Outpatient Clinic for Anxiety Disorders

Tokyo, Japan

Outpatient Clinic for Anxiety Disorders

Tokyo, Japan
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Otowa T.,University of Tokyo | Otowa T.,Virginia Commonwealth University | Kawamura Y.,University of Tokyo | Sugaya N.,Waseda University | And 12 more authors.
Progress in Neuro-Psychopharmacology and Biological Psychiatry | Year: 2011

Background: Panic disorder (PD) is a severe and chronic psychiatric disorder with genetic components underlying in its etiology. The Phosphodiesterase 4B (PDE4B) gene has been reported to be associated with several psychiatric disorders. Several studies indicated that PDE4B may be involved in the regulation of anxiety and depression. Therefore, we investigate the association of PDE4B with PD in the Japanese population. Methods: We genotyped 14 single nucleotide polymorphisms (SNPs) of PDE4B in 231 PD cases (85 males and 146 females) and 407 controls (162 males and 245 females). Differences in the genotype, allele and haplotype frequencies between the two groups were compared. Results: We found a significant association between PDE4B and PD in the haplotype analysis (haplotype C-T-T-A, permutation P=0.031, OR = 1.81, 95% CI = 1.30-2.51). Sex-specific analyses demonstrated that PDE4B was associated with PD in females in the allele/genotype and haplotype analyses (rs10454453, allele P=0.042, genotype P=0.0034; haplotype C-T-T-A, permutation P=0.028). Conclusion: Our results suggest that PDE4B may play a role in the pathophysiology of PD in the Japanese population. Replication studies using larger samples will be needed for more reliable conclusions. © 2010 Elsevier Inc.


Kawamura Y.,Outpatient Clinic for Anxiety Disorders | Kawamura Y.,Research Center for Panic Disorder | Otowa T.,University of Tokyo | Koike A.,Hitachi Ltd. | And 18 more authors.
Journal of Human Genetics | Year: 2011

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. © 2011 The Japan Society of Human Genetics All rights reserved.


Otowa T.,Virginia Commonwealth University | Otowa T.,University of Tokyo | Shimada T.,University of Tokyo | Kawamura Y.,University of Tokyo | And 14 more authors.
American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics | Year: 2011

Panic disorder (PD) is a severe and chronic psychiatric disorder with significant genetic components underlying its etiology. The gene regulator of G protein signaling 2 (RGS2) has been reported to be associated with anxiety disorders. To confirm the association of RGS2 with PD, we investigated three single nucleotide polymorphisms (SNPs) of RGS2 (rs10801152, rs4606, and rs1819741) in 677 Japanese PD cases and 460 controls. The SNP rs10801152 was suggestive of an association with PD (allele P=0.045 adjusted using sex and age as confounding factors). The three-SNP haplotype was significantly associated with PD (global permutation P=4×10-4). The haplotypes T-G-C and T-C-T showed significant association and protective effect on PD (T-G-C, permutation P=0.038, OR=0.80, 95%CI=0.68-0.95; T-C-T, permutation P=0.004, OR=0.38, 95%CI=0.21-0.70). These results provide support for an association of RGS2 with PD in a Japanese population. © 2011 Wiley-Liss, Inc.


Sugaya N.,Tokyo Metropolitan Institute of Medical Science | Sugaya N.,Waseda University | Yoshida E.,Outpatient Clinic for Anxiety Disorders | Yasuda S.,Tokyo Metropolitan Institute of Medical Science | And 18 more authors.
Psychiatry and Clinical Neurosciences | Year: 2013

Aim 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). Methods 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. Results 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. Conclusion 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. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.


Otowa T.,University of Tokyo | Tanii H.,Mie University | Sugaya N.,Outpatient Clinic for Anxiety Disorders | Yoshida E.,Outpatient Clinic for Anxiety Disorders | And 14 more authors.
Journal of Human Genetics | Year: 2010

Panic disorder (PD) is an anxiety disorder characterized by recurrent and unexpected panic attacks, subsequent worry and phobic avoidance. Although a number of association and linkage studies have been conducted, no gene has been identified as a susceptibility locus. We previously conducted a genome-wide association analysis of PD in 200 Japanese patients and the same number of controls, using a 500 K single nucleotide polymorphisms (SNPs) chip. In this study, we report a replication analysis of PD using the DigTag2 assay. The second stage sample consisted of 558 Japanese patients and 566 controls. Thirty-two markers were tested in a replication sample. As a result, no significant association was found after correction for multiple testing. However, the difference was observed at the nominal allele P-value <0.05 for two SNPs (rs6733840 and rs132617). We also conducted haplotype analyses of SNPs in the APOL3 and CLU genes. Our results failed to show any significant association with PD in these genes. Further studies on these variants with a larger sample size may be worth testing to confirm the results. © 2010 The Japan Society of Human Genetics All rights reserved.


