Longitudinal Impact of the COVID-19 Pandemic on Stress and Occupational Well-Being of Mental Health Professionals: An International Study.

BACKGROUND: Increased levels of occupational stress among health professionals during the COVID-19 pandemic have been documented. Few studies have examined the effects of the pandemic on mental health professionals despite the heightened demand for their services. METHOD: A multilingual, longitudinal, global survey was conducted at 3 time points during the pandemic among members of the World Health Organization's Global Clinical Practice Network. A total of 786 Global Clinical Practice Network members from 86 countries responded to surveys assessing occupational distress, well-being, and posttraumatic stress symptoms. RESULTS: On average, respondents' well-being deteriorated across time while their posttraumatic stress symptoms showed a modest improvement. Linear growth models indicated that being female, being younger, providing face-to-face health services to patients with COVID-19, having been a target of COVID-related violence, and living in a low- or middle-income country or a country with a higher COVID-19 death rate conveyed greater risk for poor well-being and higher level of stress symptoms over time. Growth mixed modeling identified trajectories of occupational well-being and stress symptoms. Most mental health professions demonstrated no impact to well-being; maintained moderate, nonclinical levels of stress symptoms; or showed improvements after an initial period of difficulty. However, some participant groups exhibited deteriorating well-being approaching the clinical threshold (25.8%) and persistently high and clinically significant levels of posttraumatic stress symptoms (19.6%) over time. CONCLUSIONS: This study indicates that although most mental health professionals exhibited stable, positive well-being and low stress symptoms during the pandemic, a substantial minority of an already burdened global mental health workforce experienced persistently poor or deteriorating psychological status over the course of the pandemic.

GNAO1 organizes the cytoskeletal remodeling and firing of developing neurons.

Developmental and epileptic encephalopathy (DEE) represents a group of neurodevelopmental disorders characterized by infantile-onset intractable seizures and unfavorable prognosis of psychomotor development. To date, hundreds of genes have been linked to the onset of DEE. GNAO1 is a DEE-associated gene encoding the alpha-O1 subunit of guanine nucleotide-binding protein (GαO ). Despite the increasing number of reported children with GNAO1 encephalopathy, the molecular mechanisms underlying their neurodevelopmental phenotypes remain elusive. We herein present that co-immunoprecipitation and mass spectrometry analyses identified another DEE-associated protein, SPTAN1, as an interacting partner of GαO . Silencing of endogenous Gnao1 attenuated the neurite outgrowth and calcium-dependent signaling. Inactivation of GNAO1 in human-induced pluripotent stem cells gave rise to anomalous brain organoids that only weakly expressed SPTAN1 and Ankyrin-G. Furthermore, GNAO1-deficient organoids failed to conduct synchronized firing to adjacent neurons. These data indicate that GαO and other DEE-associated proteins organize the cytoskeletal remodeling and functional polarity of neurons in the developing brain.

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) recommendations for the management of patients with bipolar disorder with mixed presentations.

OBJECTIVES: The 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) guidelines provided clinicians with pragmatic treatment recommendations for bipolar disorder (BD). While these guidelines included commentary on how mixed features may direct treatment selection, specific recommendations were not provided-a critical gap which the current update aims to address. METHOD: Overview of research regarding mixed presentations in BD, with treatment recommendations developed using a modified CANMAT/ISBD rating methodology. Limitations are discussed, including the dearth of high-quality data and reliance on expert opinion. RESULTS: No agents met threshold for first-line treatment of DSM-5 manic or depressive episodes with mixed features. For mania + mixed features second-line treatment options include asenapine, cariprazine, divalproex, and aripiprazole. In depression + mixed features, cariprazine and lurasidone are recommended as second-line options. For DSM-IV defined mixed episodes, with a longer history of research, asenapine and aripiprazole are first-line, and olanzapine (monotherapy or combination), carbamazepine, and divalproex are second-line. Research on maintenance treatments following a DSM-5 mixed presentation is extremely limited, with third-line recommendations based on expert opinion. For maintenance treatment following a DSM-IV mixed episode, quetiapine (monotherapy or combination) is first-line, and lithium and olanzapine identified as second-line options. CONCLUSION: The CANMAT and ISBD groups hope these guidelines provide valuable support for clinicians providing care to patients experiencing mixed presentations, as well as further influence investment in research to improve diagnosis and treatment of this common and complex clinical state.

