Kunio Takei

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

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Publications (15)65.65 Total impact

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    ABSTRACT: The present study examined the effect of irritable bowel syndrome (IBS), cognitive appraisal of IBS, and anxiety sensitivity on anticipatory anxiety (AA) and agoraphobia (AG) in patients with panic disorder (PD). We examined 244 PD patients who completed a set of questionnaires that included the Rome II Modular Questionnaire to assess the presence of IBS, the Anxiety Sensitivity Index (ASI), the Cognitive Appraisal Rating Scale (CARS; assessing the cognitive appraisal of abdominal symptoms in four dimensions: commitment, appraisal of effect, appraisal of threat, and controllability), and items about the severity of AA and AG. The Mini International Neuropsychiatric Interview was used to diagnose AG and PD. After excluding individuals with possible organic gastrointestinal diseases by using 'red flag items,' valid data were obtained from 174 participants, including 110 PD patients without IBS (PD/IBS[-]) and 64 with IBS (PD/IBS[+]). The PD/IBS[+] group had higher AA and higher comorbidity with AG than the PD/IBS[-] group. In the PD/IBS[+] group, the controllability score of CARS was significantly correlated with AA and ASI. Multiple regression analysis showed a significant effect of ASI but not of controllability on AA in PD/IBS[+] subjects. This study suggested that the presence of IBS may be related to agoraphobia and anticipatory anxiety in PD patients. Cognitive appraisal could be partly related to anticipatory anxiety in PD patients with IBS with anxiety sensitivity mediating this correlation.
    Psychiatry and Clinical Neurosciences 07/2013; · 2.04 Impact Factor
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    ABSTRACT: Near-infrared spectroscopy (NIRS) studies have reported that prefrontal hemodynamic dysfunction during executive function tasks may be a promising biomarker of psychiatric disorders, because its portability and noninvasiveness allow easy measurements in clinical settings. Here, we investigated the degree to which prefrontal NIRS signals are genetically determined. Using a 52-channel NIRS system, we monitored the oxy-hemoglobin (oxy-Hb) signal changes in 38 adult pairs of right-handed monozygotic (MZ) twins and 13 pairs of same-sex right-handed dizygotic (DZ) twins during a letter version of the verbal fluency task. Heritability was estimated based on a classical twin paradigm using structured equation modeling. Significant genetic influences were estimated in the right dorsolateral prefrontal cortex and left frontal pole. The degrees of heritability were 66% and 75% in the variances, respectively. This implies that the prefrontal hemodynamic dysfunction observed during an executive function task measured by NIRS may be an efficient endophenotype for large-scale imaging/genetics studies in psychiatric disorders.
    NeuroImage 04/2013; · 6.25 Impact Factor
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    Journal of Affective Disorders 01/2013; · 3.30 Impact Factor
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    ABSTRACT: BACKGROUND: We examined the rate of bipolar I (BPD-I) and bipolar II disorders (BPD-II) in panic disorder (PD) patients, and compared clinical and psychological variables between PD patients with and without bipolar disorders (BPD). METHODS: Participants were 649 Japanese patients with PD (215 men and 434 women, 38.49±10.40 years) at outpatient clinics for anxiety disorders. Constructive interviews using the Mini-International Neuropsychiatric Interview (MINI) were conducted to confirm the diagnosis of PD, agoraphobia, and BPD, as well as the presence and severity of suicide risk in each subject. Clinical records were also reviewed to confirm the diagnosis of PD and BPD. Participants then completed several questionnaires, including the State Trait Anxiety Inventory-Trait scale, the Anxiety Sensitivity Index, and the Revised Neuroticism-Extraversion- Openness Personality Inventory (NEO-PI-R). RESULTS: We found that 22.34% of the PD patients had BPD (BPD-I: 5.24%, BPD-II: 17.10%). PD patients with BPD-I showed higher prevalence and severity of suicide risk, trait anxiety, anxiety sensitivity, and neuroticism, and lower agreeableness (subscales of the NEO-PI-R) than those with BPD-II and those without BPD. LIMITATION: First, we could not investigate the order of the onset of PD and BPD. Second, BPD patients without PD were not studied as another control group for PD patients with BPD. CONCLUSION: PD patients had high prevalence of BPD. Both PD patients with BPD-I and those with BPD-II had high severity of suicide risk, trait anxiety, anxiety sensitivity, neuroticism, and agreeableness, though these characteristics were more prominent in patients with BPD-I.
