Educational challenges for 22q11.2 deletion syndrome in Japan: Findings from a mixed methods survey.

BACKGROUND: The 22q11.2 deletion syndrome (22q11DS) is characterised by a changing pattern of overlapping intellectual, physical, and mental disabilities along the course of one's life. However, the impact of overlapping disorders (multimorbidity) on educational challenges remains unclear. METHOD: A survey was conducted with 88 caregivers of individuals with 22q11DS. A quantitative analysis of educational challenges and support needs divided into age groups (7-12, 13-15, 16-18, and 19 years and over) and a qualitative analysis of the free-text items in the questionnaire was conducted. RESULTS: Caregivers were more interested in comprehensive developmental support when their children were younger, and the emphasis shifted to concerns regarding environments that matched individual characteristics at older ages. Furthermore, when there are multiple disabilities or disorders, support is concentrated on the more obvious disabilities, and the lack of support for the less superficially obvious disabilities associated with multiple difficulties, including mental health problems, can be a challenge for people with 22q11DS and their families. CONCLUSIONS: This study suggests a need for increased focus on multimorbidity and associated disabilities in school education that are difficult to observe because of their mildness or borderline levels if present alone.

Medical, welfare, and educational challenges and psychological distress in parents caring for an individual with 22q11.2 deletion syndrome: A cross-sectional survey in Japan.

Parents of children with 22q11.2 deletion syndrome (22q11DS) experience distress not only due to multimorbidity in the patients, but also due to professionals' lack of understanding about 22q11DS and insufficient support systems. This study investigated relationships between medical, welfare, and educational challenges and parental psychological distress. A cross-sectional survey was conducted on primary caregivers of children with 22q11DS. Participants included 125 parents (114 mothers, 91.2%; average age = 44.3 years) who reported their challenges, psychological distress, and child's comorbidities of 22q11DS. Results showed that the difficulty in going to multiple medical institutions (ß = 0.181, p < 0.05) and lack of understanding by welfare staff and insufficient welfare support systems for 22q11DS (ß = 0.220-0.316, all p < 0.05) were associated with parental psychological distress, even after adjusting for child's comorbidities. In the subsample of parents whose child attended an educational institution, inadequate management in classroom and mismatch between service and users in educational settings were associated with psychological distress (ß = 0.222-0.296, all p < 0.05). This study reveals the importance of assessing not only severity of comorbidities in 22q11DS, but also the medical, welfare, and educational challenges for parental mental health.

Culture-dependent and universal constructs and promoting factors for the process of personal recovery in users of mental health services: qualitative findings from Japan.

BACKGROUND: The conceptualization of personal recovery began in Europe and North America and has spread worldwide. However, the concept of personal recovery in addition to recovery-promoting factors may be influenced by culture. We explored how users of mental health services in Japan perceive their own personal recovery and the factors that promote it. METHODS: We conducted semi-structured interviews and focus group interviews with individuals using mental health services. The interview data were analysed using thematic analysis with a grouped framework analysis approach. We used a coding framework based on the existing CHIME framework (connectedness, hope and optimism about the future, identity, meaning in life, and empowerment). RESULTS: Data were obtained from 30 users of mental health services (mean age: 40.4 years; 46.7% women; 50.0% with schizophrenia). "Compassion for others" was newly extracted in "Connectedness", and "Rebuilding/redefining identity not being as shaped by social norms" was newly extracted in "Identity" as personal recovery. "Positive experiences in childhood" (including positive parenting support from neighbours) was newly extracted as a recovery-promoting factor. CONCLUSIONS: Our unique findings on the rebuilding identity/defining identity free from conformity to social norms due to interactions with familiar people, including peers, may be culture dependent. This study raises overarching questions regarding how socio-cultural values influence the development of identity and personal values and how they are in turn reflected in personal recovery.

Reliability and validity of the Japanese version of the INSPIRE measure of staff support for personal recovery in community mental health service users in Japan.

