Discrimination between healthy participants and people with panic disorder based on polygenic scores for psychiatric disorders and for intermediate phenotypes using machine learning.

OBJECTIVE: Panic disorder is a modestly heritable condition. Currently, diagnosis is based only on clinical symptoms; identifying objective biomarkers and a more reliable diagnostic procedure is desirable. We investigated whether people with panic disorder can be reliably diagnosed utilizing combinations of multiple polygenic scores for psychiatric disorders and their intermediate phenotypes, compared with single polygenic score approaches, by applying specific machine learning techniques. METHODS: Polygenic scores for 48 psychiatric disorders and intermediate phenotypes based on large-scale genome-wide association studies (n = 7556-1,131,881) were calculated for people with panic disorder (n = 718) and healthy controls (n = 1717). Discrimination between people with panic disorder and healthy controls was based on the 48 polygenic scores using five methods for classification: logistic regression, neural networks, quadratic discriminant analysis, random forests and a support vector machine. Differences in discrimination accuracy (area under the curve) due to an increased number of polygenic score combinations and differences in the accuracy across five classifiers were investigated. RESULTS: All five classifiers performed relatively well for distinguishing people with panic disorder from healthy controls by increasing the number of polygenic scores. Of the 48 polygenic scores, the polygenic score for anxiety UK Biobank was the most useful for discrimination by the classifiers. In combinations of two or three polygenic scores, the polygenic score for anxiety UK Biobank was included as one of polygenic scores in all classifiers. When all 48 polygenic scores were used in combination, the greatest areas under the curve significantly differed among the five classifiers. Support vector machine and logistic regression had higher accuracy than quadratic discriminant analysis and random forests. For each classifier, the greatest area under the curve was 0.600 ± 0.030 for logistic regression (polygenic score combinations N = 14), 0.591 ± 0.039 for neural networks (N = 9), 0.603 ± 0.033 for quadratic discriminant analysis (N = 10), 0.572 ± 0.039 for random forests (N = 25) and 0.617 ± 0.041 for support vector machine (N = 11). The greatest areas under the curve at the best polygenic score combination significantly differed among the five classifiers. Random forests had the lowest accuracy among classifiers. Support vector machine had higher accuracy than neural networks. CONCLUSIONS: These findings suggest that increasing the number of polygenic score combinations up to approximately 10 effectively improved the discrimination accuracy and that support vector machine exhibited greater accuracy among classifiers. However, the discrimination accuracy for panic disorder, when based solely on polygenic score combinations, was found to be modest.

A survey of mental health literacy in parents and guardians of teenagers.

Introduction: Parents and guardians (hereafter caregivers) of teenagers need high levels of mental health literacy (MHL) to manage mental health problems arising in teenagers in their care. Previous studies assessing MHL levels in caregivers of teenagers have reported mixed results, making it difficult to clearly estimate caregiver MHL levels. This study aimed to investigate MHL levels in Japanese caregivers of regular teenagers. Methods: Responses from caregivers (n = 1,397) of students entering junior and senior high schools to a self-administered online questionnaire were analyzed. The questionnaire assessed (a) knowledge about mental health/illnesses and (b) attitudes towards mental health problems in teens in their care (e.g., recognition of depression as a medical illness and intention to engage in helping behaviors). Results: The average proportion of correct answers to the knowledge questions (n = 7) was 55.4%; about one tenth (9.2%) of caregivers correctly answered only one or none of the questions. Few caregivers correctly answered about the life-time prevalence of any mental illnesses (46.1%) and appropriate sleep duration for teenagers' health (16.5%). The proportions of caregivers who had the intention to listen to the teen in their care, consult another person, and seek professional medical help if the teen suffered from depression were 99.5%, 91.5% and 72.7%, respectively. Conclusions: Many teenagers' caregivers appeared to be willing to help the teens in their care if they were suffering from mental health problems. However, there was much room for improvement in knowledge on mental health/illnesses and intention to seek help from medical professionals. Efforts toward better education should be made.

Detailed analysis of the effective and intra-particle diffusion coefficient of proteins at elevated pressure in columns packed with wide-pore core-shell particles.

