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Abstract The modified total Sharp score (mTSS) is often used as an evaluation index for joint destruction caused by rheumatoid arthritis. In this study, special findings (ankylosis, subluxation, and dislocation) are detected to estimate the efficacy of mTSS by using deep neural networks (DNNs). The proposed method detects and classifies finger joint regions using an ensemble mechanism. This integrates multiple DNN detection models, specifically single shot multibox detectors, using different training data for each special finding. For the learning phase, we prepared a total of 260 hand X-ray images, in which proximal interphalangeal (PIP) and metacarpophalangeal (MP) joints were annotated with mTSS by skilled rheumatologists and radiologists. We evaluated our model using five-fold cross-validation. The proposed model produced a higher detection accuracy, recall, precision, specificity, F-value, and intersection over union than individual detection models for both ankylosis and subluxation detection, with a detection rate above 99.8% for the MP and PIP joint regions. Our future research will aim at the development of an automatic diagnosis system that uses the proposed mTSS model to estimate the erosion and joint space narrowing score.

Despite the ubiquity of ultrasonography in nondestructive inspection, its application to high-attenuation materials is challenging. At frequencies less than 1 MHz, ultrasound can inspect high-attenuation materials owing to its high penetration ability. Such ultrasound data are acquired using a single-element transducer that generates single-channel signals (A-mode). However, low-frequency A-mode ultrasound signals have low-resolution caused by long wavelengths, and less information than B-mode images generated by multi-channel transducers. Discriminating low-resolution data is made possible by recent advances in machine learning technology. This study employs machine learning to develop an inspection method for high-attenuation frozen materials. This study focuses on the inspection of the freshness of frozen tuna, which has a large market but uses a destructive inspection method. We applied eight typical machine learning algorithms to A-mode signal data (43 samples, 3168 signals) of frozen tuna to calculate freshness scores; we used fast Fourier transform in the feature extraction process. Our experiments show that all algorithms could classify the freshness of frozen tuna with statistical significance ( ${p}$ < 0.05, one-tailed ${t}$ -test). Furthermore, we investigated the performance improvement in the mean (standard deviation) of the area under the receiver operating characteristic curves by taking the mean of the freshness scores on 24 signals. We observed that the best performance (quadratic discriminant analysis) increased from 0.619 (0.041) using a single signal to 0.724 (0.080) using 24 signals with statistical significance ( ${p}$ < 0.05, paired one-tailed ${t}$ -test). This is the first study that inspects frozen tuna using ultrasound and machine learning technology.

We propose a wrist joint subluxation/ankylosis classification model for an automatic radiographic scoring system for X-ray images. In managing rheumatoid arthritis, the evaluation of joint destruction is important. The modified total Sharp score (mTSS), which is conventionally used to evaluate joint destruction of the hands and feet, should ideally be automated because the required time depends on the skill of the evaluator, and there is variability between evaluators. Since joint subluxation and ankylosis are given a large score in mTSS, we aimed to estimate subluxation and ankylosis using a deep neural network as a first step in developing an automatic radiographic scoring system for joint destruction. We randomly extracted 216 hand X-ray images from an electronic medical record system for the learning experiments. These images were acquired from patients who visited the rheumatology department of Keio University Hospital in 2015. Using our newly developed annotation tool, well-trained rheumatologists and radiologists labeled the mTSS to the wrist, metacarpal phalangeal joints, and proximal interphalangeal joints included in the images. We identified 21 X-ray images containing one or more subluxation joints and 42 X-ray images with ankylosis. To predict subluxation/ankylosis, we conducted five-fold cross-validation with deep neural network models: AlexNet, ResNet, DenseNet, and Vision Transformer. The best performance on wrist subluxation/ankylosis classification was as follows: accuracy, precision, recall, F1 value, and AUC were 0.97±0.01/0.89±0.04, 0.92±0.12/0.77±0.15, 0.77±0.16/0.71±0.13, 0.82±0.11/0.72±0.09, and 0.92±0.08/0.85±0.07, respectively. The classification model based on a deep neural network was trained with a relatively small dataset; however, it showed good accuracy. In conclusion, we provided data collection and model training schemes for mTSS prediction and showed an important contribution to building an automated scoring system.

In many robotics studies, deep neural networks (DNNs) are being actively studied due to their good performance. However, existing robotic techniques and DNNs have not been systematically integrated, and packages for beginners are yet to be developed. In this study, we proposed a basic educational kit for robotic system development with DNNs. Our goal was to educate beginners in both robotics and machine learning, especially the use of DNNs. Initially, we required the kit to (1) be easy to understand, (2) employ experience-based learning, and (3) be applicable in many areas. To clarify the learning objectives and important parts of the basic educational kit, we analyzed the research and development (R&D) of DNNs and divided the process into three steps of data collection (DC), machine learning (ML), and task execution (TE). These steps were configured under a hierarchical system flow with the ability to be executed individually at the development stage. To evaluate the practicality of the proposed system flow, we implemented it for a physical robotic grasping system using robotics middleware. We also demonstrated that the proposed system can be effectively applied to other hardware, sensor inputs, and robot tasks.

Mitochondria are highly dynamic organelles that constantly fuse, divide, and move, and their function is regulated and maintained by their morphologic changes. Mitochondrial disease (MD) comprises a group of disorders involving mitochondrial dysfunction. However, it is not clear whether changes in mitochondrial morphology are related to MD. In this study, we examined mitochondrial morphology in fibroblasts from patients with MD (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and Leigh syndrome). We observed that MD fibroblasts exhibited significant mitochondrial fragmentation by upregulation of Drp1, which is responsible for mitochondrial fission. Interestingly, the inhibition of mitochondrial fragmentation by Drp1 knockdown enhanced cellular toxicity and led to cell death in MD fibroblasts. These results suggest that mitochondrial fission plays a critical role in the attenuation of mitochondrial damage in MD fibroblasts.

