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.

Association of homocysteine with white matter dysconnectivity in schizophrenia.

Several studies have shown white matter (WM) dysconnectivity in people with schizophrenia (SZ). However, the underlying mechanism remains unclear. We investigated the relationship between plasma homocysteine (Hcy) levels and WM microstructure in people with SZ using diffusion tensor imaging (DTI). Fifty-three people with SZ and 83 healthy controls (HC) were included in this retrospective observational study. Tract-Based Spatial Statistics (TBSS) were used to evaluate group differences in WM microstructure. A significant negative correlation between plasma Hcy levels and WM microstructural disruption was noted in the SZ group (Spearman's ρ = -.330, P = 0.016) but not in the HC group (Spearman's ρ = .041, P = 0.712). These results suggest that increased Hcy may be associated with WM dysconnectivity in SZ, and the interaction between Hcy and WM dysconnectivity could be a potential mechanism of the pathophysiology of SZ. Further, longitudinal studies are required to investigate whether high Hcy levels subsequently cause WM microstructural disruption in people with SZ.

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.

The longitudinal relationship between dissociative symptoms and self-harm in adolescents: a population-based cohort study.

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.

Uncovering associations between gender nonconformity, psychosocial factors, and mental health in adolescents: a birth cohort study.

BACKGROUND: Little information is available on the association between gender nonconformity during adolescence and subsequent mental health. While the distress related to gender nonconformity may be socially produced rather than attributed to individual-level factors, further research is needed to better understand the role of psychosocial factors in this context. METHOD: We analyzed data from the Tokyo Teen Cohort, obtained through random sampling of adolescents born between 2002 and 2004. We used inverse probability weighting to examine the association of gender nonconformity at ages 12 and 14 as a time-varying variable with subsequent mental health at age 16, while accounting for time-fixed and time-varying confounders. Furthermore, we used a weighting approach to investigate the mediating role of modifiable psychosocial factors in this association, addressing exposure-mediator and mediator-mediator interactions. RESULTS: A total of 3171 participants were analyzed. Persistent gender nonconforming behavior at ages 12 and 14 was associated with subsequent depression (ß = 2.02, 95% confidence interval [CI] 0.85 to 3.19) and psychotic experiences (ß = 0.33, 95% CI 0.14 to 0.52) at age 16. The results remained robust in sensitivity analyses. Approximately 30% of the association between gender nonconformity and depression was consistently mediated by a set of psychosocial factors, namely loneliness, bullying victimization, and relationships with mother, father, and friends. CONCLUSIONS: Persistent gender nonconformity during adolescence is associated with subsequent mental health. Psychosocial factors play a vital mediating role in this association, highlighting the essential need for social intervention and change to reduce stigmatization and ameliorate mental health challenges.

Adolescent psychotic experiences before and during the COVID-19 pandemic: a prospective cohort study.

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.

Sex Differences in Adolescent Depression Trajectory Before and Into the Second Year of COVID-19 Pandemic.

OBJECTIVE: Evidence on the impact of the COVID-19 pandemic on adolescent mental health is mixed and does not disentangle natural age-related changes. We compared depressive symptoms among 16-year-olds surveyed, at a fourth wave, before or during the pandemic, while accounting for expected trajectories of within-person change based on 3 prior waves. METHOD: In this longitudinal cohort of 3,171 adolescents in Tokyo, Japan, adolescents were grouped based on their age 16 survey timing: pre-pandemic (February 2019 to February 2020) and during-pandemic (March 2020 to September 2021). Depressive symptoms were self-reported using the Short Mood and Feelings Questionnaire. Mixed-effect models were fitted to assess group differences while controlling for previous trends. Variations by sex, household income, and pandemic phase (early, late first-year, and second-year) were examined. RESULTS: Of 2,034 eligible adolescents, 960 (455 girls) were assessed before and 1,074 (515 girls) during the pandemic. Overall, depressive symptoms increased by 0.80 points (95% CI 0.28-1.31, 0.15 SD of the population average). This increase varied by sex and pandemic phase. For boys the increase emerged in the late first-year phase and enlarged in the second-year phase (mean difference from pre-pandemic: 1.69, 0.14-3.24), whereas for girls it decreased in the early school-closure phase (mean difference: -1.98, -3.54 to -0.41) and returned to the pre-pandemic level thereafter, with no additional increases during the pandemic. CONCLUSION: Into the second year of the COVID-19 pandemic, depressive symptoms of 16-year-olds worsened above the expected age-related change only in boys. Continuous monitoring and preventive approaches for adolescents at the population level are warranted. DIVERSITY & INCLUSION STATEMENT: We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure sex and gender balance in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Glucuronic acid is a novel source of pentosidine, associated with schizophrenia.

