Attitude of patients with mood disorder toward clinical trials in Japan.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
Shigenobu Kanba
Publications and source records attributed to Shigenobu Kanba.
Phospholipids modulate superoxide and nitric oxide production by lipopolysaccharide and phorbol 12-myristate-13-acetate-activated microglia.
Microglial activation and inflammatory processes have been implicated in the pathogenesis of a number of neurodegenerative disorders. Recently, peroxynitrite (ONOO(-)), the reaction product of superoxide (O(2)(-)) and nitric oxide (NO) both of which can be generated by activated microglia, has been demonstrated to act as a major mediator in the neurotoxicity induced by activated microglia. On the other hand, phospholipids such as phosphatidylserine (PS) and phosphatidylcholine (PC) have been reported to modulate the immune function of phagocytes. We therefore evaluated the effects of liposomes which comprise both PS and PC (PS/PC liposomes) or PC only (PC liposomes) regarding the production of both O(2)(-) and NO by lipopolysaccharide (LPS)/phorbol 12-myristate-13-acetate (PMA)-activated microglia using electron spin resonance (ESR) spin trap technique with a DEPMPO and Griess reaction, respectively. Pretreatment with PS/PC liposomes or PC liposomes considerably inhibited the signal intensity of O(2)(-) adduct associated with LPS/PMA-activated microglia in a dose-dependent manner. In addition, pretreatment with PS/PC liposomes also significantly reduced LPS/PMA-induced microglial NO production. In contrast, pretreatment with PC liposomes had no effect on the NO production. These results indicate that PS/PC liposomes can inhibit the microglial production of both NO and O(2)(-), and thus presumably prevent a subsequent formation of ONOO(-). Therefore, PS/PC liposomes appear to have both neuroprotective and anti-oxidative properties through the inhibition of microglial activation.
Animals↗
Genetic structure of the dopamine receptor D4 gene (DRD4) and lack of association with schizophrenia in Japanese patients.
In order to investigate the contribution of genetic variation in the human dopamine receptor D4 gene (DRD4) to the risk of developing schizophrenia, we carried out a genetic analysis of 27 polymorphisms in 216 schizophrenic patients and 243 healthy controls from the Kyushu region of Japan. Twenty-two single nucleotide polymorphisms (SNPs) and five insertion/deletion polymorphisms were analyzed in this study, including four novel SNPs and a novel mononucleotide repeat. Linkage disequilibrium (LD) and haplotype analyses reveal weak LD across the DRD4 gene. In univariate analysis female individuals with allele -521C had a higher risk for schizophrenia. However, this finding was not significant after correction for multiple hypothesis testing. No other polymorphisms or haplotypes differed between schizophrenic patients and controls. Likewise, multivariate analyses did not reveal any statistically significant associations.
Adolescent↗
Suppression of cell proliferation by interferon-alpha through interleukin-1 production in adult rat dentate gyrus.
The therapeutic use of interferon-alpha (IFN-alpha), a proinflammatory cytokine, is known to cause various neuropsychiatric adverse effects. In particular, depression occurs in 30-45% of patients, frequently interrupting treatment. IFN-alpha-treated animals also show depression-like behaviors. However, mechanisms underlying the depression caused by IFN-alpha remain to be defined. Recently, a decrease in adult hippocampal neurogenesis was revealed as a possible neuropathological mechanism of depression. Therefore, we investigated the effect of subchronic IFN-alpha treatment on neurogenesis in the adult rat dentate gyrus (DG). Immediately after the administration of IFN-alpha for 1 week, a decrease in the number of 5-bromo-deoxyuridine-labeled proliferating cells was observed in the DG; however, no effect was detected on the expression of mature neuronal phenotype in the newly formed cells 3 weeks later. Also, an increase in the level of interleukin-1beta (IL-1beta), a major proinflammatory cytokine, was observed in the hippocampus following the administration of IFN-alpha. Furthermore, coadministration of an IL-1 receptor antagonist completely blocked the IFN-alpha-induced suppression of the cell-proliferative activity in the DG. Our results indicate that IFN-alpha suppresses neurogenesis in the DG, and that IL-1beta plays an essential role in the suppression. The decreased cell proliferation caused by IFN-alpha-induced IL-1beta may be responsible, at least in part, for IFN-alpha-induced depression.
Animals↗
Different SPECT findings before and after Capgras' syndrome in interictal psychosis.
