Kazuyuki Nakagome

National Center of Neurology and Psychiatry, Кодаиры, Tōkyō, Japan

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Publications (178)537.04 Total impact

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    ABSTRACT: Schizophrenia-associated cognitive deficits are resistant to treatment and thus pose a lifelong burden. The Brief Assessment of Cognition in Schizophrenia (BACS) provides reliable and valid assessments across cognitive domains. However, because the prefrontal functional abnormalities specifically associated with the level of cognitive deficits in schizophrenia have not been examined, we explored this relationship. Patients with schizophrenia (N = 87) and matched healthy controls (N = 50) participated in the study. Using near-infrared spectroscopy (NIRS), we measured the hemodynamic responses in the prefrontal and superior temporal cortical surface areas during a working memory task. Correlation analyses revealed a relationship between the hemodynamics and the BACS composite and domain scores. Hemodynamic responses of the left dorsolateral prefrontal cortex (DLPFC) and left frontopolar cortex (FPC) in the higher-level-of-cognitive-function schizophrenia group were weaker than the responses of the controls but similar to those of the lower-level-of-cognitive-function schizophrenia group. However, hemodynamic responses in the right DLPFC, bilateral ventrolateral PFC (VLPFC), and right temporal regions decreased with increasing cognitive deficits. In addition, the hemodynamic response correlated positively with the level of cognitive function (BACS composite scores) in the right DLPFC, bilateral VLPFC, right FPC, and bilateral temporal regions in schizophrenia. The correlation was driven by all BACS domains. Our results suggest that the linked functional deficits in the right DLPFC, bilateral VLPFC, right FPC, and bilateral temporal regions may be related to BACS-measured cognitive impairments in schizophrenia and show that linking the neurocognitive deficits and brain abnormalities can increase our understanding of schizophrenia pathophysiology.
    No preview · Article · Jan 2016 · Schizophrenia Research
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    ABSTRACT: The relationship between violence and neurocognitive function in schizophrenia is unclear. We examined the backgrounds and neurocognitive functions of violent and nonviolent patients with schizophrenia to identify factors associated with serious violence. Thirty male patients with schizophrenia who were hospitalized after committing serious violent acts were compared with 24 hospitalized male patients with schizophrenia and no history of violence. We evaluated psychiatric symptoms using the Positive and Negative Syndrome Scale (PANSS) and neurocognitive functions using the Brief Assessment of Cognition in Schizophrenia (BACS)-Japanese version. Repeated-measures analyses of variance on BACS subcomponents z-scores showed that the violent and control groups had different neuropsychological profiles at trend level (p = 0.095). Post hoc analyses of variance indicated that the violent group had significantly better working memory and executive function than the control group. In post hoc ANOVAs also controlling for the effect of the presence of substance abuse on cognitive function, violent or nonviolent group had a significant main effect on executive function but not on working memory. Patient with violent or non-violent schizophrenia have distinct neuropsychological profiles. These results may help develop improved psychosocial treatments.
    Full-text · Article · Dec 2015 · Annals of General Psychiatry
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    ABSTRACT: The aim of this study was to assess antidepressant efficacy and safety of venlafaxine extended release in Japanese patients with major depressive disorder (MDD). We carried out a double-blinded, placebo-controlled, randomized study using fixed (75 mg/day) and flexible (75-225 mg/day, most patients attained to 225 mg/day) doses, followed by the long-term, open-labeled, extension study. Outpatients aged at least 20 years diagnosed with MDD were included. The primary efficacy measure was change from baseline in the Hamilton Rating Scale for Depression (HAM-D17) score at week 8; secondary efficacy measures included the Montgomery-Åsberg Depression Rating Scale, the Quick Inventory of Depressive Symptomatology self-report version, HAM-D6, and Clinical Global Impression scales in the double-blinded study. Overall, 538 patients were randomized; significant differences were observed in the primary efficacy variable in the fixed-dose group (-10.76; P=0.031), but not in the flexible-dose (-10.37; P=0.106) group compared with placebo (-9.25). However, the flexible-dose group showed significant efficacy in several secondary measures. Treatment-related adverse events in the treatment period were 51.7 and 67.8% in the fixed-dose and flexible-dose groups, respectively, versus 38.8% with placebo. Throughout the study period, no Japanese-specific adverse events were observed. Thus, venlafaxine extended release was efficacious and safe for MDD treatment in Japan.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.http://creativecommons.org/licenses/by-nc/4.0/.
