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BACKGROUND: In an 8-week, randomized, placebo-controlled, double-blind study, an extended-release formulation of quetiapine, quetiapine XR, demonstrated efficacy and safety in Japanese patients with bipolar depression. Bipolar disorder is a chronic disease requiring continuous treatment. METHODS: This was a long-term (52-week), open-label, non-controlled extension study to evaluate the long-term safety and efficacy of quetiapine XR in Japanese patients with bipolar depression who had previously completed the initial 8-week double-blind study. Efficacy was determined by the Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Depression Scale 17-item (HAM-D17), and Clinical Global Impressions-Bipolar scale (CGI-BP). Safety evaluations included analysis of adverse events, clinical laboratory measures, vital signs, Drug-induced Extrapyramidal Symptoms Scale, Young Mania Rating Scale, and the Columbia Suicide Severity Rating Scale. RESULTS: The mean (SD) MADRS total score decreased from 30.9 (6.9) at baseline to 16.1 (10.6) at week 8, and eventually to 9.1 (8.7) at week 52. The sustained efficacy of quetiapine XR treatment was also shown using HAM-D17 total scores, CGI-BP-Severity and Change evaluations. The most common adverse events were somnolence, nasopharyngitis, and thirst. Long-term treatment with quetiapine XR caused no substantial changes in the safety profiles, including clinical laboratory parameters, and no new safety concerns were identified. CONCLUSIONS: The efficacy of quetiapine XR was sustained long-term and no new safety concerns were identified in Japanese patients with bipolar depression. TRIAL REGISTRATION: ClinicalTrials.gov Registration: NCT01725308. Date of registration; 12th November 2012 (retrospectively registered).
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Afeto/efeitos dos fármacos , Antidepressivos/administração & dosagem , Antipsicóticos/administração & dosagem , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/epidemiologia , Fumarato de Quetiapina/administração & dosagem , Adulto , Afeto/fisiologia , Transtorno Bipolar/psicologia , Preparações de Ação Retardada/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Asenapine is an atypical antipsychotic that is currently available for the treatment of schizophrenia and bipolar I disorder. Although the atypical antipsychotics clozapine and olanzapine are effective for depression and anxiety in schizophrenia, as demonstrated by animal model studies, this has not been clarified for asenapine. Therefore, we compared the effects of asenapine in the conditioned fear stress model with those of clozapine and olanzapine. METHOD: Rats were individually fear conditioned using electrical foot shock in a Skinner box. Approximately 24 h later, individual animals were returned to the same Skinner box (without electrical shock) and their freezing behaviour was observed for 5 min. Animals were treated with asenapine, clozapine, olanzapine, the 5-HT1A receptor partial agonist buspirone, or the 5-HT2C receptor antagonist SB242084 at 30 min before freezing behaviour assessment. The 5-HT1A receptor antagonist WAY100635 or the 5-HT2C receptor agonist Ro60-0175 was also used concomitantly with asenapine. The effects of asenapine, clozapine, and olanzapine on serotonin release in the rat hippocampus were also measured using in vivo microdialysis. RESULTS: Asenapine reduced freezing behaviour, while neither clozapine nor olanzapine reduced freezing behaviour. Buspirone and SB242084 also reduced freezing behaviour. The effect of asenapine in reducing freezing behaviour was not altered by the concomitant administration of WAY100635 or Ro60-0175. Both asenapine and clozapine, but not olanzapine, increased serotonin release in the rat hippocampus. CONCLUSION: Asenapine may have superior therapeutic effect on anxiety symptoms than other agents, although the underlying mechanism of its anxiolytic activity remains unknown.