Although many cross-sectional studies showed that psychotic experiences (PEs) and dissociation were closely related, the longitudinal association between them remains unknown. Therefore, the aim of the current study was to examine the longitudinal association of these two symptoms throughout adolescence, under the hypothesis that these two symptoms are bidirectionally associated. Data were obtained from a population-based cohort, the Tokyo Teen Cohort study (TTC; N = 3171). PEs and dissociation were assessed at 10, 12, 14, and 16 years of age. PEs were assessed using a total score from five-item self-report questionnaires derived from the Diagnostic Interview Schedule for Children (DISC-C). Dissociation was assessed using subscale scores of the Child Behavior Checklist (CBCL) completed by primary caregivers. We examined the longitudinal relationship between PEs and dissociation using the random intercept cross-lagged panel model (RI-CLPM). The within-person component of the RI-CLPM revealed no significant cross-lagged effect of dissociation on PEs at any time point. On the other hand, there was a significant (p < 0.05) association between PEs at age 14 and dissociation at age 16 (β = 0.106, 95 % CI 0.047-0.165). The between-person component revealed a significant time-invariant relationship between the two symptoms (β = 0.324, 95 % CI 0.239-0.410). The longitudinal relationship between PEs and dissociation was limited at the within-person level, whereas the between-person correlation was significant. The only significant longitudinal pathway was from PEs to dissociation, suggesting that PEs may be a predictor of dissociation in mid-adolescence., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Understanding the etiology of psychosis is essential to the development of preventive interventions. The COVID-19 pandemic provides a rare natural experiment that can expand our understanding of the role of social factors in the trajectories and etiology of psychosis across adolescence, particularly in Tokyo where the prevalence of actual COVID-19 infection remained low. We hypothesized that the likelihood of self-reporting psychotic experiences (PEs) would increase following the onset of the COVID-19 pandemic., Methods: The Tokyo Teen Cohort (TTC) is a prospective cohort study of adolescents in the general population of the Tokyo metropolitan area, followed from age 10 to 16 years. We used multi-level linear regression models to test the associations between the phase of the COVID-19 pandemic and self-reported PEs., Results: Among 1935 adolescents included in the analysis, a rapid increase in PEs occurred at the onset of the COVID-19 pandemic, following approximately 6 years of steady decline across prior waves. This association was more pronounced for boys compared to girls. This increase became more pronounced as the pandemic moved into later phases, defined based on contemporaneous sociopolitical changes in Tokyo (i.e. changes to school closure, social distancing guidelines, and the state of emergency status)., Conclusions: The steady decline in PEs across adolescence was halted and reversed concurrent with the COVID-19 pandemic onset, despite very low rates of COVID-19 infection. This implicates COVID-19 related socioenvironmental factors as contributory etiological factors in the development of PEs in this adolescent cohort., (© 2023 Association for Child and Adolescent Mental Health.)

Previous studies reported decreased glutamate levels in the anterior cingulate cortex (ACC) in non-treatment-resistant schizophrenia and first-episode psychosis. However, ACC glutamatergic changes in subjects at high-risk for psychosis, and the effects of commonly experienced environmental emotional/social stressors on glutamatergic function in adolescents remain unclear. In this study, adolescents recruited from the general population underwent proton magnetic resonance spectroscopy (MRS) of the pregenual ACC using a 3-Tesla scanner. We explored longitudinal data on the association of combined glutamate-glutamine (Glx) levels, measured by MRS, with subclinical psychotic experiences. Moreover, we investigated associations of bullying victimization, a risk factor for subclinical psychotic experiences, and help-seeking intentions, a coping strategy against stressors including bullying victimization, with Glx levels. Finally, path analyses were conducted to explore multivariate associations. For a contrast analysis, gamma-aminobutyric acid plus macromolecule (GABA+) levels were also analyzed. Negative associations were found between Glx levels and subclinical psychotic experiences at both Times 1 (n = 219, mean age 11.5 y) and 2 (n = 211, mean age 13.6 y), as well as for over-time changes (n = 157, mean interval 2.0 y). Moreover, effects of bullying victimization and bullying victimization × help-seeking intention interaction effects on Glx levels were found (n = 156). Specifically, bullying victimization decreased Glx levels, whereas help-seeking intention increased Glx levels only in bullied adolescents. Finally, associations among bullying victimization, help-seeking intention, Glx levels, and subclinical psychotic experiences were revealed. GABA+ analysis revealed no significant results. This is the first adolescent study to reveal longitudinal trajectories of the association between glutamatergic function and subclinical psychotic experiences and to elucidate the effect of commonly experienced environmental emotional/social stressors on glutamatergic function. Our findings may deepen the understanding of how environmental emotional/social stressors induce impaired glutamatergic neurotransmission that could be the underpinning of liability for psychotic experiences in early adolescence., (© 2024. The Author(s).)