We herein report a case of Capgras' syndrome observed in interictal psychosis in which the single-photon emission computed tomography (SPECT) findings before and after the appearance of the psychotic symptoms differed. SPECT with 99mTc-hexamethyl propyleneamine oxine (HMPAO) revealed worsening of hypoperfusion in the entire right hemisphere after onset of the psychotic symptoms. The enhanced hypoperfusion demonstrated by SPECT in the present case seems to indicate a right interhemispheric disconnection resulting in the occurrence of Capgras' syndrome.
Adult↗
A decreased survival of proliferated cells in the hippocampus is associated with a decline in spatial memory in aged rats.
In aged rats, although learning and memory impairment is prominent, both the number of granular cells and the degree of neuronal progenitor proliferation in the hippocampus are known to be preserved. We examined the association between the survival of newly generated neurons in the hippocampus and the learning ability in aged rats. By using BrdU, a cell proliferation marker to determine neurogenesis and contextual fear conditioning to determine learning ability, we found that in aged rats, along with memory impairment, the survival of both the proliferated cells at baseline and those enhanced by contextual fear conditioning decreased remarkably. These results suggest that the integration of newly generated neurons into hippocampal circuitry is decreased with aging, this phenomenon may, in part, explain the decline in learning and memory in aged rats.
Aging↗
Depletion of intracellular Ca2+ store itself may be a major factor in thapsigargin-induced ER stress and apoptosis in PC12 cells.
The mechanisms of intracellular calcium store depletion and store-related Ca(2+) dysregulation in relation to apoptotic cell death in PC12 cells were investigated at physiological temperatures with a leak-resistant fluorescent indicator dye Fura-PE3/AM by a cooled CCD imaging analysis system. Electron microscopic observations have shown thapsigargin (TG; 100 nM)-induced apoptosis in PC12 cells. Thorough starvation of stored Ca(2+) by BAPTA/AM (50 microM), or La(3+) (100 microM) enhanced while dantrolene (100 microM) attenuated the TG-induced apoptosis by preventing a calcium release from internal stores. An immunoblotting analysis revealed an enhanced expression of GRP78, the hallmark of endoplasmic reticulum (ER) stress when cells were treated by TG along with BAPTA/AM. These results indicate that the depletion of the intracellular Ca(2+) stores itself induces the ER stress and apoptosis in PC12 cells without any involvement of the capacitative calcium entry (CCE) or a sustained elevation of intracellular Ca(2+) concentrations ([Ca(2+)](i)).
Animals↗
Impairment of theory of mind in patients in remission following first episode of schizophrenia.
The aim of this study was to investigate theory of mind (ToM) ability in patients in remission after the first episode of schizophrenia. A ToM task which contained four pictures was given to 30 patients with schizophrenia in remission and 30 matched healthy controls. Patients with schizophrenia in remission showed statistically significant impairment in the ToM tasks. ToM impairment was not correlated with psychiatric symptoms. Thus, ToM deficit in schizophrenia may be a trait marker.
Adult↗
Cerebral white matter degeneration in frontotemporal dementia detected by diffusion-weighted magnetic resonance imaging.
RATIONALE AND OBJECTIVE: Brain tissue damage in frontotemporal dementia (FTD) has never been systematically studied using diffusion-weighted imaging (DWI). We studied FTD patients using DWI to determine whether microstructural changes in white matter can be detected in vivo. MATERIALS AND METHODS: Thirteen FTD patients and 15 aged healthy subjects were studied. Mean diffusivity (MD) abnormalities in 28 white matter regions were visually evaluated. In addition, MD values in 10 white matter regions relative to that in the ipsilateral postcentral gyrus were measured. The results were compared between healthy subjects and FTD patients. RESULTS: The visual rating resulted in a significant MD elevation in FTD patients in the bilateral high superior frontal gyri, right orbitofrontal gyrus, bilateral anterior temporal lobes, and left middle temporal lobe (P < .01, respectively). Relative MD comparison revealed a significant MD elevation in FTD patients in the bilateral high superior frontal gyri, bilateral orbitofrontal gyri, and bilateral anterior temporal lobes (P < .05 after Bonferroni correction, respectively). CONCLUSION: Our results demonstrated white matter MD abnormalities in FTD patients. It was suggested that the observed white matter MD abnormalities are secondary to damage in the overlying cortex.
Aged↗
Mapping of subcortical white matter abnormality in Alzheimer's disease using diffusion-weighted magnetic resonance imaging.