Serum Soluble Triggering Receptor Expressed on Myeloid Cells 2 as a Biomarker for Incident Dementia: The Hisayama Study.

OBJECTIVE: To investigate the association between serum soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a soluble type of an innate immune receptor expressed on the microglia, and the risk of dementia. METHODS: A total of 1,349 Japanese community residents aged 60 and older without dementia were followed prospectively for 10 years (2002-2012). Serum sTREM2 levels were quantified by using an enzyme-linked immunosorbent assay and divided into quartiles. Cox proportional hazards model was used to estimate the hazard ratios (HRs) of serum sTREM2 levels on the risk of dementia. RESULTS: During the follow-up, 300 subjects developed all-cause dementia; 193 had Alzheimer's disease (AD), and 85 had vascular dementia (VaD). The age- and sex-adjusted incidences of all-cause dementia, AD, and VaD elevated significantly with higher serum sTREM2 levels (all p for trend < 0.012). These associations were not altered after adjustment for confounding factors, including high-sensitive C-reactive protein. Subjects with the highest quartile of serum sTREM2 levels had significantly higher multivariable-adjusted risks of developing all-cause dementia, AD, and VaD than those with the lowest quartile (HR = 2.03, 95% confidence interval [CI] = 1.39-2.97, p < 0.001 for all-cause dementia; HR = 1.62, 95% CI = 1.02-2.55, p = 0.04 for AD; HR = 2.85, 95% CI = 1.35-6.02, p = 0.006 for VaD). No significant heterogeneity in the association of serum sTREM2 levels with the development of dementia was observed among the other risk factor subgroups (all p for heterogeneity > 0.11). INTERPRETATION: The present findings suggest a significant association between increased serum sTREM2 levels and the risk of developing all-cause dementia, AD, and VaD in the general elderly Japanese population. ANN NEUROL 2019;85:47-58.

Decline in Handgrip Strength From Midlife to Late-Life is Associated With Dementia in a Japanese Community: The Hisayama Study.

BACKGROUND: The association between decline in handgrip strength from midlife to late life and dementia is unclear. METHODS: Japanese community-dwellers without dementia aged 60 to 79 years (ie, individuals in late life; mean age, 68 years) were followed for 24 years (1988-2012) (n = 1,055); 835 of them had participated in a health examination in 1973-1974 (mean age, 53 years), and these earlier data were used for the midlife analysis. Using a Cox proportional hazards model, we estimated the risk conferred by a decline in handgrip strength over a 15-year period (1973-74 to 1988) from midlife to late life on the development of total dementia, Alzheimer's disease (AD), and vascular dementia (VaD) over the late-life follow-up period from 1988 to 2012. RESULTS: During the follow-up, 368 subjects experienced total dementia. The age- and sex-adjusted incidence of total dementia increased significantly with greater decline in handgrip strength (increased or unchanged handgrip strength [≥+0%] 25.1, mildly decreased [-14 to -1%] 28.4, and severely decreased [≤-15%] 38.9 per 1,000 person-years). A greater decline in handgrip strength was significantly associated with higher risk of total dementia after adjusting for potential confounding factors; subjects with severely decreased handgrip strength had 1.51-fold (95% confidence interval, 1.14-1.99, P < 0.01) increased risk of total dementia compared to those with increased or unchanged handgrip strength. Similar significant findings were observed for AD, but not for VaD. CONCLUSIONS: Our findings suggest that a greater decline in handgrip strength from midlife to late life is an important indicator for late-life onset of dementia.

Coprescription of mood stabilizers in schizophrenia, dosing, and clinical correlates: An international study.