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Ansiolíticos/administração & dosagem , Antipsicóticos/administração & dosagem , Ansiedade/tratamento farmacológico , Medo , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Estresse Psicológico/complicações , Aminopiridinas/administração & dosagem , Animais , Ansiedade/etiologia , Benzodiazepinas/administração & dosagem , Buspirona/administração & dosagem , Clozapina/administração & dosagem , Condicionamento Clássico , Dibenzocicloeptenos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eletrochoque , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Indóis/administração & dosagem , Masculino , Olanzapina , Ratos , Ratos Sprague-Dawley , Serotonina/metabolismo , Antagonistas da Serotonina/administração & dosagem , Agonistas do Receptor de Serotonina/administração & dosagemRESUMO
BACKGROUND: While the frequency and importance of antipsychotic switching in patients with schizophrenia, there is insufficient evidence with regard to switching strategy. Quetiapine is one of the drugs of choice for switch because of its unique receptor profile. However, there were no data on the long-term clinical and neurocognitive effect of quetiapine in patients who had responded inadequately to prior antipsychotics. The purpose of this study is to examine the long-term efficacy and tolerability of quetiapine in patients with schizophrenia who switched from other antipsychotics because of inadequate therapeutic response. We hypothesized that quetiapine would show long-term effectiveness in broad symptom dimensions including negative and neurocognitive symptoms while having good tolerability. METHODS: Twenty-nine subjects with schizophrenia who did not respond to their current monotherapy of antipsychotic or who could not tolerate the treatment were switched to quetiapine and assessed at baseline and at 3, 6, and 12 months. The outcome measures included the brief assessment of cognition in schizophrenia (BACS), the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions Scale (CGI), the Schizophrenia Quality of Life Scale Japanese version (JSQLS), the Athens Insomnia Scale (AIS), and the Drug Attitude Inventory with 30 items (DAI-30). The Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS), HbA1c, prolactin (PRL), and body weight were also evaluated. RESULTS: Statistically significant improvements were observed in all subscores of the PANSS, the GAF, and the symptoms and side effects subscale of the JSQLS, the DIEPSS, the AIS, and the PRL level, and nearly significant improvements were observed in the DAI-30. Quetiapine monotherapy was associated with significant improvement in the verbal memory test, even after controlling for the practice effect. Although quetiapine was well tolerated, three subjects dropped out because of the worsening of the psychotic symptoms and two additional subjects dropped out because of somnolence. CONCLUSION: In this open-label, single-arm study of 29 patients, quetiapine improved both the clinical symptoms and the neurocognitive impairment in chronic schizophrenia patients who failed to respond to prior antipsychotic treatment.
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Calcium-calmodulin dependent protein kinase IV (CaMKIV) is a protein kinase that has been suggested to participate in fluoxetine (FLX)-induced phosphorylation of cyclic AMP-response element binding protein (CREB). CREB is a key transcription factor in adult neurogenesis. The present study aimed at evaluating whether CaMKIV is involved in adult hippocampal neurogenesis with FLX treatment. Effects of chronic FLX on hippocampal cell proliferation, survival and phenotypes were assessed using bromodeoxyuridine (BrdU) immunohistochemistry or BrdU/neuronal nuclei (NeuN)/S100ß immunofluorescence staining in wild-type (WT) and CaMKIV knockout (KO) mice. Expression and phosphorylation of CaMKIV and CREB were assessed using RT-PCR and Western blotting. The behavioural action with FLX was assessed in the novelty suppressed feeding test (NSF), which is considered neurogenesis-dependent. CaMKIV KO mice have reduced cell proliferation, but not survival in the dentate gyrus of hippocampus with chronic treatment of FLX when compared to wild littermates. Phenotype analysis showed that most newborn cells matured into neurons. Phosphorylation of CaMKIV was up-regulated in WT mice and phosphorylation of CREB was impaired in CaMKIV KO mice after FLX treatment. The behavioural effects of FLX in NSF were similar in both types. These data suggest that CaMKIV is involved in some aspects of FLX-promoting hippocampal neurogenesis.