RATIONALE AND OBJECTIVES: White matter (WM) abnormality in Alzheimer's disease (AD) has been less well characterized than cortical damage. We studied the spatial distribution of the subcortical WM abnormality using diffusion-weighted magnetic resonance imaging (DWI). MATERIALS AND METHODS: Twenty-one AD patients and seven healthy, elderly subjects were included. DWIs were obtained using a cerebrospinal fluid (CSF)-nulled pulse sequence to reduce the partial volume contamination of CSF signal. Diffusivity in the subcortical WM voxels was mapped onto the cortical surface using original software so that the spatial distribution of subcortical WM damage, which was visualized as an area of increased diffusivity, could be viewed in a three-dimensional map. The damages in the lateral surface of the bilateral cerebral hemispheres were visually evaluated, and severities of the damages in five brain regions were compared with each other. In addition, the severity of the damage in each region was correlated with patient's mini-mental state examination (MMSE) score. RESULTS: In both hemispheres, clear sparing of the pericentral regions and predominant involvement of the parietal and temporal regions were revealed with statistical significance (P < .05, respectively). Marginal correlation (P < .05 uncorrected for multiple comparisons) was observed between the damage severity in the bilateral frontal and right temporal regions and patient's MMSE score. CONCLUSION: We demonstrated a subcortical WM abnormality over the parietal and temporal regions with clear sparing of the pericentral region using our mapping method, which supported the hypothesis that the subcortical WM abnormality in AD originates in Wallerian degeneration.
Aged↗
Assessment of the dexamethasone/CRH test as a state-dependent marker for hypothalamic-pituitary-adrenal (HPA) axis abnormalities in major depressive episode: a Multicenter Study.
There is compelling evidence for the involvement of hypothalamic-pituitary-adrenal (HPA) axis abnormalities in depression. Growing evidence has suggested that the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test is highly sensitive to detect HPA axis abnormalities. We organized a multicenter study to assess the DEX/CRH test as a state-dependent marker for major depressive episode in the Japanese population. We conducted the DEX/CRH test in 61 inpatients with major depressive episode (Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV)) and 57 healthy subjects. In all, 35 patients were repeatedly assessed with the DEX/CRH test on admission and before discharge. The possible relationships between clinical variables and the DEX/CRH test were also examined. Significantly enhanced pituitary-adrenocortical responses to the DEX/CRH test were observed in patients on admission compared with controls. Such abnormalities in patients were significantly reduced after treatment, particularly in those who underwent electroconvulsive therapy (ECT) in addition to pharmacotherapy. Age and female gender were associated with enhanced hormonal responses to the DEX/CRH test. Severity of depression correlated with DEX/CRH test results, although this was explained, at least in part, by a positive correlation between age and severity in our patients. Medication per se was unrelated to DEX/CRH test results. These results suggest that the DEX/CRH test is a sensitive state-dependent marker to monitor HPA axis abnormalities in major depressive episode during treatment. Restoration from HPA axis abnormalities occurred with clinical responses to treatment, particularly in depressed patients who underwent ECT.
Adult↗
Interictal psychosis after stroke with forced normalization.
Explore the source record for details and available documents.
Electroencephalography↗
[Understanding psychiatric diseases caused by stress: neurogenesis in hippocampus and mental functions].
Explore the source record for details and available documents.
Animals↗
Prediction of medication noncompliance in outpatients with schizophrenia: 2-year follow-up study.
Neuroleptic noncompliance is a major reason for relapse in outpatients with schizophrenia. In a 2-year follow-up study, we used the Japanese version of the Rating of Medication Influences Scale (ROMI-J) to investigate the reasons for compliance and noncompliance in outpatients with schizophrenia. Ninety outpatients who were confirmed by interview to have had good compliance for more than 3 months completed the initial interview, which included the Clinical Global Impressions Scale (CGI), the Brief Psychiatric Rating Scale (BPRS), the Global Assessment of Functioning Scale (GAF), the UKU Side Effect Rating Scale, and the ROMI-J. All the outpatients were followed up for 2 years. At the initial interview, the most frequent reason for compliance was "relapse prevention," while the most frequent reason for noncompliance was "distressed by side effects." Fifteen outpatients who proved to be noncompliant in the follow-up period had higher baseline BPRS "agitation" scores and ROMI-J "no perceived daily benefit" ratings than compliant patients. Sixty-four outpatients who maintained compliance during the follow-up had higher baseline ROMI-J ratings of "fulfillment of life goals" than their noncompliant counterparts. It is important to understand the attitudes of patients with schizophrenia toward drug therapy in order to predict better compliance and provide psychoeducation designed to forestall relapses.
Adolescent↗
Effectiveness of aroma on work efficiency: lavender aroma during recesses prevents deterioration of work performance.