OBJECTIVE: Studies examining coprescription and dosages of mood stabilizers (MSs) with antipsychotics for psychotic disorders are infrequent. Based on sparse extant data and clinical experience, we hypothesized that adjunctive MS use would be associated with certain demographic (e.g., younger age), clinical factors (e.g., longer illness duration), and characteristics of antipsychotic treatment (e.g., multiple or high antipsychotic doses). METHODS: Within an Asian research consortium focusing on pharmaco-epidemiological factors in schizophrenia, we evaluated rates of MS coprescription, including high doses (>1000 mg/day lithium-equivalents) and clinical correlates. RESULTS: Among 3557 subjects diagnosed with schizophrenia in 14 Asian countries, MSs were coprescribed with antipsychotics in 13.6% (n = 485) of the sample, with 10.9% (n = 53) on a high dose. Adjunctive MS treatment was associated (all p < 0.005) with demographic (female sex and younger age), setting (country and hospitalization), illness (longer duration, more hospitalizations, non-remission of illness, behavioral disorganization, aggression, affective symptoms, and social-occupational dysfunction), and treatment-related factors (higher antipsychotic dose, multiple antipsychotics, higher body mass index, and greater sedation). Patients given high doses of MSs had a less favorable illness course, more behavioral disorganization, poorer functioning, and higher antipsychotic doses. CONCLUSIONS: Schizophrenia patients receiving adjunctive MS treatment in Asian psychiatric centers are more severely ill and less responsive to simpler treatment regimens.

Clinical characteristics of boys with comorbid autism spectrum disorder and attention deficit/hyperactivity disorder.

BACKGROUND: Autism spectrum disorder (ASD) and attention deficit / hyperactivity disorder (ADHD) are frequently comorbid and, as both are defined as neurodevelopmental disorders in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, simultaneous diagnosis is possible. However, despite the frequency of this comorbid state, its endophenotypic features remain unclear. This study thus aimed to describe the behavioral and emotional problems in boys with comorbid ASD and ADHD using the Strengths and Difficulties Questionnaire (SDQ). METHODS: In total, 102 boys (age, 6-12 years) diagnosed with one or both disorders were divided into three groups according to their clinical diagnosis: ASD + ADHD (N = 39), ASD (N = 37), and ADHD (N = 25). Symptoms and related behaviors were compared among the groups using parents' ratings of the autism spectrum quotient, ADHD rating scale-IV, and SDQ. RESULTS: In the ASD + ADHD group, the proportion of "clinical-range" cases was as high as 76.9% for the SDQ total difficulties score (TDS). The ASD + ADHD and ADHD groups had significantly higher TDS as well as behavioral problems and hyperactivity subscale scores than did the ASD group; however, the ASD + ADHD group did not have significantly different scores on any subscale compared with the other two groups. The ASD + ADHD and ASD groups also had significantly lower prosocial behavior scores than the ADHD group. CONCLUSIONS: When using the SDQ as a screening tool for neurodevelopmental disorders, a high TDS, conduct problems, hyperactivity, and low prosocial behavior can be considered characteristic of ASD and ADHD comorbidity in 6- to 12-year-old boys.

Association of self-reported religiosity with the development of major depression in multireligious country Japan.

AIM: In Western Christian countries, religiosity is generally believed to be associated with a lower risk for depression, which is supported by epidemiological evidence. However, the association between religiosity and depression in multireligious countries is unknown. The objective was to evaluate the association between religiosity and subsequent depression in a multireligious population. METHODS: A longitudinal study was conducted in a large hospital in Tokyo, Japan, from 2005 to 2018. All participants who underwent health check-ups without a prior history of depression or depression at baseline were included. Our outcome was development of major depressive disorder (MDD), which was compared according to the degree of religiosity, adjusting for potential confounders. RESULTS: Among 67 723 adult participants, those who were more religious tended to be older, female, married, and to have healthier habits but also more medical comorbidities at baseline. During a median follow-up of 2528 days, 1911 (2.8%) participants developed MDD. Compared to the reference group, religious group participants tended to have higher odds ratios (OR) for developing MDD in a dose-dependent manner. Among them, the extremely religious group (OR, 1.51; 95% confidence interval [CI], 1.28-1.78) and the moderately religious group (OR, 1.30; 95% CI, 1.14-1.49) were statistically associated with increased development of MDD compared to the not-religious-at-all group. Those who had increased their religiosity from baseline had statistically lower development of MDD (OR, 0.85; 95% CI, 0.75-0.97) compared to those who remained in the same degree of religiosity from baseline. CONCLUSION: Religiosity was associated with future MDD in a dose-dependent manner in a multireligious population, which was in the opposite direction from that seen in previous Western longitudinal studies.

Autism spectrum conditions in hikikomori: A pilot case-control study.