BACKGROUND: Supporting personal recovery in people with mental health difficulties is central to mental health services. This study aimed to develop the Japanese version of INSPIRE and Brief INSPIRE measure of staff support for personal recovery and to evaluate its reliability and validity. METHODS: A questionnaire survey was conducted from October to December 2015. The authors asked users to participate in the survey of 14 community mental health services in the Kanto region of Japan. The service users completed self-administered questionnaires that include the Japanese version of INSPIRE, the Recovery Assessment Scale, the Client Satisfaction Questionnaire, the patient version of the Scale to Assess Therapeutic Relationship in Community Mental Health care and the Short Form Health Survey. Internal consistency was assessed using Cronbach's alpha coefficient, and test-retest reliability was assessed using the intraclass correlation coefficient (ICC) and weighted kappa. Convergent validity was examined by assessing correlation with other scales. Factor validity was evaluated by exploratory factor analysis (EFA) with generalized least-squares mean and oblimin rotation. In addition, confirmatory factor analysis was used to check the fitness of the factor structure models derived from the EFA. RESULTS: A total of 195 out of 212 users gave written informed consent and participated in the study. Data from 190 respondents were analyzed (response rate 89.6%). INSPIRE, Brief INSPIRE, and the subscales all showed Cronbach's alpha coefficient over 0.78. ICC and weighted kappa derived more than 0.92 for subscales and Brief INSPIRE. These numerical values indicated good reliability. The convergent validity of Brief INSPIRE and the subscales was significantly positively correlated with the other scales. Different from the previous study, the factor structure was extracted using EFA. Both factor structures were checked by CFA, but the degree of fitness index was not good in either. Therefore, the factor analysis did not show goodness of fit. CONCLUSIONS: This study found the Japanese version of INSPIRE and Brief INSPIRE to be reliable and valid for use among community mental health service users in Japan.

Correction to: The Japanese version of the questionnaire about the process of recovery: development and validity and reliability testing.

After publication of our article [1] we were notified that the 5-point Likert-type scale in Additional file 1 needs to change from "1 to 5" to "0 to 4". The updated Additional file 1 is included in this correction.

The Japanese version of the questionnaire about the process of recovery: development and validity and reliability testing.

BACKGROUND: Personal recovery is increasingly recognised as an important outcome measure in mental health services. This study aimed to develop a Japanese version of the Questionnaire about the Process of Recovery (QPR-J) and test its validity and reliability. METHODS: The study comprised two stages that employed the cross-sectional and prospective cohort designs, respectively. We translated the questionnaire using a standard translation/back-translation method. Convergent validity was examined by calculating Pearson's correlation coefficients with scores on the Recovery Assessment Scale (RAS) and the Short-Form-8 Health Survey (SF-8). An exploratory factor analysis (EFA) was conducted to examine factorial validity. We used intraclass correlation and Cronbach's alpha to examine the test-retest and internal consistency reliability of the QPR-J's 22-item full scale, 17-item intrapersonal and 5-item interpersonal subscales. We conducted an EFA along with a confirmatory factor analysis (CFA). RESULTS: Data were obtained from 197 users of mental health services (mean age: 42.0 years; 61.9% female; 49.2% diagnosed with schizophrenia). The QPR-J showed adequate convergent validity, exhibiting significant, positive correlations with the RAS and SF-8 scores. The QPR-J's full version, subscales, showed excellent test-retest and internal consistency reliability, with the exception of acceptable but relatively low internal consistency reliability for the interpersonal subscale. Based on the results of the CFA and EFA, we adopted the factor structure extracted from the original 2-factor model based on the present CFA. CONCLUSION: The QPR-J is an adequately valid and reliable measure of the process of recovery among Japanese users with mental health services.

[Recovery-oriented Practice Using a Question Prompt Sheet].

Shared decision making (SDM) is being considered increasingly important in today's medical practice. This approach should also be promoted in the field of mental health. We developed a question prompt sheet (QPS) for persons with schizophrenia as a decision aid to empower them with autonomy. We published it on the website as a free download available to the general public. The therapeutic relationships respecting otherness between mental health service users and professionals can be the basis of recovery-oriented support. This article aims to introduce the background and process of making a QPS and to rethink recovery and growth from the viewpoint of dialogism.

Risk and protective factors for early dropout from telephone monitoring for individuals with drug convictions in community mental health centers in Japan.