The present study investigated whether exposure to aromas during recess periods affects work performance. Subjects comprised 36 healthy male students (mean age, 24.2 +/- 2.2 years) who were randomly divided into three groups: (1) control group, not exposed to aroma during recesses; (2) jasmine group, exposed to jasmine aroma during recesses; and (3) lavender group, exposed to lavender aroma during recesses. All participants completed five work sessions performing a task requiring concentration on a computer monitor, with each session lasting 60 min. Recess periods of 30 min were provided between each session. To clarify the time at which work concentration was lowest, work performance for the control group was analyzed. Concentration was lowest in the afternoon period, where afternoon drowsiness is strongest. Comparison of the three groups for this time period indicated significantly higher concentration levels for the lavender group than for the control group. No such effect was noted for the jasmine group. Although lavender is a sedative-type aroma, use during recess periods after accumulation of fatigue seems to prevent deterioration of performance in subsequent work sessions.
Adult↗
Age-related disturbance of memory and CREB phosphorylation in CA1 area of hippocampus of rats.
In the early process of long-term memory formation, cyclic AMP response element-binding protein (CREB), a transcription factor on which multiple signal transduction pathways converge, has been implicated. We examined whether the age difference in the performance of contextual fear conditioning (CFC) is associated with a change in activation of CREB in the hippocampus which is an important neural structure for long-term memory. The activation of CREB in the hippocampus in young (15 weeks old) and old (120 weeks old) male rats was determined immunohistochemically with an antibody that specifically recognizes the phosphorylated form of CREB (pCREB). Young rats exhibited better performance than old rats with respect to the freezing time in CFC. Phosphorylation of CREB as revealed by the ratio of the pCREB-immunoreactive cell number to the CREB-immunoreactive cell number was increased in the CA1 region, but not in other hippocampal regions following training for CFC. The close relationship between behavioral performance and CREB phosphorylation in the CA1 region suggests that hippocampal CREB is involved in age-related decline of learning and memory.
Aging↗
Brain activation of patients with obsessive-compulsive disorder during neuropsychological and symptom provocation tasks before and after symptom improvement: a functional magnetic resonance imaging study.
BACKGROUND: Functional neuroimaging studies have implicated hyperactivity of the frontal cortex in obsessive-compulsive disorder (OCD); however, relationships between abnormal brain activity, clinical improvement, and neuropsychological function have not been clarified in OCD. To clarify the pathophysiology of this disorder, regional changes in brain function were examined during administration of cognitive and symptom provocation tasks in patients with OCD before and after treatment. METHODS: Ten outpatients with OCD participated in the study. Functional magnetic resonance imaging (fMRI) was performed before and after treatment. Stroop and symptom provocation tasks were administered during fMRI. Each patient was randomly allocated to receive either pharmacotherapy with fluvoxamine 200 mg/day (n = 4) or behavior therapy (n = 6) for 12 weeks. RESULTS: After 12-week treatment, mean (+/- SD) total score on the Yale-Brown Obsessive-Compulsive Scale decreased from 29.00 +/- 3.59 to 14.60 +/- 9.22, representing symptomatic improvement from moderate to mild. After symptom improvement, symptom provocation-related activation in the orbitofrontal, dorsolateral-prefrontal, and anterior cingulate cortices decreased. Conversely, Stroop task-related activation in the parietal cortex and cerebellum increased. CONCLUSIONS: After improvement of OCD with either fluvoxamine or behavioral therapy, hyperactivation of the frontal lobe related to a symptom-provocative state decreases, and posterior brain activity related to action-monitoring function increases.
Antidepressive Agents, Second-Generation↗
Characterization of human and mouse TRPM2 genes: identification of a novel N-terminal truncated protein specifically expressed in human striatum.
Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable cation channel activated by ADP-ribose or reactive oxygen species. In human, a major transcript of 6.5 kb is expressed in various tissues, whereas a minor transcript of 5.5 kb is detected only in striatum (caudate nucleus and putamen). We found that the 5.5-kb shorter transcript is transcribed from the intron 4 of the TRPM2 gene and encodes the striatum short form protein (SSF-TRPM2) with 1289 amino acid residues as compared to the long form protein (LF-TRPM2), in which the N-terminal 214 amino acid residues are removed. The SSF-TRPM2 protein still maintained H2(O2)-induced Ca2+ influx activity. In addition, we found that the major transcripts in human and mouse start from a novel 5' non-coding exon; however, we could not detect any striatum short transcript in mouse brain. These new findings are invaluable to further study the regulation of TRPM2 gene expression and to examine the possible involvement of the TRPM2 gene in the pathophysiology of bipolar disorder.
Amino Acid Sequence↗