Previous studies have reported that dissociative symptoms (DIS) are associated with self-harm (SH) in adolescents. However, most of these studies were cross-sectional, which limits the understanding of their theoretical relationship. We aimed to investigate the longitudinal relationship between DIS and SH in the general adolescent population. We used data from the Tokyo Teen Cohort study (N = 3007). DIS and SH were assessed at times 1 and 2 (T1 and T2) (12 years of age and 14 years of age, respectively). DIS were assessed using the parent-report Child Behavior Checklist (CBCL), and severe dissociative symptoms (SDIS) were defined as a score above the top 10th percentile. The experience of SH within 1 year was assessed by a self-report questionnaire. The longitudinal relationship between DIS and SH was examined using regression analyses. Using logistic regression analyses, we further investigated the risk for SH at T2 due to persistent SDIS and vice versa. DIS at T1 tended to predict SH at T2 (odds ratio (OR) 1.11, 95% CI 0.99 to 1.25, p = 0.08), while SH at T1 did not predict DIS at T2 (B = - 0.03, 95% CI - 0.26 to 0.20, p = 0.81). Compared with adolescents without SDIS, those with persistent SDIS had an increased risk of SH at T2 (OR 2.61, 95% CI 1.28 to 5.33, p = 0.01). DIS tended to predict future SH, but SH did not predict future DIS. DIS may be a target to prevent SH in adolescents. Intensive attention should be given to adolescents with SDIS due to their increased risk of SH., (© 2023. The Author(s).)

Poly( N -isopropylacrylamide) (pNIPAm) undergoes a hydrophilicity/hydrophobicity change around its lower critical solution temperature (LCST). Therefore, pNIPAm-based polymer nanoparticles (NPs) shrink above their LCST and swell below their LCST. Although temperature responsiveness is an important characteristic of synthetic polymers in drug and gene delivery, few studies have investigated the temperature-responsive catch and release of low-molecular-weight drugs (LMWDs) as their affinity to the target changes. Since LMWDs have only a few functional groups, preparation of NPs with high affinity for LMWDs is hard compared with that for peptides and proteins. However, LMWDs such as anticancer drugs often have a stronger effect than peptides and proteins. Therefore, the development of NPs that can load and release LMWDs is needed for drug delivery. Here, we engineered pNIPAm-based NPs that capture paclitaxel (PTX), an anticancer LMWD that inhibits microtubules, above their LCST and release it below their LCST. The swelling transition of the NPs depended on their hydrophobic monomer structure. NPs with swelling ratios (=NP size at 25 °C/NP size at 37 °C) exceeding 1.90 released captured PTX when cooled to below their LCST by changing the affinity for PTX. On the other hand, NPs with a swelling ratio of only 1.14 released melittin. Therefore, optimizing the functional monomers of temperature-responsive NPs is essential for the catch and release of the target in a temperature-dependent manner. These results can guide the design of stimuli-responsive polymers that catch and release their target molecules., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Adolescents with high autistic traits are at increased risk of depression. Despite the importance of seeking help for early intervention, evidence on help-seeking intentions amongst this population is scarce. Using a population-based cohort in Japan, we examined adolescents' help-seeking intentions and preferences by the level of autistic traits and tested its mediating role on the association between high autistic traits and depressive symptoms. At age 12, we measured parent-rated autistic traits using the short version of the Autism Spectrum Quotient and classified the adolescents into two groups (≥ 6 as AQhigh, < 6 as AQlow); help-seeking intentions and preferences were assessed through a depression vignette. At age 14, depressive symptoms were self-rated using the Short Mood and Feelings Questionnaire. Hypothesised associations between autistic traits and help-seeking intentions or depressive symptoms were tested applying multivariable regression modelling, while mediation was tested with structural equation modelling. Of the 2505 adolescent participants, 200 (8%) were classified as AQhigh. In both groups, the main source of help-seeking was their family; however, 40% of the AQhigh group reported having no help-seeking intentions compared to 27% in the AQlow. The AQhigh group was at increased risk of not having help-seeking intentions (OR 1.84, 95% CI 1.35-2.50) and higher depressive symptoms (b coefficient 1.06, 0.33-1.79). Help-seeking intentions mediated 18% of the association mentioned above. Interventions to promote help-seeking intentions among adolescents with high autistic traits could reduce their subsequent depressive symptoms. Ideally, such interventions should be provided prior to adolescence and with the involvement of their parents., (© 2021. The Author(s).)