Pentosidine (PEN) is an advanced glycation end-product (AGEs), where a fluorescent cross-link is formed between lysine and arginine residues in proteins. Accumulation of PEN is associated with aging and various diseases. We previously reported that a subpopulation of patients with schizophrenia showed PEN accumulation in the blood, having severe clinical features. PEN is thought to be produced from glucose, fructose, pentoses, or ascorbate. However, patients with schizophrenia with high PEN levels present no elevation of these precursors of PEN in their blood. Therefore, the molecular mechanisms underlying PEN accumulation and the molecular pathogenesis of schizophrenia associated with PEN accumulation remain unclear. Here, we identified glucuronic acid (GlcA) as a novel precursor of PEN from the plasma of subjects with high PEN levels. We demonstrated that PEN can be generated from GlcA, both in vitro and in vivo. Furthermore, we found that GlcA was associated with the diagnosis of schizophrenia. Among patients with high PEN, the proportion of those who also have high GlcA is 25.6%. We also showed that Aldo-keto reductase (AKR) activity to degrade GlcA was decreased in patients with schizophrenia, and its activity was negatively correlated with GlcA levels in the plasma. This is the first report to show that PEN is generated from GlcA. In the future, this finding will contribute to understanding the molecular pathogenesis of not only schizophrenia but also other diseases with PEN accumulation.

Longitudinal Relationships Between Help-Seeking Intentions and Depressive Symptoms in Adolescents.

PURPOSE: Cross-sectional studies have shown an association between lower help-seeking intentions and greater depressive symptoms among adolescents. However, no longitudinal study has examined the direction of this association. The current study investigated whether help-seeking intentions and depressive symptoms are reciprocally associated at the within-person (individual) level during early to mid-adolescence. METHODS: Longitudinal data on help-seeking intentions and depressive symptoms in adolescents were obtained from a population-based birth cohort study (Tokyo Teen Cohort; N = 3,171) at four time points (10y, 12y, 14y, and 16y). A random intercept cross-lagged panel model was used to evaluate the within-person prospective associations between help-seeking intentions and depressive symptoms. RESULTS: At the within-person level, significant associations were consistently observed between antecedent greater depressive symptoms and subsequent lower help-seeking intentions across all time points (10y-12y: standardized regression coefficient (ß) = -0.12, p < .001; 12y-14y: ß = -0.07, p < .05; and 14y-16y: ß = -0.09, p < .01). Meanwhile, significant within-person associations were partly observed between antecedent lower help-seeking intentions and subsequent greater depressive symptoms from 10y to 12y (ß = -0.07, p < .05) and from 14y to 16y (ß = -0.12, p < .001). These prospective associations were almost the same when adjusted for the number of potential confidants as a time-varying confounder. DISCUSSION: Adolescents with worsening depressive symptoms may become increasingly reluctant to seek help over time. Proactive early recognition and intervention with support from parents, teachers, and other individuals may facilitate the management of depression in adolescents.

Association between menopause and suicidal ideation in mothers of adolescents: A longitudinal study using data from a population-based cohort.

BACKGROUND: Midlife suicide among women has attracted increasing research attention. This study aimed to investigate the longitudinal association between menopause and suicidal ideation among middle-aged women. METHODS: Our data were derived from the Tokyo Teen Cohort, a population-based survey of early adolescents (N = 3171) and their primary caregivers (typically, mothers) in Japan. A total of 2944 mothers (baseline mean age = 44.0 years) were included in the analysis. The baseline assessment in this study was performed at second-wave survey from July 2014 to January 2017. A follow-up assessment was conducted at fourth-wave survey from February 2019 to September 2021. Suicidal ideation at baseline and follow-up was assessed using the Suicidal Ideation subscale of the 28-item General Health Questionnaire. Menopausal stage was classified based on self-report at fourth-wave survey. RESULTS: Participants who started the perimenopausal stage after baseline were significantly more likely to have suicidal ideation at follow-up than those who did not have experienced menopausal transition yet. Participants with greater social support were less likely to report suicidal ideation at follow-up, even after adjusting for baseline suicidal ideation. LIMITATIONS: This study was based on self-report regarding menopausal stage and only included mothers of adolescents from Japan. An exact length of time from the onset to the presence of suicidal ideation was unavailable. CONCLUSIONS: Women who have experienced the onset of menopausal transition presented an increased risk of suicidal ideation. Psychosocial interventions to increase social support may be beneficial in preventing mental health inequalities during menopausal transitions.