    No preview · Article · Oct 2015 · International clinical psychopharmacology
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    ABSTRACT: Impaired social functioning is a characteristic of schizophrenia that affects patients' quality of life. The aim of the study was to assess prefrontal hemodynamic responses during a cognitive task and establish its influence on psychiatric symptoms, cognitive function, global functioning, and self-reported social functioning in patients with schizophrenia. Thirty-three patients with schizophrenia and 30 age-and sex-matched healthy controls participated in the study. We measured hemodynamic responses in the prefrontal and superior temporal cortical surface areas with 52-channel near-infrared spectroscopy (NIRS) during a verbal fluency task (VFT). Self-reported social functioning was assessed using the Social Functioning Scale (SFS). Regional hemodynamic responses were significantly smaller in the prefrontal and temporal regions in subjects with schizophrenia than in the controls, and prefrontal hemodynamic responses during the VFT showed a strong correlation with SFS total scores. These results suggest an association between self-reported social functioning and prefrontal activation in subjects with schizophrenia. The present study provides evidence that NIRS imaging could be helpful in understanding the neural basis of social functioning.
    No preview · Article · Sep 2015
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    ABSTRACT: Background: Eosinophils play important roles in the development of asthma exacerbation. Viral infection is a major cause of asthma exacerbation, and the expression of IFN-γ-inducible protein of 10 kDa (IP-10) and cysteinyl leukotrienes (cysLTs) is up-regulated in virus-induced asthma. As β2-adrenergic agonists, such as formoterol or salbutamol, are used to treat asthma exacerbation, we examined whether formoterol or salbutamol could modify eosinophil functions such as adhesiveness, particularly those activated by cysLTs or IP-10. Methods: Eosinophils were isolated from the blood of healthy subjects and were pre-incubated with either formoterol or salbutamol, and subsequently stimulated with IL-5, LTD4, or IP-10. Adhesion of eosinophils to intercellular cell adhesion molecule (ICAM)-1 was measured using eosinophil peroxidase assays. The generation of eosinophil superoxide anion (O2(-)) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) release was evaluated by ELISA as a marker of degranulation. Results: Neither formoterol nor salbutamol suppressed the spontaneous adhesion of eosinophils to ICAM-1. However, when eosinophils were activated by IL-5, LTD4, or IP-10, formoterol, but not salbutamol, suppressed the adhesion to ICAM-1. Formoterol also suppressed IL-5, LTD4, or IP-10 induced eosinophil O2(-) generation or EDN release. Conclusions: These findings suggest that formoterol, but not salbutamol, suppresses eosinophil functions enhanced by IL-5, LTD4, or IP-10. As these factors are involved in the development of asthma exacerbation, our results strongly support the hypothesis that administration of formoterol is a novel strategy for treating asthma exacerbation.
    Preview · Article · Sep 2015 · Allergology International
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    ABSTRACT: Background: Eosinophils recognize various stimuli, such as cytokines, chemokines, immunoglobulins, complement, and external pathogens, resulting in their accumulation in mucosal tissues and the progression of inflammation. Eosinophils are also involved in innate Th2-type immune responses mediated through endogenous danger signals, including IL-33, uric acid (UA), or ATP, in non-sensitized mice exposed to environmental allergens. However, the mechanism involved in eosinophil responses to these danger signals remains insufficiently understood. Methods: We examined migration, adhesion, superoxide production and degranulation of human eosinophils. Isolated eosinophils were incubated with monosodium urate (MSU) crystals and ATPγS, a non-hydrolysable ATP analogue. To determine the involvement of P2 or P2Y2 receptors in eosinophil responses to UA and ATP, eosinophils were preincubated with a pan-P2 receptor inhibitor, oxidized ATP (oATP), or anti-P2Y2 antibody before incubation with MSU crystals or ATPγS. Results: MSU crystals induced adhesion of eosinophils to recombinant human (rh)-ICAM-1 and induced production of superoxide. oATP abolished eosinophil responses to MSU crystals, suggesting involvement of endogenous ATP and its receptors. Furthermore, exogenous ATP, as ATPγS, induced migration of eosinophils through a model basement membrane, adhesion to rh-ICAM-1, superoxide generation, and degranulation of eosinophil-derived neurotoxin (EDN). oATP and anti-P2Y2 significantly reduced these eosinophil responses. Conclusions: ATP serves as an essential mediator of functional responses in human eosinophils. Eosinophil responses to ATP may be implicated in airway inflammation in patients with asthma.