    Journal of affective disorders 11/2012; · 3.76 Impact Factor
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    ABSTRACT: Family and twin studies have indicated that genetic factors have an important role in panic disorder (PD), whereas its pathogenesis has remained elusive. We conducted a genome-wide copy number variation (CNV) association study to elucidate the involvement of structural variants in the etiology of PD. The participants were 2055 genetically unrelated Japanese people (535 PD cases and 1520 controls). CNVs were detected using Genome-Wide Human SNP array 6.0, determined by Birdsuite and confirmed by PennCNV. They were classified as rare CNVs (found in <1% of the total sample) or common CNVs (found in ≥5%). PLINK was used to perform global burden analysis for rare CNVs and association analysis for common CNVs. The sample yielded 2039 rare CNVs and 79 common CNVs. Significant increases in the rare CNV burden in PD cases were not found. Common duplications in 16p11.2 showed Bonferroni-corrected P-values <0.05. Individuals with PD did not exhibit an increased genome-wide rare CNV burden. Common duplications were associated with PD and found in the pericentromeric region of 16p11.2, which had been reported to be rich in low copy repeats and to harbor developmental disorders, neuropsychiatric disorders and dysmorphic features.
    Journal of Human Genetics 12/2011; 56(12):852-6. · 2.37 Impact Factor
  • Biological psychiatry 08/2011; · 8.93 Impact Factor
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    ABSTRACT: The study was conducted to evaluate simultaneously gray matter changes and white matter changes in patients with schizophrenia. Cortical thickness, gray matter volume, and white matter anisotropy and diffusivity changes in schizophrenic patients (n = 21) were assessed relative to age-, gender-, and parental socioeconomic status-matched healthy controls (n = 21). We used a newly described semi-automated method (FreeSurfer version 4.5) to determine cortical thickness and gray matter volume and used the tract-based spatial statistics method to evaluate white matter anisotropy and diffusivity. Schizophrenic patients showed a significant decrease in hippocampal volume compared with healthy controls. No significant thickness deficits or anisotropy and diffusivity changes were found in schizophrenic patients compared with healthy controls. Stepwise multivariate analysis revealed that hippocampal volume was positively related to duration of illness in schizophrenic patients. Our results suggest that hippocampal volume is smaller in schizophrenic patients compared with healthy controls and that progressive hippocampal volume loss occurs in the early course of illness in schizophrenic patients but not in the more chronic stages.
    Neuroradiology 01/2011; 53(11):859-66. · 2.70 Impact Factor
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    ABSTRACT: Recent studies have suggested that oxytocin affects social cognition and behavior mediated by the oxytocin receptor (OXTR) in amygdala in humans as well as in experimental animals. Genetic studies have revealed a link between the OXTR gene and the susceptibility to autism spectrum disorders (ASD), especially in the social dysfunctional feature of ASD. We examined the relationship between amygdala volume measured with manual tracing methodology and seven single nucleotide polymorphisms and one haplotype-block in OXTR, which were previously reported to be associated with ASD, in 208 socially intact Japanese adults with no neuropsychiatric history or current diagnosis. The rs2254298A allele of OXTR was significantly associated with larger bilateral amygdala volume. The rs2254298A allele effect on amygdala volume varied in proportion to the dose of this allele. The larger the number of rs2254298A alleles an individual had, the larger their amygdala volume. Such an association was not observed with hippocampal volume or with global brain volumes, including whole gray, white matter, and cerebrospinal-fluid space. Furthermore, two three-single nucleotide polymorphism haplotypes, including rs2254298G allele, showed significant associations with the smaller bilateral amygdala volume. The present results suggest that OXTR might be associated with the susceptibility to ASD, especially in its aspects of social interaction and communication mediated by a modulation of amygdala development, one of the most distributed brain regions with high density of OXTR. Furthermore, amygdala volume measured with magnetic resonance imaging could be a useful intermediate phenotype to uncover the complex link between OXTR and social dysfunction in ASD.
    Biological psychiatry 12/2010; 68(11):1066-72. · 8.93 Impact Factor
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    ABSTRACT: The purpose of this study is to elucidate sex differences in global and regional gray/white matter volume, mean diffusivity (MD), and fractional anisotropy (FA) during normal aging using voxel-based analysis. We studied 245 healthy right-handed subjects with a wide range of ages (115 women, 22-70 years; 130 men, 21-71 years). Regarding global effects, inclusion of a quadratic age term improved the fit to data for white matter fraction and MD, but not for global gray matter volume/fraction or FA. Regarding regional effects, we found anterior-dominant volume loss, FA decrease predominantly in the anterior white matter, and MD increase predominantly in perisylvian regions and periventricular white matter against age for both sexes. Compared with women, we found a steeper FA decline for men in the right inferior fronto-temporal areas, extending to the anterior cingulate cortex, and an accelerated MD increase for men in the bilateral frontal, temporal, and parietal areas. There was no area in which interaction of sex with age was significant for regional volume, or in which a steeper FA decline or accelerated MD increase for women was significant. Our results provide strong evidence of sex dimorphism in global and focal diffusion characteristics during normal aging.
