513I schemic stroke is one of the leading causes of death and disability in the world, resulting from the disruption of blood supply to the brain. Intervention requires the restoration of blood flow, which can lead to reperfusion injury. Oxidative stress is thought to be the primary event during this process 1 because reperfusion stimulates an overproduction of reactive oxygen species (ROS), such as hydrogen peroxide (H 2 O 2 ), which leads to the oxidation of proteins, lipids, and DNA and can induce cell proliferation, growth arrest, apoptosis, and necrosis.2 Meanwhile, the dysfunction of superoxide dismutase (SOD) and glutathione peroxidase can compromise endogenous antioxidant defense mechanisms and further exacerbate oxidative stress and ischemic/reperfusion (I/R) injury.3,4 Nuclear factor erythroid 2-related factor (Nrf)2 activates the transcription of antioxidant stress genes whose products act concertedly to remove ROS through sequential enzymatic reactions. 5 Studies have uncovered the potential for Nrf2-mediated transcription to protect from neurodegeneration resulting from mechanisms involving oxidative stress. For this reason, Nrf2 is considered a valuable therapeutic target for free radical damage in brain after ischemia and reperfusion.MicroRNAs (miRs) are small (≈22 nt), noncoding, singlestranded RNA molecules that regulate gene expression at the posttranscriptional level by inhibiting translation or by cleaving RNA transcripts in a sequence-specific manner.6 MiR-424 is a tumor marker that is involved in cancer cell proliferation, Background and Purpose-We previously showed that the microRNA miR-424 protects against permanent cerebral ischemic injury in mice by suppressing microglia activation. This study investigated the role of miR-424 in transient cerebral ischemia in mice with a focus on oxidative stress-induced neuronal injury. Methods-Transient cerebral ischemia was induced in C57/BL6 mice by middle cerebral artery occlusion for 1 hour followed by reperfusion (ischemia/reperfusion). The miR-424 level in the peri-infarct cortex was quantified. Mice were also administered miR-424 angomir by intracerebroventricular injection. Cerebral infarct volume, neuronal apoptosis, and levels of oxidative stress markers and antioxidants were evaluated. In an in vitro experiment, primary cortical neurons were exposed to H 2 O 2 and treated with miR-424 angomir, nuclear factor erythroid 2-related factor 2 siRNA, and superoxide dismutase (SOD) inhibitor; cell activity, lactate dehydrogenase release, malondialdehyde level, and manganese (Mn)SOD activity were then evaluated. Results-MiR-424 levels in the peri-infarct cortex increased at 1 and 4 hours then decreased 24 hours after reperfusion.Treatment with miR-424 decreased infarct volume and inhibited neuronal apoptosis after ischemia/reperfusion, reduced reactive oxygen species and malondialdehyde levels in the cortex, and increased the expression and activation of MnSOD as well as the expression of extracellular SOD and the redox-sensitive transcription fact...

Postmortem studies have documented abnormalities in the dorsolateral prefrontal cortex (dlPFC) in depressed subjects. In this study we used magnetic resonance imaging to test for dlPFC volume differences between older depressed and non-depressed individuals. Eighty-eight subjects meeting DSM IV criteria for major depressive disorder and thirty-five control subjects completed clinical evaluations and cranial 3T magnetic resonance imaging. After tissue types were identified using an automated segmentation process, the dlPFC was measured in both hemispheres using manual delineation based on anatomical landmarks. Depressed subjects had significantly lower gray matter in left and right dorsolateral prefrontal cortex (standardized to cerebral parenchyma) after controlling for age and sex. Our study confirmed the reduction of dorsolateral prefrontal cortex in elderly depressed subjects, especially in the gray matter. These regional abnormalities may be associated with psychopathological changes in late-life depression.

Group music therapy is an economical and easily implemented method of improving depression and psychiatric symptoms in patients with schizophrenia.

