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Panic disorder (PD), a common anxiety disorder, is modestly heritable. The genetic basis of anxiety disorders overlaps with that of other psychiatric disorders and their intermediate phenotypes in individuals of European ancestry. Here, we investigated the transethnic polygenetic features shared between Japanese PD patients and European patients with psychiatric disorders and their intermediate phenotypes by conducting polygenic risk score (PRS) analyses. Large-scale European genome-wide association study (GWAS) datasets (n = 7,556–1,131,881) for ten psychiatric disorders and seven intermediate phenotypes were utilized as discovery samples. PRSs derived from these GWASs were calculated for Japanese target subjects [718 PD patients and 1,717 healthy controls (HCs)]. The effects of these PRSs from European GWASs on the risk of PD in Japanese patients were investigated. The PRSs from European studies of anxiety disorders were marginally higher in Japanese PD patients than in HCs (p = 0.013). Regarding other psychiatric disorders, the PRSs for depression in European patients were significantly higher in Japanese PD patients than in HCs (p = 2.31×10–4), while the PRSs for attention-deficit/hyperactivity disorder in European patients were nominally lower in Japanese PD patients than in HCs (p = 0.024). Regarding health-related, personality-based and cognitive intermediate phenotypes, the PRSs for loneliness (especially isolation) in European individuals were significantly higher in Japanese PD patients than in HCs (p = 9.02×10–4). Furthermore, Japanese PD patients scored nominally higher than HCs in PRSs for neuroticism in European people (p = 3.37×10–3), while Japanese PD patients scored nominally lower than HCs in PRSs for tiredness (p = 0.025), educational attainment (p = 0.035) and cognitive function (p = 9.63×10–3). Our findings suggest that PD shares transethnic genetic etiologies with other psychiatric disorders and related intermediate phenotypes.

Aim: This is the third version of the guideline of the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive–Compulsive and Posttraumatic Stress Disorders (published in 2002, revised in 2008). Method: A consensus panel of 33 international experts representing 22 countries developed recommendations based on efficacy and acceptability of available treatments. In total, 1007 RCTs for the treatment of these disorders in adults, adolescents, and children with medications, psychotherapy and other non-pharmacological interventions were evaluated, applying the same rigorous methods that are standard for the assessment of medications. Result: This paper, Part I, contains recommendations for the treatment of panic disorder/agoraphobia (PDA), generalised anxiety disorder (GAD), social anxiety disorder (SAD), specific phobias, mixed anxiety disorders in children and adolescents, separation anxiety and selective mutism. Selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are first-line medications. Cognitive behavioural therapy (CBT) is the first-line psychotherapy for anxiety disorders. The expert panel also made recommendations for patients not responding to standard treatments and recommendations against interventions with insufficient evidence. Conclusion: It is the goal of this initiative to provide treatment guidance for these disorders that has validity throughout the world.

Aim: This is the third version of the guideline of the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive–Compulsive and Posttraumatic Stress Disorders which was published in 2002 and revised in 2008. Method: A consensus panel of 34 international experts representing 22 countries developed recommendations based on efficacy and acceptability of the treatments. In this version, not only medications but also psychotherapies and other non-pharmacological interventions were evaluated, applying the same rigorous methods that are standard for the assessment of medication treatments. Result: The present paper (Part II) contains recommendations based on published randomised controlled trials (RCTs) for the treatment of OCD (n = 291) and PTSD (n = 234) in children, adolescents, and adults. The accompanying paper (Part I) contains the recommendations for the treatment of anxiety disorders. For OCD, first-line treatments are selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioural therapy (CBT). Internet-CBT was also superior to active controls. Several second-line medications are available, including clomipramine. For treatment-resistant cases, several options are available, including augmentation of SSRI treatment with antipsychotics and other drugs. Other non-pharmacological treatments, including repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS) and others were also evaluated. For PTSD, SSRIs and the SNRI venlafaxine are first-line treatments. CBT is the psychotherapy modality with the best body of evidence. For treatment-unresponsive patients, augmentation of SSRI treatment with antipsychotics may be an option. Conclusion: OCD and PTSD can be effectively treated with CBT and medications.