INTRODUCTION: Individuals involved with the criminal justice system face challenges in receiving and maintaining substance use disorder (SUD) treatment and support. Although telephone monitoring (TM) could reduce these barriers, data on TM for community-dwelling individuals involved with the criminal justice system and research on individuals who drop out of TM are scarce. We examined the factors associated with dropping out early from the Voice Bridges Project, which provides TM for individuals on probation for drug-related convictions through community mental health centers in Japan. METHODS: Participants (n = 546) were individuals aged ≥20 years with methamphetamine-related convictions who were on probation. Univariate analyses examine the associations between one-year follow-up status and baseline variables, and multivariate Cox proportional hazards regression analyses identify the risk and protective factors associated with dropping out. Stratified analyses report results based on sex and halfway-house residency. RESULTS: The one-year dropout rate was 43.6 % (n = 238). Multivariate analysis identified two risk factors for dropping out-halfway-house residency and suicide attempts in the past year, and two protective factors-higher education and the current use of SUD services. Sex-stratified analyses showed that halfway-house residency was a risk factor for both men and women. Attempted suicide was a risk factor for women. Conversely, higher education and current use of SUD services were protective factors for men. CONCLUSIONS: Our results identify unique risk factors for women, such as a recent history of suicide attempts, and distinctive protective factors for men, including higher education and current use of SUD services, emphasizing the importance of sex-specific approaches. Furthermore, the study reveals that irrespective of sex, vulnerable individuals, such as halfway-house residents, are at a higher risk of dropping out from TM.

"World-Informed" Neuroscience for Diversity and Inclusion: An Organizational Change in Cognitive Sciences.

By nature, humans are "tojisha (participating subjects/player-witnesses)" who encounter an unpredictable real world. An important characteristic of the relationship between the individual brain and the world is that it creates a loop of interaction and mutual formation. However, cognitive sciences have traditionally been based on a model that treats the world as a given constant. We propose incorporating the interaction loop into this model to create "world-informed neuroscience (WIN)". Based on co-productive research with people with minority characteristics that do not match the world, we hypothesize that the tojisha and the world interact in a two-dimensional way of rule-based and story-based. By defining the cognitive process of becoming tojisha in this way, it is possible to contribute to the various issues of the real world and diversity and inclusion through the integration of the humanities and sciences. The critical role of the brain dopamine system as a basis for brain-world interaction and the importance of research on urbanicity and adolescent development as examples of the application of WIN were discussed. The promotion of these studies will require bidirectional translation between human population science and animal cognitive neuroscience. We propose that the social model of disability should be incorporated into cognitive sciences, and that disability-informed innovation is needed to identify how social factors are involved in mismatches that are difficult to visualize. To promote WIN to ultimately contribute to a diverse and inclusive society, co-production of research from the initial stage of research design should be a baseline requirement.

Relationship between high trait anxiety in 22q11.2 deletion syndrome and the difficulties in medical, welfare, and educational services.

Aim: The 22q11.2 deletion syndrome (22q11DS) is associated with a high prevalence of mental health comorbidities. However, not enough attention has been paid to the elevated prevalence of high trait anxiety that begins early in life and may be enduring. We sought to identify specific medical, welfare, or educational difficulties associated with high trait anxiety in 22q11DS. Methods: A questionnaire-based survey was conducted for the parents of 22q11DS individuals (N = 125). First, a multiple regression analysis was conducted to confirm the hypothesis that high trait anxiety in individuals with 22q11DS would be associated with parents' psychological distress. This was based on 19 questionnaire options regarding what difficulties the parents currently face about their child's disease, characteristics, and traits. Next, we explored what challenges faced in medical, welfare, and educational services would be associated with the trait anxiety in their child. Results: The multiple regression analysis confirmed that the high trait anxiety was significantly associated with parental psychological distress (ß = 0.265, p = 0.018) among the 19 clinical/personal characteristics of 22q11DS. Furthermore, this characteristic was associated with various difficulties faced in the medical care, welfare, and education services, and the parent-child relationship. Conclusion: To our knowledge, this is the first study to clarify quantitatively how the characteristic of high anxiety level in 22q11DS individuals is related to the caregivers' perceived difficulties in medical, welfare, and educational services. These results suggest the necessity of designing service structures informed of the fact that high trait anxiety is an important clinical feature of the syndrome.

Effectiveness of an Online Peer Gatekeeper Training Program for Postsecondary Students on Suicide Prevention in Japan: Protocol for a Randomized Controlled Trial.