The association between the dopamine D3 receptor (DRD3) ser9gly genetic polymorphism and tardive dyskinesia (TD), a serious adverse motor disorder after long-term antipsychotic treatment, has been studied extensively in recent years. However, the existence of inconsistent reports makes the role of the DRD3 ser9gly polymorphism in TD development questionable. In rodent studies, the DRD3 expression could be controlled by the brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family. In this study, we examined the association between the DRD3 ser9gly and BDNF val66met genetic polymorphisms and TD occurrence in 216 schizophrenic patients (TD/non-TD = 102/114). In addition, we also studied the effects of the DRD3 ser9gly and BDNF val66met genotypes and their gene-gene interaction on the clinical expression of TD in these TD patients. We found that the TD patients who were heterozygous for the BDNF genotypes had significantly higher abnormal involuntary movement scale (AIMS) orofacial scores (corrected p = 0.021, Bonferroni correction), and a trend of higher AIMS total and limb-trunk scores than the combined homozygous analogs. The correlation between the DRD3 ser9gly genotypes and its interaction with the BDNF val66met polymorphism, and the three classes of AIMS scores were not statistically significant. Furthermore, neither the DRD3 nor the BDNF genotypes and alleles were demonstrated to be associated with TD occurrence. We concluded that the BDNF val66met genetic polymorphism may exert its effect on the clinically phenotypic variability after TD has occurred. Further replication studies with larger sample size and stringent definition for TD is necessary.

Typical antipsychotic treatment had been postulated to be a risk factor for the susceptibility to tardive dyskinesia (TD). The cytochrome P-450 debrisoquine/sparteine hydroxylase (CYP2D6) metabolizes a majority of antipsychotics and exhibits various phenotypes on enzymatic activities from poor metabolizers to ultrarapid metabolizers. The various phenotypes are encoded by polymorphic genetic variants on the CYP2D6 gene. Although several studies had explored the association between the CYP2D6*10 C188T polymorphism, which encodes the phenotype intermediate metabolizers, and TD in Orientals, the findings were inconclusive. In the present study, we examined the relationship between the CYP2D6*10 C188T polymorphism and the TD occurrence in 216 Chinese schizophrenic patients (113 patients with TD and 103 patients without TD) and explored the correlation between the TD severity assessed by the Abnormal Involuntary Movement Scale (AIMS) and each C188T genotype in the 113 TD patients. Using logistic regression analysis, we found a modest association (p = 0.045) between TD and C188T genotypes. This positive finding was only observed in male patients (p = 0.001), but not in females. Our findings also support the correlation between AIMS scores and C188T polymorphism within the TD group after adjusting for confounding effects with the multiple regression analysis (p = 0.033). We concluded that the CYP2D6*10 C188T polymorphism may be associated with the susceptibility to the occurrence of TD induced by typical antipsychotics, especially in male patients, and may also be correlated with AIMS scores in TD patients.

ObjectiveThe therapeutic effect of methylphenidate (MPH) in treating attention-deficit/hyperactivity disorder (ADHD) has been related to the alpha-2A adrenergic receptor (ADRA2A) gene -1291C/G single nucleotide polymorphism (SNP). We investigated the effect of MPH in treating Taiwanese children and adolescent with ADHD and its relation to the ADRA2A gene -1291C/G SNP. MethodsThe subjects with DSM-IV ADHD diagnosis underwent a titration period to find out the dose of MPH for maintenance treatment. After 4 weeks maintenance treatment, the effect of MPH was evaluated by the Swanson, Nolan and Pelham version IV total scores. The subjects with more than 25% score reduction were referred to responders and those with ≥50% improvement were considered as better responders. The -1291C/G variant of the ADRA2A gene was identified by DNA sequencing and what relevance it has to the MPH response was examined by binary logistic regression analysis. ResultsOf the 59 subjects, 44 (74.6%) were responsive to MPH treatment and the responsiveness was not shown to be associated with the ADRA2A gene -1291C/G SNP. As the responsive subjects were categorized as moderate responders and better responders and subjected to statistical analysis, the GG homozygotes showed a greater chance to have a better response to MPH treatment than CC homozygotes (p=0.02), with an odds ratio of 32.14 (95% CI=1.64–627.80). ConclusionThe ADRA2A gene -1291C/G SNP is associated with the efficacy of MPH for the treatment of ADHD in Taiwanese children and adolescents. The responsive subjects bearing homozygous -1291G allele are more likely to have a better response to MPH treatment.

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Tardive dyskinesia (TD) is an involuntary movement disorder induced by long-term antipsychotic treatments. Estrogen is suggested to modulate dopamine receptors in the central nervous system and may decrease the incidence and/or relieve the symptoms of TD. In this study, 118 schizophrenia patients with antipsychotic-induced TD and 128 sex- and age-matched non-TD schizophrenia patients were recruited. All patients were assessed by the Abnormal Involuntary Movement Scale and genotyped for the polymorphisms of estrogen receptor-α gene (ESR 1). There was a marginal association of the genotypes determined by Pvu II between TD and non-TD patients (p = 0.057), but not of the genotypes determined by Xba I (p = 0.896). However, further studies on other polymorphisms of ESR 1 or other estrogen receptors are necessary to clarify the role of estrogen in the pathogenesis of TD.