To determine the efficiency that can be obtained in a packed-bed liquid-chromatography column for a particular analyte, a correct determination of the molecular and effective diffusion coefficients (Dm and Deff) of the analyte is required. The latter is usually obtained via peak parking experiments wherein the flow is stopped. As a result, the column pressure rapidly dissipates and the measurement is essentially conducted at ambient pressure. This is problematic for analytes whose retention depends on pressure, such as proteins and potentially other large (dipolar) molecules. In that case, a conventional peak parking experiment is expected to lead to large errors in Deff. To obtain a better estimate ofDeff, the present study reports on the use of a set-up enabling peak parking measurements under pressurized conditions. This approach allowed us to report, for the first time, Deff for proteins at elevated pressure under retained conditions. First, Deff was determined at a (average) pressure of about 105 bar for a set of proteins with varying size, namely: bradykinin, insulin, lysozyme, ß-lactoglobulin, and carbonic anhydrase in a column packed with 400 Å core-shell particles. The obtained data were then compared to those of several small analytes: acetophenone, propiophenone, benzophenone, valerophenone, and hexanophenone. A clear trend between Deff and analyte size was observed. The set-up was then used to determine Deff of bradykinin and lysozyme at variable (average) pressures ranging from 28 bar to 430 bar. These experiments showed a decrease in intra-particle and surface diffusion with pressure, which was larger for lysozyme than bradykinin. The data show that pressurized peak parking experiments are vital to correctly determine Deff when the analyte retention varies significantly with pressure.

A survey of suicide literacy in Japanese school teachers.

School teachers are in a unique position to recognize suicide-related problems in their students and to appropriately support them; teachers may need high levels of suicide literacy. However, few studies have examined current levels of suicide literacy in teachers. This study aimed to investigate suicide literacy in school teachers. Teachers (n = 857) from 48 Japanese schools (primary and junior-/senior-high) answered a self-administered questionnaire assessing (a) knowledge about suicide, (b) intention to ask about students' suicidal thoughts/plans, and (c) attitudes towards talking to students with mental health problems. The average proportion of correct answers to the knowledge questions (10 items) was 55.2%. Over half of the teachers knew that suicide is a leading cause of death in adolescents (55.0%), and that asking about suicidality is needed (56.2%). Half of the teachers intended to ask students about their suicidal thoughts (50.2%) and fewer intended to ask about experiences of planning suicide (38.8%). Most of the teachers (90.4%) agreed with the idea that talking to students with mental health problems was a teacher's responsibility. Intention to ask about students' suicidal thoughts/plans were higher in teachers in their 20s (vs. 40s-60s) and working at junior-/senior-high schools (vs. primary schools). Suicide literacy in Japanese school teachers was observed to be limited. However, teachers felt responsibility for helping students with mental health problems. The development and implementation of education programs may help improve teachers' suicide literacy, which, in turn, could encourage effective helping behaviors of teachers for students struggling with suicidality.

Association between copy number variations in parkin (PRKN) and schizophrenia and autism spectrum disorder: A case-control study.

AIM: The present study aimed to examine the association between copy number variations (CNVs) in parkin (PRKN) and schizophrenia (SCZ) and autism spectrum disorder (ASD) in a large case-control sample. METHOD: Array comparative genomic hybridization was performed on 3111 cases with SCZ, 1236 cases with ASD, and 2713 controls. We systematically prioritized likely pathogenic CNVs (LP-CNVs) in PRKN and examined their association with SCZ and ASD. RESULTS: In total, 3014 SCZ cases (96.9%), 1205 ASD cases (97.5%), and 2671 controls (98.5%) passed quality control. We found that monoallelic carriers of LP-CNVs in PRKN were common (70/6890, 1.02%) and were not at higher risk of SCZ (p = 0.29) or ASD (p = 0.72). We observed that the distribution pattern of LP-CNVs in the Japanese population was consistent with those in other populations. We also identified a patient diagnosed with SCZ and early-onset Parkinson's disease carrying biallelic pathogenic CNVs in PRKN. The absence of Parkinson's symptoms in 10 other monoallelic carriers of the same pathogenic CNV further reflects the lack of effect of monoallelic pathogenic variants in PRKN in the absence of a second hit. CONCLUSION: The present findings suggest that monoallelic CNVs in PRKN do not confer a significant risk for SCZ or ASD. However, further studies to investigate the association between biallelic CNVs in PRKN and SCZ and ASD are warranted.