Background:The use of mindfulness in the treatment of anxiety and depression is becoming more and more widespread, but there are few reports that it has fundamentally changed patients' sense of life. Case Presentation:This report showed 9 year’s progress of treatment for Social Anxiety Disorder and Persistent Depressive Disorder in a 41year-old female patient experiencing a long-term painful married life with a carefree husband and controlling mother-in-law. During the past 25 months, she received 180 sessions of mindfulness training, resulting in complete remission of the anxiety and depression symptoms. After the 30th session she experienced an episode of the catharsis during the mindfulness training and experienced what can be called Mindfulness-To-Meaning, which is characterized by durable eudaimonic well-being in the face of adversity. Discussion and Conclutions:The psychological mechanisms that supported arriving at Mindfulness-To-Meaning were delineated as: Heightened (1) awareness which promoted (2) verbalization of the primary theme of suppression, in which the stress was (3) appraised metacognitively. Then (4) decentering permitted integrating this painful theme into a new adaptive self and world view, which resulted in (5) emotional catharsis, or release. Furthermore (6) positive appraisal of this experience enhanced awareness and led to the experience of (7) Mindfulness-To-Meaning .

Background Anxious-depressive attack (ADA) is a symptom complex that comprises sudden intense feelings of anxiety or depression, intrusive rumination of regretful memories or future worries, emotional distress due to painful thoughts, and coping behaviors to manage emotional distress. ADA has been observed trans-diagnostically across various psychiatric disorders. Although the importance of ADA treatment has been indicated, a scale to measure the severity of ADA has not been developed. This study aimed to develop an Anxious-Depressive Attack Severity Scale (ADAS) to measure the severity of ADA symptoms and examine its reliability and validity. Methods A total of 242 outpatients responded to a questionnaire and participated in an interview, which were designed to measure the severity of ADA, depressive, anxiety, anxious depression, and social anxiety symptoms. Based on the diagnostic criteria for ADA, 54 patients were confirmed to have ADA and were included in the main study analyses. Results The exploratory factor analysis of the ADAS identified a two factor structure: severity of ADA symptoms and ADA frequency and coping behaviors. McDonald’s ωt coefficients were high for the overall scale and the first factor (ωt = .78 and ωt = .83, respectively) but low for the second factor (ωt = .49). The ADAS score was significantly positively correlated with clinical symptoms related to anxiety and depression. Conclusion The present study demonstrated that the ADAS has sufficient reliability and validity; however, internal consistency was insufficient for the second factor. Overall, the ADAS has potential to be a valuable tool for use in clinical trials of ADA.

Background Cultural factors influence both the expression of social anxiety and the interpretation and functioning of social anxiety measures. This study aimed to test the measurement equivalence of two commonly used social anxiety measures across two sociocultural contexts using individuals with social anxiety disorder (SAD) from Australia and Japan. Methods Scores on the straightforwardly-worded Social Interaction Anxiety Scale (S-SIAS) and the Social Phobia Scale (SPS) from two archival datasets of individual with SAD, one from Australia (n = 201) and one from Japan (n = 295), were analysed for measurement equivalence using a multigroup confirmatory factor analysis (CFA) framework. Results The best-fitting factor models for the S-SIAS and SPS were not found to be measurement equivalent across the Australian and Japanese samples. Instead, only a subset of items was invariant. When this subset of invariant items was used to compare social anxiety symptoms across the Australian and Japanese samples, Japanese participants reported lower levels of fear of attracting attention, and similar levels of fear of overt evaluation, and social interaction anxiety, relative to Australian participants. Limitations We only analysed the measurement equivalence of two social anxiety measures using a specific operationalisation of culture. Future studies will need to examine the measurement equivalence of other measures of social anxiety across other operationalisations of culture. Conclusions When comparing social anxiety symptoms across Australian and Japanese cultures, only scores from measurement equivalent items of social anxiety measures should be used. Our study highlights the importance of culturally-informed assessment in SAD.