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Proteína Quinase Tipo 4 Dependente de Cálcio-Calmodulina/biossíntese , Fluoxetina/administração & dosagem , Hipocampo/enzimologia , Neurogênese/fisiologia , Neurônios/enzimologia , Animais , Proliferação de Células/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Resultado do TratamentoRESUMO
OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) have been widely used in the treatment of most anxiety disorders. In this study, to clarify the mechanism of the anxiolytic effect, we investigated the mechanism underlying the effect of the SSRI citalopram on rat contextual conditioned fear stress (CFS), an animal model of anxiety. METHODS: Rats individually received footshocks in a shock chamber. More than 1 day later, they were given citalopram and/or dl-p-chlorophenylalanine (PCPA), various subtype-selective serotonin (5-HT) receptor antagonists: the 5-HT1A receptor antagonist WAY 100635, the 5-HT2A receptor antagonist MDL 100907, the 5-HT2C receptor antagonist SB 242084, the 5-HT3 receptor antagonist tropisetron, the 5-HT4 receptor antagonist GR 125487, the 5-HT6 receptor antagonist SB 258585 or the 5-HT7 receptor antagonist SB 269970. After drug administration, freezing behaviour, which was used as an index of anxiety, was analysed in the same shock chamber without shocks. RESULTS: Citalopram dose dependently reduced conditioned freezing behaviour. The anxiolytic-like effect of citalopram was prevented completely by pretreatment with the 5-HT-depleting agent PCPA, but not by the 5-HT1A receptor antagonist WAY 100635. Furthermore, none of the subtype-selective 5-HT receptor antagonists significantly affected conditioned freezing or affected the anxiolytic-like effect of citalopram. CONCLUSION: The anxiolytic-like effect of citalopram in contextual CFS model depends on 5-HT availability. In addition, contextual CFS model is suggested to be completely different from conventional anxiety models in neural mechanism or manners of serotonergic involvement. However, further studies are needed to identify the pharmacological mechanisms responsible for the anxiolytic-like effect of citalopram.
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OBJECTIVE: Glycine regulates glutamatergic neurotransmission, and several papers have reported the relationship between glycine and schizophrenia. The dysbindin-1 (DTNBP1: dystrobrevin-binding protein 1) gene is related to glutamatergic neurotransmission and has been found to be a strong candidate gene for schizophrenia. In this study, we clarified the relationship between dysbindin, glutamate, and glycine with in vivo microdialysis methods. METHODS: We measured extracellular glycine and glutamate levels in the striatum of sandy (sdy) mice using in vivo microdialysis methods. Sdy mice express no dysbindin protein owing to a deletion in the dysbindin-1 gene. In addition, we measured changes in those amino acids after methamphetamine (METH) administration. RESULTS: The basal levels of extracellular glycine and glutamate in the striatum of sdy mice were elevated. These extracellular glutamate levels decreased gradually after METH administration and were not subsequently different from those of wild-type mice. CONCLUSIONS: These results suggest that dysbindin might modulate glycine and glutamate release in vivo.
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The appropriate therapeutic serum valproate level in maintenance therapy for bipolar disorder is not well known. We studied the serum valproate levels in seventeen bipolar I and twenty-four bipolar II disorder outpatients who had been treated with stable doses of valproate successfully for at least 12 months as prophylactic therapy. The trough serum valproate levels were 52.2 +/- 20.4 microg/ml in bipolar I, and 41.0 +/- 18.3 microg/ml in bipolar II disorder patients, respectively. A greater trend towards a higher trough level (p = 0.07) was indicated in the bipolar I disorder group. We speculate that these valproate levels may be an approximation to the appropriate valproate levels in maintenance therapy and that there may be a correlation between the level of valproate required for stabilization and the subtype of the bipolar disorder. However, when interpreting these findings, certain limitations to this study? Need to be taken into account as follows. The sample size was small. We could not look at a group on valproate that had relapsed and a group that had dropped out of maintenance therapy. Further studies are needed.