AIM: Hikikomori, a form of pathological social withdrawal, has been suggested to have comorbidity with autism spectrum disorder (ASD). This study aimed to clarify how characteristics of hikikomori are associated with ASD, including undiagnosed autism spectrum conditions (ASC), in clinical settings. METHODS: A total of 416 clinical patients were recruited through the Mood Disorder/Hikikomori Clinic at Kyushu University Hospital. A total of 103 hikikomori cases and 221 clinical controls without hikikomori conditions were extracted using a semi-structured interview, and completed a series of self-rated scales, including the Japanese version of the Autism-Spectrum Quotient (AQ-J). RESULTS: Compared to non-hikikomori controls, hikikomori cases were more likely to have higher autistic tendency based on the AQ-J. The cases showed more severe subjective depressive symptoms based on the self-rated Beck Depression Inventory II, whereas no significant difference was found on interview-based severity evaluation using the Hamilton Depression Rating Scale. Comparison within hikikomori cases based on the AQ-J cut-off score revealed that hikikomori cases with high ASC were significantly more likely to have higher traits of modern-type depression, smaller social networks, and less social support. CONCLUSION: The present data suggest that hikikomori sufferers are more likely to have autistic tendency, and that hikikomori sufferers with high ASC may have much more difficulty in social communication and social interaction. In addition, those with high ASC may also have lower self-esteem and higher complaint tendencies as aspects of modern-type depression traits, which may relate to the occurrence of hikikomori. Thus, evaluating autistic tendencies is important for appropriate interventions in hikikomori. Further investigations should be conducted to validate our pilot findings using structured diagnostic systems of ASD.

Longitudinal evaluation of visual P300 amplitude in clinical high-risk subjects: An event-related potential study.

AIM: We previously reported abnormal P300 and N200 in a visual oddball task, and progressive P300 amplitude reduction at 1-year follow-up in patients with first-episode schizophrenia. P300 reduction as well as intact P1/N1 were also observed in clinical high-risk subjects (CHR), but whether or not these components change over time is unknown. This study evaluates, longitudinally, the visual P300, as well as P1, N1, and N200, in CHR. METHODS: Visual event-related potentials (ERP) were recorded twice, once at baseline and once at 1-year follow-up in CHR (n = 19) and healthy comparison subjects (HC; n = 28). Participants silently counted infrequent target stimuli ('x') among standard stimuli ('y') presented on the screen while the 64-channel electroencephalogram was recorded. RESULTS: No CHR converted to psychosis from baseline to 1-year follow-up in this study. Visual P300 amplitude was reduced and the latency was delayed significantly in CHR at both time points compared with HC. Furthermore, CHR subjects who had more positive symptoms showed more amplitude reduction at both time points. P1, N1, and N200 did not differ between groups. CONCLUSION: Visual P300 amplitude was found to be reduced in CHR individuals compared with HC. We note that this finding is in subjects who did not convert to psychosis at 1-year follow-up. The association between visual P300 amplitude and symptoms suggests that for CHR who often experience clinical symptoms and seek medical care, visual P300 may be an important index that reflects the pathophysiological impairment underlying such clinical states.

Network analysis of the depressive symptom profiles in Asian patients with depressive disorders: Findings from the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD).

AIM: We aimed to estimate the network structures of depressive symptoms using network analysis and evaluated the geographic regional differences in theses network structures among Asian patients with depressive disorders. METHODS: Using data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD), the network of the ICD-10 diagnostic criteria for depressive episode was estimated from 1174 Asian patients with depressive disorders. The node strength centrality of all ICD-10 diagnostic criteria for a depressive episode was estimated using a community-detection algorithm. In addition, networks of depressive symptoms were estimated separately among East Asian patients and South or Southeast Asian patients. Moreover, networks were estimated separately among Asian patients from high-income countries and those from middle-income countries. RESULTS: Persistent sadness, fatigue, and loss of interest were the most centrally situated within the network of depressive symptoms in Asian patients with depressive disorders overall. A community-detection algorithm estimated that when excluding psychomotor disturbance as an outlier, the other nine symptoms formed the largest clinically meaningful cluster. Geographic and economic variations in networks of depressive symptoms were evaluated. CONCLUSION: Our findings demonstrated that the typical symptoms of the ICD-10 diagnostic criteria for depressive episode are the most centrally situated within the network of depressive symptoms. Furthermore, our findings suggested that cultural influences related to geographic and economic distributions of participants could influence the estimated depressive symptom network in Asian patients with depressive disorders.