Background and Hypotheses: A wealth of evidence suggests that adolescent psychotic experiences (PEs), and especially auditory hallucinations (AHs), are associated with an increased risk for self-injurious behavior (SIB). However, the directionality and specificity of this association are not well understood, and there are no published studies investigating within-person effects over time. The present study aimed to test whether AHs and SIB prospectively increase reciprocal risk at the individual level during early-to-middle adolescence., Study Design: Three waves (12y, 14y, and 16y) of self-reported AHs and SIB data from a large Tokyo-based adolescent birth cohort (N = 2825) were used. Random Intercept Cross-Lagged Panel Model (RI-CLPM) analysis was conducted to test the within-person prospective associations between AHs and SIB., Study Results: At the within-person level, AHs were associated with subsequent SIB over the observation period (12y-14y: β = .118, P < .001; 14-16y: β = .086, P = .012). The reverse SIB->AHs relationship was non-significant at 12-14y (β = .047, P = .112) but emerged from 14y to 16y as the primary direction of influence (β = .243, P < .001). Incorporating depression as a time-varying covariate did not meaningfully alter model estimates., Conclusions: A complex bi-directional pattern of relationships was observed between AHs and SIB over the measurement period, and these relationships were independent of depressive symptoms. Adolescent AHs may be both a predictor of later SIB and also a manifestation of SIB-induced psychological distress., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Aim: Studies showed that cognitive function affects occupational function in patients with schizophrenia. This study aimed to determine the effects of cognitive function on occupational function in Japanese patients with schizophrenia using the Brief Assessment of Cognition in Schizophrenia (BACS)., Methods: Participants were 198 outpatients with schizophrenia or schizoaffective disorder (66 females; mean age 34.5 ± 6.8 years). Occupational function was assessed using the work subscale of the Life Assessment Scale for Mental Ill (LASMI-w). Multiple regression analysis was performed using the BACS as the independent variable and LASMI-w as the dependent variable. Furthermore, we divided the LASMI-w score into three groups, <11, 11-20, and >21, and performed a multinomial logistic regression analysis., Results: Multiple regression analysis revealed that LASMI-w score was negatively associated with BACS composite score (β = -0.20, p < 0.01). Among the sub-items of the BACS, only the symbol-coding score showed a significant negative association (β = -0.19, p < 0.05). Multinomial logistic analysis showed that the better the composite and symbol coding scores, the smaller the impairment of the occupational function (composite score: β = 2.39 between mild and moderate occupational impairments, p < 0.05; symbol coding score: β = 2.44 between mild and severe impairments, p < 0.05)., Conclusion: The occupational function of patients with schizophrenia was associated with overall cognitive function (composite score). In particular, the symbol coding score of the BACS was suggested to be related to work ability. These results might be useful in the assessment and training of cognitive rehabilitation aimed at employment support., (© 2023 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Purpose: This study aimed to investigate the association between parenting stress, maternal depressive symptoms, and use of physical punishment when the child is 10 years old., Methods: Data from the Tokyo Early Adolescence Survey on early adolescents and primary caregivers (N = 4478) were used. Frequency of using physical punishment, level of depressive symptoms (Kessler Psychological Distress Scale 6), and maternal parenting stress experienced at 1, 3, 9, 18, and 36 months after birth were evaluated. Multiple linear and multinomial logistic regression analyses were conducted., Results: Mothers (1633) who provided information on parenting stress at all the five points were included for the analysis. After controlling for the child's age, sex, birth weight, maternal age, and annual household income, presence of maternal parenting stress at every time point, except at three months after birth, was significantly associated with an increased risk of using physical punishment with the 10-year-old. After adjusting for levels of depressive symptoms, significant associations were found between use of physical punishment and maternal parenting stress at 1 month (adjusted odds ratio [OR] 1.71, 95% confidence interval [Cl] 1.12-2.61) and 36 months (adjusted OR 1.70, 95% CI 1.10-2.61) after birth., Conclusion: Maternal parenting stress experienced at 1 and 36 months after birth predicted use of physical punishment, even after adjusting for maternal depressive symptoms. Maternal support should, therefore, be provided to mothers to cope with parenting stress even three years after birth to prevent the use of physical punishment in early adolescence., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Problematic Internet use (PIU), hyperactivity/inattention, and depressive symptoms are comorbid problems in adolescence, but the causal relationships among these issues are unclear. To assess the relationships among PIU, hyperactivity/inattention, and depressive symptoms in adolescents in the general population. This longitudinal cohort study used data from the Tokyo Teen Cohort study in Tokyo, Japan, for two years between October 2012 and January 2015. Of the 3171 pairs of children and parents, 3007 pairs continued to participate in the second wave of the Tokyo Teen Cohort study. A total of 3007 children were included in the analysis (mean [standard deviation] age, 9.7 [0.4] years; 1418 women [47.2%]. Cross-lagged panel analysis revealed that PIU at timepoint 1 was significantly associated with hyperactivity/inattention at timepoint 2 (β = 0.03; 95% confidence interval (CI) 0.01-0.06), and hyperactivity/inattention at timepoint 1 was also significantly associated with PIU at timepoint 2 (β = 0.07; 95% CI 0.04-0.10), even after adjustments were made for depressive symptoms. Furthermore, PIU at timepoint 1 was significantly associated with depressive symptoms at timepoint 2 (β = 0.05; 95% CI 0.01-0.12), and depressive symptoms at timepoint 1 were also significantly associated with PIU at timepoint 2 (β = 0.05; 95% CI 0.02-0.07), even after adjustments were made for hyperactivity/inattention. These results support the bidirectional relationships among PIU, hyperactivity/inattention, and depressive symptoms. PIU may be a target to improve hyperactivity/inattention and depressive symptoms in adolescents., (© 2021. The Author(s).)

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., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Previous reports have suggested a cross-sectional association between autistic traits and psychotic experiences (PEs) in adolescents. However, while both autistic traits and PEs show sex-related differences, no studies have directly assessed whether such differences exist in the longitudinal association between autistic traits and PEs. Using a population-based adolescent cohort sample (n = 3007), we tested whether the longitudinal association between autistic traits and positive PEs was affected by sex-based differences using regression analyses. Autistic traits were assessed at 12 years old (timepoint 1 [T1]), and PEs were assessed at 12 and 14 years old (T1 and T2). Subsequently, we tested whether subdomains of autistic traits (difficulties in social interaction, communication, imagination, attention to detail, and attention switching) were associated with subtypes of PEs (auditory hallucinations, visual hallucinations, and delusions) using structural equation modeling, after controlling for PEs at T1, socio-economic status, school performance and parents' psychiatric disorders. After controlling for PEs at T1, we did not find any associations between autistic traits at T1 and PEs at T2 in both sexes. There was no significant positive or negative association between all subdomains of autistic traits and subtypes of PEs in both sexes. Autistic traits do not seem to predict future PEs in general adolescents regardless of sex., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Depression is highly prevalent and causes a heavy burden in adolescent life. Being praised for prosocial behavior might be a preventive factor because both being praised and prosocial behavior are protective against depression. Here, we investigated the longitudinal relationship between being praised for prosocial behavior and depressive symptoms in adolescents., Methods: In Tokyo Teen Cohort study (TTC), an ongoing prospective population-based cohort study, we collected 3,171 adolescents' data on self-reported experiences of being praised for prosocial behavior, depressive symptoms, and caregiver-evaluated prosocial behavior. Ten-year-old children were asked to freely describe answers to the question "What are you praised for?". Only children who clearly answered that they were praised for their prosocial behavior were designated the "prosocial praise group." The degree of depression at ages 10 and 12 was measured with the Short Mood and Feelings Questionnaire (SMFQ), a self-report questionnaire about depression. Objective prosocial behavior of the 10 year-old children was assessed by the Strength and Difficulty Questionnaire (SDQ). Multiple linear regression analysis was performed using the SMFQ score at age 12 as the objective variable and being praised for prosocial behavior as the main explanatory variable, and the SMFQ score at age 10 and the objective prosocial behavior at age 10 were included as confounders., Results: Depressive symptoms (SMFQ scores) in the "prosocial praise group" were significantly lower than those in the other group both at age 10 (4.3 ± 4.4 vs. 4.9 ± 4.6, p < 0.001) and at age 12 (3.4 ± 4.2 vs. 4.0 ± 4.6, p < 0.01). In the single regression analysis, the children who reported being praised for prosocial behavior at age 10 had significantly lower depressive symptoms at age 12 (partial regression variable: -0.57, 95% confidence interval (CI) [-0.96, -0.17]). This association remained significant after adjusting for confounders, including baseline depressive symptoms (partial regression variable: -0.44, 95% CI [-0.80, -0.08]). Prosocial behavior alone was not associated with depressive symptoms., Conclusions: Being praised for prosocial behavior rather than objective prosocial behavior at 10 years of age predicted lower depressive symptoms 2 years later. Praise for adolescents' prosocial behavior can be encouraged to prevent depression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nagaoka, Tomoshige, Ando, Morita, Kiyono, Kanata, Fujikawa, Endo, Yamasaki, Fukuda, Nishida, Hiraiwa-Hasegawa and Kasai.)