Introduction: Panic disorder (PD) has many comorbidities such as depression, bipolar disorder (BPD), and agoraphobia (AG). PD is a moderately heritable anxiety disorder whose pathogenesis is not well understood. Recently, a tri-allelic serotonin transporter (5-HTTLPR/rs25531) polymorphism was reported to be more sensitive to personality traits compared to the bi-allelic 5-HTTLPR polymorphism. We hypothesized that the 5-HTTLPR/rs25531 polymorphism may lead to a pathological anxious state depending on the presence or absence of a comorbidity in PD. Methods: In this study, we investigated the relationship between comorbidities in PD and tri-allelic 5-HTTLPR polymorphisms. A total of 515 patients with PD (148 males, 367 females) were genotyped, and the Revised NEO Personality Inventory as well as anxiety-related psychological tests were administered. Depression, BPD, and AG were diagnosed as comorbidities. Results: For the tri-allele 5-HTTLPR genotype, a significant interaction effect was found between openness to experience and comorbid depression. Examination of the interaction between AG and the tri-allelic 5-HTTLPR genotype revealed that L’ allele carriers are associated with higher trait anxiety than the S’S’ genotype group in PD without AG. Conclusion: Some anxiety and personality traits can be characterized by the tri-allelic gene effect of 5-HTTLPR. These results suggest that tri-allelic 5-HTTLPR genotypes have genetic effects on the presence of comorbidities of PD.

Background Copy number variants (CNVs) have been reported to be associated with diseases, traits, and evolution. However, it is hard to determine which gene should have priority as a target for further functional experiments if a CNV is rare or a singleton. In this study, we attempted to overcome this issue by using two approaches: by assessing the influences of gene dosage sensitivity and gene expression sensitivity. Dosage sensitive genes derived from two-round whole-genome duplication in previous studies. In addition, we proposed a cross-sectional omics approach that utilizes open data from GTEx to assess the effect of whole-genome CNVs on gene expression. Methods Affymetrix Genome-Wide SNP Array 6.0 was used to detect CNVs by PennCNV and CNV Workshop. After quality controls for population stratification, family relationship and CNV detection, 287 patients with narcolepsy, 133 patients with essential hypersomnia, 380 patients with panic disorders, 164 patients with autism, 784 patients with Alzheimer disease and 1280 healthy individuals remained for the enrichment analysis. Results Overall, significant enrichment of dosage sensitive genes was found across patients with narcolepsy, panic disorders and autism. Particularly, significant enrichment of dosage-sensitive genes in duplications was observed across all diseases except for Alzheimer disease. For deletions, less or no enrichment of dosage-sensitive genes with deletions was seen in the patients when compared to the healthy individuals. Interestingly, significant enrichments of genes with expression sensitivity in brain were observed in patients with panic disorder and autism. While duplications presented a higher burden, deletions did not cause significant differences when compared to the healthy individuals. When we assess the effect of sensitivity to genome dosage and gene expression at the same time, the highest ratio of enrichment was observed in the group including dosage-sensitive genes and genes with expression sensitivity only in brain. In addition, shared CNV regions among the five neuropsychiatric diseases were also investigated. Conclusions This study contributed the evidence that dosage-sensitive genes are associated with CNVs among neuropsychiatric diseases. In addition, we utilized open data from GTEx to assess the effect of whole-genome CNVs on gene expression. We also investigated shared CNV region among neuropsychiatric diseases.

Fukuyama congenital muscular dystrophy (FCMD) is the second most common form of muscular dystrophy in the Japanese population and is caused by mutations in the fukutin (FKTN) gene. In 2011, the Japan Muscular Dystrophy Association (JMDA) developed a nationwide registry of genetically confirmed patients with FCMD. We retrospectively reviewed the registry dataset of patients with FCMD to obtain data, including age, sex, developmental milestones, intellectual level, complications, and primary treatments. In total, 207 patients with FCMD (104 boys and 103 girls) were registered by the end of September 2013. Mean patient age at first registration was 8.1 ± 7.8 years (median, 6 years; range, 0–42 years). A homozygous 3-kb founder insertion mutation in the FKTN gene was present in 80% of registrants, whereas 20% had a compound heterozygous mutation. Sixty-nine patients (33%) had febrile seizures and/or epilepsy. Myopia was the most frequently detected abnormality (8.7%), followed by strabismus (5.9%). Overall, 16% of patients required respiratory support and this percentage increased with age. Cardiac dysfunction was detected in 16%, and dysphagia was observed in 22% of patients with FCMD. The FCMD patient registry is useful for clarifying the natural history of FCMD and recruiting patients for clinical trials.

