Cognitive Impairments in Clinically Stable Late-Life Depression : Relationship to Cardiovascular Risk : A Pilot Study

OBJECTIVE: The purpose of this study was to test the hypothesis that cardiovascular risk is associated with cognitive impairments in clinically stable late-life depression. METHODS: A total of 59 clinically stable late-life depression patients over age 60 were enrolled in a cross-sectional study. Evaluation tools used in this study include Hamilton Rating Scale for Depression, Geriatric Depression Scale, State-Trait Anxiety Inventory, the Framingham general cardiovascular disease risk profile and the cognitive function battery designed for this study. Correlation analysis, analysis of variance and analysis of covariance were performed. RESULTS: Patients with higher cardiovascular risk performed significantly poorer in the domains of executive function and short-term or long-term memory. In models adjusted for age, sex, education, 10% higher cardiovascular risk was associated with poorer executive function. CONCLUSION: Our findings suggested that cardiovascular risk could be a significant factor associated with poor executive function in clinically stable late-life depression and the management which is necessary as a component of treatment planning. This pilot study provided good prospects for future studies to document this relationship on larger samples.

The Relationship among Psychopathology, Cognitive Function, Insight and Quality of Life in Elderly Patients with Chronic Schizophrenia

OBJECTIVE: The aim of this study was to investigate the association with psychopathology, cognitive function, insight and quality of life (QOL) in elderly patients with chronic schizophrenia over age 55. METHODS: 103 schizophrenic patients over age 55 with illness duration over 10 years, are enrolled in a cross-sectional study. The subjects were assessed by the Korean version of 4th Revision of Schizophrenia Quality of Life Scale, Korean Version of Scales to Assessment Unawareness of Mental Disorder, Positive and Negative Syndrome Scale (PANSS) and the cognitive function battery designed for this study. Multiple regression stepwise selection models were executed to identify the relations among variables, and the contributing factors to QOL. RESULTS: Among schizophrenic patients with lower illness-severity with PANSS total score below 75, higher PANSS positive subscale score and lower number of hospitalization were related to lower QOL. Among patients with higher illness-severity with PANSS total score of 75 and over, higher PANSS general psychopathology subscale score, better intelligence, better delayed recall function, worse attention, better awareness of medication effect and later onset were related to lower QOL. CONCLUSION: Results of our study suggest that improvement in positive symptom and general psychopathology could increase the QOL in elderly patients with chronic schizophrenia over age 55. And the management which could improve attention, awareness of need for medication would attribute the QOL.

Efficacy and Tolerability of Aripiprazole: A 26-Week Switching Study from Oral Antipsychotics

OBJECTIVE: To determine if the maintenance effectiveness and tolerability of aripiprazole demonstrated in a 12-week study were maintained in an extension phase (up to 26 weeks). METHODS: This study was the extension of our switching study from other antipsychotics to aripiprazole in symptomatically stable patients with schizophrenia or schizoaffective disorder. All the patients were randomly assigned to the aripiprazole group or the non-aripiprazole group. The effectiveness analysis consisted of the comparison of the upper bound of the 95% confidence interval (CI) of the mean Clinical Global Impression-Improvement (CGI-I) score to 4 (no change) at the end of the study. RESULTS: At the baseline, the aripiprazole group (n=135) and the non-aripiprazole group (n=31) were comparable with respect to their mean ages, gender distribution, baseline Positive and Negative Syndrome Scale scores, and Clinical Global Impression-Severity (CGI-S) scores. The study showed that the mean CGI-I score was 2.92 (95% CI: 2.72-3.12) in the aripiprazole group and 2.81 (95% CI: 2.35-3.26) in the non-aripiprazole group at 26 weeks. In the aripiprazole group, the remission rates at 12 and 26 weeks were 74.8% and 72.6%, respectively, and 80.2% of the patients with remission at 12 weeks maintained their remission state until the end of the study. About one-fourth of the patients in the aripiprazole group reported one or more spontaneous treatment-emergent adverse events, such as insomnia, headache, and nausea. CONCLUSION: This study suggested that most clinically stable outpatients with schizophrenia maintain their remission states after being switched to aripiprazole, without serious symptom aggravation and adverse events over a course of 26 weeks.