Background: Attention-deficit/hyperactivity disorder (ADHD) develops in early childhood and carries lifelong impact, but early identification and intervention ensure optimal clinical outcomes. Prolonged or excessive parenting stress may be a response to infant behavioral differences antecedent to developmental disorders such as ADHD, and therefore represents a potentially valuable inclusion in routine early-life assessment. To investigate the feasibility of using routinely-collected self-reported maternal parenting stress as a risk marker for child ADHD, this study investigated the longitudinal association between maternal parenting stress from 1 to 36 months after childbirth and child ADHD in early adolescence., Methods: The sample comprised 2,638 children (1,253 girls) from the Tokyo Teen Cohort population-based birth cohort study. Mothers recorded parenting stress five times from 1 to 36 months following childbirth in the Maternal and Child Health Handbook, a tool used for routine early-life assessment in Japan. Nine years later, mothers evaluated their child's ADHD symptoms at 12 y using the hyperactivity/inattention subscale from the Strength and Difficulties Questionnaire., Results: Approximately 7.5% of parents reported that they had parenting stress at 36 m after childbirth. 6.2% of children were evaluated as above the cut-off for ADHD symptoms at 12 y. Parenting stress at 1 and 3-4 m was not associated with child ADHD symptoms at 12 y. However, child ADHD symptoms at 12 y was significantly associated with parenting stress at 9-10 m (unadjusted OR = 1.42, p =.047, 95% CI [1.00, 2/00]), 18 m (unadjusted OR = 1.57, p =.007, 95% CI [1.13, 2.19]) and 36 m (unadjusted OR = 1.67, p =.002, 95% CI [1.20, 2.31]). These associations remained after adjustment for child's sex, age in months and family income., Conclusions: We identified associations between parenting stress at 9-10, 18 and 36 m after childbirth and child ADHD symptoms at 12 years old. Self-reported parenting stress data may have utility as an early indicator for ADHD risk. Participation in early-life health checks, assessment of parenting stress, and tailoring support to family needs should be promoted for early identification and intervention for ADHD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Endo, Stanyon, Yamasaki, Nakanishi, Niimura, Kanata, Fujikawa, Morimoto, Hosozawa, Baba, Oikawa, Nakajima, Suzuki, Miyashita, Ando, Hiraiwa-Hasegawa, Kasai and Nishida.)

Muscular strength, assessed by handgrip, is a risk indicator for psychiatric disorders, including psychosis. However, the biological mechanisms underlying this association remain unclear. Since advanced glycation end products (AGEs) play a key role in skeletal muscle underdevelopment and psychosis, we examined the role of AGEs in the longitudinal association between muscular strength and psychotic symptoms among adolescents. We first evaluated the direction of the relationship between handgrip strength and urine levels of pentosidine, a representative AGEs in a population-based birth cohort of 1,542 adolescents at ages 12 and 14. Then, we examined the role of AGEs in the longitudinal association between handgrip strength and thought problems (TP), as a psychotic symptom indicator, in a subsample of 256 adolescents at ages 13 and 14. An autoregressive cross-lagged model revealed that handgrip strength at age 12 negatively predicted pentosidine levels at age 14 (β = -0.20, p < 0.001), whereas pentosidine levels at age 12 did not predict handgrip strength at age 14 (β = 0.04, p = 0.062). Moreover, pentosidine levels had a significant indirect effect on the relationship between handgrip strength and TP (standard indirect effect = -0.051, p = 0.012), which remained significant after adjusting for gender and preceded TP and pentosidine levels. Thus, adolescents with low muscular strength are at a high risk of developing psychotic symptoms, which could be mediated by AGEs. Future studies need to investigate whether interventions focused on muscular strength prevent the accumulation of AGEs and thereby prevent the development of psychosis., (© 2022. The Author(s).)