Longitudinal relationships of psychotic-like experiences with suicidal ideation and self-harm in adolescents.

Research in adolescents suggests associations between psychotic-like experiences (PLEs) and self-injurious thoughts and behaviors (SITBs), but insights into their temporal relationship, which may inform prediction, have been limited. Psychological distress (PD; symptoms of depression and anxiety) has been related to both PLEs and SITBs, and may modulate this relationship. Given that PLEs have been linked to the development of several mental disorders, and the relationships between SITBs and suicide, it is important to better understand their relationship. The present study sought to investigate these factors using a longitudinal school-based design. Adolescents (n = 1685, ages 12-18) completed annual self-report assessments (6 time points) on PLEs, SITBs (suicidal ideation (SI) and self-harm (SH)), as well as PD. The longitudinal associations between PLEs and SITBs were analyzed, employing two cross-lagged panel models (CLPMs), with and without adjustment for PD. Unadjusted CLPMs revealed significant bidirectional temporal associations between PLEs and SITBs (both SI and SH), suggesting that PLEs both predicted and were predicted by SITBs. When adjusting for PD, the effect of SI on PLEs remained significant, but not PLEs on SI; bidirectional associations between PLEs and SH also remained significant. A bidirectional longitudinal relationship where both PLEs and SITBs can precede (and perhaps predict) each other was suggested in adolescents. PD may play a particular role in situations where PLEs are followed by SI. Heightened awareness about relationships between these phenotypes may be an important step toward facilitating timely interventions for both mental disorders and suicide.

The longitudinal relationship between sleep length and psychotic-like experiences in adolescents.

The longitudinal relationship between psychotic-like experiences (PLEs) and short habitual sleep in adolescents remains to be investigated. We examined the effect of habitual sleep length (time-in-bed: TIB) on the risk of subsequent year PLEs and vice versa, in grade 7-12 students (ages: 12-18, n = 1,685) followed over 6 years. Yearly longitudinal data were analyzed using cross-lagged panel models. Shorter weekday TIB was associated with a higher risk of subsequent year PLEs; PLEs did not affect subsequent year TIB. Compared to a TIB of 8-9 h, 5-6 h increased PLEs likelihood 1.8 times; <5 h increased this 6-fold.

Cross-Disorder Analysis of Genic and Regulatory Copy Number Variations in Bipolar Disorder, Schizophrenia, and Autism Spectrum Disorder.

BACKGROUND: We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD). METHODS: Based on high-resolution CNV data from 8708 Japanese samples, we performed to our knowledge the largest cross-disorder analysis of genic and regulatory CNVs in BD, SCZ, and ASD. RESULTS: In genic CNVs, we found an increased burden of smaller (<100 kb) exonic deletions in BD, which contrasted with the highest burden of larger (>500 kb) exonic CNVs in SCZ/ASD. Pathogenic CNVs linked to neurodevelopmental disorders were significantly associated with the risk for each disorder, but BD and SCZ/ASD differed in terms of the effect size (smaller in BD) and subtype distribution of CNVs linked to neurodevelopmental disorders. We identified 3 synaptic genes (DLG2, PCDH15, and ASTN2) as risk factors for BD. Whereas gene set analysis showed that BD-associated pathways were restricted to chromatin biology, SCZ and ASD involved more extensive and similar pathways. Nevertheless, a correlation analysis of gene set results indicated weak but significant pathway similarities between BD and SCZ or ASD (r = 0.25-0.31). In SCZ and ASD, but not BD, CNVs were significantly enriched in enhancers and promoters in brain tissue. CONCLUSIONS: BD and SCZ/ASD differ in terms of CNV burden, characteristics of CNVs linked to neurodevelopmental disorders, and regulatory CNVs. On the other hand, they have shared molecular mechanisms, including chromatin biology. The BD risk genes identified here could provide insight into the pathogenesis of BD.