Major depressive disorder is a common psychiatric disorder that is thought to be triggered by both genetic and environmental factors. Depressive symptoms are an important public health problem and contribute to vulnerability to major depression. Although a substantial number of genetic and epigenetic studies have been performed to date, the detailed etiology of depression remains unclear and there are no validated biomarkers. DNA methylation is one of the major epigenetic modifications that play diverse roles in the etiology of complex diseases. In this study, we performed an epigenome-wide association study (EWAS) of DNA methylation on subjects with (N = 20) or without (N = 27) depressive symptoms in order to examine whether different levels of DNA methylation were associated with depressive tendencies. Employing methylation-array technology, a total of 363,887 methylation sites across the genomes were investigated and several candidate CpG sites associated with depressive symptoms were identified, especially annotated to genes linked to a G-protein coupled receptor protein signaling pathway. These data provide a strong impetus for validation studies using a larger cohort and support the possibility that G-protein coupled receptor protein signaling pathways are involved in the pathogenesis of depression.

Objective: The quality of life of individuals with panic disorder and agoraphobia can be improved by the alleviation of agoraphobia. In other words, examining panic disorder in terms of whether agoraphobia is present is crucial. The current study examined panic disorder from this perspective. Methods: Subjects were 253 patients who met the diagnostic criteria for panic disorder (lifetime) according to the Mini International Neuropsychiatric Interview (MINI). Of those patients, 179 had agoraphobia and 74 did not. Statistical analysis was used to examine gender differences in the presence (or absence) of agoraphobia, comorbidities, and the effects of the presence of agoraphobia (severity, assessment of depression, assessment of anxiety, and personality) in these patients. Results: Results indicated gender differences in the presence (or absence) of agoraphobia. Compared to patients without agoraphobia, significantly more patients with agoraphobia were female (p

Panic disorder (PD) is characterized by recurrent and unexpected panic attacks, subsequent anticipatory anxiety, and phobic avoidance. Recent epidemiological and genetic studies have revealed that genetic factors contribute to the pathogenesis of PD. We performed whole-exome sequencing on one Japanese family, including multiple patients with panic disorder, which identified seven rare protein-altering variants. We then screened these genes in a Japanese PD case–control group (384 sporadic PD patients and 571 controls), resulting in the detection of three novel single nucleotide variants as potential candidates for PD (chr15: 42631993, T>C in GANC; chr15: 42342861, G>T in PLA2G4E; chr20: 3641457, G>C in GFRA4). Statistical analyses of these three genes showed that PLA2G4E yielded the lowest p value in gene-based rare variant association tests by Efficient and Parallelizable Association Container Toolbox algorithms; however, the p value did not reach the significance threshold in the Japanese. Likewise, in a German case–control study (96 sporadic PD patients and 96 controls), PLA2G4E showed the lowest p value but again did not reach the significance threshold. In conclusion, we failed to find any significant variants or genes responsible for the development of PD. Nonetheless, our results still leave open the possibility that rare protein-altering variants in PLA2G4E contribute to the risk of PD, considering the function of this gene.

Social anxiety disorder (SAD) is characterized by strong fear and anxiety during social interactions. Although ventrolateral prefrontal cortex (VLPFC) activity in response to emotional stimuli is related to pathological anxiety, little is known about the relationship between VLPFC activity and social anxiety. This study aimed to investigate whether VLPFC activity was involved in SAD and whether VLPFC activity was related to the level of social anxiety. Twenty-four drug-naïve patients with SAD and 35 healthy controls underwent near-infrared spectroscopy (NIRS) scanning while performing a verbal fluency task (VFT). Results indicated that, compared to the healthy controls, the SAD patients exhibited smaller changes of oxygenated hemoglobin (oxy-Hb) concentrations in the VLPFC during the VFT. Furthermore, the right VLPFC activation was negatively correlated with social avoidance. In contrast to the latter, the healthy controls exhibited a positive correlation between changes of oxy-Hb concentrations in the bilateral VLPFC and social fear. Our findings provide evidence for VLPFC dysfunction in SAD, and indicate that the VLPFC dysfunction may contribute to the difference between normal and abnormal social anxiety., Highlights • We investigated ventrolateral prefrontal cortex (VLPFC) activity induced by the performance of the verbal fluency task. • Smaller changes of oxygenated hemoglobin (oxy-Hb) concentrations in bilateral VLPFC in SAD patients • Negative correlation between changes of oxy-Hb concentrations in right VLPFC and social avoidance in SAD patients • Positive correlation between changes of oxy-Hb concentrations in bilateral VLPFC and social fear in healthy subjects

Recent studies indicate that early-onset panic disorder (PD) may show distinct clinical characteristics. The authors compared patients with early-onset PD, patients with late-onset PD, and healthy control subjects in terms of brain-derived neurotrophic factor (BDNF), the Val66Met polymorphism, State-Trait Anxiety Inventory (STAI) scores, and the Revised NEO Personality Inventory. In patients with early-onset PD, the STAI-T score was high in the Met/Met group, whereas the STAI-T score of the Val/Val group tended to be higher for healthy control subjects. The conflicting effect of the BDNF genotype between patients with early-onset PD and healthy control subjects suggests that the BDNF Met/Met genotype may increase trait anxiety in early-onset PD.

