Published papers

Objectives: Concentrations of soluble amyloid precursor proteins-α (sAPPα) and -β (sAPPβ) in cerebrospinal fluid (CSF) may reflect the neuropathology of Alzheimer’s disease (AD). We previously reported that the concentrations of both sAPPα and sAPPβ were significantly higher in patients with mild cognitive impairment (MCI) due to AD (MCI-AD) than in control subjects without cognitive impairment. The present study analyzed whether these sAPPs are useful in the differential diagnosis of MCI. Methods: A modified and sensitive method was used to analyze concentrations of sAPPα and sAPPβ in CSF of patients with MCI-AD (n = 30) and MCI due to other causes (MCI-others) (n = 24). Phosphorylated tau (p-tau) and amyloid β-protein 42 (Aβ42) were also analyzed using standard methods. Results: CSF concentrations of sAPPα and sAPPβ were significantly higher in the MCI-AD than in the MCI-others group (p < 0.001). Furthermore, concentrations of both sAPPα and sAPPβ were highly correlated with the concentration of p-tau, consistent with our previous report. Conclusions: Measurement of both sAPPs in CSF using sensitive methods can be helpful in the precise differential diagnosis of patients with MCI.

Aims: Pharmacotherapy for methamphetamine dependence has not yet been developed in Japan or elsewhere in the world. Ifenprodil is a blocker of G protein-activated inwardly rectifying potassium channels that play a key role in the mechanism of action of addictive substances. Our aim is to examine the safety, efficacy, and outcomes of ifenprodil for the treatment of methamphetamine dependence in a randomized, double-blind, placebo-controlled trial. Methods: The recruitment of outpatients with methamphetamine dependence began in January 2018. The patients will be randomized into three arms: placebo, 60 mg/d ifenprodil, or 120 mg/d ifenprodil. Placebo or ifenprodil will be taken for 84 days. We will use Cerocral fine granule 4% (ifenprodil tartrate). Follow-up assessments will be conducted for 84 d after the drug administration period. All of the patients will be assessed by self-administered questionnaires and urine tests. The primary outcome will be the presence or absence of methamphetamine use during the 84-day administration period in the 120 mg/d ifenprodil and placebo groups. Secondary outcomes will include the number of days and percentage of days of abstinence from methamphetamine use, positive urine for methamphetamine, relapse risk, and drug craving. Discussion: This study is the first clinical trial of ifenprodil treatment for methamphetamine dependence and is designed as an intervention test with off-label drug use. The present study is expected to provide evidence of the effects of ifenprodil treatment on methamphetamine dependence. Trial registry: This trial was registered in the UMIN clinical trial registry (UMIN000030849; date of registration: January 17, 2018). ®

Background: Patients with Duchenne muscular dystrophy (DMD) exhibit increased prostaglandin D (PGD ) expression in necrotic muscle and increased PGD metabolites in their urine. In mouse models, inhibiting PGD production suppresses muscle necrosis, suggesting a possible intervention through PGD -mediated activities. Objective: We investigated the involvement of PGD and its potential use as a marker of pathological progression in DMD. Methods: Sixty-one male children with DMD and thirty-five age-matched controls were enrolled in the study. DMD patients were divided into “ambulant” and “non-ambulant” groups, which were further subdivided into “steroid” and “non-steroid” therapy groups. Levels of the PGD metabolite tetranor-PGDM (t-PGDM) and creatinine were measured in both spot and 24-hour urine samples, with comparisons between groups made according to geometric mean values. Results: DMD patients had significantly higher levels of creatinine-corrected t-PGDM in spot urine samples as compared with the control group. Additionally, both ambulant and non-ambulant DMD groups had significantly higher levels of t-PGDM as compared with controls, with no significant difference in t-PGDM levels observed between steroid and non-steroid groups. Moreover, total creatinine excretion in 24-hour urine samples was significantly lower in DMD patients as compared with controls, and although DMD patients had lower muscle mass than controls, their overall levels of t-PGDM did not differ significantly from those in the non-ambulant and control groups. Conclusion: PGD might help explain the progression and symptomatic presentations (e.g., ambulatory difficulty) associated with DMD, suggesting it as a useful pathological marker and use of a selective PGD inhibitor as a potential treatment modality. 2 2 2 2 2 2 2 2 2

