Identify adolescents' help-seeking intention on suicide through self- and caregiver's assessments of psychobehavioral problems: deep clustering of the Tokyo TEEN Cohort study.

Background: Psychopathological and behavioral problems in adolescence are highly comorbid, making their developmental trajectories complex and unclear partly due to technical limitations. We aimed to classify these trajectories using deep learning and identify predictors of cluster membership. Methods: We conducted a population-based cohort study on 3171 adolescents from three Tokyo municipalities, with 2344 pairs of adolescents and caregivers participating at all four timepoints (ages 10, 12, 14, and 16) from 2012 to 2021. Adolescent psychopathological and behavioral problems were assessed by using self-report questionnaires. Both adolescents and caregivers assessed depression/anxiety and psychotic-like experiences. Caregivers assessed obsession/compulsion, dissociation, sociality problem, hyperactivity/inattention, conduct problem, somatic symptom, and withdrawal. Adolescents assessed desire for slimness, self-harm, and suicidal ideation. These trajectories were clustered with variational deep embedding with recurrence, and predictors were explored using multinomial logistic regression. Findings: Five clusters were identified: unaffected (60.5%), minimal problems; internalizing (16.2%), persistent or worsening internalizing problems; discrepant (9.9%), subjective problems overlooked by caregivers; externalizing (9.6%), persistent externalizing problems; and severe (3.9%), chronic severe problems across symptoms. Stronger autistic traits and experience of bullying victimization commonly predicted the four "affected" clusters. The discrepant cluster, showing the highest risks for self-harm and suicidal ideation, was predicted by avoiding help-seeking for depression. The severe cluster predictors included maternal smoking during pregnancy, not bullying others, caregiver's psychological distress, and adolescent's dissatisfaction with family. Interpretation: Approximately 40% of adolescents were classified as "affected" clusters. Proactive societal attention is warranted toward adolescents in the discrepant cluster whose suicidality is overlooked and who have difficulty seeking help. Funding: Japan Ministry of Health, Labor and Welfare, Japan Agency for Medical Research and Development, and Japan Science and Technology Agency.

Suicidal Thoughts and Trajectories of Psychopathological and Behavioral Symptoms in Adolescence.

Importance: The suicidal risk of psychopathology in adolescence is suggested to differ based on its longitudinal trajectory, but the comorbidity of these symptom trajectories has not been well examined. This study comprehensively clustered trajectories of multiple psychopathological and behavioral symptoms and examined their associations with suicidal thoughts in adolescence. Objective: To determine which categories and trajectories of psychopathological and behavioral symptoms are associated with suicidal thoughts in adolescence, accounting for comorbid symptoms. Design, Setting, and Participants: This population-based cohort study in Japan used data from the Tokyo Teen Cohort (TTC) study, which was established in 2012 and is currently ongoing. Data from 3 waves of surveys conducted at ages 10, 12, and 16 years from October 2012 to September 2021 were used. Of the adolescents in the cohort, participants with at least 2 evaluations of psychopathological and behavioral symptoms were included. Data were analyzed from December 2022 to March 2023. Exposure: Latent class growth analysis was used to cluster the trajectory of each psychopathological and behavioral symptom. Main Outcomes and Measures: The associations between symptom trajectories and suicidal thoughts at age 16 were examined. Suicidal thoughts were assessed using a self-report questionnaire. Psychopathological and behavioral symptoms were assessed using the 8 subscale scores of the caregiver-report Child Behavior Checklist. Results: This study included 2780 adolescents (1306 female participants [47.0%]). Of the 1920 adolescents with data on suicidal thoughts, 158 (8.2%) had suicidal thoughts. The median (IQR) age was 10.2 (10.0-10.3) years at the first evaluation, 11.9 (11.8-12.1) years at the second evaluation, and 16.3 (16.1-16.5) years at the last evaluation. The clustering pattern of trajectories varied depending on symptom categories. After adjusting for each symptom trajectory and confounders, adolescents with persistent high withdrawn symptoms (odds ratio [OR], 1.88; 95% CI, 1.10-3.21) and those with increasing somatic symptoms (OR, 1.97; 95% CI, 1.16-3.34) had a significantly higher risk of suicidal thoughts than adolescents without these symptoms. There was no interaction between these symptom trajectories and the risk of suicidal thoughts. Conclusions and Relevance: This cohort study found that persistent withdrawn symptoms and increasing somatic symptoms during early to midadolescence were associated with an increased risk of suicidal thoughts in midadolescence, even after accounting for comorbid symptoms and confounders. Attention should be paid to the suicidal risk associated with these symptoms, particularly when they persist or increase in the longitudinal follow-up.

"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.

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.

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.

Rapid temporal improvement of pembrolizumab-induced pneumonitis using the anti-TNF-α antibody infliximab.

Immune checkpoint inhibitors are associated with a wide spectrum of immune-related adverse events (irAEs) that are typically transient but are sometimes severe or even fatal. No consensus exists for the treatment of severe immune-mediated pneumonitis that is refractory to corticosteroids. Here, we report an autopsy case of pembrolizumab-induced pneumonitis that was transiently improved using infliximab. A 67-year-old male with advanced lung adenocarcinoma developed pneumonitis two weeks after a single dose of first-line pembrolizumab. The pneumonitis was refractory to corticosteroids, and the patient required mechanical ventilation. Addition of a single dose of infliximab rapidly improved the respiratory status and chest CT showed resolution of ground-glass opacities in the right upper and middle lobes. However, the patient died from re-exacerbation of pneumonitis 17 days after infliximab administration. The autopsy confirmed organizing phase diffuse alveolar damage in the right lower lobe, while the right upper lobe remained almost intact consistent with the CT findings, which is suggestive of the therapeutic effect of infliximab. The half-life of infliximab is 7-12 days, and a second dose of infliximab two weeks after the first dose is sometimes required for the treatment of gastrointestinal toxicity induced by anti-CTLA4 antibodies. Although the current guidelines do not recommend repeated administration of infliximab for immune-mediated pneumonitis, the present case suggests that repeated infliximab therapy may be beneficial in the treatment of immune-mediated pneumonitis.

Stent placement for benign portal vein stenosis following pancreaticoduodenectomy in a hybrid operating room.

Benign portal vein stenosis is a rare complication following pancreaticoduodenectomy. Because a direct surgical approach to the portal vein is difficult due to severe adhesions following pancreaticoduodenectomy, portal vein stent placement is considered a good treatment option. Herein, we report 3 cases of severe portal vein stenosis following pancreaticoduodenectomy that were treated with portal venous stent placement in a hybrid operating room, combining a conventional operating room with an angiography suite. High-resolution images on digital subtraction angiography provide better contrast and support accurate stent placement compared to using a mobile C-arm.