Weiwei Sha

Association of a polymorphism in the promoter region of the serotonin 5-HT2C receptor gene with tardive dyskinesia in patients with schizophrenia.

Association of a polymorphism in the promoter region of theserotonin 5-HT2Creceptor gene with tardive dyskinesia in patients with schizophrenia

The increased activity of plasma manganese superoxide dismutase in tardive dyskinesia is unrelated to the Ala-9Val polymorphism

That tardive dyskinesia (TD) may have its origins in free-radical toxicity has stimulated investigations into one enzyme important in the control of oxidative free radicals: superoxide dismutase (SOD). The manganese-containing form of this enzyme (MnSOD) is the major superoxide scavenger in mitochondria; a weak association between a functional genetic polymorphism (Ala-9Val) in the mitochondrial targeting sequence (MTS) of this enzyme and TD has been reported in a Japanese population. We have undertaken to determine both the plasma activity of MnSOD and the association of the Ala-9Val polymorphism in a well-matched series of male Chinese schizophrenic patients with (n=42) and without (n=59) TD, and normal male controls (n=50). MnSOD activity was elevated in the TD subjects over those without TD (P<0.05) and normal controls (P<0.05), an effect that was independent of age, age at first antipsychotic treatment, drug dosage and duration of illness. A significant positive correlation between total AIMS score and MnSOD activity was also observed (P<0.0001). No significant reduction in the frequency of the Ala allele was observed in the TD group (0.14) below non-TD (0.18) or control subjects (0.17); nor was there any relationship between MnSOD activity and the polymorphism. There was no difference between the mean AIMS scores for the two genotypes (V/V and A/V) in the TD group. We conclude that while we have further evidence of a disturbance in the mechanisms regulating oxidative free radicals in TD, this effect is not under the control of the genetic polymorphism investigated here.

Effect of treatment on serum glial cell line-derived neurotrophic factor in depressed patients

Post-mortem studies have demonstrated a decreased number of glia, reduced glial density, and a decreased glia/neuron ratio in different brain areas of patients diagnosed with a major depressive disorder (MDD). Researchers have therefore suggested that neurotrophic growth factor systems might be involved in the aetiology of MDD. This study aimed to test whether glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor beta family, in serum was associated with MDD. Serum concentrations were measured in MDD patients before treatment (n=76), after 8 weeks of antidepressant treatment (n=39), and in control subjects (n=50) using a sandwich ELISA method. Serum GDNF was significantly lower in MDD patients before treatment than in control subjects (P<0.001). From baseline to remission after 8 weeks of treatment, the increase in serum GDNF was statistically significant (P<0.001). The present study suggests that lower serum GDNF might be involved in the pathophysiology of MDD and antidepressant treatment increases the GDNF in MDD.

Effect of treatment on serum glial cell line-derived neurotrophic factor in bipolar patients

OBJECTIVE Post-mortem studies have demonstrated various glial deficits in different brain areas of patients diagnosed with bipolar disorder (BD). Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor from the transforming growth factor beta family which has been implicated in the pathophysiology of BD. This study aimed to determine whether GDNF in serum was abnormal in BD, and how it responded to drug treatment of BD. METHOD Serum GDNF concentrations were measured in BD patients before treatment, after 8 weeks of drug treatment, and in control subjects using a sandwich ELISA method. RESULTS Before treatment, serum GDNF was significantly lower in BD patients during both manic (P<0.001) and depressive (P<0.001) episodes than in control subjects. From baseline to remission after 8 weeks of treatment, the increase in serum GDNF was statistically significant (P<0.001). CONCLUSIONS The present study suggests that lower GDNF levels might be involved in the pathophysiology of BD and drug treatment increases the GDNF in BD.

Electroconvulsive therapy increases glial cell-line derived neurotrophic factor (GDNF) serum levels in patients with drug-resistant depression

Electroconvulsive therapy (ECT) can be effective in patients with depression resistant to pharmacologic medication. We report that serum levels of glial cell-line derived neurotrophic factor (GDNF) were increased following ECT of patients with drug-resistant depression. When patients were sub-classified into ECT responders and non-responders, serum GDNF levels were significantly increased (58%) in responsive patients following ECT. No significant increase was seen in non-responders. These results suggest that successful ECT may be associated with elevated serum GDNF levels.