    NMR in Biomedicine 03/2010; 23(5):446-58. · 3.45 Impact Factor
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    ABSTRACT: Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin (5-HT). Genetic variations in human TPH2, a newly identified isoform of TPH, have been shown to impact on enzymatic activity of TPH and to be associated with emotion-related personality traits and mood/anxiety disorders. Identification of an intermediate phenotype that bridges the relationship between genes and behavior may be of great importance in the further clarification of how hTPH2 contributes to emotional regulation. Previous studies have shown that a polymorphism in the upstream regulatory region of hTPH2 (SNP G-703T, rs4570625) correlates functional MRI response of the amygdala. In this study, we examined the effect of this genotype on amygdalar and hippocampal volumes in 208 mentally healthy individuals. To measure volumes of amygdala and hippocampus, gray matter regions of interest were outlined manually on three-dimensional MRI data obtained using a 1.5-T scanner. Additionally, personality traits were evaluated using the Temperament and Character Inventory (TCI). Those subjects with T allele carriers were associated with significantly smaller volumes in bilateral amygdala and hippocampus and higher reward dependence than those with G allele homozygotes. These results suggest that amygdalar and hippocampal volumes assessed using MRI may be a useful intermediate phenotype that will uncover the biological pathway linking 5-HT synthesis and emotional behaviors and affective disorders.
    Brain research 03/2010; 1331:51-7. · 2.46 Impact Factor
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    ABSTRACT: Previous literature has suggested an important role of inferior frontal gyrus, which mainly consists of Brodmann's Area (BA) 44 and 45, in the pathophysiology of schizophrenia. While recent neuroimaging techniques have revealed differential functional correlates of BA 44 and 45 in healthy individuals, previous studies have not yet separately evaluated the gray matter volume reduction of BA 44 and 45 and their relationships to psychotic symptoms in patients with schizophrenia. In the present study, magnetic resonance images were obtained from 29 right-handed male patients with schizophrenia and from 29 age- and handedness-matched healthy male controls. The reliable manual tracing methodology was employed to measure the gray matter volume of BA 44 and BA 45. The severities of psychotic symptoms were evaluated using the five-factor model of positive and negative syndrome scale in the patient group. A significant gray matter volume reduction of both the BA 44 and BA 45 was found bilaterally in the patients with schizophrenia compared with the healthy controls. Among these inferior frontal sub-regions, reduced volume of right BA 45 revealed the largest effect size. In addition, the reduced volume of BA 45 in left hemisphere showed a significant association with the increased severity of delusional behavior, while the severity of disorganized and positive symptoms were correlated with the bilateral BA 45 volumes in the patient group. The findings support an important role of inferior frontal gyrus in the pathophysiology of schizophrenia. The present study further demonstrated that BA 45 might especially contribute to the production of psychotic symptoms in the patients with schizophrenia.
    European Archives of Psychiatry and Clinical Neuroscience 12/2009; 260(6):465-73. · 3.36 Impact Factor
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    ABSTRACT: The purpose of this study is to use voxel-based analysis to simultaneously elucidate regional changes in gray/white matter volume, mean diffusivity (MD), and fractional anisotropy (FA) in patients with unipolar major depressive disorder. We studied 21 right-handed patients and 42 age- and gender-matched right-handed normal subjects. Local areas showing significant gray matter volume reduction in depressive patients compared with controls were observed in the right parahippocampal gyrus, hippocampus, bilateral middle frontal gyri, bilateral anterior cingulate cortices, left parietal and occipital lobes, and right superior temporal gyrus. Local areas showing an increase of MD in depressive patients were observed in the bilateral parahippocampal gyri, hippocampus, pons, cerebellum, left frontal and temporal lobes, and right frontal lobe. There was no significant difference between the two groups for FA and white matter volume in the entire brain. Although there was no local area where brain volume and MD were significantly correlated with disease severity, FA tended to correlate negatively with total days depressed in the right anterior cingulate and the left frontal white matter. These results suggest that the frontolimbic neural circuit might play an important role in the neuropathology of patients with major depressive disorder.