Mental Health Literacy Programs for Parents of Adolescents: A Systematic Review.

Introduction: Many mental illnesses begin during adolescence. Parents of adolescents need to have sufficient mental health literacy (MHL) to recognize mental health problems in their children and to assist them with help-seeking. Although several educational programs have been developed to enhance parental MHL, their effectiveness has not been established. This study provides a systematic review for the effectiveness of MHL programs in parents of adolescents. Methods: PubMed, PsycINFO, CINAHL, ERIC and Web of Science were searched from the earliest date possible until February 2022; references of studies which met eligibility criteria were also screened. Studies that assessed quantitative change in at least one of the following components of parental MHL were included: knowledge of mental health/illnesses; stigma toward people with mental health problems; confidence in helping children with mental health problems, and intention, knowledge or behavior of helping children with mental health problems. Risk of bias (ROB) for each outcome within the included studies was rated using the revised Cochrane risk-of-bias tool for randomized trials for randomized controlled trials (RCTs), and the Risk of Bias Assessment Tool for Nonrandomized Studies for nonrandomized studies. Results: Nine studies (four RCTs, three controlled before-and-after studies, and two case series), reported in 10 articles, were included. Mental health knowledge and/or confidence was significantly improved in several studies, while no studies observed significant improvement in stigma and/or intention/behavior of helping children. ROB was high in five out of nine studies (10 out of 18 outcomes) and unclear in the others. Conclusions: A limited number of studies have evaluated effects of MHL program in parents and inconsistent quality contributes to difficulty in establishing their overall effectiveness. More studies with appropriate methods of recruitment, measurement and analysis, and transparent reporting are needed. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020193072, Identifier: CRD42020193072.

Influence of perceived trauma on the cognitive processing model of posttraumatic growth among university students.

This study examined whether perceiving an event as a trauma influenced a cognitive processing model explaining posttraumatic growth (PTG). A cross-sectional questionnaire survey was conducted with 311 university students from eight universities in Japan. The participants provided information about the most stressful event they had experienced and completed the expanded version of the PTG Inventory, Core Belief Inventory, Event Related Rumination Inventory, and Cognitive and Emotional Processing from Disclosure Inventory. A multi-group structural equation modeling was conducted by dividing the participants into two groups depending on whether they identified the most stressful event as a trauma. The model with no constraint showed a good fit. The model with partial constraint showed a better fit than the models with no constraint or full constraint. The difference of the model was seen as a covariance between the Event Related Rumination Inventory and the Cognitive and Emotional Processing from Disclosure Inventory. The results demonstrated configural invariance and partial metric invariance. This indicated that PTG would be recognized irrespective of whether the event was perceived as a trauma. This study also indicated that different factors out of the model could be associated with the ruminative process and disclosure process. The importance of focusing on the process of PTG, regardless of an individual's perception of the event, was emphasized, especially for factors related to rumination and disclosure.

A survey of mental health literacy in Japanese high school teachers.

BACKGROUND: School teachers are well-positioned to recognize mental health problems in their students and to help them seek appropriate help. Therefore, teachers need to have high levels of mental health literacy (MHL). In East Asia, however, few studies have examined MHL levels in teachers. In this study, MHL levels were investigated in Japanese teachers. METHODS: Teachers (n = 665) from 27 Japanese high schools answered a self-administered questionnaire which assessed (a) knowledge about mental health/illnesses, (b) correct recognition of specific illnesses (depression, schizophrenia and panic disorder), (c) confidence in helping students with depressive symptoms, and (d) confidence in teaching mental health knowledge to students. RESULTS: The average proportion of correct answers to the knowledge questions (n = 20) was 58.1%. The proportion of those who correctly answered about the presence of a sharp increase of mental illnesses in adolescence was 51.7%. Few teachers correctly answered about the life-time prevalences of major mental illness in general (21.9%), depression (37.8%) and schizophrenia (19.8%). Depression, schizophrenia and panic disorder in vignette were correctly recognized by 54.1, 35.3 and 78.0% of teachers, respectively. Correct recognition was significantly lower in male than in female teachers. Only a small proportion of teachers had confidence in helping depressed students (19.9%) and in teaching mental health knowledge to students (11.1%). CONCLUSIONS: MHL in Japanese high school teachers appears to be low. Education programs should be developed and implemented to improve teacher MHL with the aim of helping them to support students suffering from mental health problems.