Clinical Subtypes in Children with Attention-Deficit Hyperactivity Disorder According to Their Child Behavior Checklist Profile.

This study sought to identify subgroups of attention-deficit hyperactivity disorder (ADHD) defined by specific patterns of emotional and behavioral symptoms according to the parent-rated Child Behavior Checklist (CBCL). Our clinical sample comprised 314 children (aged 4 to 15 years) diagnosed with ADHD according to the DSM-5. In addition, comorbid psychiatric disorders, general functioning, and medication status were assessed. Cluster analysis was performed on the CBCL syndrome subscales and yielded a solution with four distinct subgroups. The "High internalizing/externalizing" group displayed an overlap between internalizing and externalizing problems in the CBCL profile. In addition, the "High internalizing/externalizing" group revealed a high rate of comorbid autism spectrum disorder and elevated autistic traits. The "Inattention and internalizing" group revealed a high rate of the predominantly inattentive presentation according to ADHD specifier from the DSM-5. The "Aggression and externalizing" group revealed a high rate of comorbid oppositional defiant disorder and conduct disorder. The "Less psychopathology" group scored low on all syndrome scales. Children with ADHD were subdivided into four distinct subgroups characterized by psychopathological patterns, with and without internalizing and externalizing problems. The overlap between internalizing and externalizing problems may be mediated with emotional dysregulation and associated neurobiological bases.

Study design and baseline characteristics of a population-based prospective cohort study of dementia in Japan: the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD).

BACKGROUND: The burden of dementia is growing rapidly and has become a medical and social problem in Japan. Prospective cohort studies have been considered an effective methodology to clarify the risk factors and the etiology of dementia. We aimed to perform a large-scale dementia cohort study to elucidate environmental and genetic risk factors for dementia, as well as their interaction. METHODS: The Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) is a multisite, population-based prospective cohort study of dementia, which was designed to enroll approximately 10,000 community-dwelling residents aged 65 years or older from 8 sites in Japan and to follow them up prospectively for at least 5 years. Baseline exposure data, including lifestyles, medical information, diets, physical activities, blood pressure, cognitive function, blood test, brain magnetic resonance imaging (MRI), and DNA samples, were collected with a pre-specified protocol and standardized measurement methods. The primary outcome was the development of dementia and its subtypes. The diagnosis of dementia was adjudicated by an endpoint adjudication committee using standard criteria and clinical information according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd Revised Edition. For brain MRI, three-dimensional acquisition of T1-weighted images was performed. Individual participant data were pooled for data analyses. RESULTS: The baseline survey was conducted from 2016 to 2018. The follow-up surveys are ongoing. A total of 11,410 individuals aged 65 years or older participated in the study. The mean age was 74.4 years, and 41.9% were male. The prevalence of dementia at baseline was 8.5% in overall participants. However, it was 16.4% among three sites where additional home visit and/or nursing home visit surveys were performed. Approximately two-thirds of dementia cases at baseline were Alzheimer's disease. CONCLUSIONS: The prospective cohort data from the JPSC-AD will provide valuable insights regarding the risk factors and etiology of dementia as well as for the development of predictive models and diagnostic markers for the future onset of dementia. The findings of this study will improve our understanding of dementia and provide helpful information to establish effective preventive strategies for dementia in Japan.

Long-term mood/antidepressant effects of quetiapine extended-release formulation: an open-label, non-controlled extension study in Japanese patients with bipolar depression.

BACKGROUND: In an 8-week, randomized, placebo-controlled, double-blind study, an extended-release formulation of quetiapine, quetiapine XR, demonstrated efficacy and safety in Japanese patients with bipolar depression. Bipolar disorder is a chronic disease requiring continuous treatment. METHODS: This was a long-term (52-week), open-label, non-controlled extension study to evaluate the long-term safety and efficacy of quetiapine XR in Japanese patients with bipolar depression who had previously completed the initial 8-week double-blind study. Efficacy was determined by the Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Depression Scale 17-item (HAM-D17), and Clinical Global Impressions-Bipolar scale (CGI-BP). Safety evaluations included analysis of adverse events, clinical laboratory measures, vital signs, Drug-induced Extrapyramidal Symptoms Scale, Young Mania Rating Scale, and the Columbia Suicide Severity Rating Scale. RESULTS: The mean (SD) MADRS total score decreased from 30.9 (6.9) at baseline to 16.1 (10.6) at week 8, and eventually to 9.1 (8.7) at week 52. The sustained efficacy of quetiapine XR treatment was also shown using HAM-D17 total scores, CGI-BP-Severity and Change evaluations. The most common adverse events were somnolence, nasopharyngitis, and thirst. Long-term treatment with quetiapine XR caused no substantial changes in the safety profiles, including clinical laboratory parameters, and no new safety concerns were identified. CONCLUSIONS: The efficacy of quetiapine XR was sustained long-term and no new safety concerns were identified in Japanese patients with bipolar depression. TRIAL REGISTRATION: ClinicalTrials.gov Registration: NCT01725308. Date of registration; 12th November 2012 (retrospectively registered).