Informal Caregiving in Adolescents from 10 to 16 Years Old: A Longitudinal Study Using Data from the Tokyo Teen Cohort.

There is growing evidence of the impact of informal caregiving on adolescent mental health, and its role is often hidden unintentionally or intentionally, which may hamper early identification and support for young informal caregivers. However, the quantitative evidence regarding household factors relating to informal caregiving has mostly been based on cross-sectional findings. This study examines the longitudinal associations between household characteristics and the duration of informal caregiving in adolescents from 10 to 16 years of age. Child-household respondent pairs (n = 2331) from the Tokyo Teen Cohort in Japan were followed every 2 years from 10 to 16 years of age. Informal caregiving was assessed repeatedly based on the household respondent's survey responses. Persistent caregiving was defined as daily caregiving at two or more waves. There were 2.2% of children who gave daily care at two or more waves. Cross-sectional associations with daily informal caregiving at each wave were found with girls, low household income, and cohabiting with grandparents. A significant association with persistent caregiving was found only in cohabiting with grandparents at 10 years of age after adjusting for sex, number of siblings, single parent, and household income. Our longitudinal examination highlighted cohabiting with grandparents as a preceding factor for persistent caregiving. Identification and support for young informal caregivers should be integrated into social care service systems for older adults. The mechanism of persistent caregiving requires clarification.

Depression and Anxiety in Older Adults with Dementia During the COVID-19 Pandemic.

This study examined the longitudinal association between dementia, activity participation, the coronavirus disease 2019 pandemic period, and 1-year mental health changes. We obtained data from the National Health and Aging Trends Study in the United States. We included 4,548 older adult participants of two or more survey rounds between 2018 and 2021. We identified baseline dementia status, and assessed depressive symptoms and anxiety at baseline and follow-up. Dementia and poor activity participation were independently associated with an increased prevalence of depressive symptoms and anxiety. Dementia care and support should address emotional and social needs under continued public health restrictions.

Urinary exosomal microRNAs as predictive biomarkers for persistent psychotic-like experiences.

Psychotic-like experiences (PLEs) occur occasionally in adolescence and mostly disappear with increasing age. Their presence, if persistent, is considered a robust risk factor for subsequent psychiatric disorders. To date, only a few biological markers have been investigated for persistent PLE prediction. This study identified urinary exosomal microRNAs that can serve as predictive biomarkers for persistent PLEs. This study was part of a population-based biomarker subsample study of the Tokyo Teen Cohort Study. A total of 345 participants aged 13 (baseline) and 14 (follow-up) years underwent PLE assessments by experienced psychiatrists using semi-structured interviews. We defined remitted and persistent PLEs based on longitudinal profiles. We obtained urine at baseline and the expression levels of urinary exosomal miRNAs were compared between 15 individuals with persistent PLEs and 15 age- and sex-matched individuals with remitted PLEs. We constructed a logistic regression model to examine whether miRNA expression levels could predict persistent PLEs. We identified six significant differentially expressed microRNAs, namely hsa-miR-486-5p, hsa-miR-199a-3p, hsa-miR-144-5p, hsa-miR-451a, hsa-miR-143-3p, and hsa-miR-142-3p. The predictive model showed an area under the curve of 0.860 (95% confidence interval: 0.713-0.993) for five-fold cross-validation. We found a subset of urinary exosomal microRNAs that were differentially expressed in persistent PLEs and presented the likelihood that a microRNA-based statistical model could predict them with high accuracy. Therefore, urine exosomal miRNAs may serve as novel biomarkers for the risk of psychiatric disorders.