Duchenne muscular dystrophy (DMD) is a lethal hereditary muscle disease caused by mutations in the gene encoding the muscle protein dystrophin. These mutations result in a shift in the open reading frame leading to loss of the dystrophin protein. Antisense oligonucleotides (ASOs) that induce exon skipping correct this frame shift during pre-mRNA splicing and partially restore dystrophin expression in mouse and dog models. We conducted a phase 1, open-label, dose-escalation clinical trial to determine the safety, pharmacokinetics, and activity of NS-065/NCNP-01, a morpholino ASO that enables skipping of exon 53. Ten patients with DMD (6 to 16 years old), carrying mutations in the dystrophin gene whose reading frame would be restored by exon 53 skipping, were administered NS-065/NCNP-01 at doses of 1.25, 5, or 20 mg/kg weekly for 12 weeks. The primary endpoint was safety; the secondary endpoints were pharmacokinetics and successful exon skipping. No severe adverse drug reactions were observed, and no treatment discontinuation occurred. Muscle biopsy samples were taken before and after treatment and compared by reverse transcription polymerase chain reaction (RT-PCR), immunofluorescence, and Western blotting to assess the amount of exon 53 skipping and dystrophin expression. NS-065/NCNP-01 induced exon 53 skipping in dystrophin-encoding mRNA in a dose-dependent manner and increased the dystrophin/ spectrin ratio in 7 of 10 patients. Furthermore, the amount of exon skipping correlated with the maximum drug concentration in plasma (C ) and the area under the concentration-time curve in plasma (AUC ). These results indicate that NS-065/NCNP-01 has a favorable safety profile and promising pharmacokinetics warranting further study in a phase 2 clinical trial. max 0-t

Duchenne muscular dystrophy (DMD) is an X-linked muscle disorder characterized by primary muscle degeneration. Patients with DMD reveal progressive muscle weakness leading to ambulatory dysfunction. Novel outcome measures are needed for more sensitive evaluation of therapeutic effects in clinical trials. Multiple parameters of acceleration and angular velocity are used as efficient indicators to quantify the motion of subjects, and these parameters have been recently applied for evaluation of motor function in DMD. In the present study, we evaluated gait in a dystrophic dog model, CXMD , by measuring three-axial acceleration and angular velocity over the course of months. Hybrid sensors were placed on the dorsal thoracic and lumbar regions of dogs to detect a wide range of acceleration (±8 G) and angular velocity (±1000 degrees per second). Multiple parameters showed lower values in dystrophic dogs compared to wild-type (WT) dogs, and declined over the course of months. Acceleration magnitude (AM) at the thoracic region in dystrophic dogs was prominently lower compared with WT dogs, even at the age of 2 months, the onset of muscle weakness, whereas AM at the lumbar region drastically declined throughout the disease course. The angular velocity index in the vertical direction in the lumbar region increased in dystrophic dogs, suggesting waddling at the girdle. These parameters also accordingly decreased with exacerbation of clinical manifestations and a decrease in spontaneous locomotor activity. The AM of dystrophic dogs was analyzed with magnetic resonance imaging to look for a correlation with crus muscle involvement. Results showed that acceleration and angular velocity are multifaceted kinematic indices that can be applied to assess outcomes in clinical trials for hereditary neuromuscular disorders including DMD. J