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.

In the Diagnostic and Statistical Manual of Mental Disorders (DSM), panic disorder is one type of anxiety disorder. There have been few detailed reports on the relationship between suicide and panic disorder. We examined the comorbidities and personality inventory tendencies in panic disorder with an increased suicide risk. Our participants were patients with panic disorder. We found that an increased risk of suicide must be kept in mind when treating patients with panic disorder that is accompanied by mood disorders or anxiety disorders. This study also found that such patients are thought to be “very sensitive and emotional and easily distracted”, “introverted, humble and serious”, and “hedonistic”. The risk of suicide must be ascertained during the treatment of panic disorder.

In humans, narcolepsy is a sleep disorder that is characterized by sleepiness, cataplexy and rapid eye movement (REM) sleep abnormalities. Essential hypersomnia (EHS) is another type of sleep disorder that is characterized by excessive daytime sleepiness without cataplexy. A human leukocyte antigen (HLA) class II allele, HLA-DQB1*06:02, is a major genetic factor for narcolepsy. Almost all narcoleptic patients are carriers of this HLA allele, while 30–50% of EHS patients and 12% of all healthy individuals in Japan carry this allele. The pathogenesis of narcolepsy and EHS is thought to be partially shared. To evaluate the contribution of common single-nucleotide polymorphisms (SNPs) to narcolepsy onset and to assess the common genetic background of narcolepsy and EHS, we conducted a polygenic analysis that included 393 narcoleptic patients, 38 EHS patients with HLA-DQB1*06:02, 119 EHS patients without HLA-DQB1*06:02 and 1582 healthy individuals. We also included 376 individuals with panic disorder and 213 individuals with autism to confirm whether the results were biased. Polygenic risks in narcolepsy were estimated to explain 58.1% (PHLA-DQB1*06:02=2.30 × 10−48, Pwhole genome without HLA-DQB1*06:02=6.73 × 10−2) including HLA-DQB1*06:02 effects and 1.3% (Pwhole genome without HLA-DQB1*06:02=2.43 × 10−2) excluding HLA-DQB1*06:02 effects. The results also indicated that small-effect SNPs contributed to the development of narcolepsy. Reported susceptibility SNPs for narcolepsy in the Japanese population, CPT1B (carnitine palmitoyltransferase 1B), TRA@ (T-cell receptor alpha) and P2RY11 (purinergic receptor P2Y, G-protein coupled, 11), were found to explain 0.8% of narcolepsy onset (Pwhole genome without HLA-DQB1*06:02=9.74 × 10−2). EHS patients with HLA-DQB1*06:02 were estimated to have higher shared genetic background to narcoleptic patients than EHS patients without HLA-DQB1*06:02 even when the effects of HLA-DQB1*06:02 were excluded (EHS with HLA-DQB1*06:02: 40.4%, PHLA-DQB1*06:02=7.02 × 10−14, Pwhole genome without HLA-DQB1*06:02=1.34 × 10−1, EHS without HLA-DQB1*06:02: 0.4%, Pwhole genome without HLA-DQB1*06:02=3.06 × 10−1). Meanwhile, the polygenic risks for narcolepsy could not explain the onset of panic disorder and autism, suggesting that our results were reasonable.

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

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

To investigate whether prefrontal function during a cognitive task reflects the severity of panic disorder, the prefrontal function during a word fluency task in 109 panic disorder patients with or without agoraphobia was measured by multi-channel near-infrared spectroscopy (NIRS). [Oxy-Hb] changes in the left inferior prefrontal cortex were significantly associated with the frequency of panic attacks, and, in addition, [deoxy-Hb] changes in the anterior area of the right prefrontal cortex were significantly associated with the severity of agoraphobia. These results suggest that the prefrontal function in patients with panic disorder is associated with the disease state of disease in patients with panic disorder.