Concurrent benzodiazepine use in older adults treated with antidepressants in Asia.

ABSTRACTBackground:Little is known about the combined use of benzodiazepines and antidepressants in older psychiatric patients. This study examined the prescription pattern of concurrent benzodiazepines in older adults treated with antidepressants in Asia, and explored its demographic and clinical correlates. METHODS: The data of 955 older adults with any type of psychiatric disorders were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Both univariate and multiple logistic regression analyses were performed. RESULTS: The proportion of benzodiazepine and antidepressant combination in this cohort was 44.3%. Multiple logistic regression analysis revealed that higher doses of antidepressants, younger age (<65 years), inpatients, public hospital, major comorbid medical conditions, antidepressant types, and country/territory were significantly associated with more frequent co-prescription of benzodiazepines and antidepressants. CONCLUSIONS: Nearly, half of the older adults treated with antidepressants in Asia are prescribed concurrent benzodiazepines. Given the potentially adverse effects of benzodiazepines, the rationale of benzodiazepines and antidepressants co-prescription needs to be revisited.

Pathophysiology and treatment of hoarding disorder.

Hoarding disorder (HD) is a newly listed disease in the new category of Obsessive-Compulsive and Related Disorders in the DSM-5. Patients with HD find it difficult to discard possessions regardless of their actual value and to organize those things. As a result, the possessions overflow the living space and hinder living functions. Though the hoarding symptom had been regarded as a subtype of obsessive-compulsive disorder (OCD) to date, recent studies have revealed many differences in clinical characteristics, including onset, course, degree of insight, and treatment responses, between hoarding and other subtypes. Moreover, several neuroimaging studies have found specific changes of brain structure and function in OCD patients with hoarding symptoms compared to patients with non-hoarding OCD. Meanwhile, strategies for treatment of HD have not been standardized. At present, psychological treatment using cognitive behavioral therapy techniques has a certain effect. In this review, we outline the pathophysiology and treatment of HD.

Hikikomori : Multidimensional understanding, assessment, and future international perspectives.

Hikikomori, a severe form of social withdrawal, has long been observed in Japan mainly among youth and adolescents since around the 1970s, and has been especially highlighted since the late 1990s. Moreover, hikikomori-like cases have recently been reported in many other countries. Hikikomori negatively influences not only the individual's mental health and social participation, but also wider education and workforce stability, and as such is a novel urgent global issue. In this review, we introduce the history, definition, diagnostic evaluation, and interventions for hikikomori and also the international prevalence of hikikomori outside Japan. We propose a hypothesis regarding the globalization of hikikomori based on domestic and international perspectives. In addition, we introduce our latest assessment system for hikikomori (including the latest version of the 'proposed diagnostic criteria of hikikomori for the future DSM/ICD diagnostic systems') and propose therapeutic strategies, including family approaches and individualized therapies. Finally, we present future challenges that may lead to solutions for an internationalized hikikomori.

Development and validation of the 22-item Tarumi's Modern-Type Depression Trait Scale: Avoidance of Social Roles, Complaint, and Low Self-Esteem (TACS-22).