OBJECTIVE This study aimed to reveal the associations between the risk of new-onset type 2 diabetes and the duration of antidepressant use and the antidepressant dose, and between antidepressant use after diabetes onset and clinical outcomes. RESEARCH DESIGN AND METHODS In this large-scale retrospective cohort study in Japan, new users of antidepressants (exposure group) and nonusers (nonexposure group), aged 20–79 years, were included between 1 April 2006 and 31 May 2015. Patients with a history of diabetes or receipt of antidiabetes treatment were excluded. Covariates were adjusted by using propensity score matching; the associations were analyzed between risk of new-onset type 2 diabetes and the duration of antidepressant use/dose of antidepressant in the exposure and nonexposure groups by using Cox proportional hazards models. Changes in glycated hemoglobin (HbA ) level were examined in groups with continuous use, discontinuation, or a reduction in the dose of antidepressants. RESULTS Of 90,530 subjects, 45,265 were in both the exposure and the nonexposure group after propensity score matching; 5,225 patients (5.8%) developed diabetes. Antidepressant use was associated with the risk of diabetes onset in a time- and dose-dependent manner. The adjusted hazard ratio was 1.27 (95% CI 1.16–1.39) for short-term low-dose and 3.95 (95% CI 3.31–4.72) for long-term high-dose antidepressant use. HbA levels were lower in patients who discontinued or reduced the dose of antidepressants (F[2,49] 5 8.17; P < 0.001). CONCLUSIONS Long-term antidepressant use increased the risk of type 2 diabetes onset in a time- and dose-dependent manner. Glucose tolerance improved when antidepressants were discontinued or the dose was reduced after diabetes onset. 1c 1c

Background: Understanding the area-specific resource use of inpatient psychiatric care is essential for the efficient use of the public assistance system. This study aimed to assess the geographical variation in psychiatric admissions and to identify the prefecture-level determinants of psychiatric admissions among recipients of public assistance in Japan. Methods: We identified all recipients of public assistance who were hospitalized in a psychiatric ward in May 2014, 2015, or 2016 using the Fact-finding Survey on Medical Assistance. The age- and sex-standardized number of psychiatric admissions was calculated for each of the 47 prefectures, using direct and indirect standardization methods. Results: A total of 46,559 psychiatric inpatients were identified in May 2016. The number of psychiatric admissions per 100,000 population was 36.6. We found a 7.1-fold difference between the prefectures with the highest (Nagasaki) and lowest (Nagano) numbers of admissions. The method of decomposing explained variance in the multiple regression model showed that the number of psychiatric beds per 100,000 population and the number of recipients of public assistance per 1,000 population were the most important determinants of the number of psychiatric admissions (R = 28% and R = 23%, respectively). The sensitivity analyses, using medical cost as the outcome and data from different survey years and subgroups, showed similar findings. Conclusions: We identified a large geographical variation in the number and total medical cost of psychiatric admissions among recipients of public assistance. Our findings should encourage policy makers to assess the rationale for this variation and consider strategies for reducing it. 2 2

Background Descriptive analyses of 2009-2016 were performed using the data of the Universal Coverage Scheme (UCS) which covers nearly 70 percent of the Thai population. The analyses described the time and geographical trends of nationwide admission rates of type 2 diabetes mellitus (T2DM) and its complications, including chronic kidney disease (CKD), myocardial infarction, cerebrovascular diseases, retinopathy, cataract, and diabetic foot amputation. Methods and findings The database of T2DM patients aged 15-100 years who were admitted between 2009 and 2016 under the UCS and that of the UCS population were retrieved for the analyses. The admitted cases of T2DM were extracted from the database using disease codes of principal and secondary diagnoses defined by the International Classification of Diseases 9th and 10th Revisions. The T2DM admission rates in 2009-2016 were the number of admissions divided by the number of the UCS population. The standardized admission rates (SARs) were further estimated in contrast to the expected number of admissions considering age and sex composition of the UCS population in each region. A linearly increased trend was found in T2DM admission rates from 2009 to 2016. Female admission rates were persistently higher than that of males. In 2016, an increase in the T2DM admission rates was observed among the older ages relative to that in 2009. Although the SARs of T2DM were generally higher in Bangkok and central regions in 2009, except that with CKD and foot amputation which had higher trends in northeastern regions, the geographical inequalities were fairly reduced by 2016. Conclusion Admission rates of T2DM and its major complications increased in Thailand from 2009 to 2016. Although the overall geographical inequalities in the SARs of T2DM were reduced in the country, further efforts are required to improve the health system and policies focusing on risk factors and regions to manage the increasing T2DM.