We examined the relationship between the catechol-O-methyltransferase (COMT) Val158Met genotype and frontal lobe function by using multi-channel near-infrared spectroscopy (NIRS). The present study investigated oxygenated ([oxy-Hb]) and deoxygenated ([deoxy-Hb]) hemoglobin concentration changes during the performance of a verbal fluency task in the frontal region of 71 patients with panic disorder (PD). The activation of [oxy-Hb] on the right lateral prefrontal cortex was observed in the Met/Met genotype of the COMT gene polymorphism of PD patient groups in the analysis of NIRS, which seems to be related to the autonomic dysfunction in the pathogenesis of PD.

Panic disorder (PD) is an anxiety disorder characterized by panic attacks and anticipatory anxiety. Although a number of association studies have been conducted, no gene has been identified as a susceptibility locus. In this study, we conducted a genome-wide association study of PD in 200 Japanese patients and the same number of controls, using the GeneChip Human Mapping 500 K Array Set. Genotypes were determined using the Bayesian Robust Linear Model with Mahalanobis (BRLMM) genotype calling algorithm. The genotype data were data-cleaned using criteria for SNP call rate (or=95%), Hardy-Weinberg equilibrium (Por=0.1%) and minor allele frequency (or=5%). The significance level of the allele P-value was set at 1.0 x 10(-6), to make false discovery rate (FDR)0.05. As a result, seven SNPs were significantly associated with PD, which were located in or adjacent to genes including PKP1, PLEKHG1, TMEM16B, CALCOCO1, SDK2 and CLU (or APO-J). Studies with other samples are required to confirm the results.

In this report, which is an update of a guideline published in 2002 (Bandelow et al. 2002, World J Biol Psychiatry 3:171), recommendations for the pharmacological treatment of anxiety disorder, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) are presented. Since the publication of the first version of this guideline, a substantial number of new randomized controlled studies of anxiolytics have been published. In particular, more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs. The recommendations, developed by the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-traumatic Stress Disorders, a consensus panel of 30 international experts, are now based on 510 published randomized, placebo- or comparator-controlled clinical studies (RCTs) and 130 open studies and case reports. First-line treatments for these disorders are selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs) and the calcium channel modulator pregabalin. Tricyclic antidepressants (TCAs) are equally effective for some disorders, but many are less well tolerated than the SSRIs/SNRIs. In treatment-resistant cases, benzodiazepines may be used when the patient does not have a history of substance abuse disorders. Potential treatment options for patients unresponsive to standard treatments are described in this overview. Although these guidelines focus on medications, non-pharmacological were also considered. Cognitive behavioural therapy (CBT) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders, OCD, and PTSD to support them being recommended either alone or in combination with the above medicines.

Background: The aim of the present study is to show the causative factors of suicide among the elderly (over 65) in Mie Prefecture, Japan, and to discuss the prevention of the suicidal influences in elderly patients. Methods: We investigated all inquest records during the 14-year period 1989‐2002 in cooperation with the First Department of Criminal Investigation of Mie Prefectural Police Headquarters. From all cases classified as suicides, we extracted data on age, sex and background, and we focused on suicide in the elderly group. Results: During the test period, there were 5048 suicides (3276 male and 1772 female suicides) of which 1513 (691 male and 822 female) were in the elderly group. The rate of suicide in the elderly group was approximately 30% of the total in all age groups. The rate of female suicides in the elderly group was approximately 46.3%. The major causative factors of suicide among the elderly were ‘suffering from physical illness’, and ‘psychiatric disorders’. ‘Physical diseases’ were not negligible backgrounds in middle and elderly groups. Among physical diseases, the number of malignant neoplasm was clearly less than the other diseases. Notably, ‘cardiovascular disease’ and ‘orthopedic disorders’ were most frequent causative factors of suicide other than malignant neoplasm. Conclusion: It is consequently concluded that improvements in the system of home nursing and health care should be involved in the suicidal prevention of the elderly who ‘suffer from physical illness’. The patients who ‘suffer from physical illness’ should be given physical and mental support. In order to prevent suicide, not only psychiatrists but also general practitioners as well as medical staff and general public should be provided with education regarding depression among ‘psychiatric disorders’.