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Antimaníacos/sangue , Antimaníacos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Ácido Valproico/sangue , Ácido Valproico/uso terapêutico , Adulto , Idoso , Assistência Ambulatorial , Antimaníacos/efeitos adversos , Transtorno Bipolar/sangue , Transtorno Bipolar/diagnóstico , Distribuição de Qui-Quadrado , Monitoramento de Medicamentos , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Ácido Valproico/efeitos adversosRESUMO
BACKGROUND: The Patient Health Questionnaire-9 (PHQ-9), despite its excellent reliability and validity in primary care, has not been examined for administration to psychiatric patients. This study assesses the accuracy of PHQ-9 in screening for major depressive episode and in diagnosing major depressive episode in patients of a psychiatric specialty clinic. METHODS: We compared operational characteristics of PHQ-9 as a screening and diagnostic instrument to DSM-IV-TR diagnosis by a trained psychiatrist as a reference standard. The reference criteria were "current major depressive episode" or "current major depressive episode with major depressive disorder". PHQ-9 was used with two thresholds: diagnostic algorithm and summary scores (PHQ-9 ≥ 10). The optimal cut-off points of PHQ-9 summary scores were analyzed using a receiver operational characteristics (ROC) curve. RESULTS: For "current major depressive episode", PHQ-9 showed high sensitivity and high negative predictive value at both thresholds, but its specificity and positive predictive value were low. For "current major depressive episode with major depressive disorder", PHQ-9 also showed high sensitivity and high negative predictive value at both thresholds, but the positive predictive value decreased more than that for "current major depressive episode". The ROC analysis showed the optimal cut-off score of 13/14 for "current major depressive episode". CONCLUSIONS: PHQ-9 is useful for screening, but not for diagnosis of "current major depressive episode" in a psychiatric specialty clinic.
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Transtorno Depressivo Maior/diagnóstico , Escalas de Graduação Psiquiátrica , Inquéritos e Questionários , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde , Psicometria , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
In this study, quantitative reciprocal-space analyses of magnetic domain structures in magnetic artificial lattices of patterned elements were performed by means of the small-angle electron scattering (SAES) technique. Using a conventional transmission electron microscope with a LaB(6) thermal-emission electron gun, Lorentz deflection due to magnetic moments in patterned elements and Bragg diffraction due to the lattice periodicity are simultaneously recorded at an angle of the order of less than 1 10(-)(6) rad when using electron waves with high spatial coherency and large camera length. The present SAES technique together with TEM real-space imaging methods such as Lorentz microscopy will be useful in analyzing electromagnetic fields in nano-scaled materials.
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BACKGROUND: Taijin-kyofu (TK), especially the 'convinced' subtype of TK (c-TK; also known as the 'offensive' subtype of TK), is described as a Japanese culture-bound syndrome similar to social anxiety disorder (SAD). Recently, in Western countries, the symptoms of c-TK have been investigated in patients with SAD. We developed the Social Anxiety/Taijin-Kyofu Scale (SATS), a 12-item structured clinician-rated instrument designed to rate the severity of TK symptoms, and examined its reliability and validity. METHODS: The SATS was administered to 15 patients with c-TK diagnosed using the traditional Japanese TK criteria. Interviews used to score patients' symptoms were recorded on videotape. Additionally, the Clinical Global Impression-Severity Scale (CGI-S) was administered to assess convergent validity. Interrater reliability was assessed on 15 videotaped interviews; the interviews were independently rated by 10 other raters. Test-retest re-liability was assessed on 15 videotaped interviews by the same rater at an interval of more than 4 weeks. RESULTS: The SATS had high internal consistency (Cronbach's α = 0.97) and good interrater reliability (ICC = 0.88-0.93) and test-retest reliability (ICC = 0.94-0.99). The SATS total score correlated with the CGI-S scores (r = 0.77, p < 0.0001). CONCLUSION: The SATS appears to be a reliable and valid measure of the symptoms of TK.
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Ansiedade/diagnóstico , Ansiedade/etnologia , Transtornos Fóbicos/diagnóstico , Transtornos Fóbicos/etnologia , Adolescente , Adulto , Feminino , Humanos , Japão , Masculino , Escalas de Graduação Psiquiátrica , Psicometria/instrumentação , Reprodutibilidade dos TestesRESUMO
Antipsychotic drugs have been widely used in the treatment of organic, including symptomatic, mental disorders. The guidelines for the treatment of delirium suggest using atypical antipsychotic drugs for the patients with excitement. Atypical antipsychotic drugs show higher affinity for 5-HT2A receptor than D2 receptor. The extrapyramidal side effects of atypical antipsychotic drugs are less than of conventional antipsychotic drugs, so they can be used more safely in the medication for elderly patients. However, we must pay attention to the risk of hyperglycemia, diabetic ketoacidosis and sudden cardiac death. Because of off-label use, well informed consents about effectiveness and safety are necessary.