BACKGROUND: Postsecondary student suicide is one of Japan's most severe public health problems. Gatekeeper training (GKT) programs are a generally recommended suicide prevention intervention in Japan. For suicide countermeasures, an online program tailored to students may enhance self-efficacy as a gatekeeper. OBJECTIVE: This study aims to describe a research protocol to investigate the effect of a newly developed internet-delivered online peer GKT program to improve postsecondary student self-efficacy as gatekeepers for suicide countermeasures in Japan. METHODS: This study is a 2-arm, parallel, randomized controlled trial with a 1:1 (intervention: waiting list) allocation. Participants (n=320) will be recruited, and those who meet the inclusion criteria will be randomly allocated to the intervention or waiting list control group. An approximately 85-minute, 6-section, internet-based gatekeeper program for postsecondary students has been developed that includes videos to help participants acquire skills as gatekeepers. The intervention group will complete the program within 10 days. The primary outcome, self-efficacy as a gatekeeper, is measured using the Gatekeeper Self-Efficacy Scale at baseline, immediately after taking the program, and 2 months after the survey after completing the program follow-up. To compare the primary outcomes, a t test, where the significance level is 5% (2-sided), will be used to test the intervention effect on an intention-to-treat basis. RESULTS: The study was at the stage of data collection at the time of submission. We recruited participants for this study during August and September 2021, and data collection will continue until December 2021. The data analysis related to the primary outcome will start in December 2021, and we hope to publish the results in 2022 or 2023. CONCLUSIONS: This is the first study to investigate the effectiveness of an online GKT program for postsecondary students to improve self-efficacy as a gatekeeper using a randomized controlled trial design. The study will explore the potential of an online peer gatekeeper program for postsecondary students that can be disseminated online to a large number of students with minimal cost. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry UMIN000045325; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000051685. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/34832.

Personalized values in life as point of interaction with the world: Developmental/neurobehavioral basis and implications for psychiatry.

Behavioral neuroscience has dealt with short-term decision making but has not defined either daily or longer-term life actions. The individual brain interacts with the society/world, but where that point of action is and how it interacts has never been an explicit scientific question. Here, we redefine value as an intrapersonal driver of medium- and long-term life actions. Value has the following three aspects. The first is value as a driving force of action, a factor that commits people to take default-mode or intrinsic actions daily and longer term. It consists of value memories based on past experiences, and a sense of values, the source of choosing actions under uncertain circumstances. It is also a multilayered structure of unconscious/automatic and conscious/self-controlled. The second is personalized value, which focuses not only on the value of human beings in general, but on the aspect that is individualized and personalized, which is the foundation of diversity in society. Third, the value is developed through the life course. It is necessary to clarify how values are personalized through the internalization of parent-child, peer, and social experiences through adolescence, a life stage almost neglected in neuroscience. This viewpoint describes the brain and the behavioral basis of adolescence in which the value and its personalization occur, and the importance of this personalized value as a point of interaction between the individual brain and the world. Then the significance of personalized values in psychiatry is discussed, and the concept of values-informed psychiatry is proposed.

Young carers in Japan: Reliability and validity testing of the BBC/University of Nottingham young carers survey questionnaire and prevalence estimation in 5000 adolescents.

Aim: Young carers (YCs) refer to children under the age of 18 who assume responsibilities that would normally be assumed by adults, such as caring for family members in need of care. In recent years, the concept of YCs has been expanding in Japan, and the government has been rapidly implementing strategies to support them. There is a need for a survey scale for YCs that uses standardized methods that can be compared internationally. Method: The BBC/University of Nottingham Survey for estimating the prevalence of YCs and caring activities of United Kingdom adolescents was translated into Japanese, and its reliability and validity were tested with 313 adolescents. Moreover, the prevalence of YCs was estimated in a school-based survey among 5000 adolescents. Results: The Young Carers Scale Japanese version (YCS-J) was acceptably reliable and valid. The original six-factor model for caring activity in the Multidimensional Assessment of Caring Activities Checklist for Young Carers (MACA-YC18) was supported by confirmatory factor analysis. The prevalence of YCs among 5000 adolescents in the Tokyo metropolitan area was estimated to be 7.4%, comparable to that reported in Western countries and in recent surveys in Japan using nonstandardized methods. YCs exhibited significantly higher scores for prosocial behavior and emotional symptoms than non-YCs. Conclusions: The YCS-J, as an internationally comparable instrument, will be useful for understanding the actual situation of YCs in Japan, and to disseminate and implement support through cooperation among education, welfare, and healthcare sectors.