This study aims to show the causative factors of suicide among the elderly (over 65) in Mie Prefecture, and to discuss the prevention of the factors contributing to suicide in the elderly group. We obtained an agreement from the Mie Prefectural Police Headquarters and investigated all inquest records collected between 1996 and 2002 in Mie Prefecture and focused on suicide in the elderly group. During the test period, the number of suicides in the elderly group was 842. In causative factors, the two major causative factors of suicide were "suffering from physical illness" and "psychiatric disorders". In particular, the three most frequent physical illnesses were "cardiovascular disease", "orthopedic disorder", and "digestive organ disease", and these physical illnesses are mentally stressful, and thus have a psychiatric component, the same as psychiatric illnesses do. Consequently, it is concluded that improvements in the home nursing and mental health care should include the prevention of suicide in the elderly who "suffer from physical illness" and "psychiatric disorders" to prevent suicide. In addition, medical staff and the general public should be educated on the factors that can influence elderly persons' mental condition, and should be cautioned to observe elderly persons for suicidal signs and symptoms.

The patient, a 77-year-old man, was diagnosed with senile depression. He was also diagnosed with depression at other hospitals, and pharmacotherapy by antidepressants was carried out. He was given sulpiride, selective serotonin reuptake inhibitors, a serotonin-norepinephrine reuptake inhibitor, an atypical antidepressant, and tricyclic and tetracyclic antidepressants, but conventional pharmacotherapies using these antidepressant drugs did not alleviate his symptoms. The patient was then administered 0.5 mg/day of clonazepam at bed time. Following 2 weeks of administration, his symptoms were alleviated. The dosage of clonazepam was increased to 0.75 mg/day and remission was facilitated. Four weeks later, the patient displayed further alleviation of his depressive symptoms, so he has been continued on 0.75 mg/day of clonazepam. Essential drug selections for senile depression includes selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and atypical antidepressants, but when these are ineffective, tricyclic antidepressants or tetracyclic antidepressants are alternatively selected. When a patient’s symptoms are not alleviated by essential drug selection, as occurred in the current case, clonazepam is considered to be another therapeutic candidate. If they fail to alleviate symptoms, however, then early referral to a specialist is crucial. Enhancing primary-care physicians’ understanding of senile depression and coordination with specialists is essential in the medical care of elderly patients with depression.

We herein report an association between TMEM132D and panic disorder (PD) in a Japanese population, evaluating the effects of HLA-DRB1*13:02, which we previously reported as a susceptibility genetic factor for PD. SNPs in TMEM132D showed significant associations with PD in subjects without HLA-DRB1*13:02 (rs4759997; P=5.02×10−6, odds ratio=1.50) but not in those with the HLA allele. TMEM132D might have a role in the development of PD in subjects without HLA-DRB1*13:02.

Background 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 = 38.7 years) with PD. Diagnoses were confirmed using the Mini-International Neuropsychiatric Interview. Illness duration ranged from less than a year to 51 years. 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 (9 years) as a cut-off because of the skewed distribution of the duration. Patients with an illness duration of 9 years (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.

The number of suicides in Japan has increased from approximately 22 000 per year from 1988 to 1997 to >30 000 per year since 1998. Likewise, the number of suicides has been increasing in Mie Prefecture. The purpose of the present study was to examine the incidence of and circumstances surrounding all suicide cases during 1996-2002 in Mie Prefecture and to compare the data with those from 1989 to 1995. In Mie Prefecture, the age-specific suicide rate during the second 7-year period included marked increases among men aged 50-59 and 60-69 years. Among women, the age-specific suicide rate increased with age during both 7-year periods. During the second period, psychiatric disorders as causative factors increased in all generations. They were especially important for women of the younger generation, whereas economic problems were the most common causative factor among men aged 40-64. Physical illness as a causative factor in suicide was high among the elderly, but among the other age groups this factor trailed behind economic difficulties for men and psychiatric disorders for women. To prevent suicide, social cooperation as well as a plenitude of visiting nurses and psychiatric care is required, and early detection and treatment are also important.

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for panic disorder. Tricyclic antidepressants (TCAs) are equally effective, but they are less well tolerated than the SSRIs. In treatment-resistant cases, benzodiazepines like alprazolam may be used when the patient does not have a history of dependency and tolerance. Due to possible serious side effects and interactions with other drugs and food components, the irreversible monamine oxidase inhibitor (MAOI) phenelzine should be used only when first-line drugs have failed.