The fear of cancer recurrence (FCR) is the most common and most severe unmet need among cancer survivors. Safe treatments for the FCR that are easily disseminated are greatly needed. Our primary aim is a preliminary evaluation of the efficacy and effect size of perilla oil, which is rich in omega-3 fatty acids, and Bifidobacterium, a probiotic, on FCR in breast cancer survivors after the completion of chemotherapy. This study has been planned as an exploratory clinical study (phase II) and will be conducted as a three-arm, 12-week parallel group, masked-rater randomized controlled trial. Fifteen participants will be randomized with 1:1:1 allocation to receive Bifidobacterium plus perilla oil, Bifidobacterium alone, or no intervention (control). Interventions will end within 12 weeks after the random allocation of each participant. The participants will be outpatients with invasive breast cancer aged 20 years or older whose chemotherapy was completed at least 6 months before registration; hormone therapy may be ongoing. The primary outcome will be severity of FCR at 12 weeks assessed by masked raters using the 4-item Concerns about Recurrence Scale concerning overall fear of recurrence. The study protocol for the current study is registered in the Japan Registry of Clinical Trials (jRCTs031200029).

Objective: To investigate the association of area response rate with prevalence estimates of mental disorders in the 2nd World Mental Health Survey (WMHJ2). Methods: The sample of the WMHJ2 was selected from community residents in 129 areas from three regions of Japan. The surveys were conducted between 2013 and 2015, and 2450 (43.4%) responded. Mental disorders as well as three disorder classes (mood, anxiety, and substance use disorders) were identified using the WHO CIDI/DSM-IV. Response rates and 12-month and lifetime prevalences were calculated for each area. A generalized linear mixed model analysis was conducted to associate area response rate with the prevalence of mental disorders, controlling for sex, age, urbanity, and geographical region. Results: Area response rates ranged from 0.05 to 0.80 across the 129 areas. Area response rate was not significantly associated with 12-month or lifetime prevalence of mental disorder. Lifetime prevalences of substance use disorder were significantly lower in a survey with a higher response rate than a survey of the same area with a lower response rate. Conclusion: Response rate may not strongly affect the prevalence estimates of mental disorders in a community-based survey of the prevalence of common mental disorders during a particular time frame. However, a lower response rate could be associated with overestimation of lifetime prevalence of substance use disorder. This needs further elucidation.

Aim: We aimed to examine the association between attention-deficit/hyperactivity disorder (ADHD) symptoms and suicidal behavior in psychiatric outpatients and whether this association differs among patients with different psychiatric disorders. Methods: Cross-sectional data came from the Japan Prevalence Study of Adult ADHD at Psychiatric Outpatient Care, which included psychiatric outpatients aged 18–65 years recruited from one university hospital and three general psychiatric outpatient clinics in Kitakyushu City, Fukuoka, Japan from April 2014 to January 2015 (N = 864). The Adult ADHD Self-Report Scale (ASRS) Screener was used to collect information on ADHD symptoms. Reports of current and lifetime suicidal behavior were also obtained. A multivariable Poisson regression analysis was used to examine the association between ADHD symptoms and suicidal behavior. Results: After adjusting for covariates there was a strong association between possible ADHD (ASRS ≥14) and suicidal behavior with prevalence ratios ranging from 1.17 (lifetime suicidal ideation) to 1.59 (lifetime suicide attempt) and 2.36 (current suicidal ideation). When ASRS strata were used, there was a dose–response association between increasing ADHD symptoms and suicidal ideation and suicide attempts. Analyses of individual ICD-10 psychiatric disorders showed that associations varied across disorders and that for anxiety disorder, ADHD symptoms were significantly linked to all forms of suicidal behavior. Conclusion: ADHD symptom severity is associated with an increased risk for suicidal behavior in general psychiatric outpatients. As ADHD symptoms are common among adult psychiatric outpatients, detecting and treating ADHD in this population may be important for preventing suicidal behavior.