    Preview · Article · Sep 2015 · Allergology International
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    ABSTRACT: Despite the known relationship between prefrontal function and increased suicidality during major depressive episodes, the links between prefrontal function and suicidality remain unclear in major depressive disorder (MDD). Suicidal ideation usually precedes a suicide attempt. If prefrontal cortex (PFC) activity is a biomarker for suicidal ideation in depression, monitoring it could be useful for suicide prevention. Therefore, in this study, we assessed the association between prefrontal function and suicidal ideation in MDD. Prefrontal function in 67 patients with MDD (31 with suicidal ideation and 36 without) and 67 age-, gender-, and intelligence quotient-matched healthy controls (HCs) was evaluated using near-infrared spectroscopy (NIRS) during a verbal fluency task (VFT). Suicidal ideation was assessed using item 3 of the Hamilton Depression Rating Scale (HAMD). Regional hemodynamic changes were significantly smaller in patients with MDD than in HCs in prefrontal and temporal regions. Hemodynamic changes in the right dorsolateral PFC (DLPFC), orbitofrontal cortex (OFC), and right frontopolar cortex (FPC) regions in patients with MDD with suicidal ideation were significantly smaller than in those without suicidal ideation. In addition, hemodynamic changes correlated negatively with the severity of suicidal ideation in the DLPFC, OFC, and FPC in patients with MDD. Further studies with a larger sample size are required to verify our findings. These results suggest that the DLPFC, OFC, and FPC are brain substrates of suicidal ideation in depressive states in patients with MDD, and that NIRS data can be employed as a clinically useful biomarker for the assessment of suicide risk. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · Aug 2015 · Journal of Affective Disorders
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    ABSTRACT: Facial emotion perception is considered to provide a measure of social cognition. Numerous studies have examined the perception of emotion in patients with schizophrenia, and the majority has reported impaired ability to recognize facial emotion perception. We aimed to investigate the correlation between facial expression recognition and other domains of social cognition and neurocognition in Japanese patients with schizophrenia. Participants were 52 patients with schizophrenia and 53 normal controls with no history of psychiatric diseases. All participants completed the Hinting Task and the Social Cognition Screening Questionnaire (SCSQ). The Brief Assessment of Cognition in Schizophrenia (BACS) was administered only to the patients. Facial emotion perception measured by The Facial Emotion Selection Test (FEST) was compared between the patients and normal controls. Patients performed significantly worse on the FEST compared to normal control subjects. The FEST Total score was significantly positively correlated with scores of the BACS attention subscale, Hinting Task, SCSQ Verbal Working Memory and Metacognition subscales. Stepwise multiple regression analysis revealed that verbal working memory function was positively related to the facial emotion perception ability in patients with schizophrenia. These results point to the concept that facial emotion perception and some types of working memory use common cognitive resources. Our findings may provide implications in the field of cognitive rehabilitation and related interventions in schizophrenia. This article is protected by copyright. All rights reserved.