Attributes of auditory hallucinations that are associated with self-harm: A prospective cohort study.

There is a well-documented epidemiological association between auditory hallucinations and self-harm in the general population. However, there has been limited research examining specific characteristics of auditory hallucinations (e.g., type, source, or context of voices) as correlates of self-harm. We used prospective data from the Tokyo Teen Cohort to explore whether characteristics of voices reported at age 14 were differentially associated with self-harm behaviors at ages 14 and 16. Among respondents with auditory hallucinations, respondents who experienced voices that "said something bad" about them or commented on their thoughts and actions were most likely to report concurrent self-harm, whereas positive or praising voices were protective. Negative voices continued to predict self-harm two years later, at age 16, even with adjustment for self-harm at age 14. The age of the voices, source of the voices, and context (e.g., falling asleep or while sick) was not associated with likelihood of reporting concurrent or subsequent self-harm behaviors. Assessing for negative voices in particular, rather than auditory hallucinations or psychotic experiences more broadly, may provide a more specific indicator of risk for self-harm among adolescents. The real-world utility of these epidemiological findings should be further examined in clinical settings.

Auditory Hallucinations and Self-Injurious Behavior in General Population Adolescents: Modeling Within-Person Effects in the Tokyo Teen Cohort.

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: ß = .118, P < .001; 14-16y: ß = .086, P = .012). The reverse SIB->AHs relationship was non-significant at 12-14y (ß = .047, P = .112) but emerged from 14y to 16y as the primary direction of influence (ß = .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.

Predictors of chronic loneliness during adolescence: a population-based cohort study.

BACKGROUND: Adolescent loneliness is a growing public health issue owing to its adverse health impact. Although adolescent loneliness is common, its trajectories can show distinct patterns over time. However, there is limited knowledge regarding their determinants, particularly for chronic loneliness. We aimed to determine the predictors of loneliness trajectories across early-to-mid adolescence and examine their association with later suicidality. METHODS: Data were collected from 3165 participants from the population-based Tokyo Teen Cohort. Participants reported their loneliness at 10, 12, 14, and 16 years. Loneliness trajectories were identified using latent class growth analysis. We examined the predictive role of bullying victimization and parental psychological distress at age 10 via a multinomial logistic regression. Sociodemographic and child-related factors (i.e., chronic health conditions and cognitive delay) were included as covariates. The association between the trajectories, self-harm, and suicidal ideation by age 16 was investigated using Poisson regression. RESULTS: Four trajectories were identified: "consistently low" (2448, 77.3%), "moderate-decreasing" (185, 5.8%), "moderate-increasing" (508, 16.1%), and "consistently high" (24, 0.8%). Taking "consistently low" as a reference, experiences of bullying victimization predicted all the remaining trajectories [adjusted relative risk ratio 1.64, 95% confidence interval (CI) 1.18-2.28 for "moderate-decreasing," 1.88, 1.52-2.33 for "moderate-increasing," and 4.57, 1.97-10.59 for "consistently high"]. Parental psychological distress predicted the "moderate-increasing" (1.84, 1.25-2.71) and "consistently high" (5.07, 1.78-14.42) trajectories. The "consistently high" trajectory showed the greatest risk for self-harm and suicidal ideation (adjusted relative risk ratio 6.01, 95% CI 4.40-8.22; 2.48, 1.82-3.37, respectively); however, the "moderate-increasing" and "moderate-decreasing" trajectories were also at increased risk (moderate-increasing: 2.71, 2.23-3.30 for self-harm, 1.93, 1.69-2.19 for suicidal ideation; moderate-decreasing: 2.49, 1.91-3.26 for self-harm, 1.59, 1.33-1.91 for suicidal ideation). CONCLUSIONS: Bullying victimization and parental psychological distress at age 10 were independent determinants of increased and chronic loneliness trajectories across early-to-mid adolescence. Compared with "consistently low," all other loneliness trajectories were associated with an increased risk of adolescent suicidality. Interventions targeting adolescent loneliness should include approaches to mitigate bullying and parental psychological distress. These strategies may help prevent adolescent suicidality.

Hair zinc levels and psychosis risk among adolescents.