Otowa T.,University of Tokyo | Otowa T.,Virginia Commonwealth University | Kawamura Y.,Sakae Seijinkai Hospital | Nishida N.,University of Tokyo | And 31 more authors.
Translational Psychiatry | Year: 2012

Panic disorder (PD) is a moderately heritable anxiety disorder whose pathogenesis is not well understood. Due to the lack of power in previous association studies, genes that are truly associated with PD might not be detected. In this study, we conducted a genome-wide association study (GWAS) in two independent data sets using the Affymetrix Mapping 500K Array or Genome-Wide Human SNP Array 6.0. We obtained imputed genotypes for each GWAS and performed a meta-analysis of two GWAS data sets (718 cases and 1717 controls). For follow-up, 12 single-nucleotide polymorphisms (SNPs) were tested in 329 cases and 861 controls. Gene ontology enrichment and candidate gene analyses were conducted using the GWAS or meta-analysis results. We also applied the polygenic score analysis to our two GWAS samples to test the hypothesis of polygenic components contributing to PD. Although genome-wide significant SNPs were not detected in either of the GWAS nor the meta-analysis, suggestive associations were observed in several loci such as BDKRB2 (P=1.3 × 10 -5, odds ratio=1.31). Among previous candidate genes, supportive evidence for association of NPY5R with PD was obtained (gene-wise corrected P=6.4 × 10 -4). Polygenic scores calculated from weakly associated SNPs (P<0.3 and 0.4) in the discovery sample were significantly associated with PD status in the target sample in both directions (sample I to sample II and vice versa) (P<0.05). Our findings suggest that large sets of common variants of small effects collectively account for risk of PD. © 2012 Macmillan Publishers Limited All rights reserved.


Sugaya N.,Yokohama City University | Yoshida E.,Outpatient Clinic for Anxiety Disorders | Yasuda S.,Outpatient Clinic for Anxiety Disorders | Yasuda S.,Kinkou Hospital | And 14 more authors.
BioPsychoSocial Medicine | Year: 2015

Several studies have reported an increased tendency towards anger in patients with panic disorder (PD). If this propensity for anger arises from the pathological process of PD, it may be associated with the duration of the illness. The present study therefore examined the relationship between duration of PD and the personality tendency to experience anger in PD patients. Methods: Participants were 413 patients (132 men and 281 women; age=38.7years) with PD. Diagnoses were confirmed using the Mini-International Neuropsychiatric Interview. Illness duration ranged from less than a year to 51years. After participants completed the Revised NEO Personality Inventory, we examined the association between illness duration and the Angry Hostility and Impulsiveness subscale scores. In the analysis, participants were divided into two groups by duration of illness (long group, n = 186 and short group, n=200) using the median value (9years) as a cut-off because of the skewed distribution of the duration. Patients with an illness duration of 9years (n=27) were excluded from the comparison. Results: The duration of illness was significantly correlated with the Angry Hostility score (p=0.002) after controlling for age. Scores were significantly higher in the long group than in the short group (p=0.04). No significant association was observed between Impulsiveness scores and duration of illness. Conclusion: The present study suggests that longer PD duration is related to a stronger tendency to experience anger. © Sugaya et al.


Sugaya N.,Tokyo Metropolitan Institute of Medical Science | Sugaya N.,Waseda University | Yoshida E.,Outpatient Clinic for Anxiety Disorders | Yasuda S.,Outpatient Clinic for Anxiety Disorders | And 18 more authors.
Journal of Affective Disorders | Year: 2013

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. © 2012 Elsevier B.V. All rights reserved.


PubMed | Outpatient Clinic for Anxiety Disorders
Type: Journal Article | Journal: Journal of human genetics | Year: 2011

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.


PubMed | Research Center for Panic Disorder, Waseda University, Koseikai Michinoo Hospital, University of Tokyo and 5 more.
Type: | Journal: BioPsychoSocial medicine | Year: 2015

Several studies have reported an increased tendency towards anger in patients with panic disorder (PD). If this propensity for anger arises from the pathological process of PD, it may be associated with the duration of the illness. The present study therefore examined the relationship between duration of PD and the personality tendency to experience anger in PD patients.Participants were 413 patients (132 men and 281 women; age=38.7years) with PD. Diagnoses were confirmed using the Mini-International Neuropsychiatric Interview. Illness duration ranged from less than a year to 51years. After participants completed the Revised NEO Personality Inventory, we examined the association between illness duration and the Angry Hostility and Impulsiveness subscale scores. In the analysis, participants were divided into two groups by duration of illness (long group, n=186 and short group, n=200) using the median value (9years) as a cut-off because of the skewed distribution of the duration. Patients with an illness duration of 9years (n=27) were excluded from the comparison.The duration of illness was significantly correlated with the Angry Hostility score (p=0.002) after controlling for age. Scores were significantly higher in the long group than in the short group (p=0.04). No significant association was observed between Impulsiveness scores and duration of illness.The present study suggests that longer PD duration is related to a stronger tendency to experience anger.

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