Valproic Acid Regulates alpha-Synuclein Expression through JNK Pathway in Rat Primary Astrocytes

Although the role of alpha-synuclein aggregation on Parkinson's disease is relatively well known, the physiological role and the regulatory mechanism governing the expression of alpha-synuclein are unclear yet. We recently reported that alpha-synuclein is expressed and secreted from cultured astrocytes. In this study, we investigated the effect of valproic acid (VPA), which has been suggested to provide neuroprotection by increasing alpha-synuclein in neuron, on alpha-synuclein expression in rat primary astrocytes. VPA concentration-dependently increased the protein expression level of alpha-synuclein in cultured rat primary astrocytes with concomitant increase in mRNA expression level. Likewise, the level of secreted alpha-synuclein was also increased by VPA. VPA increased the phosphorylation of Erk1/2 and JNK and pretreatment of a JNK inhibitor SP600125 prevented the VPA-induced increase in alpha-synuclein. Whether the increased alpha-synuclein in astrocytes is involved in the reported neuroprotective effects of VPA awaits further investigation.

Efficacy and Safety of Olanzapine in the Treatment of Korean Patients with Schizophrenia and Schizophreniform Disorder: Open Multicenter Clinical Trial / 신경정신의학

OBJECTIVE: This multicenter clinical trial was carried out to investigate the efficacy and the safety of olanzapine for the treatment of Korean patients. METHOD: 105 patients with schizophrenia and schizophreniform disorder, visited at 10 mental or university hospitals, had received an open and non-comparative treatment with olanzapine for 8 weeks. Patients had psychotic or depressive symptoms with the severity above moderate degree or intolerable side effects to previous antipsychotics. After a wash-out period of 2-7 days, 10mg olanzapine was prescribed initially to all the patients, and then the dosage could be adjusted within the range of 5-20mg/day of olanzapine by 3-7 days. RESULTS: 90(85.7%) of 105 patients completed the 8-weeks trial and the mean modal dose of olanzapine was 16.1(+/-4.7)mg/day. At the end of the trial, 73 patients(69.5%) were classified as responder, which was defined as 40% or more improvement in BPRS(Brief Psychiatric Rating Scale) score comparing to baseline. There was a significant reduction in the scores of PANSS(Positive and Negative Syndrome Scale) and subscales including negative symptom scores and CGI. Also weekly analysis showed that the reductions in scores were kept on for the whole period of the trial. 43.8% of all the patients had depressive symptoms at the baseline and total scores of MADRS(Montgomery-sberg Depression Rating Scale) and HAM-A(Hamilton Rating Scale for Anxiety) were also reduced after the trials. Vital signs revealed no clinically significant changes but continuous weight gain was observed during the treatment with olanzapine. The scores of SAS(Simpson-Angus Scale) and AIMS(Abnormal Involuntary Movement Scale) for assessing the EPS(extrapyramidal symptoms) and tardive dyskinesia respectively were significantly decreased and only a few patients reported EPS as adverse events. Although mild and clinically non-significant elevation of ALT/SGPT was observed, most laboratory parameters including plasma prolactin level showed no significant changes during the trial. CONCLUSIONS: Although this trial had many limitations because it was a non-comparative and open study, olanzapine showed high efficacy on the positive, negative and depressive symptoms in schizophrenia and schizophreniform disorder. In addition to that, olanzapine showed a substantially favorable safety profile, such as low incidence of EPS and hyperprolactinemia.

Quality of Life and Insight in Patients with Schizophrenia / 신경정신의학

OBJECTIVES: This study was designed to evaluate differences in the quality of life(QOL) according to insight in patients with schizophrenia. The author speculated that insight might have an effect on individual's QOL, especially subjective QOL. METHOD: The study group consisted of patients with schizophrenia(N=55). Subjects were divided into two groups, patients with insight(N=22)and without insight(N=15), based on Scale of Unawareness of Mental Disorders(SUMD). All of the patients were administered the Quality of Life Interview (QOLI)by Lehman and compared in objective and subjective QOL between two groups. Additionally, they completed BDI and F scale on MMPI. RESULTS: The patients with insight showed a tendency of lower scores in total subjective QOLI scores and the safety issues compared to the patients without insight although not significant statistically. And they showed significantly less satisfaction with social relations. In objective QOL, there are no statistically significant differences between two groups. CONCLUSION: Such differences support the notion that schizophrenic patients with insight are less satisfied with their lives, especially in the aspect of interpersonal relations. It reflects the awareness of functional decline due to lifetime disability, disconnection from social relations, poor resources and supports, social stigma, and also depressive or anxiety symptoms. The authors propose that the treatment strategies for schizophrenia must include concern and support for domains of life with which patients feel themselves least satisfied, to increase effectiveness and efficacy of treatment and improve QOL.