Oral corticosteroid dosage and clinical presentation of psychiatric conditions after steroid use: A consultation-liaison psychiatry service's experience.

AIM: Psychiatric disturbances are the major adverse effects of corticosteroids. There are no consistent conclusions regarding changes in steroid dosage and the incidence of psychiatric conditions, due in part to the lack of consistent evaluation criteria. The purpose of this research was to determine the incidence and dose-dependency of psychiatric conditions as assessed by trained psychiatrists. METHODS: A retrospective chart review was conducted at a university hospital in Japan. We identified inpatients receiving oral prednisolone treatment, who were referred to the consultation-liaison psychiatry team from April 2015 to March 2018. Patients were divided into high-dose (≥0.5 mg/kg/day) and low-dose (<0.5 mg/kg/day) groups. We investigated the associations between steroid dosage and incidence of psychiatric conditions. RESULTS: A total of 93 patients (35 in the high-dose group, 58 in the low-dose group) were included. Various psychiatric conditions, such as insomnia, delirium, depression, and psychosis, occurred during steroid therapy. The most common condition was insomnia (72%). We observed no significant differences in the patient background characteristics and the incidence of most psychiatric conditions between the high-dose and low-dose groups. However, there were more patients with delirium in the low-dose group than in the high-dose group. CONCLUSIONS: Based on the accurate assessment of psychiatric conditions by psychiatrists, our analysis suggests that, among inpatients referred to a consultation-liaison psychiatry team, the incidence of psychiatric conditions, with the exception of delirium, is independent of the dose of oral prednisolone.

"Staying at home" to tackle COVID-19 pandemic: rhetoric or reality? Cross-cutting analysis of nine population groups vulnerable to homelessness in Japan.

Although the "stay-at-home" order is advocated against the coronavirus disease 2019 (COVID-19), the lives of individuals lacking adequate housing are threatened. We developed a framework to assess various populations with unstable housing in terms of socio-economic consequences of COVID-19, risk of COVID-19 infection and progression, existing/urgent measures, and remaining challenges. Within the framework, nine groups vulnerable to homelessness in Japan were classified into (i) "people without accommodation," (ii) "people living in temporary or crisis accommodation," and (iii) populations that include "people living in severely inadequate and insecure accommodation." The assessment revealed that "staying at home" was physically and practically unattainable across groups. The study identified specific institutional, social, and cultural challenges apart from the common economic crisis, whereas the utilization of social welfare was low. Findings suggest that the rapid increase of groups classified as "(i)" and "(ii)" should be addressed by engaging stakeholders to enhance the availability and accessibility of social welfare and rescue measures, and to ensure safe and private accommodations for all groups. It is critical to enhance multi-sectoral collaboration in responding to the common and specific vulnerabilities of these population groups from health, socio-economic, and humanitarian perspectives. Under the pandemic, homelessness should be regarded less as a peculiar problem for specific populations but an extension of daily life. The framework can be a reference when planning the comprehensive yet concise assessment of populations with unstable housing in other countries to inform responses to the pandemic.

A case of interictal dysphoric disorder comorbid with interictal psychosis: Part of the same spectrum or separate entities?

Depressive disorders in epilepsy often present characteristic clinical manifestations atypical in primary, endogenous depression. Here, we report a case of a 64-year-old woman with right mesial temporal lobe epilepsy, who complained of bizarre, antipsychotic-refractory cenesthetic hallucinations in her interictal phase, and was hospitalized after a suicide attempt. Detailed clinical observations revealed mood symptoms, which led to the diagnosis of interictal dysphoric disorder comorbid with interictal psychosis. Sertraline with low-dose aripiprazole markedly alleviated both depressive and psychotic symptoms. This case suggested that the two diagnostic entities may overlap and that depressive symptoms tend to be concurrent when concurring with psychosis, which hampers the appropriate choice of a treatment option.

Emotional stimuli-provoked seizures potentially misdiagnosed as psychogenic non-epileptic attacks: A case of temporal lobe epilepsy with amygdala enlargement.