Background: People living in temporary housing for long periods after a disaster are at risk of poor mental health. This study investigated the post-disaster incidence and remission of common mental disorders among adults living in temporary housing for the 3 years following the 2011 Great East Japan Earthquake. Methods: Three years after the disaster, face-to-face interviews were conducted with 1089 adult residents living in temporary housing in the disaster area, i.e., the shelter group, and a random sample of 852 community residents from non-disaster areas of East Japan. The World Health Organization Composite International Diagnostic Interview was used to diagnose DSM-IV mood, anxiety, and alcohol use disorders. Information on demographic variables and disaster experiences was also collected. Results: Response rates were 49 and 46% for the shelter group and the community residents, respectively. The incidence of mood/anxiety disorder in the shelter group was elevated only in the first year post-disaster compared to that of the general population. The rate of remission for mood and anxiety disorders was significantly lower in the shelter group than in the community residents. The proportion seeking medical treatment was higher in the shelter group. Conclusions: The onset of common mental disorders increased in the first year, but then levelled off in the following years among residents in temporary housing after the disaster. Remission from incident post-disaster mental disorders was slower in the shelter group than in the general population. Post-disaster mental health service could consider the greater incidence in the first year and prolonged remission of mental disorders among survivors with a long-term stay in temporary housing after a disaster.

Objective: Patients with chronic insomnia are prone to long-term use of hypnotics. Reported risk factors include aging, female sex, and comorbid psychiatric disorders. However, most previous studies have been cross-sectional cohort studies. Method: We conducted a retrospective cohort study using medical service payment data for 330,000 people to determine the duration of prescription of hypnotics and the risk factors for long-term use. We followed up 3981 patients (2382 M, 1599 F, age 40.3 ± 12.4 years) who were prescribed hypnotics for the first time between April 2005 and March 2008. Results: Of these 3981 patients, 59.6% were prescribed hypnotics for only 1 month, 11.3% were prescribed hypnotics for 2 consecutive months, and 10.1% of patients continued receiving prescriptions for the entire 12-month observation period. In multiple logistic time-dependent Cox analyses, use of antidepressants, mean dose of hypnotics, and advanced age were significantly associated with long-term use of hypnotics (p < 0.01). In an analysis of the association between long-term use of hypnotics and prescribed dosage, high monthly dose, advanced age, and department of first visit were significantly associated with long-term use (p < 0.01). Conclusion: These clinical indicators may be effective for early identification of patients with insomnia who are at high risk of developing physical dependence on hypnotics.

Background: Current Japanese forensic mental health legislation (Medical Treatment and Supervision Act [MTSA]) was enacted in 2003. Little is known, however, about the actual outcomes for the offender patients detained within hospitals under this provision. Aim: This study aimed to quantify reoffending and readmission following patients' discharge from forensic psychiatric hospital units across Japan and explore related risk factors. Methods: We followed up 526 offenders with mental disorder who had been detained under the MTSA and who were subsequently discharged from any of the 28 hospitals nationwide between 2007 and 2015. Results: The total cumulative reoffence rate was found to be 2.5% (1.1–3.9%) after 1 year and 7.5% (4.6–10.4%) after 3 years. The rate of serious reoffending was 0.4% (−0.18% to 0.99%) after 1 year and 2.0% (0.4–3.6%) after 3 years. The cumulative admission rate to local psychiatric hospitals following a discharge was 21.8% after 6 months and 37.6% after 1 year. Patients who had been discharged from their MTSA order but transferred to a general psychiatric hospital before open community residence—because it was necessary to build community supports—were more likely to reoffend than those discharged directly to the community. Patients who had been diagnosed with a substance use disorder (F10–F19) and had one subsequent admission were at higher risk of further readmissions. Conclusions: The low reoffending rates could be attributed to the intensive treatment and care plans required by the MTSA. The high rate of readmission to psychiatric hospitals may indicate shortcomings in community mental health services in Japan.