Microarray Analysis of Gene Expression in Rat Glioma after Ethanol Treatment

Objetives: Identification of target genes for ethanol in neurons is important for understanding its molecular and cellular mechanism of action and the neuropathological changes seen in alcoholics. The purpose of this study is to identify of altered gene expression after acute treatmet of ethanol in rat gliom cells. METHODS: We used high density cDNA microarray chip to measure the expression patterns of multiple genes in cultured rat glioma cells. DNA microarrays allow for the simultaneous measurement of the expression of several hundreds of genes. RESULTS: After comparing hybridized signals between control and ethanol treated groups, we found that treatment with ethanol increased the expression of 15 genes and decreased the expression of 12 genes. Upregulated genes included Orthodenticle(Drosophila) homolog 1, procollagen type II, adenosine A2a receptor, GATA-bindning protein 2. Downregulated genes included diacylglycerol kinase beta, PRKC, Protein phosphatase 1, clathrin-associated protein 17, nucleoporin p58, proteasome. CONCLUSION: The gene changes noted were those related to the regulation of transcription, signal transduction, second messenger systems. modulation of ischemic brain injury, and neurodengeneration.Although some of the genes were previously known to be ethanol responsive, we have for the most part identified novel genes involved in the brain response to ethanol.

Comparison between Alcohol Dependence and Alzheimer Disease in the Elderly Patients using the Cognitive Assessment Reference Diagnoses System

BACKGROUND: Alcohol dependence and Alzheimer's disease induce cognitive dysfunction in common. However, the cognitive dysfunction from alcohol dementia can be improved with appropriate treatment while that from Alzhimer's disease is usually irreversible and progressive. Nevertheless, the discrete diagnosis for the cause is delicate or sometimes impossible in those patients showing both characteristics of alcohol dementia and Alzhimer's disease. Thus, we investigated the feasibility of the computerized comprehensive neuropsychological test, Cognitive Assessment and Reference Diagnoses System(CARDS), to differentiate the diagnoses between alcohol dementia and Alzhiemr's disease in their early stages. METHODS:32 elderly subjects with cognitive dysfunction were recruited. They are divided by two groups; 16 subjects with alcohol dependence and 16 subjects without alcohol dependence(as early Alzhiemr's disease) We assessed the cognitive dysfunctions of each group using CARDS. The subscales of the CARDS include; (1) Amnesia, (2) Aphasia, (3) Apraxia, (4) Dysexecution, (5) Attention/Calculation. RESULTS: Alcohol dependence group showed lower mean score in amnesia subscale, but showed higher mean scores in apraxia and dysexcution subscales than early Alzheimer group. And both groups didn't show significant differences of mean scores in agonisa, aphagia, and attention/calculation subscale. CONCLUSION: In summary, this study shows that the elderly patients with alcohol dependence have cognitive deficits mainly in the amnesia domain of CARDS assessment, whereas early Alzhiemr's disease patients show equal or worse cognitive function in other domains except amnesia. Thus, we suggest that CARDS will be helpful to differentiate alcoholic dementia and Alzhiemr's disease in their early stages.

Gene Expression Profiling of SH-SY5Y Human Neuroblastoma Cells Treated with Ginsenoside Rg1 and Rb1

OBJECTIVES: The ginsenoside Rg1 and Rb1, the major components of ginseng saponin, have neurotrophic and neuroprotective effects including promotion of neuronal survival and proliferation, facilitation of learning and memory, and protection from ischemic injury and apoptosis. In this study, to investigate the molecular basis of the effects of ginsenoside on neuron, we analyzed gene expression profiling of SH-SY5Y human neuroblastoma cells treated with ginsenoside Rg1 or Rb1. METHODS: SH-SY5Y cells were cultured and treated in triplicate with ginsenoside Rg1 or Rb1(80micrometer, 40micrometer, 20micrometer). The proliferation rates of SH-SY5Y cells were determined by MTT assay and microscopic examination. We used a high density cDNA microarray chip that contained 8K human genes to analyze the gene expression profiles in SH-SY5Y cells. We analyzed using the Significance Analysis of Microarray(SAM) method for identifying genes on a microarray with statistically significant changes in expression. RESULTS: Treatment of SH-SY5Y cells with 80microliter ginsenoside Rg1 or Rb1 for 36h showed maximal proliferation compared with other concentrations or control. The results of the microarray experiment yielded 96 genes were upregulated(> or =3 fold) in Rg1 treated cells and 40 genes were up-regulated(> or =2 fold) in Rb1 treated cells. Treatment with ginsenoside Rg1 for 36h induced the expression of some genes associated with protein biosynthesis, regulation of transcription or translation, cell proliferation and growth, neurogenesis and differentiation, regulation of cell cycle, energy transport and others. Genes associated with neurogenesis and neuronal differentiation such as SCG10 and MLP increased in ginsenoside Rg1 treated cells, but such changes did not occur in Rb1- group. CONCLUSION: Our data provide novel insights into the gene mechanisms involved in possible role for ginsenoside Rg1 or Rb1 in mediating neuronal proliferation or cell viability, which can elicit distinct patterns of gene expression in neuronal cell line. Ginsenoside Rg1 have more broad and strong effects than ginsenoside Rb1 in gene expression and related cellular physiology. In addition, we suggest that SCG10 gene, which is known to be expressed in neuronal differentiation during development and neuronal regeneration during adulthood, may have a role in enhancement of activity dependent synaptic plasticity or cytoskeletal regulation following treatment of ginsenoside Rg1. Further, ginsenoside Rg1 may have a possible role in regeneration of injured neuron, promotion of memory, and prevention from aging or neuronal degeneration.