    Psychiatry Research 12/2009; 181(1):64-70. · 2.68 Impact Factor
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    ABSTRACT: Previous diffusion tensor imaging (DTI) studies have shown structural abnormalities of the cingulum bundle (CB) in patients with schizophrenia. However, regional specificity and functional relevance of the pregenual and dorsal CB subdivisions has not been fully studied. In the current study, 31 patients with schizophrenia and 65 age- and gender-matched healthy subjects underwent DTI to measure fractional anisotropy (FA) and mean diffusivity (MD) in cross sections of dorsal and pregenual CB tractography. To test the hypothesis of region-specific association with neurocognition, all of the patients and 31 controls performed the Stroop task, which is assumed to mainly involve dorsal cingulate function. The verbal memory subscale of Wechsler Memory Scale-Revised and premorbid IQs estimated from the Japanese version of the National Adult Reading Test, which were non-specific to dorsal cingulate function, were also employed as control neurocognitive indices. Significant bilateral FA reductions in the pregenual and dorsal CB, and bilateral MD increases in the dorsal CB were observed in the patients compared with the controls. As predicted, significant associations between DTI measures and neurocognition were found in the schizophrenia group only: double-dissociable correlation between higher MD in the dorsal, not in the pregenual CB, and a longer reaction time in the Stroop task, not verbal memory or premorbid IQs. The current DTI study suggests that structural disruption of the dorsal CB has region-specific functional relevance to selective attention deficits, although structural disruption also exists in the pregenual CB in patients with schizophrenia.
    Schizophrenia Research 07/2009; 114(1-3):119-27. · 4.59 Impact Factor
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    ABSTRACT: Chronic excessive alcohol intake results in alcohol-related brain damage. Many previous reports have documented alcohol-related global or local brain shrinkage or diffusional abnormalities among alcoholics and heavy to moderate drinkers; however, the influence of relatively low levels of alcohol consumption on brain structural or diffusional abnormality is unclear. We investigated structural or diffusional abnormalities related to lifetime alcohol consumption (LAC) using voxel-based morphometry (VBM) among Japanese non-alcohol-dependent individuals (114 males, 97 females). High-resolution three-dimensional magnetic resonance images and diffusion tensor imaging were acquired in all subjects. The collected images were normalized, segmented, and smoothed using SPM 5. Gray matter volume (GMV) and white matter volume (WMV) were normalized for each total intracranial volume (TIV), and partial correlation coefficients were estimated between normalized GMV or WMV and lifetime alcohol consumption (LAC) adjusted for age. To investigate regional GMV or WMV abnormalities related to LAC, multiple regression analyses were performed among regional GMV or WMV and LAC, age, and TIV. To investigate subtle regional abnormalities, multiple regression analyses were performed among fractional anisotropy (FA) or mean diffusivity (MD), and LAC and age. No LAC-related global or regional GMV or WMV abnormality or LAC-related regional FA abnormality was found among male or female subjects. Significant LAC-related MD increase was found in the right amygdala among female subjects only. The current results suggest female brain vulnerability to alcohol, and a relation between subtle abnormality in the right amygdala and alcohol misuse.
    NeuroImage 03/2009; 46(2):505-10. · 6.25 Impact Factor
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    ABSTRACT: The fornix is a major projection of the hippocampus to and from other brain regions. A previous diffusion tensor imaging (DTI) study has reported disrupted integrity of the fornix in patients with schizophrenia. However, functional significance of the DTI abnormalities of the fornix in schizophrenia has not been fully studied yet. We investigated an association between DTI abnormalities of the fornix and impairment of memory organization in schizophrenia. Thirty-one patients with schizophrenia and 65 age- and gender-matched healthy controls underwent DTI, and fractional anisotropy (FA) and mean diffusivity (MD) were measured in cross-sections of fornix tractography. In addition, all of the patients and 32 controls performed a verbal learning task specialized for evaluating memory organization, the verbal memory subscale of the Wechsler Memory Scale-Revised, the category- and letter fluency tests, and the Japanese version of National Adult Reading Test. Statistically significant reduction of FA and increase of MD were found in the fornix of patients with schizophrenia compared with controls with no significant lateralization. A significant patients-specific correlation was found between increased MD in the left fornix and lower scores on utilization of semantic organization in the verbal learning task. In addition, increased MD in the right fornix showed a patients-specific association with poorer performance on the category fluency test, which indexes organization of long-term semantic memory. These patients-specific correlations, however, were not statistically lateralized to either hemisphere. These results indicate that disrupted integrity of the fornix contributes to impaired memory organization in schizophrenia.
    Schizophrenia Research 09/2008; 103(1-3):52-61. · 4.59 Impact Factor

Publication Stats

205 Citations
65.65 Total Impact Points


  • 2013
    • National Center of Neurology and Psychiatry
      Кодаиры, Tōkyō, Japan
  • 2008–2013
    • The University of Tokyo
      • • Department of Neuropsychiatry
      • • Faculty & Graduate School of Medicine
      • • Department of Neuroscience
      Edo, Tōkyō, Japan