Background: Cross-sectional studies have suggested that the occurrence of psychotic experiences is associated with loneliness in the general adolescent population. However, there has been a scarcity of prospective longitudinal studies on this topic., Methods: We investigated the longitudinal association between the presence of psychotic experiences and loneliness among adolescents using data from a population-based birth cohort study (Tokyo Teen Cohort; N = 3171). Psychotic experiences and loneliness were assessed at three timepoints with two-year intervals through early adolescence (age 10, 12, and 14)., Results: After adjusting for demographic characteristics and potential confounding factors, linear regression analyses showed a significant longitudinal association between psychotic experiences and subsequent loneliness (for age 10 to 12: B = 0.041, 95% CI: 0.009-0.074, p = .013; for age 12 to 14: B = 0.061, 95% CI: 0.026-0.096, p = .001). The reverse association, between preceding loneliness and later psychotic experiences, was not significant (for age 10 to 12: B = 0.003, 95% CI: -0.052-0.057, p = .926; for age 12 to 14: B = -0.028, 95% CI: -0.088-0.032, p = .355)., Discussion: Loneliness could be a sign of underlying psychotic experiences among adolescents but does not appear to be antecedent to these symptoms. Clinicians and teachers should assess for the presence of psychotic experiences in young adolescents who report loneliness. Future studies capturing PEs and loneliness at narrower time intervals, and including other potential mediators and confounders, may be insightful., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Autistic traits are associated with psychotic experiences in adolescence; however, the mechanisms underlying this relationship are not well understood. Prior research indicates that bullying victimization increases the risk of psychotic experiences in general adolescent populations, and autistic youth are at higher risk of being bullied than their non-autistic peers. Using longitudinal data from general population adolescents aged 10-14 in the Tokyo Teen Cohort study, we tested the hypothesis that bullying is responsible for the association between autistic traits and psychotic experiences in adolescence. We identified an indirect effect (estimate = 0.033 [95% CIs: 0.014-0.057], p < 0.001) between autistic traits and psychotic experiences via bullying victimization, even after controlling for known confounders. Prevention of bullying victimization may be one avenue for reducing risk of psychosis among adolescents with high levels of autistic traits., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Previous studies have revealed an association between maternal depressive/anxious symptoms and children's tics. However, the longitudinal relationships between these symptoms remain unclear. We examined the longitudinal relationships between maternal depressive/anxious symptoms and children's tic frequency in early adolescence with a population-based sample. Methods: The participants consisted of 3,171 children and their mothers from the Tokyo Teen Cohort (TTC) study, a population-representative longitudinal study that was launched in Tokyo in 2012. Maternal depressive/anxious symptoms and children's tics were examined using self-report questionnaires at the ages of 10 (time 1, T1) and 12 (time 2, T2). A cross-lagged model was used to explore the relationships between maternal depressive/anxious symptoms and children's tic frequency. Results: Higher levels of maternal depressive/anxious symptoms at T1 were related to an increased children's tic frequency at T2 (β = 0.06, p < 0.001). Furthermore, more frequent children's tics at T1 were positively related to maternal depressive/anxious symptoms at T2 (β = 0.06, p < 0.001). Conclusions: These findings suggest a longitudinal bidirectional relationship between maternal depressive/anxious symptoms and children's tic frequency in early adolescence that may exacerbate each other over time and possibly create a vicious cycle. When an early adolescent has tics, it might be important to identify and treat related maternal depressive/anxious symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yagi, Ando, Usami, Yamasaki, Morita, Kiyono, Hayashi, Endo, Iijima, Morimoto, Kanata, Fujikawa, Koike, Kano, Hiraiwa-Hasegawa, Nishida and Kasai.)

Birth order is a crucial environmental factor for child development. For example, later-born children are relatively unlikely to feel secure due to sibling competition or diluted parental resources. The positive effect of being earlier-born on cognitive intelligence is well-established. However, whether birth order is linked to social behavior remains controversial, and the neural correlates of birth order effects in adolescence when social cognition develops remain unknown. Here, we explored the birth order effect on prosociality using a large-scale population-based adolescent cohort. Next, since the amygdala is a key region for sociality and environmental stress, we examined amygdala substrates of the association between birth order and prosociality using a subset neuroimaging cohort. We found enhanced prosociality in later-born adolescents (N = 3160), and observed the mediating role of larger amygdala volume (N = 208) and amygdala-prefrontal functional connectivity with sex-selective effects (N = 183). We found that birth order, a non-genetic environmental factor, affects adolescent social development via different neural substrates. Our findings may indicate the later-born people's adaptive survival strategy in stressful environments., (© 2021. The Author(s).)