AIM: Understanding premorbid personality is important, especially when considering treatment selection. Historically, the premorbid personality of patients with major depression in Japan was described as Shuchaku-kishitsu [similar to Typus melancholicus], as proposed by Shimoda in the 1930s. Since around 2000, there have been increased reports in Japan of young adults with depression who have had premorbid personality differing from the traditional type. In 2005, Tarumi termed this novel condition 'dysthymic-type depression,' and more recently the condition has been called Shin-gata/Gendai-gata Utsu-byo [modern-type depression (MTD)]. We recently developed a semi-structured diagnostic interview to evaluate MTD. Development of a tool that enables understanding of premorbid personality in a short time, especially at the early stage of treatment, is desirable. The object of this study was to develop a self-report scale to evaluate the traits of MTD, and to assess the scale's psychometric properties, diagnostic accuracy, and biological validity. METHODS: A sample of 340 participants from clinical and community settings completed measures. Psychometric properties were assessed with factor analysis. Diagnostic accuracy of the MTD traits was compared against a semi-structured interview. RESULTS: The questionnaire contained 22 items across three subscales, thus we termed it the 22-item Tarumi's Modern-Type Depression Trait Scale: Avoidance of Social Roles, Complaint, and Low Self-Esteem (TACS-22). Internal consistency, test-retest reliability, and convergent validity were all satisfactory. Among patients with major depression, the area under the curve was 0.757 (sensitivity of 63.1% and specificity of 82.9%) and the score was positively correlated with plasma tryptophan. CONCLUSION: The TACS-22 possessed adequate psychometric properties and diagnostic accuracy in an initial sample of Japanese adults. Additional research on its ability to support clinical assessment of MTD is warranted.

Cannabis use correlates with aggressive behavior and long-acting injectable antipsychotic treatment in Asian patients with schizophrenia.

Background: Although cannabis use has been linked with schizophrenia in a dose-response pattern, to our knowledge, the relationship between cannabis and schizophrenia has rarely been reported in Asian population. Aim: We compared the clinical characteristics and psychotropic prescription patterns between cannabis users and non-users among Asian patients with schizophrenia. Moreover, we aimed to identify the independent correlates of cannabis use in these subjects. Methods: We performed the analysis of the data from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP), a collaborative consortium survey used to collate the prescription patterns for antipsychotic and other psychotropic medications in patients with schizophrenia in Asia. We included 132 schizophrenia patients in the group of lifetime cannabis use and 1756 in the group that had never used cannabis. A binary logistic model was fitted to detect the clinical correlates of lifetime cannabis use. Results: Adjusting for the effects of age, sex, geographical region, income group, duration of untreated psychosis, and Charlson comordity index level, a binary logistic regression model revealed that lifetime cannabis use was independently associated with aggressive behavior [adjusted odds ratio (aOR) = 1.582, 95% confidence interval (CI) = 1.006-2.490, p = .047] and with long-acting injectable antipsychotic treatment (aOR = 1.796, 95% CI = 1.444-2.820, p = .001). Conclusion: Our findings indicate a close link between lifetime cannabis use and aggressive behavior. The use of long-acting, injectable antipsychotics preferentially treats the aggressive behavior cannabis users among patients with schizophrenia in Asia, especially, the South or Southeast Asia.

Psychotropic drug-prescribing correlates of disorganized speech in Asians with schizophrenia: The REAP-AP study.

BACKGROUND: Although disorganized speech is seen as one of the nuclear features of schizophrenia, there have been few reports of disorganized speech-associated psychotropic drug-prescribing patterns in large samples of schizophrenia patients. OBJECTIVE: We aimed to examine the prevalence of disorganized speech and its correlates in terms of psychotropic drug prescribing, using the data from the Research on Asian Psychotropic Patterns for Antipsychotics (REAP-AP) study. METHOD: A total of 3744 patients with the ICD-10 diagnosis of schizophrenia were enrolled from 71 survey centers in 15 Asian countries/areas. An essential criterion of disorganized speech was that it was "severe enough to impair substantially effective communication" as defined in the DSM-5. A binary logistic model was fitted to identify the psychotropic drug-prescribing correlates of disorganized speech. RESULTS: After adjusting for the potential effects of confounding variables, the binary logistic regression model showed that the presence of disorganized speech was directly associated with adjunctive use of mood stabilizers (P < 0.001) and cumulative diazepam equivalent dose (P < 0.0001), and inversely associated with adjunctive use of anti-Parkinson drugs (P < 0.0001). CONCLUSION: The association between disorganized speech and adjunctive use of mood stabilizers could perhaps be understood in the context of a relationship with impulsiveness/aggressiveness, or in terms of deconstructing the Kraepelinian dualism.