OBJECTIVE: To identify the characteristic pathologic features of dermatomyositis (DM) associated with anti-Mi-2 autoantibodies (anti-Mi-2 DM). METHODS: We reviewed 188 muscle biopsies from patients (1) pathologically diagnosed with DM through the sarcoplasmic expression for the myxovirus-resistant protein A and (2) serologically positive for 1 of 5 DM-specific autoantibodies (DMSAs) (anti-Mi-2, n = 30; other DMSAs, n = 152) or negative for all 5 DMSAs (n = 6). We then compared the histopathologic and immunohistochemical features of patients with anti-Mi-2 DM to those with non-Mi-2 DM and patients with anti-synthetase syndrome (ASS) (n = 212) using the t test, Fisher exact test, and a logistic regression model. RESULTS: Patients with anti-Mi-2 DM showed significantly higher severity scores in muscle fiber and inflammatory domains than non-Mi-2 DM patients. The presence of perifascicular necrosis, increased perimysial alkaline phosphatase activity, and sarcolemmal membrane attack complex deposition was more frequent in patients with anti-Mi-2 DM (p < 0.01). After Bonferroni correction, there were no significant differences in the percentages of the features mentioned above between the patients with anti-Mi-2 DM and those with ASS (p > 0.01). CONCLUSION: Perifascicular necrosis and perimysial pathology, features previously reported in ASS, are common in patients with anti-Mi-2 DM. Our findings not only assist in differentiating anti-Mi-2 DM from other DM subtypes but also suggest the possibility of an overlapping mechanism between anti-Mi-2 DM and ASS. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the muscle biopsies of DM patients with anti-Mi-2 autoantibodies are more likely to demonstrate higher severity scores in muscle fiber and inflammatory domains.

Background: Despite numerous changes in the mental health care system in Japan in 2000's, little is known about changes in the prevalence or treatment rates of mental disorders. Methods: The World Mental Health Japan (WMHJ) 2nd Survey was a nationally representative face-to-face household survey of residents aged 20–75 years old conducted between 2013 and 2015. We compared the findings with those of an earlier study, the first WMHJ (WMHJ1) survey, conducted in 2002–2006. Results: Overall, 2450 residents completed the interview. Lifetime prevalence of any common mental disorder was 22%, with high prevalence of alcohol abuse (15.1%). Twelve-month prevalence rates of any common mental disorder and major depressive disorder were 5.2% and 2.7%, respectively. Severe cases comprised 24% of 12-month disorders. Lifetime prevalence of any common mental disorder was greater for males. The persistence of any common mental disorder was greater for females. Proportion of those with 12-month disorders who sought treatment was 34%. Mental health care use was the most prevalent among 12-month cases. Twelve-month prevalence of any common mental disorder was similar to that of the WMHJ1 while the proportion of seeking treatment increased for disorders with moderate severity. Limitations: Institutionalized people were not included. The lower response rate might also limit the interpretation of the findings. Conclusions: The study found lower prevalence of mental disorders in Japan than in Western countries in the mid 2010's, suggesting that the prevalence of mental disorders remained stable in the last decade in Japan. Treatment rate increased for those with moderate disorders, which might reflect the government's attempt to raise people's awareness of mental health.

Background: A better understanding of resource use of new psychiatric admissions is important for healthcare providers and policymakers to improve psychiatric care. This study aims to describe the pattern of new psychiatric admissions and length of stay in Japan. Methods: A retrospective cohort study was conducted using data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). All patients newly admitted to psychiatric wards from April 2014 through March 2016 were included and followed up until discharge to the community. Results: Our sample included 605,982 admissions from 1,621 hospitals over 2 years. The average monthly number of admissions was 25,024 in fiscal year 2014 and 25,475 in fiscal year 2015. There was a seasonal trend in the number of admissions, with a peak in summer (in July). The discharge rates within 90 days and 360 days were 64.1% and 85.7%, respectively, and varied by type of hospital fee and by hospital. For example, the range of hospital-level discharge rate within 90 days in psychiatric emergency units was 46.0–75.3% in the 1st (lowest) quintile, while it was 83.6–96.0% in the 5th (highest) quintile. The prefecture-level indicators in the NDB and the 630 survey had correlations of >0.70. Conclusions: Our study provides fundamental information on resource use of new psychiatric admissions in Japan. Although using the NDB has substantial benefits in monitoring resource use, the results should be interpreted with some caution owing to methodological issues inherent in the database.

