by paroxetine. Conclusions: Although corticosterone and antidepressants were found to affect cell proliferation in hippocampus, this is the first report to demonstrate that 1) corticosterone decreases cell proliferation in SVZ; 2) paroxetine promotes SVZ cell proliferation and 3) the suppressive effect on SVZ cell proliferation by corticosterone could be attenuated by paroxetine. These findings provide new insights into basic mechanisms of antidepressants, potential impact of steroid therapy on CNS neurogenesis, antidepressant mechanisms of action and potential involvement of the olfactory system in depression. © 2007 - IOS Press and the authors. All rights reserved.link_to_subscribed_fulltex

Is adult neurogenesis relevant in human depression

The 7th International Conference on Cognitive Sciences (ICCS 2010), Beijing, China, 17-20 August 2010