| 1 | Rev Neurosci 2001 -1 12: 95-110 |
|---|---|
| PMID | 11392459 |
| Title | The role of neurotrophic factors in psychostimulant-induced behavioral and neuronal plasticity. |
| Abstract | Several neurotrophic factors influence the development, maintenance and survival of dopaminergic neurons in the mammalian central nervous system (CNS), including neurotrophin-3 (NT-3), brain derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), basic fibroblast growth factor (bFGF) and glial derived neurotrophic factor (GDNF). This review focuses on the role of these neurotrophic factors in psychostimulant-induced behavioral sensitization, a form of dopamine-mediated neuronal plasticity that models aspects of paranoid schizophrenia as well as drug craving among psychostimulant addicts. Whereas NT-3, CNTF and bFGF appear to play a positive role in psychostimulant-induced behavioral sensitization, GDNF inhibits this form of behavioral plasticity. The role of BDNF in behavioral sensitization, however, remains elusive. While it has been shown that neurotrophic factors can influence the behavioral, structural and biochemical phenomena related to psychostimulant-induced neuronal plasticity, it is unclear which neurotrophic factors are important physiologically and which have purely pharmacological effects. In either case, examining the role of neurotrophic factors in behavioral sensitization may enhance our understanding of the mechanisms underlying the development of paranoid psychosis and drug craving and lead to the development of novel pharmacological treatments for these disorders. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 2 | Schizophr. Res. 2001 Apr 49: 65-71 |
| PMID | 11343865 |
| Title | Association study of schizophrenia with polymorphisms at six candidate genes. |
| Abstract | Clinical studies have shown that there is a genetic contribution to the pathogenesis of schizophrenia. The molecular mechanisms of effective antipsychotic drugs and recent advances in neural development suggest that several dopamine receptor, serotonin receptor and neurotrophic factor genes might be involved in the disorder. In this study, we assessed the associations between schizophrenia and polymorphisms in the D2 and D3 dopamine receptor (DRD2, DRD3), the serotonin 2A receptor (5HTR2A), the brain-derived neurotrophic factor (BDNF), the ciliary neurotrophic factor (CNTF) and the neurotrophin-3 (NT-3) genes. Our results suggest that the polymorphisms at the DRD3, 5HTR2A, CNTF and BDNF gene loci are unlikely to make our sample more genetically susceptible to schizophrenia. However, we found significant differences in microsatellite allele frequencies between schizophrenic and control groups for DRD2 in the whole sample and for DRD2 and NT-3 only in women. Therefore, clinical differences in the presentation of schizophrenia between gender might be related to genetic factors. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 3 | Schizophr. Res. 2001 Apr 49: 65-71 |
| PMID | 11343865 |
| Title | Association study of schizophrenia with polymorphisms at six candidate genes. |
| Abstract | Clinical studies have shown that there is a genetic contribution to the pathogenesis of schizophrenia. The molecular mechanisms of effective antipsychotic drugs and recent advances in neural development suggest that several dopamine receptor, serotonin receptor and neurotrophic factor genes might be involved in the disorder. In this study, we assessed the associations between schizophrenia and polymorphisms in the D2 and D3 dopamine receptor (DRD2, DRD3), the serotonin 2A receptor (5HTR2A), the brain-derived neurotrophic factor (BDNF), the ciliary neurotrophic factor (CNTF) and the neurotrophin-3 (NT-3) genes. Our results suggest that the polymorphisms at the DRD3, 5HTR2A, CNTF and BDNF gene loci are unlikely to make our sample more genetically susceptible to schizophrenia. However, we found significant differences in microsatellite allele frequencies between schizophrenic and control groups for DRD2 in the whole sample and for DRD2 and NT-3 only in women. Therefore, clinical differences in the presentation of schizophrenia between gender might be related to genetic factors. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 4 | Schizophr. Res. 2004 Dec 71: 353-60 |
| PMID | 15474906 |
| Title | Meta-analyses of the association between genetic polymorphisms of neurotrophic factors and schizophrenia. |