    Full-text · Article · Jul 2015 · Psychiatry and Clinical Neurosciences
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    ABSTRACT: The purpose of this study was to evaluate the clinical impact of addition of (11) C-PiB PET on routine clinical diagnosis of Alzheimer's disease (AD) dementia and mild cognitive impairment (MCI), and to assess diagnostic agreement between clinical criteria and research criteria of the NIA-AA. The diagnosis in 85 patients was made according to clinical criteria. Imaging examinations, including both MRI and SPECT/CT to identify neuronal injury (NI), and (11) C-PiB PET to identify amyloid were performed, and all subjects were re-categorized according to research criteria. Among 40 patients with probable AD dementia (ProAD), 37 were NI-positive, 29 were (11) C-PiB-positive, and 27 who were both NI- and (11) C-PiB-positive were categorized as having "ProAD dementia with a high level of evidence of the AD pathophysiological process". Among 20 patients with possible AD dementia (PosAD), 17 were NI-positive, and 6 who were both NI- and (11) C-PiB-positive were categorized as having "PosAD with evidence of the AD pathophysiological process". Among 25 patients with MCI, 18 were NI-positive, 13 were (11) C-PiB-positive, and 10 who were both NI- and (11) C-PiB-positive were categorized as having "MCI due to AD-high likelihood". Diagnostic concordance between clinical criteria and research criteria may not be high in this study. (11) C-PiB PET may be of value in making the diagnosis of dementia and MCI in cases with high diagnostic uncertainty. This article is protected by copyright. All rights reserved.
    No preview · Article · Jun 2015 · Psychiatry and Clinical Neurosciences
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    ABSTRACT: The purpose of this study was to examine the relationship between fish consumption and prefrontal function during a cognitive task in male Japanese workers. The study included 208 male workers who underwent medical health examinations 3 months after a change in their work assignment. We measured the hemoglobin concentration changes in the prefrontal region during working memory tasks using 52-channel near-infrared spectroscopy. The frequency of fish consumption was calculated on the basis of the subjects' self-reported customary intake frequency over the previous 3 months. A significant positive relationship was observed between fish consumption and left dorsolateral prefrontal function during a working memory task. To our knowledge, this is the first study to report an association between fish consumption and functional cortical activity with an ample sample size, suggesting that fish consumption modulates functional activity in the left dorsolateral prefrontal cortex.
    Preview · Article · Apr 2015 · PLoS ONE
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    ABSTRACT: Recent studies have indicated the potential clinical use of near infrared spectroscopy (NIRS) as a tool in assisting the diagnosis of major depressive disorder (MDD); however, it is still unclear whether NIRS signal changes during cognitive task are state- or trait-dependent, and whether NIRS could be a neural predictor of treatment response. Therefore, we conducted a longitudinal study to explore frontal haemodynamic changes following antidepressant treatment in medication-naïve MDD using 52-channel NIRS. This study included 25 medication-naïve individuals with MDD and 62 healthy controls (HC). We performed NIRS scans before and after antidepressant treatment and measured changes of [oxy-Hb] activation during a verbal fluency task (VFT) following treatment. Individuals with MDD showed significantly decreased [oxy-Hb] values during a VFT compared with HC in the bilateral frontal and temporal cortices at baseline. There were no [oxy-Hb] changes between pre- and post-antidepressant treatment time points in the MDD cohort despite significant improvement in depressive symptoms. There was a significant association between mean [oxy-Hb] values during a VFT at baseline and improvement in depressive symptoms following treatment in the bilateral inferior frontal and middle temporal gyri in MDD. These findings suggest that hypofrontality response to a VFT may represent a potential trait marker for depression rather than a state marker. Moreover, the correlation analysis indicates that the NIRS signals before the initiation of treatment may be a biological marker to predict patient's clinical response to antidepressant treatment. The present study provides further evidence to support a potential application of NIRS for the diagnosis and treatment of depression.
    Full-text · Article · Mar 2015 · PLoS ONE
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    ABSTRACT: The Rhinovirus C (RV-C) were discovered in 2006 and these agents are an important cause of respiratory morbidity. Little is known about their biology. RV-C15 (C15) can be produced by transfection of recombinant viral RNA into cells and subsequent purification over a 30% sucrose cushion, even though yields and infectivity of other RV-C genotypes with this protocol are low. The goal of this study was to determine whether poor RV-C yields were due to capsid instability, and moreover, to develop a robust protocol suitable for the purification of many RV-C types. Capsid stability assays indicated that virions of RV-C41 (refractory to purification) have similar tolerance for osmotic and temperature stress as RV-A16 (purified readily), although C41 is more sensitive to low pH. Modification to the purification protocol by removing detergent increased the yield of RV-C. Addition of nonfat dry milk to the sucrose cushion increased the virus yield but sacrificed purity of the viral suspension. Analysis of virus distribution following centrifugation indicated that the majority of detectable viral RNA (vRNA) was found in pellets refractory to resuspension. Reduction of the centrifugal force with commiserate increase in spin-time improved the recovery of RV-C for both C41 and C2. Transfection of primary lung fibroblasts (WisL cells) followed by the modified purification protocol further improved yields of infectious C41 and C2. Described herein is a higher-yield purification protocol suitable for RV-C types refractory to the standard purification procedure. The findings suggest that aggregation-adhesion problems rather than capsid instability influence RV-C yield during purification. Copyright © 2015. Published by Elsevier B.V.