The Influences of Risperidone and Clozapine on Body Weight and Glucose Level in Patients with Chronic Schizophrenia: Comparison Study with Haloperidol

OBJECT: The goal of this study was to examine the changes in body weight and glucose levels of the patients treated with risperidone, clozapine or haloperidol in order to compare the effect of risperidone or clozapine with that of haloperidol. METHODS: For nine months(January to September, 2003), a prospective study was performed in 60 patients with chronic schizophrenia who were in Seoul National Hospital. Two-week period was required for a drug wash-out. The patients were randomly assigned to risperidone, clozapine and haloperidol groups. They were given risperidone(n=20), clozapine(n=20) and haloperidol(n=20), respectively, everyday for 12 weeks. To examine the effects of these drugs on body weight and fasting glucose levels, we measured body weight and glucose levels of all the patients first without the drug treatment and at each end of 4, 8, and 12-week periods with the treatment. And we examined the differences among three groups in the changes of body weight and fasting glucose levels. RESULTS: There were no significant differences in the changes of the body weight and fasting glucose levels between the atypical antipsychotics(risperidone or clozapine) and the typical antipsychotics(haloperidol). CONCLUSION: The study in the patients with chronic schizophrenia suggests that risperidone or clozapine do not cause any additional effects on body weight or glucose levels compared to haloperidol.

The Effects of Venlafaxine on Neurite Growth of PC12 Cells

OBJECTIVES: The purpose of this study is to examine the effects of venlafaxine, one of novel antidepressant drugs, on neurite growth in PC12 cells. METHODS: PC12 cells were cultured with NGF for eight days. Then different concentrations(0micrometer, 1micrometer, 5micrometer) of venlafaxine were mixed with cultured PC12 cells. After 24 hours and 48 hours of culture, we compared the effects of venlafaxine on the total length of neurites of cultured PC12 cells between no venlafaxine treated group(0micrometer) and venlafaxine treated groups(1micrometer and 5micrometer). Additionally, we studied the concentration-dependent effect of venlafaxine on differentiation in PC12 cells. RESULTS: Experimental results showed that 1) the mean length of neurites in 1micrometer and 5micrometer venlafaxine treated group was more increased than no venlafaxine treated group(p=0.002). 2) the length of neurite in 5micrometer venlafaxine treated group was more elongated than 1micrometer venlafaxine treated group(p=0.046). 3) the length of neurite in 6micrometer venlafaxine treated group was more elongated than all the other concentrations in our experiment. Above 6micrometer, the length of neurite was shortened in inverse proportion to the concentration of venlafaxine. CONCLUSIONS: This results suggest that venlafaxine, one of novel antidepressant drugs, promotes the differentiation of neuron. This study is believed to be a first step toward understanding the molecular and cellular mechanisms of antidepressant treatment.

The Mechanisms of Atypical Antipsychotics-Induced Weight Gain and Related Pharmacogenetics

The use of atypical antipsychotics is limited by occurrence of adverse reactions such as weight gain, despite of their benefits. This article provides a comprehensive review and discussion of the most significant findings regarding obesity-related pathways and integrates these with the known mechanism of atypical antipsychotic action. The focus of this article is primarily on the genetics of obesity related pathways that may be disrupted by atypical antipsychotics. This review also discussed weight gain, hyperglycemia or occurrence of diabetes while being treated with atypical antipsychotics from the point of view of pharmacogenetics. Pharmacogenetic research seeks to uncover genetic factors that will help clinicians identify the best treatment strategies for their patients. It will aid clinically in the prediction of response and side effects, such as antipsychotic-induced weight gain, and minimize the current "trial and error" approach to prescribing in the near future. This article also presents the genetics of both central and peripheral pathways putatively involved in antipsychotic-induced weight gain while providing a comprehensive review of the obesity literature. This article also review obesity related candidate molecules which may be disrupted during atypical antipsychotic drug treatment.