Maternal breastfeeding has an impact on motor and emotional development in children of the next generation. Elucidating how breastfeeding during infancy affects brain regional structural development in early adolescence will be helpful for promoting healthy development. However, previous studies that have shown relationships between breastfeeding during infancy and cortical brain regions in adolescence are usually based on maternal retrospective recall of breastfeeding, and the accuracy of the data is unclear. In this study, we investigated the association between breastfeeding duration and brain regional volume in a population-neuroimaging study of early adolescents in Japan (N ​= ​207; 10.5-13.4 years) using voxel-based morphometry, which enabled us to analyze the whole brain. We evaluated breastfeeding duration as indexed by maternal and child health handbook records during infancy. The results showed a significant positive correlation between the duration of breastfeeding and gray matter volume in the dorsal and ventral striatum and the medial orbital gyrus. Post hoc exploratory analyses revealed that the duration of breastfeeding was significantly correlated with emotional behavior. Additionally, the volume in the medial orbital gyrus mediated an association between breastfeeding duration and emotional behavior. This is the first study to evaluate the effect of breastfeeding during infancy on regional brain volumes in early adolescence based on maternal and child health handbook records. Our findings shed light upon the importance of maternal breastfeeding for brain development related to emotional and motivational processing in early adolescence., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Parent-child personality transmission can occur via biological gene-driven processes as well as through environmental factors such as shared environment and parenting style. We recently revealed a negative association between prosociality, a highly valued personality attribute in human society, and anterior cingulate cortex (ACC) γ-aminobutyric acid (GABA) levels in children at the age of 10 years. We thus hypothesized that prosociality would be intergenerationally transmitted, and that transmission would be underwritten by neurometabolic heritability. Here, we collected prosociality data from children aged 10 years and their parents in a large-scale population-based birth cohort study. We also measured ACC GABA+ and glutamate plus glutamine (Glx) levels in a follow-up assessment with a subsample of the participants (aged 11 years) using magnetic resonance spectroscopy. We analyzed the associations among children's and parents' prosociality and GABA+/Glx ratios. We also examined the effect of socioeconomic status (SES) and verbalized parental affection (VPA) on these associations. We found a significant positive parent-child association for prosociality (N ​= ​3026; children's mean age 10.2 years) and GABA+/Glx ratio (N ​= ​99; children's mean age 11.4 years). There was a significant negative association between GABA+/Glx ratio and prosociality in both children (N ​= ​208) and parents (N ​= ​128). Our model accounting for the effects of neurometabolic heritability on prosociality transmission fitted well. Moreover, in this model, a significant positive effect of VPA but not SES on children's prosociality was observed independently of the effect of neurometabolic transmission, while SES but not VPA was significantly associated with parental prosociality. Our results provide novel insights into the neurometabolic substrates of parent-child transmission of social behavior., Competing Interests: Declaration of competing interest All authors declare no conflict of interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Early-maturing girls are relatively likely to experience compromised psychobehavioral outcomes. Some studies have explored the association between puberty and brain morphology in adolescents, while the results were non-specific for females or the method was a region-of-interest analysis. To our knowledge, no large-scale study has comprehensively explored the effects of pubertal timing on whole-brain volumetric development or the neuroanatomical substrates of the association in girls between pubertal timing and psychobehavioral outcomes. We collected structural magnetic resonance imaging (MRI) data of a subsample (N ​= ​203, mean age 11.6 years) from a large-scale population-based birth cohort. Tanner stage, a scale of physical maturation in adolescents, was rated almost simultaneously with MRI scan. The Strengths and Difficulties Questionnaire total difficulties (SDQ-TD) scores were rated by primary parents some duration after MRI scan (mean age 12.1 years). In each sex group, we examined brain regions associated with Tanner stage using whole-brain analysis controlling for chronological age, followed by an exploration of brain regions also associated with the SDQ-TD scores. We also performed mediation analyses. In girls, Tanner stage was significantly negatively correlated with gray matter volumes (GMVs) in the anterior/middle cingulate cortex (ACC/MCC), of which the subgenual ACC (sgACC) showed a negative correlation between GMVs and SDQ-TD scores. Smaller GMVs in the sgACC mediated the association between higher Tanner stages and higher SDQ-TD scores. We found no significant results in boys. Our results from a minimally biased, large-scale sample provide new insights into neuroanatomical correlates of the effect of pubertal timing on developmental psychological difficulties emerging in adolescence., Competing Interests: Declaration of competing interest All authors declare no conflict of interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Desire for slimness (DS) is a well-established risk factor for eating disorders among adolescents, particularly girls. It is known that exposure to traditional media such as television can increase DS. However, the association between DS and the use of new media, such as social networking sites (SNS), adjusting for relevant potential confounders, has not been examined to-date. In this study, we assessed the relationship between DS and SNS use among early adolescent girls and boys, adjusting for body mass index (BMI), time spent watching television, and Internet use., Method: DS, SNS use, and confounding variables were assessed using self-report questionnaires and face-to-face interviews from a cross-sectional population-based survey of 4,478 10-year-old Japanese adolescents (2,100 girls and 2,378 boys)., Results: After adjusting for confounding variables, SNS use was associated with increased risk of DS among girls (odds ratio [OR] = 1.93; 95% confidence interval [CI], 1.17-3.18, p = .010), but not among boys (OR = 1.07; 95% CI, 0.64-1.80, p = .786)., Discussion: Exposure to SNS was associated with an increased risk of DS among early adolescents, especially girls. Targeting SNS use in early adolescence seems a promising approach to prevention of DS and subsequent eating problems, particularly among girls., (© 2019 Wiley Periodicals, Inc.)

Introduction: Epigenetic information such as DNA methylation is a useful biomarker that reflects complex gene-environmental interaction. Peripheral tissues such as blood and saliva are commonly collected as the source of genomic DNA in cohort studies. Epigenetic studies mainly use blood, while a few studies have addressed the epigenetic characteristics of saliva., Methods: The effects of methods for DNA extraction and purification from saliva on DNA methylation were surveyed using Illumina Infinium HumanMethylation450 BeadChip. Using 386 661 probes, DNA methylation differences between blood and saliva from 22 healthy volunteers, and their functional and structural characteristics were examined. CpG sites with DNA methylation levels showing large interindividual variations in blood were evaluated using saliva DNA methylation profiles., Results: Genomic DNA prepared by simplified protocol from saliva showed a similar quality DNA methylation profile to that derived from the manufacturer provided protocol. Consistent with previous studies, the DNA methylation profiles of blood and saliva showed high correlations. Blood showed 1,514 hypomethylated and 2099 hypermethylated probes, suggesting source-dependent DNA methylation patterns. CpG sites with large methylation difference between the two sources were underrepresented in the promoter regions and enriched within gene bodies. CpG sites with large interindividual methylation variations in blood also showed considerable variations in saliva., Conclusion: In addition to high correlation in DNA methylation profiles, CpG sites showing large interindividual DNA methylation differences were similar between blood and saliva, ensuring saliva could be a suitable alternative source for genomic DNA in cohort studies. Consideration of source-dependent DNA methylation differences will, however, be necessary., (© 2019 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Society of NeuropsychoPharmacology.)

Purpose: Self-regulation is the capacity to regulate attention, emotion, and behaviour to pursue long-term goals. The current study examined the associations between role model presence and self-regulation during early adolescence, controlling for hopefulness, using a large population-based data set from the Tokyo Teen Cohort study., Methods: Adolescents, aged 12 years, identified a role model using a single item on a paper questionnaire: 'Who is the person you most look up to?' Level of hopefulness was also assessed using a single question: 'To what extent do you feel hopeful about the future of your life?' Trained investigators evaluated self-regulation., Results: Of 2550 adolescents, 2279 (89.4%) identified a role model. After adjusting for level of hopefulness, identifying a role model was associated with higher levels of self-regulation in comparison to indications of no role model. Hopeful future expectations were also associated with higher self-regulation; however, the beta coefficient was smaller than role model presence in the multivariate linear regression analysis., Conclusions: Role model presence was significantly associated with higher self-regulation among early adolescents. Educational environments should focus on support for adolescents with no role models., Competing Interests: The authors have declared that no competing interests exist.

Aim: Adolescence is a crucial stage of psychological development and is critically vulnerable to the onset of psychopathology. Our understanding of how the maturation of endocrine, epigenetics, and brain circuit may underlie psychological development in adolescence, however, has not been integrated. Here, we introduce our research project, the population-neuroscience study of the Tokyo TEEN Cohort (pn-TTC), a longitudinal study to explore the neurobiological substrates of development during adolescence., Methods: Participants in the first wave of the pn-TTC (pn-TTC-1) study were recruited from those of the TTC study, a large-scale epidemiological survey in which 3171 parent-adolescent pairs were recruited from the general population. Participants underwent psychological, cognitive, sociological, and physical assessment. Moreover, adolescents and their parents underwent magnetic resonance imaging (MRI; structural MRI, resting-state functional MRI, and magnetic resonance spectroscopy), and adolescents provided saliva samples for hormone analysis and for DNA analysis including epigenetics. Furthermore, the second wave (pn-TTC-2) followed similar methods as in the first wave., Results: A total of 301 parent-adolescent pairs participated in the pn-TTC-1 study. Moreover, 281 adolescents participated in the pn-TTC-2 study, 238 of whom were recruited from the pn-TTC-1 sample. The instruction for data request is available at: http://value.umin.jp/data-resource.html., Conclusion: The pn-TTC project is a large-scale and population-neuroscience-based survey with a plan of longitudinal biennial follow up. Through this approach we seek to elucidate adolescent developmental mechanisms according to biopsychosocial models. This current biomarker research project, using minimally biased samples recruited from the general population, has the potential to expand the new research field of population neuroscience., (© 2018 The Authors. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and Neurology.)

Epidemiological studies have suggested that maternal diabetes in pregnancy increases the risk of schizophrenia in offspring. A recent cohort study observed that maternal diabetes in early pregnancy is also associated with psychotic experiences in the general adolescent population. However, it remains unclear whether maternal diabetes in early pregnancy is specifically associated with psychotic experiences, or is generally associated with broader mental health problems, including depressive symptoms in adolescence. The present study investigated the longitudinal associations between maternal diabetes in early pregnancy, and psychotic experiences and depressive symptoms in 10-year-old offspring. Our data were derived from the Tokyo Early Adolescence Survey, a population-based survey of early adolescents (N = 4478) and their primary caregivers. Diabetes in early pregnancy was determined by records in the mother's Maternal and Child Health Handbook, documented during the pregnancy. Psychotic experiences and depressive symptoms were established through self-report by the offspring at 10 years of age. Diabetes in early pregnancy was associated with an increased risk of hallucination in the offspring (auditory hallucination [odds ratio {OR} 4.33, 95% confidence interval {CI} 1.12-16.75]; visual hallucination [OR 6.58, 95% CI 1.69-25.66]), even after adjusting for depressive symptoms and other covariates. However, the association between maternal diabetes and delusional thoughts was not significant and diabetes in early pregnancy was not associated with adolescent depressive symptoms. Our investigation suggests that maternal diabetes in early pregnancy may specifically affect the risk of hallucinatory experiences in adolescent offspring., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Anxiety disorders are prevalent among adolescents; however, without objective behavioral markers, anxiety disorders in adolescent populations may often go undiagnosed. Response inhibition is considered as a possible behavioral marker, based on the results with two-gate design, which can aid in early detection of anxiety disorders. The aim of this study was to investigate the relationship between response inhibition and anxiety using a large-scale population-based adolescent sample with single-gate design., Methods: We used data from the Tokyo Teen Cohort study which was a population-based survey in adolescence. Anxiety was assessed by the Child Behavior Checklist answered by primary caregivers. Response inhibition was measured using the Go/No-Go task. We estimated Pearson's correlation coefficient to test the relationship between response inhibition and anxiety., Results: A total of 2,434 adolescents aged 11-13 years were included in our analyses. We found a significant but weak correlation between response inhibition and adolescent anxiety (r = 0.07, confidence interval 0.03-0.11, p < 0.001). Similar results were shown in most of subgroups according to gender, age, and intelligence., Limitations: The primary outcome was assessed only via parent-reported questionnaire, leading to potential informant bias., Conclusions: Response inhibition may not be considered as a suitable behavioral marker of adolescent anxiety., (Copyright © 2018. Published by Elsevier B.V.)