    No preview · Article · Feb 2015 · Journal of Virological Methods
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    ABSTRACT: Cortisol dysregulation has been proposed to be involved in depression. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation associated with major depressive disorder (MDD) was previously reported to be higher in the elderly. Furthermore, insulin resistance and the prevalence of type 2 diabetes are known to increase with aging. The aim of the present study was to determine whether a relationship existed between plasma cortisol levels following the dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test and insulin resistance evaluated by the homeostasis model assessment of insulin resistance (HOMA-R) in elderly MDD subjects. Fifteen unmedicated MDD inpatients and 17 age- and sex-matched healthy controls participated in this study. After overnight fasting, blood samples were collected to measure plasma glucose and insulin concentrations, estimate HOMA-R, and perform the DEX/CRH test to evaluate HPA axis function. The value of the area under the time curve of plasma cortisol concentrations (CortAUC) and peak cortisol values (Cortpeak) following the administration of DEX/CRH both correlated with HOMA-R in MDD group. In contrast, neither CortAUC nor Cortpeak correlated with HOMA-R in controls. This is the first study to directly demonstrate the relationship between HPA axis dysregulation assessed with the DEX/CRH test and the index of insulin resistance estimated as HOMA-R in elderly MDD patients. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
    Full-text · Article · Feb 2015 · Psychiatry Research
  • Kazuyuki Nakagome · Takehito Kobayashi · Tomoyuki Soma · Makoto Nagata

    No preview · Article · Feb 2015 · Journal of Allergy and Clinical Immunology
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    ABSTRACT: The activation of oxygenated hemoglobin (oxy-Hb) has been shown to be lacking in the prefrontal cortex (PFC) of patients with late-onset depression (LOD), in verbal fluency task (VFT)-related near-infrared spectroscopy (NIRS). In our previous studies, we have emphasized the connection between the lack of activation in the frontopolar cortex and social functioning disorder in patients with LOD. In this study, we investigated whether the responsiveness to medical treatment of untreated patients with LOD, particularly social functioning improvements, could be predicted by NIRS findings at the initial examination. The subjects were 29 patients with LOD who were diagnosed with major depression at 65 years or older at the initial examination (mean age ± standard deviation, 72.4 ± 5.71 years). We measured the changes in hemoglobin concentration in the prefrontal and temporal cortex regions during a VFT by using 52-channel NIRS. In addition, depression status and social functioning were evaluated with the Hamilton Depression Rating Scale and the Social Adaptation Self-evaluation Scale, respectively, at the initial examination and 8 weeks after the treatment. A negative correlation was found between the NIRS activation in the right ventrolateral PFC region before treatment and the improvement in social functioning. These results suggested that the social functioning improvements were greater in LOD with initially lower NIRS activation in the right ventrolateral PFC region. NIRS is a simple technique that can be used before treatment to evaluate the social functioning levels of patients with LOD, and predict social functioning improvement after treatment.