| Abstract | Based on the neurodevelopmental hypothesis of schizophrenia, neurotrophic factors (NTFs) may be involved in its pathogenesis. Previous association studies between schizophrenia and neurotrophic factors have shown inconsistent results, which might be due to the heterogeneity and small sample size of the studies. To reach a conclusive understanding of the association, we used a meta-analytic method to study the association of schizophrenia with the polymorphisms in two candidate genes, ciliary neurotrophic factor (CNTF) and neurotrophin 3 (NT3). In our study, two meta-analyses were performed. One included eight studies examining the association of schizophrenia with the A3 allele in a dinucleotide repeat polymorphism of the NT3 gene promoter (N=1938). The other was employed in nine studies examining the association with a null mutation of the CNTF gene (N=2393). Neither of these analyses provided evidence for association. However, our sub-analyses showed a trend of association between the NT3 polymorphism and schizophrenics in Japanese, as well as an association between the CNTF null mutation and schizophrenics without psychiatric family history. These results suggested that the variations at the NT3 and the CNTF genes do not influence the schizophrenia risk, but a role in the susceptibility of subgroups of the patients cannot be excluded. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 5 | Schizophr. Res. 2004 Dec 71: 353-60 |
| PMID | 15474906 |
| Title | Meta-analyses of the association between genetic polymorphisms of neurotrophic factors and schizophrenia. |
| Abstract | Based on the neurodevelopmental hypothesis of schizophrenia, neurotrophic factors (NTFs) may be involved in its pathogenesis. Previous association studies between schizophrenia and neurotrophic factors have shown inconsistent results, which might be due to the heterogeneity and small sample size of the studies. To reach a conclusive understanding of the association, we used a meta-analytic method to study the association of schizophrenia with the polymorphisms in two candidate genes, ciliary neurotrophic factor (CNTF) and neurotrophin 3 (NT3). In our study, two meta-analyses were performed. One included eight studies examining the association of schizophrenia with the A3 allele in a dinucleotide repeat polymorphism of the NT3 gene promoter (N=1938). The other was employed in nine studies examining the association with a null mutation of the CNTF gene (N=2393). Neither of these analyses provided evidence for association. However, our sub-analyses showed a trend of association between the NT3 polymorphism and schizophrenics in Japanese, as well as an association between the CNTF null mutation and schizophrenics without psychiatric family history. These results suggested that the variations at the NT3 and the CNTF genes do not influence the schizophrenia risk, but a role in the susceptibility of subgroups of the patients cannot be excluded. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 6 | Psychiatr. Genet. 2006 Oct 16: 217-9 |
| PMID | 16969278 |
| Title | No association between the CNTF null mutation and schizophrenia or personality. |
| Abstract | The ciliary neurotrophic factor (CNTF) is a neurotrophic cytokine that plays a critical role in neurodevelopment. On the basis of neurodevelopmental hypothesis, the CNTF gene has been a candidate locus for schizophrenia. Several studies have investigated the association between the null mutation of the gene and schizophrenia, however, with inconsistent results. In the present study, we investigated the association in 222 Japanese patients with schizophrenia and 237 controls. The association between the mutation and personality traits was also studied, to investigate the effect of the mutation in participants from the general population. As a result, no association was observed between the mutation and schizophrenia nor personality traits, evaluated by using the Revised NEO Personality Inventory scores. The present study did not provide evidence for the association between the CNTF gene and schizophrenia or personality traits in the Japanese population. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 7 | Pharmacogenomics 2008 Mar 9: 289-301 |
| PMID | 18303965 |
| Title | Effect of a ciliary neurotrophic factor polymorphism on schizophrenia symptom improvement in an iloperidone clinical trial. |
| Abstract | Presence of the null FS63TER allele of the rs1800169 polymorphism in the gene encoding the ciliary neurotrophic factor (CNTF) may increase the risk of schizophrenia. This study prospectively evaluated the CNTF rs1800169 genotype (G/G vs non-G/G) effects on response to iloperidone. Iloperidone 24 mg/day was evaluated in a study of patients with schizophrenia. Efficacy measurements included Positive and Negative Syndrome Scale total (PANSS-T), Brief Psychiatric Rating Scale (BPRS) and Clinical, Global, Impression (CGI) scores. The step-down primary end point was the difference in PANSS-T scores based on CNTF rs1800169 G/G genotype. This study genotyped 417 patients (279 iloperidone and 138 placebo) for the rs1800169 polymorphism. Iloperidone significantly improved PANSS-T, PANSS positive subscale (PANSS-P), PANSS negative subscale (PANSS-N), BPRS, Clinical Global Impression of Change (CGI-C) and Clinical Global Impression of Severity (CGI-S) scores versus placebo. G/G versus non-G/G patients had greater improvement with iloperidone versus placebo in PANSS, BPRS and CGI scores. The relative treatment benefit of iloperidone compared with placebo in patients with schizophrenia is enhanced in patients homozygous G/G for the rs1800169 polymorphism. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |