ABSTRACT
Electroconvulsive therapy (ECT) is one of the most effective treatments used in psychiatry to date. The mechanisms of ECT action, however, are the least understood and still unclear. As a tool to elucidate the mechanisms of action of ECT, we employed proteomic analysis based on the identification of differentially expressed proteins after exposure to repeated ECT in rat brains. The expression of proteins was visualized by silver stain after two-dimensional gel electrophoresis. Of 24 differentially expressed protein spots (p<0.05 by Student t-test), six different proteins from 7 spots were identified by matrix-assisted laser desorption/ionization time-of flight (MALDI-TOF)/mass spectrometry. Among the identified proteins, there were five dominantly expressed proteins in the ECT-treated rat brain tissues (p<0.05); S100 protein beta chain, 14-3-3 protein zeta/delta, similar to ubiquitin-like 1 (sentrin) activating enzyme subunit 1, suppressor of G2 allele of SKP1 homolog, and phosphatidylinositol transfer protein alpha. The expression of only one protein, ACY1 protein, was repressed (p<0.05). These findings likely serve for a better understanding of mechanisms involved in the therapeutic effects of ECT.
Subject(s)
Animals , Rats , Brain/metabolism , Electroconvulsive Therapy , Electrophoresis, Gel, Two-Dimensional , Proteome/metabolism , Proteomics/methods , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Up-RegulationABSTRACT
OBJECTIVE: Delirium is defined as an alteration in mental status characterized by brief disturbances in consciousness and attention, cognition, and perception that tend to fluctuate during the course of the day. Traditionally, haloperidol has been used to treat agitation as it may occur in delirium. However, atypical antipsychotics are increasingly used to treat delirium itself. A comparative study was undertaken to compare the clinical efficacy of haloperidol and aripiprazole for the treatment of delirium. METHODS: Forty patients (20 patients assigned to haloperidol and 20 to aripiprazole) diagnosed with delirium by DSM IV-TR were recruited and randomly assigned to receive a flexible-dose regimen of haloperidol or aripiprazole over 7 days. The severity of delirium was assessed by using the Delirium Rating Scale-Revised-98 scores (DRS-R-98). RESULTS: DRS-R-98 severity scores for each group decreased significantly over the study period (p<0.01), but no statistically significant difference was detected between the two groups (p=0.607). CONCLUSION: These data show no statistically significant difference in efficacy between haloperidol and aripiprazole in the treatment of delirium. Since haloperidol has great potential for causing extrapyramidal symptoms(EPS), aripiprazole, a medication with known low side effects, may be an effective alternative agent in the treatment of delirium.
Subject(s)
Humans , Antipsychotic Agents , Cognition , Consciousness , Delirium , Dihydroergotamine , Haloperidol , AripiprazoleABSTRACT
OBJECTIVES: We investigated the association of SNP A and P1763 polymorphisms on dystrobrevin binding protein 1(DTNBP1) gene with smooth pursuit eye movement(SPEM) abnormality in Korean schizophrenic patients. METHODS: We measured SPEM function in 217 Korean schizophrenics(male 116, female 101) and divided them into two groups, one is a good SPEM function group and the other is a poor SPEM function group. We then analyzed SNP A polymorphism and P1763 polymorphism on DTNBP1 gene from their DNAs extracted from their blood. We compared the differences of genotype and allele distributions of the two polymorphisms on DTNBP1 gene between the two groups. RESULTS: The Ln S/N ratio(mean+/-SD) of the good SPEM function group was 4.39+/-0.33 and the ratio of poor SPEM function group was 3.17+/-0.71. There were no statistically significant differences of age and male/female ratio between the two groups. There were no significant differences of genotype or allele distributions of the SNP A polymorphism and P1763 polymorphism on DTNBP1 gene between the two schizophrenic groups divided by SPEM function. CONCLUSION: The results suggest that SNP A polymorphism and P1763 polymorphism on DTNBP1 gene might not be related to SPEM function abnormality in schizophrenia.
Subject(s)
Female , Humans , Alleles , Carrier Proteins , DNA , Genotype , Polymorphism, Genetic , Pursuit, Smooth , SchizophreniaABSTRACT
OBJECTIVE: We investigated the association of P1635 and P1655 polymorphisms on dystrobrevin binding protein 1 (DTNBP1) gene with smooth pursuit eye movement (SPEM) abnormality in Korean schizophrenia patients. METHODS: We measured SPEM function in 216 Korean schizophrenia patients (male 116, female 100) and divided them into two groups, one is a good SPEM function group and the other is a poor SPEM function group. We then analyzed P1635 polymorphism and P1655 polymorphism on DTNBP1 gene from their DNAs extracted from their blood. We compared the differences of genotype and allele distributions of the two polymorphisms on DTNBP1 gene between the two groups. RESULTS: The Ln S/N ratio (mean+/-sd) of the good SPEM function group was 4.39+/-0.33 and the ratio of poor SPEM function group was 3.18+/-0.71. There were no statistically significant differences of age and male/female ratio between the two groups. There were no significant differences of genotype or allele distributions of the P1635 polymorphism and P1655 polymorphism on DTNBP1 gene between the two schizophrenia groups divided by SPEM function. CONCLUSION: The results suggest that P1635 polymorphism and P1655 polymorphism on DTNBP1 gene might not be related to SPEM function abnormality in schizophrenia.
Subject(s)
Female , Male , HumansABSTRACT
OBJECTIVES: The authors investigated the possibility of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations in plasma to be biological markers before and after the pharmacological treatment of schizophrenia. METHODS: Twenty-six patients with schizophrenia were enrolled after two week washout of neuroleptics. Baseline sampling was done after washout. Consequent samplings were done at two and four week time-points after neuroleptic treatment. The concentrations of HVA and MHPG were analysed with clinical variables, such as age, age of onset, duration of illness, period of hospitalization, and changes of clinical state. The HVA and MHPG were assayed using high pressure liquid chromatographyelectrochemical detection method. RESULTS: A significant association was observed between the age of onset and plasma HVA concentration in washout state of antipsychotics. The earlier onset group had lower plasma HVA concentration than the late onset group. A significant association was observed between the age of onset and plasma MHPG concentration in washout state of antipsychotics. The earlier onset group had lower plasma MHPG concentration than the late onset group. CONCLUSIONS: The present findings suggest that the activities of dopamine and norepinephrine are different with respect to age of onset in the neuroleptic-naive schizophrenia. Plasma HVA and MHPG concentration can be biological markers for the subgrouping of schizophrenia.
Subject(s)
Humans , Age of Onset , Antipsychotic Agents , Biomarkers , Dopamine , Homovanillic Acid , Hospitalization , Methoxyhydroxyphenylglycol , Norepinephrine , Plasma , SchizophreniaABSTRACT
The authors tried to confirm the significant changes of plasma homovanillic acid(HVA) concentration after insulin administration in comparison with those of usual diurnal variation in the same subjects. Male patients with schizophrenia taking neuroleptics were participated in a study of diurnal variation and insulin induced dopaminergic perturbation, with multiple samplings at baseline. 30minutes, 60minutes and 90minutes after insulin administration(n=18). Ten patients were sampled at baseline and 60minutes after insulin administration. There was a diurnal variation of plasma HVA concentrations, which decreased gradually from 8 am to 9 : 30 am. We confirmed that regular insulin(0.1 unit/kg) blocked the normal diurnal variations and increased plasma HVA concentrations. This pattern was not correlated with clinical variables, such as age, onset age, duration of illness and presence of family history. Schizophrenic patients were grouped by the positive and negative syndrome scale. In contrast to our previous study, the concentrations of positive and negative groups were similar at baseline. The HVA concentrations of negative group after insulin administration were higher than those of positive group without statistical significance. We have a plan modify the current insulin-HAV method. In the near future, we will try to confirm whether the modified insulin-HVA method can be used as a biological indicator for the elucidation of complex clinical manifestations of schizophrenia.
Subject(s)
Humans , Male , Age of Onset , Antipsychotic Agents , Homovanillic Acid , Insulin , Plasma , SchizophreniaABSTRACT
There is no doubt that dopamine plays a critical role in the etiopathogenesis of schizophrenia. However, there appeared some limitations in explaining the complex phenomena of schizophrenia. Recent research data suggest that dysfunction in serotonergic system may be involved Before the dopamine hypothesis of schizophrenia became established, the interest in serotonin(5-ydroxytryptamine, 5-HT) as an etiological substrate of this illness occurred. Recently the importance and extent of 5-HT's involvement in the pathophysiology and mechanism of action of antipsychotic drug is actively investigated. In recent years, therapeutic success of clozapine and risperidones has increased attention on the interaction between the 5-HT and dopamine systems in schizophrenia. This led to the serotonin-dopamine for antipsychotic. The authors review the evidence for the role of 5-HT in schizophrenia and serotonin-dopamine interaction.