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Antipsicóticos/administração & dosagem , Idoso , Antipsicóticos/efeitos adversos , Humanos , Transtornos Mentais/tratamento farmacológicoRESUMO
The pharmacological treatment of schizophrenia now faces a turning point where we are preparing for the introduction of medications which have the mechanism of modulating glutamatergic neurotransmission, in contrast to antipsychotics which have the main mechanism of blocking and modulating D2-type dopamine receptor-mediated dopaminergic neurotransmission. In order to predict the effects of new medications modulating glutamatergic neurotransmission, we have to understand the pathophysiology of schizophrenia in the light of the dynamic time-axis. In the present review article, we have proposed a new "comprehensive progressive pathophysiology model" based on the "dopamine to glutamate hypothesis". Using this model, we distinguish the progressive pathophysiology-stage and subsequent residual-stage, to predict the effects of antipsychotics, mood stabilizers, and new glutamatergic modulators.
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Modelos Animais de Doenças , Esquizofrenia/fisiopatologia , AnimaisRESUMO
Many discussions have been made related to diagnosis of bipolar disorder in recent years. Especially, much attention has been devoted to the activation syndrome induced by antidepressants and the bipolar spectrum disorder proposed by Gahemi. Differential diagnosis between bipolar depression and monopolar depression is extremely important when planning treatment strategy, but it is difficult to differentiate between them using symptomatic information alone. Therefore, if an easily-accessible biological marker can differentiate between them, it is expected to be extremely useful in clinical practice. Several trait biological markers associated with the pathophysiology of bipolar disorder have been identified with a high evidence level. Abnormality of cellular calcium signaling is regarded as one such replicable trait marker. Especially because human platelets are easily accessible, increasingly numerous reports describe studies of intracellular calcium concentration increase induced by various agonists in patients with bipolar disorder. Summarizing previous reports, the agonist-stimulated calcium response is enhanced significantly in patients with bipolar disorder compared to normal subjects, although resting intraplatelet calcium concentration does not differ between them. Moreover, serotonin-induced calcium response in monopolar depression and the other psychiatric diseases is not significantly different from that in normal subjects, which suggests that the enhanced calcium response to serotonin is specific to bipolar disorder among various diseases. However, several problems arise in using this marker as a supplemental tool of clinical diagnosis. First, the calcium response has a fairly common distribution between bipolar depression and monopolar depression groups although the means of the responses are significantly different. Consequently, it is difficult to differentiate clearly between bipolar depression and monopolar depression merely by setting a discriminating value. Second, it is necessary to measure calcium response as soon as possible after blood collection. Third, drugs taken at the time of blood collection might affect the calcium response. Finally little evidence exists showing whether functions in peripheral tissue actually reflect brain function. Therefore, many obstacles remain to be solved before using this marker in clinical practice.
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Transtorno Bipolar/diagnóstico , Sinalização do Cálcio , Cálcio/sangue , Biomarcadores/sangue , Transtorno Bipolar/metabolismo , Plaquetas/metabolismo , Diagnóstico Diferencial , Humanos , Serotonina/metabolismoRESUMO
The amygdala is one of the crucial brain structures for conditioned fear, in which conditioned stimuli are received by the basolateral nucleus of the amygdala (BLA), inducing a fear reaction via the central nucleus of the amygdala (CeA). Whereas BLA sends glutamatergic projections into CeA, the intercalated nucleus of the amygdala (ITC) sends GABAergic projections into CeA, which is doubly regulated by BLA and ITC. In the present study, we investigated the characteristics of the neural cells activated by retrieval of conditioned fear in BLA and ITC using immunohistochemistry, in situ hybridization, and Western blot analysis of transcription factors and neural cell markers. Because most conditioned fear-induced c-Fos-positive cells in BLA were glutaminase positive and 67-kDa isomer of glutamic acid decarboxylase (GAD67) negative, these cells are speculated to be glutamatergic. Seventy-eight percent of the phosphorylated CREB (pCREB)-positive cells were glutaminase double positive and 13% of the pCREB-positive cells were GAD67 double positive, indicating that many of the conditioned fear-induced pCREB-positive cells in BLA were glutamatergic, but at least some of the pCREB-positive cells were GABAergic. These results suggested that CREB phosphorylation was increased both in glutamatergic and in GABAergic neurons, but c-Fos expression was increased mainly in glutamatergic neurons in BLA. CREB phosphorylation but not c-Fos expression in ITC was specifically increased by retrieval of conditioned fear. It is therefore speculated that ITC GABAergic neurons were activated by retrieval of conditioned fear and that transcription factors other than c-Fos were relevant to the activation.