Recent meta-analyses have shown lower zinc and higher copper levels in the serum of people with schizophrenia than in healthy controls. However, the relationship between trace elements (TEs) and the pathophysiology of psychosis, including schizophrenia, remains unclear due to the antipsychotic effects on mineral levels. In this study, we aimed to determine the relationship between zinc and copper levels in hair and psychosis risk among drug-naïve adolescents. This study was conducted as a part of a population-based biomarker subsample study of the Tokyo Teen Cohort Study, including 252 community-dwelling 14-year-old drug-naïve adolescents. Zinc and copper levels in hair were measured using inductively coupled plasma mass spectrometry. The thought problems (TP) scale from the Child Behavior Checklist was used to evaluate psychosis risk. Regression analysis showed that hair zinc levels were negatively correlated with the TP scale (T-score) (ß = -0.176, P = 0.005). This result remained significant after adjusting for age and sex (ß = -0.175, P = 0.005). In contrast, hair copper levels were not associated with the TP scale (T-score) (ß = 0.026, P = 0.687). These findings suggest that lower zinc levels could be involved in the pathophysiology of psychosis, independent of antipsychotics. Further longitudinal studies are required to investigate whether hair zinc level is a useful new biomarker for assessing psychosis risk.

Plasma unconjugated bile acids as novel biomarker for schizophrenia.

In this study, we measured conjugated and unconjugated free bile acids (BAs) in plasma from patients with schizophrenia and healthy subjects to examine the possibility of BA as a biomarker for schizophrenia. Although the levels of each BA conjugate showed no significant differences, significant differences for three unconjugated bile acids were observed in the plasma between patients with schizophrenia and healthy subjects. Additionally, a more than three times difference between patients and healthy subjects was observed in the mean value of the total concentrations of primary BAs. These results indicate that cholic acid and chenodeoxycholic acid levels in plasma may be novel diagnostic markers for a sub-population of patients with schizophrenia. Thus, future studies should elucidate the relationship between this increase in BA levels and the pathology of schizophrenia and verify the potential of unconjugated BA in plasma as biomarkers for schizophrenia.

The development and clinical application of a novel schizophrenia screening system using yoga-induced autonomic nervous system responses.

Background: In severe cases, schizophrenia can result in suicide and social isolation. Diagnosis delay can lead to worsening symptoms, and often results in prolonged therapy. An estimated 50%-80% of patients with schizophrenia are unaware of their condition. Biomarkers for schizophrenia are important for receiving a diagnosis from a psychiatrist at an early stage. Although previous studies have investigated near-infrared spectroscopy as a biomarker for schizophrenia, the required equipment is expensive and not designed for home use. Hence, we developed a novel home-use schizophrenia screening system that uses a wearable device to measure autonomic nervous system responses induced by yoga, which is frequently adopted in rehabilitation for schizophrenia. Materials and methods: The schizophrenia screening system automatically distinguishes patients with schizophrenia from healthy subjects via yoga-induced transient autonomic responses measured with a wearable wireless electrocardiograph (ECG) using linear discriminant analysis (LDA; Z score ≥ 0 → suspected schizophrenia, Z-score < 0 → healthy). The explanatory variables of LDA are averages of four indicators: components of heart rate variability (HRV): the very low-frequency (VLF), the low-frequency (LF), HR, and standard deviation of the NN intervals (SDNN). In the current study, HRV is defined as frequency domain HRV, which is determined by integrating RRI power spectrum densities from 0.0033 to 0.04 Hz (VLF) and 0.04-0.15 Hz (LF), and as time domain HRV, SDNN of which is calculated as the mean of the standard deviations of the RR intervals. These variables were measured before (5 min), during (15 min), and after (5 min) yoga in a 15-min mindfulness-based yoga program for schizophrenia (MYS). The General Health Questionnaire-28 (GHQ28) score was used to assess the severity of mental disorders for patients with schizophrenia and healthy volunteers. Twelve patients with schizophrenia (eight female and four male, 23-60 years old) and 16 healthy volunteers (seven female and nine male, 22-54 years old) were recruited. Results: The schizophrenia screening system achieved sensitivity of 91% and specificity of 81%. Z-scores of LDA were significantly correlated with GHQ28 scores (r = 0.45, p = 0.01). Conclusion: Our proposed system appears to be promising for future automated preliminary schizophrenia screening at home.