A loss-of-function variant in SUV39H2 identified in autism-spectrum disorder causes altered H3K9 trimethylation and dysregulation of protocadherin ß-cluster genes in the developing brain.

Recent evidence has documented the potential roles of histone-modifying enzymes in autism-spectrum disorder (ASD). Aberrant histone H3 lysine 9 (H3K9) dimethylation resulting from genetic variants in histone methyltransferases is known for neurodevelopmental and behavioral anomalies. However, a systematic examination of H3K9 methylation dynamics in ASD is lacking. Here we resequenced nine genes for histone methyltransferases and demethylases involved in H3K9 methylation in individuals with ASD and healthy controls using targeted next-generation sequencing. We identified a novel rare variant (A211S) in the SUV39H2, which was predicted to be deleterious. The variant showed strongly reduced histone methyltransferase activity in vitro. In silico analysis showed that the variant destabilizes the hydrophobic core and allosterically affects the enzyme activity. The Suv39h2-KO mice displayed hyperactivity and reduced behavioral flexibility in learning the tasks that required complex behavioral adaptation, which is relevant for ASD. The Suv39h2 deficit evoked an elevated expression of a subset of protocadherin ß (Pcdhb) cluster genes in the embryonic brain, which is attributable to the loss of H3K9 trimethylation (me3) at the gene promoters. Reduced H3K9me3 persisted in the cerebellum of Suv39h2-deficient mice to an adult stage. Congruently, reduced expression of SUV39H1 and SUV39H2 in the postmortem brain samples of ASD individuals was observed, underscoring the role of H3K9me3 deficiency in ASD etiology. The present study provides direct evidence for the role of SUV39H2 in ASD and suggests a molecular cascade of SUV39H2 dysfunction leading to H3K9me3 deficiency followed by an untimely, elevated expression of Pcdhb cluster genes during early neurodevelopment.

Impact of pre-brachytherapy magnetic resonance imaging on dose-volume histogram of locally advanced cervical cancer patients treated with radiotherapy including high-dose-rate brachytherapy.

PURPOSE: This study investigated the suitability of brachytherapy technique selection based on pre-brachytherapy magnetic resonance imaging (MRI) findings in cervical cancer by evaluating dose-volume histogram parameters. MATERIAL AND METHODS: We retrospectively evaluated data from 61 patients with cervical cancer who underwent pre-brachytherapy MRI within 7 days before their first high-dose-rate brachytherapy treatment, selected according to pre-brachytherapy MRI findings. Combined intracavitary brachytherapy with interstitial techniques (IC/ISBT) or interstitial brachytherapy (ISBT) were favored treatments for poor-responding tumors after concurrent chemoradiotherapy, asymmetrical tumors, bulky parametrial extensions, bulky primary disease, and extensive paravaginal or distal vaginal involvement. Intracavitary brachytherapy (ICBT) was the preferred treatment for small tumors without extensive involvement of the vagina and parametrium. RESULTS: The median tumor size was 58 mm on pre-treatment MRI and 38 mm on pre-brachytherapy MRI. On pre-brachytherapy MRI, 13 patients had a tumor with severe vaginal invasion, 15 patients presented with an asymmetrical bulky tumor, and 4 patients had bulky residual tumors. IC/ISBT or ISBT were administered to 26 patients (43%). Median equivalent dose in 2 Gy fractions of clinical target volume D90 was 70.8 Gy for all patients. Median clinical target volume D90 in each brachytherapy session exceeded the prescribed dose in both patients treated with ICBT and IC/ISBT or ISBT. Median equivalent dose in 2 Gy fractions of D2cc to the bladder, sigmoid colon, and rectum was 69.5, 52.0, and 58.4 Gy, respectively. All cases remained within the doses recommended for organs at risk. CONCLUSIONS: Pre-brachytherapy MRI may be helpful in selecting suitable candidates for each type of brachytherapy and deliver the recommended doses to the tumor and organs at risk, particularly in cases with large tumors, poor response to concurrent chemoradiotherapy, asymmetrical tumors, severe vaginal invasion, extensive parametrial invasion, and/or corpus invasion.