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Tonsila do Cerebelo/metabolismo , Química Encefálica/fisiologia , Condicionamento Psicológico/fisiologia , Medo/fisiologia , Memória/fisiologia , Ácido gama-Aminobutírico/fisiologia , Tonsila do Cerebelo/citologia , Tonsila do Cerebelo/fisiologia , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Déjà vu is a common experience among the normal population. However, in individuals with temporal lobe epilepsy, it often occurs as a seizure manifestation. The specific cause of such déjà vu is not yet known. Here, we report a case of epilepsy with persistent déjà vu. The patient described the state as if he were living the same life he had lived before. Blood perfusion single-photon-emission computed tomography (SPECT) performed during the persistent déjà vu showed hyperperfusion in the left medial temporal area; discontinuation of déjà vu was accompanied by disappearance of the hyperperfused area on SPECT. Analysis with three-dimensional co-registration of SPECT and MRI revealed that the hyperperfused area during the persistent déjà vu was in the entorhinal cortex of the left temporal lobe. According to recent theories of recognition memory, malfunction of the parahippocampal area may cause déjà vu. It is also suggested that epileptic activity in the parahippocampal area, especially the entorhinal cortex, may elicit déjà vu.
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Anticonvulsivantes/efeitos adversos , Déjà Vu , Córtex Entorrinal/fisiopatologia , Transtornos da Memória/induzido quimicamente , Cisteína/análogos & derivados , Córtex Entorrinal/diagnóstico por imagem , Córtex Entorrinal/efeitos dos fármacos , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/tratamento farmacológico , Epilepsia do Lobo Temporal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Compostos de Organotecnécio , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único/métodosRESUMO
After random assignment of 20 schizophrenia patients to either an explicit or normal instruction group, the Japanese Verbal Learning Test was administered to them. Results reveal that explicit instruction group patients demonstrated more improved memory performance using semantic clustering, suggesting that explicit and direct teaching facilitates patients' learning of information.
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Transtornos da Memória/terapia , Ensino/métodos , Aprendizagem Verbal/fisiologia , Adulto , Análise de Variância , Feminino , Humanos , Japão , Masculino , Transtornos da Memória/etiologia , Testes Neuropsicológicos , Estudos Prospectivos , Esquizofrenia/complicações , Psicologia do Esquizofrênico , Adulto JovemRESUMO
OBJECTIVE: Olanzapine augmentation of fluoxetine, a selective serotonin reuptake inhibitor, is an effective augmentation therapy for treatment-resistant depression (TRD). However, studies of olanzapine augmentation of other antidepressants are few. We investigated the efficacy and safety of olanzapine augmentation of milnacipran, a serotonin-norepinephrine reuptake inhibitor, for TRD. METHODS: This study covered patients with stage 2 TRD, defined by Thase and Rush. Olanzapine was added to milnacipran, and its dosage was adjusted according to each patient. Previous treatments were continued, but no new treatments were allowed. Response was measured using Hamilton Depression Rating Scale (HAMD) and Clinical Global Impression at weeks 0, 1, 2, 3, 4, and 8. RESULTS: Eleven patients aged 53.2 ± 24.0 years received olanzapine at 5.0 ± 1.9 mg/day with milnacipran. HAMD and Clinical Global Impression scores improved significantly from baseline to endpoint. This improvement occurred in week 1. At endpoint, seven of 11 (64%) were responders on HAMD (≥ 50% reduction). Four patients (36%) discontinued the trial because of no efficacy. No severe adverse effect occurred. CONCLUSIONS: Olanzapine augmentation of milnacipran for stage 2 TRD might be effective and well tolerated. However, our study is open label and uncontrolled. Therefore, a double-blind controlled trial is necessary to confirm our results.