    No preview · Article · Jan 2015 · Journal of Psychiatric Research
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    Tomiki Sumiyoshi · Hiroshi Kunugi · Kazuyuki Nakagome
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    ABSTRACT: Negative symptoms (e.g., decreased spontaneity, social withdrawal, blunt affect) and disturbances of cognitive function (e.g., several types of memory, attention, processing speed, executive function, fluency) provide a major determinant of long-term outcome in patients with schizophrenia. Specifically, motivation deficits, a type of negative symptoms, have been attracting interest as (1) a moderator of cognitive performance in schizophrenia and related disorders, and (2) a modulating factor of cognitive enhancers/remediation. These considerations suggest the need to clarify neurobiological substrates regulating motivation. Genetic studies indicate a role for the monoamine systems in motivation and key cognitive domains. For example, polymorphism of genes encoding catecholamine-O-methyltransferase, an enzyme catabolizing dopamine (DA), affects performance on tests of working memory and executive function in a phenotype (schizophrenia vs. healthy controls)-dependent fashion. On the other hand, motivation to maximize rewards has been shown to be influenced by other genes encoding DA-related substrates, such as DARPP-32 and DA-D2 receptors. Serotonin (5-HT) receptors may also play a significant role in cognitive and motivational disabilities in psychoses and mood disorders. For example, mutant mice over-expressing D2 receptors in the striatum, an animal model of schizophrenia, exhibit both decreased willingness to work for reward and up-regulation of 5-HT2C receptors. Taken together, genetic predisposition related to 5-HT receptors may mediate the diversity of incentive motivation that is impaired in patients receiving biological and/or psychosocial treatments. Thus, research into genetic and neurobiological measures of motivation, in association with 5-HT receptors, is likely to facilitate intervention into patients seeking better social consequences.
    Full-text · Article · Dec 2014 · Frontiers in Neuroscience
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    ABSTRACT: Background Epidemiologic studies provide evidence of differential virulence of rhinovirus species (RV). We recently reported that RV-A and RV-C induced more severe illnesses than RV-B, which suggests that the biology of RV-B might be different from RV-A or RV-C. Objective To test the hypothesis that RV-B has lower replication and induces lesser cytokine responses than RV-A or RV-C. Methods We cloned full-length cDNA of RV-A16, A36, B52, B72, C2, C15, and C41 from clinical samples and grew clinical isolates of RV-A7 and RV-B6 in cultured cells. Sinus epithelial cells were differentiated at the air-liquid interface. We tested for differences in viral replication in epithelial cells after infection with purified viruses (108 RNA copies) and measured virus load by quantitative RT-PCR. We measured lactate dehydrogenase (LDH) concentration as a marker of cellular cytotoxicity, and cytokine and/or chemokine secretion by multiplex ELISA. Results At 24 hours after infection, the virus load of RV-B (RV-B52, RV-B72, or RV-B6) in adherent cells was lower than that of RV-A or RV-C. The growth kinetics of infection indicated that RV-B types replicate more slowly. Furthermore, RV-B released less LDH than RV-A or RV-C, and induced lower levels of cytokines and chemokines such as CXCL10, even after correction for viral replication. RV-B replicates to lower levels also in primary bronchial epithelial cells. Conclusions Our results indicate that RV-B types have lower and slower replication, and lower cellular cytotoxicity and cytokine and/or chemokine production compared with RV-A or RV-C. These characteristics may contribute to reduced severity of illnesses that has been observed with RV-B infections.
    No preview · Article · Aug 2014 · The Journal of allergy and clinical immunology
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    ABSTRACT: Social functioning has received widespread attention as one of the most important outcomes in psychiatric disorders and has been related to cognitive functioning and the underlying brain activity. Cognitive decline, however, appears not only in the psychiatric population but also in aged individuals. In our previous study, we demonstrated a significant relationship between social functioning and prefrontal cortex (PFC) activity in patients with depression. However, it has not been shown whether the above relationship could be extended to healthy populations. The purpose of the present study was to investigate a possible association between social functioning and prefrontal hemodynamic responses in healthy elderly adults by using a non-invasive and low-constraint functional neuroimaging technique, near-infrared spectroscopy (NIRS). Study subjects included 55 healthy, elderly volunteers. We measured hemodynamic responses over prefrontal cortical (PFC) areas during the verbal fluency task by using multi-channel NIRS and analyzed the relationship between task-associated hemodynamic responses and social functioning as measured by the Social Adaptation Self-Evaluation Scale (SASS). A significant positive relationship was observed between the SASS total score and PFC activation. Our findings suggest that PFC activation is associated with social functioning in healthy elderly adults. Furthermore, hemodynamic responses assessed using non-invasive NIRS could be a useful biological marker of these characteristics.