A Randomized Controlled Trial Evaluating the Effectiveness of a Short Video-Based Educational Program for Improving Mental Health Literacy Among Schoolteachers.

Background: Mental illness-related stigma represents a barrier to seeking and receiving appropriate mental health care. Mental health literacy (MHL) can improve mental health knowledge, decrease stigmatizing attitudes, and enhance help-seeking behavior. Starting from 2022, mental illness-related education is due to be introduced in high schools in Japan. For this current situation, we conducted a parallel group, randomized controlled trial to examine the effectiveness of MHL educational program for teachers. Methods: The educational program described in this study comprised a 50-min video lesson designed to improve teachers' MHL. All participants were schoolteachers and were assigned either to an educational group or a waitlist control group. The assessment was conducted for both groups twice: first at baseline and then at 1-h post-intervention. The outcome measures for this trial were changes in knowledge, attitudes, and intended behaviors. Results: The educational group showed a greater improvement in knowledge regarding mental health than did the control group. The program was not effective for decreasing stigma toward mental illness. However, the educational group showed an increased intention to assist students with depression. Limitations: No long-term follow-up was implemented, which means the persistence of the educational program's effect could not be determined. Further, we could not report whether the program induced a change in teachers' behaviors regarding providing support for their students. Conclusions: The short video-based MHL educational program could improve schoolteachers' MHL and increase their intention to assist students. These findings can help in the development of similar educational programs in countries/regions experiencing similar issues regarding mental health.

Identification and functional characterization of the extremely long allele of the serotonin transporter-linked polymorphic region.

SLC6A4, which encodes the serotonin transporter, has a functional polymorphism called the serotonin transporter-linked polymorphic region (5-HTTLPR). The 5-HTTLPR consists of short (S) and long (L) alleles, each of which has 14 or 16 tandem repeats. In addition, the extralong (XL) and other rare alleles have been reported in 5-HTTLPR. Although they are more frequent in Asian and African than in other populations, the extent of variations and allele frequencies (AFs) were not addressed in a large population. Here, we report the AFs of the rare alleles in a large number of Japanese subjects (N = 2894) consisting of two cohorts. The first cohort (case-control study set, CCSS) consisted of 1366 subjects, including 485 controls and 881 patients with psychosis (bipolar disorder or schizophrenia). The second cohort (the Arao cohort study set, ACSS) consisted of 1528 elderly subjects. During genotyping, we identified 11 novel 5-HTTLPR alleles, including 3 XL alleles. One novel allele had the longest subunit ever reported, consisting of 28 tandem repeats. We named this XL28-A. An in vitro luciferase assay revealed that XL28-A has no transcriptional activity. XL28-A was found in two unrelated patients with bipolar disorder in the CCSS and one healthy subject in the ACSS who did not show depressive symptoms or a decline in cognitive function. Therefore, it is unlikely that XL28-A is associated with psychiatric disorders, despite its apparent functional deficit. Our results suggest that unraveling the complex genetic variations of 5-HTTLPR will be important for further understanding its role in psychiatric disorders.

Shorter sleep duration is associated with potential risks for overwork-related death among Japanese truck drivers: use of the Karoshi prodromes from worker's compensation cases.