The association between emotional stimuli and temporal lobe epilepsy (TLE) is largely unknown. Here, we report the case of a depressed, 50-year-old female complaining of episodes of a "spaced out" experience precipitated by emotional stimuli. Psychogenic non-epileptic attacks were suspected. However, video-EEG coupled with emotional stimuli-provoked procedures and MRI findings of amygdala enlargement, led to the diagnosis of left TLE. Accurate diagnosis and explanation improved her subjective depression and seizure frequency. This case demonstrated that emotional stimuli can provoke seizures in TLE and suggested the involvement of the enlarged amygdala and the modulation of emotion-related neural circuits.

Directional asymmetry in vertical smooth-pursuit and cancellation of the vertical vestibulo-ocular reflex in juvenile monkeys.

Young primates exhibit asymmetric eye movements during vertical smooth-pursuit across a textured background such that upward pursuit has low velocity and requires many catch-up saccades. The asymmetric eye movements cannot be explained by the un-suppressed optokinetic reflex resulting from background visual motion across the retina during pursuit, suggesting that the asymmetry reflects most probably, a low gain in upward eye commands (Kasahara et al. in Exp Brain Res 171:306-321, 2006). In this study, we examined (1) whether there are intrinsic differences in the upward and downward pursuit capabilities and (2) how the difficulty in upward pursuit is correlated with the ability of vertical VOR cancellation. Three juvenile macaques that had initially been trained only for horizontal (but not vertical) pursuit were trained for sinusoidal pursuit in the absence of a textured background. In 2 of the 3 macaques, there was a clear asymmetry between upward and downward pursuit gains and in the time course of initial gain increase. In the third macaque, downward pursuit gain was also low. It did not show consistent asymmetry during the initial 2 weeks of training. However, it also exhibited a significant asymmetry after 4 months of training, similar to the other two monkeys. After 6 months of training, these two monkeys (but not the third) still exhibited asymmetry. As target frequency increased in these two monkeys, mean upward eye velocity saturated at approximately 15 degrees /s, whereas horizontal and downward eye velocity increased up to approximately 40 degrees /s. During cancellation of the VOR induced by upward whole body rotation, downward eye velocity of the residual VOR increased as the stimulus frequency increased. Gain of the residual VOR during upward rotation was significantly higher than that during horizontal and downward rotation. The time course of residual VOR induced by vertical whole body step-rotation during VOR cancellation was predicted by addition of eye velocity during pursuit and VOR x1. These results support our view that the directional asymmetry reflects the difference in the organization of the cerebellar floccular region for upward and downward directions and the preeminent role of pursuit in VOR cancellation.

Premature deaths among individuals with severe mental illness after discharge from long-term hospitalisation in Japan: a naturalistic observation during a 24-year period.

BACKGROUND: Premature death in individuals with severe mental illness (SMI) in countries without nationally collected data, including Japan, is structurally underreported. AIMS: To elucidate excess mortality among individuals with SMI in Japan. METHOD: We retrospectively investigated all deaths among users of a non-clinical community-based mental health service provider in suburban Tokyo from 1992 to 2015. RESULTS: During the study period, 45 individuals died among 254 qualified registrants. Deaths were by natural causes in 33 cases (73.3%). The mean years of life lost was 22.2 years and the overall standard mortality ratio (SMR) was 3.28 (95% CI 2.40-4.39). The cause-specific SMR was 5.09 (95% CI 2.33-9.66) for cardiovascular disease and 7.38 (95% CI 2.40-17.22) for suicide. CONCLUSIONS: Although Japan leads the world in longevity, individuals with SMI suffer premature death and excess mortality due to physical conditions as well as suicide. Revealing this underreported disparity of life is the first step to improving physical care for individuals with SMI. DECLARATION OF INTEREST: S.K. received personal fees from Pfizer and Dainippon-Sumitomo, outside the submitted work, and was a medical adviser to Sudachi-kai. Y.K. received grants from Japan Foundation for Neuroscience and Mental Health (JFNMH), during the conduct of the study, and personal fees from Dainippon-Sumitomo, outside the submitted work. K.K. received grants from Japan Society for the Promotion of Science (JSPS) and Japan Agency for Medical Research and Development (AMED), during the conduct of the study; personal fees from Daiichi-Sankyo, Otsuka, Meiji-Seika Pharma, Yoshitomi, Mochida and Fuji-Film RI Pharma; grants and personal fees from MSD, Astellas, Dainippon-Sumitomo and Eisai; and grants from Lily, Takeda and Tanabe-Mitsubishi, outside the submitted work. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.