Performance on the Wisconsin card-sorting test and serum levels of glial cell line-derived neurotrophic factor in patients with major depressive disorder

Some evidence suggests that neurotrophic growth factor systems might be involved in the etiology of major depressive disorder (MDD). Glial cell line‐derived neurotrophic factor (GDNF) is a neurotrophic factor from the transforming growth factor‐β family that plays a role in the development and function of the brain. This study aimed to test whether GDNF in serum was abnormal in MDD, and whether it was related to the cognitive impairment of MDD.

Cognitive impairment in first-episode drug-naïve patients with schizophrenia: Relationships with serum concentrations of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor

Objectives: Evidence suggests that brain‐derived neurotrophic factor (BDNF) and glial cell line ‐derived neurotrophic factor (GDNF) are important in the regulation of synaptic plasticity, which plays a key role in the cognitive processes in psychiatric disorders. Our work aimed at exploring the associations between serum BDNF and GDNF levels and cognitive functions in first‐episode drug‐naïve (FEDN) patients with schizophrenia. Methods: The BDNF and GDNF levels of 58 FEDN patients and 55 age‐ and sex‐matched healthy controls were measured and test subjects were examined using several neurocognitive tests including the verbal fluency test (VFT), the trail making test (TMT), the digit span test (DST), and the Stroop test. Results: Patients performed significantly worse than controls in nearly all neurocognitive performances except the forward subscale part of the DST. BDNF levels were inversely correlated to TMT‐part B scores and positively correlated to VFT‐action in the FEDN group. GDNF levels showed a positive correlation with VFT‐action scores and a negative correlation with TMT‐part B scores of these patients. Conclusion: Current data suggests that cognitive dysfunction widely exists in the early stages of schizophrenia. BDNF and GDNF may be jointly contributed to the pathological mechanisms involved in cognitive impairment in FEDN patients with schizophrenia. HighlightsFirst‐episode drug‐naïve schizophrenia patients performed significantly worse than controls on nearly all cognitive tests.Serum concentrations of BDNF and GDNF were markedly lower in these patients compared to heatlhy controls.For the patients only, BDNF and GDNF were both related to cognitive function.

Atypical antipsychotic treatment increases glial cell line-derived neurotrophic factor serum levels in drug-free schizophrenic patients along with improvement of psychotic symptoms and therapeutic effects.

Glial cell line-derived neurotrophic factor (GDNF) plays an increasingly vital role in the pathogenesis of neuropsychiatric illnesses. Antipsychotic medications were shown to stimulate GDNF secretion from C6 glioma cells. The aims of this study were to investigate the serum concentration of GDNF, to monitor the therapeutic effect of atypical antipsychotics related to GDNF levels in drug-free schizophrenia patients, and to examine these levels in relation to psychotic symptoms. We recruited 138 drug-free schizophrenic patients and compared them with 77 matched healthy subjects. All patients were treated with atypical antipsychotic monotherapy. GDNF serum levels and psychiatric symptoms were assessed at baseline and after 2, 4, 6 and 8 weeks. GDNF levels gradually increased accompanied by a reduction in psychiatric symptoms during antipsychotic therapy. The levels of GDNF in responders were significantly increased after 8 weeks of treatment, however, no significant change was found in non-responders. Furthermore, a negative association between GDNF levels following pharmacotherapy and disease duration in schizophrenic subjects could be observed. The present study suggests that GDNF may be involved in the etiology of schizophrenia and pharmacological treatment.

Relationship of serum testosterone levels with cognitive function in chronic antipsychotic-treated male patients with schizophrenia

Some evidence suggests that testosterone might be involved in the cognitive impairments of schizophrenia. We assessed major cognitive domains and serum testosterone levels in male long‐term inpatients with schizophrenia. This study aimed to test whether testosterone in serum was abnormal in patients, and whether it was related to the cognitive impairment of schizophrenia.

Serum prolactin and smoking status in chronic antipsychotic-treated male patients with schizophrenia

We investigated the effects of smoking status on the serum prolactin levels in schizophrenia. The serum prolactin concentration was significantly higher in nonsmokers compared with smokers. Moreover, smoking was an independent predictor of prolactin concentration. These findings suggest that smoking has an impact on prolactin concentration in male schizophrenic patients.