    Full-text · Article · Jun 2014 · Behavioural Brain Research
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    ABSTRACT: Allergic airway inflammation is generally considered to be a Th2-type immune response. Recent studies, however, have demonstrated that Th17-type immune responses also play important roles in this process, particularly in the pathogenesis of neutrophilic airway inflammation, a hallmark of severe asthma. We scrutinized several Kampo extracts that reportedly exhibit anti-inflammatory activity by using in vitro differentiation system of human and mouse naïve T cells. We found that hange-shashin-to (HST) and oren-gedoku-to (OGT) possess inhibitory activity for Th17 responses in vitro. Indeed, wogonin and berberine, major components common to HST and OGT, exhibit Th17-inhibitory activities in both murine and human systems in vitro. We therefore evaluated whether wogonin suppresses OVA-induced neutrophilic airway inflammation in OVA TCR-transgenic DO11.10 mice. Consequently, oral administration of wogonin significantly improved OVA-induced neutrophilic airway inflammation. Wogonin suppressed the differentiation of naïve T cells to Th17 cells, while showing no effects on activated Th17 cells.
    Preview · Article · May 2014
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    ABSTRACT: The present study aimed to test the construct validity and internal consistency of the Social Cognition Screening Questionnaire (SCSQ)(1) (Japanese version). We first tested whether the subscale scores and the total score of the SCSQ could discriminate patients with schizophrenia from normal controls. Next, we tested the internal consistency. Finally, we investigated the relationship between the subscale scores and other measures of social cognition and social functioning that were presumed to correspond to the subscale's scores, including the Hinting task, the Ambiguous Intentions Hostility Questionnaire (AIHQ), the Beck Cognitive Insight Scale (BCIS) and the Social Functioning Scale (SFS). The subscale scores and the total score appeared to show more robust between-group differences than other measures of social cognition, such as the AIHQ and the Hinting task. The total score distinguished the patients from normal controls with the area under the receiver-operator characteristics (ROC) curve being 0.84, which was fairly well. The Cronbach's alpha for the four subscales was 0.72, which was considered acceptable. In terms of criterion-related validity, theory of mind, metacognition and hostility bias subscale scores showed significant correlations with the Hinting task, BCIS and AIHQ, respectively. Moreover, the theory of mind subscale score showed a significant correlation with four domain scores of the SFS. The present results indicated good construct validity and internal consistency of the SCSQ. Although this is an interim report with a small sample size, the SCSQ holds promise as an efficient measure for social cognition.
    Full-text · Article · Mar 2014 · Psychiatry and Clinical Neurosciences

Publication Stats

2k Citations
537.04 Total Impact Points


  • 2012-2015
    • National Center of Neurology and Psychiatry
      Кодаиры, Tōkyō, Japan
    • University of Wisconsin–Madison
      • Department of Pediatrics
      Madison, Wisconsin, United States
  • 2009-2015
    • Saitama Medical University
      • • Allergy Center
      • • Department of Respiratory Medicine
      Саитама, Saitama, Japan
    • Kyoto University
      • Institute for Frontier Medical Sciences
      Kioto, Kyōto, Japan
  • 2006-2015
    • Tottori University
      • • Department of Brain and Neurosciences
      • • Faculty of Medicine
      • • Department of Multidisciplinary Internal Medicine
      • • School of Medicine
      TTJ, Tottori, Japan
  • 1990-2013
    • The University of Tokyo
      • • Department of Allergy and Rheumatology
      • • Department of Neuropsychiatry
      • • Department of Child Psychiatry
      Tōkyō, Japan
  • 2001-2008
    • Showa University
      • • Department of Psychiatry
      • • Department of Medicine
      Shinagawa, Tōkyō, Japan
  • 2007
    • Aino University
      Takatuki, Ōsaka, Japan
  • 2000
    • Gunma University
      Maebashi, Gunma, Japan
  • 1999-2000
    • Teikyo University Hospital
      Edo, Tōkyō, Japan
  • 1993-1999
    • Teikyo University
      • Department of Medicine
      Edo, Tōkyō, Japan