Background: Psychological distress is prevalent and heterogenous. Checking a history of depression may contribute to identifying those who need intensive preventive support, but few studies have examined how different the dysfunction of people with and without a history of depression among those with psychological distress are. The study aimed to compare the two groups in physical health problems, level of social and familial support. Methods: The World Mental Health Japan 2nd Survey (WMHJ2), a cross-sectional, nationally representative face-to-face survey of residents aged 20–75 years old, was conducted from 2013 to 2015. We defined psychological distress as a K6 score of 5 or more. A history of major depressive disorder (MDD) was assessed by the WHO Composite International Diagnostic Interview version 3.0. Multinomial logistic regression analysis was used to examine the associations of sociodemographic characteristics, physical health problems, social support and mental health service use among those with no psychological distress, with psychological distress having no history of MDD, and with psychological distress having a history of MDD, adjusted for sociodemographic characteristics. Results: Unemployment, physical health problems, and lack of social support were much more common among those with psychological distress without a history of MDD than those with no psychological distress, and were largely comparable with those with psychological distress having a history of MDD. Limitations: The relatively low response rate might limit generalizability. Conclusions: The dysfunction in psychological distress without a history of MDD was largely equivalent to that seen in distress with a history of MDD.

Psychotic experiences (PEs) may be associated with hikikomori. In the present study, we analyzed interview data from a community-based representative sample (N = 1,616) in Japan to know the association of PEs over a life time, as well as the two components, hallucinatory experiences (HEs) and delusional experiences (DEs), with lifetime experience of hikikomori (severe social withdrawal). Logistic regression analysis was used to estimate the association between any PE, any HE, and any DE; and hikikomori, adjusting for socio-demographics and other psychopathologies (mental disorder in the past 12 months or having autistic spectrum disorder trait). Any PE was significantly associated with hikikomori [odds ratio (OR) =3.44, 95% CI = 1.14–10.33] after adjustment for sociodemographic factors, although the association attenuated after adjusting for other psychopathologies. Any DE remained significantly associated with hikikomori, even after adjustment for all the covariates (OR = 10.50, 95% CI = 1.57–70.29). Any HE was not significantly associated with hikikomori. DEs may be associated with hikikomori. However, because the study sample was small and the temporal association between DEs and hikikomori was unclear, a future study is needed to examine a causal relationship between DEs and hikikomori.

Mood disorders are common, tend to recur, cause sickness absence, and lead to economic loss. Since past experiences of mood disorder episodes often increase future vulnerability, it is imperative to assist those mood disorder patients who want to resume working to build resilience to prevent relapse. Paralleling efforts in the West, a resilience-building program utilizing the principles of the Illness Management and Recovery program was first developed in Japan in 1997. The purpose of this survey is to introduce the concept and theory behind the Re-Work program and to review studies that report on program assessment, content, effects and associated factors, and prognosis of participants. A literature search performed with PubMed and Igaku chuou zasshi (Ichushi) identified 30 relevant studies. One of these reported on a tool developed to assess readiness for returning to work. Concerning program content, a group therapy setting and cognitive behavioral therapy were found to be effective. Physical exercise and relaxation techniques may be useful as secondary program components. Several studies report on program effects, but there may be factors that limit these effects. The prognosis for relapse prevention after the resumption of work may be better for Re-Work program participants than for a control group. Further research in this area is needed to confirm program effectiveness and related factors.