PURPOSE: We aimed to cross-sectionally investigate how work and sleep conditions could be associated with excessive fatigue symptoms as an early sign of Karoshi (overwork-related cerebrovascular and cardiovascular diseases; CCVDs). METHODS: We distributed a questionnaire regarding work, sleep, and excessive fatigue symptoms to 5410 truck drivers, as the riskiest occupation for overwork-related CCVDs, and collected 1992 total samples (response rate: 36.8%). The research team collected 1564 investigation reports required for compensation for Karoshi. Of them, 190 reports listed the prodromes of Karoshi, which were used to develop the new excessive fatigue symptoms inventory. RESULTS: One-way analyses of variance showed that the excessive fatigue symptoms differed significantly by monthly overtime hours (p < 0.001), daily working time (p < 0.001), work schedule (p = 0.025), waiting time on-site (p = 0.049), number of night shifts (p = 0.011), and sleep duration on workdays (p < 0.001). Multivariate mixed-model regression analyses revealed shorter sleep duration as the most effective parameter for predicting excessive fatigue symptoms. Multiple logistic regression analysis confirmed that the occurrences of CCVDs were significantly higher in the middle [adjusted ORs = 3.56 (1.28-9.94)] and high-score groups [3.55 (1.24-10.21)] than in the low-score group. CONCLUSION: The findings suggested that shorter sleep duration was associated more closely with a marked increase in fatigue, as compared with the other work and sleep factors. Hence, ensuring sleep opportunities could be targeted for reducing the potential risks of Karoshi among truck drivers.

Does cognitive behavioral therapy for anxiety disorders assist the discontinuation of benzodiazepines among patients with anxiety disorders? A systematic review and meta-analysis.

Long-term use of benzodiazepines (BZD) is not recommended for the treatment of anxiety disorders. Cognitive behavioral therapy (CBT) is an effective treatment option for discontinuation of BZD in patients with anxiety disorders. This systematic review and meta-analysis sought to clarify whether CBT is effective for discontinuing BZD anxiolytics in patients with anxiety disorders. This study was preregistered with PROSPERO (registration number: CRD42019125263). A literature search of major electronic databases was conducted in December 2018. Three randomized controlled trials were included in this review, and meta-analyses were performed. The proportion of discontinuing BZD anxiolytics was significantly higher in the CBT plus gradual tapering group than in the gradual tapering alone group, both in the short term (3 months after allocation; number needed to treat: 3.2, 95% confidence interval [CI]: 2.1 to 7.1; risk ratio: 1.96, 95%CI: 1.29 to 2.98, P = 0.002, three studies) and long term (6 to 12 months after allocation; number needed to treat: 2.8, 95%CI: 1.9 to 5.3; risk ratio: 2.16, 95%CI: 1.41 to 3.32, P = 0.0004, three studies). CBT may be effective for discontinuing BZD anxiolytics, both in the short term and in the long term after the allocation. Further studies with larger sample sizes are necessary to draw definitive conclusions regarding the efficacy and safety of CBT for discontinuing BZD anxiolytics in patients with anxiety disorders.

Shared transethnic genetic basis of panic disorder and psychiatric and related intermediate phenotypes.

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

Immersive 3-Dimensional Virtual Reality Modeling for Case-Specific Presurgical Discussions in Cerebrovascular Neurosurgery.

BACKGROUND: Adequate surgical planning includes a precise understanding of patient-specific anatomy and is a necessity for neurosurgeons. Although the use of virtual reality (VR) technology is emerging in surgical planning and education, few studies have examined the effectiveness of immersive VR during surgical planning using a modern head-mounted display. OBJECTIVE: To investigate if and how immersive VR aids presurgical discussions of cerebrovascular surgery. METHODS: A multiuser immersive VR system, BananaVisionTM, was developed and used during presurgical discussions in a prospective patient cohort undergoing cerebrovascular surgery. A questionnaire/interview was administered to multiple surgeons after the surgeries to evaluate the effectiveness of the VR system compared to conventional imaging modalities. An objective assessment of the surgeon's knowledge of patient-specific anatomy was also conducted by rating surgeons' hand-drawn presurgical illustrations. RESULTS: The VR session effectively enhanced surgeons' understanding of patient-specific anatomy in the majority of cases (83.3%). An objective assessment of surgeons' presurgical illustrations was consistent with this result. The VR session also effectively improved the decision-making process regarding minor surgical techniques in 61.1% of cases and even aided surgeons in making critical surgical decisions about cases involving complex and challenging anatomy. The utility of the VR system was rated significantly higher by trainees than by experts. CONCLUSION: Although rated as more useful by trainees than by experts, immersive 3D VR modeling increased surgeons' understanding of patient-specific anatomy and improved surgical strategy in certain cases involving challenging anatomy.