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Benzodiazepinas/administração & dosagem , Ciclopropanos/administração & dosagem , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/psicologia , Adolescente , Adulto , Idoso , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Resistente a Tratamento/epidemiologia , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Milnaciprano , Olanzapina , Adulto JovemRESUMO
AIM: The Japanese blood glucose monitoring guidance for patients receiving second-generation antipsychotics has been newly developed. We aimed to report a cross-sectional study using the baseline data of the Japanese monitoring guidance to find undiagnosed hyperglycemia systematically as a routine clinical practice and to quantify the frequency of glucose abnormalities in schizophrenia patients treated with second-generation antipsychotics. METHODS: Data for 537 patients with schizophrenia, who had not been diagnosed as having diabetes prior to baseline screening and started the monitoring between June 2008 and January 2009, were collected from medical records in 25 hospitals. Blood glucose (fasting or casual), hemoglobin(A1c) , serum lipids, height/weight, clinical diabetic symptoms, and family history of diabetes were assessed. Patients were classified into normal, pre-diabetic or probable diabetic type based on their values of blood glucose or hemoglobin(A1c) , and various background characteristics and serum lipid values were compared among the three types. RESULTS: Out of 537 patients, 13 (2.4%) met criteria for probable diabetic type, 51 (9.5%) for pre-diabetic type, and 473 (88.1%) for normal type. Individuals categorized as probable diabetic type had a higher body mass index and higher frequency of family history of diabetes mellitus than those with normal type. CONCLUSION: Glucose abnormalities were newly detected in 11.9% of schizophrenia patients treated with second-generation antipsychotics by the baseline monitoring. To assess the detective power and usefulness of the guidance, longitudinal investigations are necessary.
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Antipsicóticos/efeitos adversos , Diabetes Mellitus Tipo 2/diagnóstico , Esquizofrenia/tratamento farmacológico , Adulto , Idoso , Antipsicóticos/uso terapêutico , Povo Asiático , Glicemia , Automonitorização da Glicemia , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/etiologia , Feminino , Hemoglobinas Glicadas , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/complicaçõesRESUMO
To evaluate the characteristics of Pb(Zr,Ti)O3 (PZT) thin films (about [Formula: see text] thick) with three different sputtering configurations-single-layer (SL) deposition, multilayer (ML) deposition with internal electrodes, and multistep (MS) deposition-were prepared. The SL films exhibited poorer dielectric characteristics than the ML and MS films. The reliability and piezoelectric characteristics were especially high in the MS film, with an [Formula: see text] constant of -9.5 C · m-2. To investigate the porosity of the films, reconstructed 3-D SEM technique is employed. Reconstructed 3-D SEM images revealed decreased void densities in the ML and MS films, which improved their performance. The MS configuration provided the best dielectric and piezoelectric performance of PZT films.
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The prevalence of depression in Parkinson's disease (PD) varies greatly. In this study, we investigated major depressive disorder (MDD) and depressive symptoms without MDD in patients with PD. The psychopathological characteristics of depressive symptoms were assessed by a psychiatric interview. A total of 105 Japanese patients with PD without dementia were included. The Japanese version of the Beck Depression Inventory-II (BDI-II) with a cutoff score of 13/14 was used to screen for depression. Using a structured interview, a comprehensive psychiatric evaluation of patients with BDI-II scores >13 (high BDI patients) was completed using the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR. Forty patients (38%) had a BDI-II >13, but 29 did not show any depressed mood. Five cases met the criteria for MDD (three current, two past) and one patient was diagnosed with minor depressive disorder. A slight depressed mood that was associated with worrying about PD was seen in 6 of 34 patients without any depressive disorder and fluctuated with aggravation of PD symptoms in two of these patients. For the diagnosis of MDD, the number of positive items from the DSM-IV-TR definition of MDD is most important and useful for differentiating MDD and non-MDD. The low-prevalence rate of MDD in our patient population suggests that PD may be a psychological stressor for MDD, but does not necessarily induce MDD.