Association of Problematic Internet Use With Psychotic Experiences and Depression in Adolescents: A Cohort Study.

BACKGROUND AND HYPOTHESIS: Problematic internet use (PIU) is prevalent among adolescents. Past research suggested cross-sectional associations between PIU and psychotic experiences, but little information is available on the longitudinal association. We hypothesized that PIU in adolescence may be longitudinally associated with psychotic experiences, adjusting for confounders. STUDY DESIGN: We analyzed a random sample of adolescents in the Tokyo Teen Cohort to examine how PIU at ages 10 (2012-2015), 12 (2014-2017), and 16 (2019-2021) was associated with mental health issues at age 16. PIU was evaluated by the modified Compulsive Internet Use Scale, psychotic experiences by the Adolescent Psychotic-like Symptom Screener, and depression by the Short Mood and Feelings Questionnaire. We also examined the mediating role of social withdrawal. STUDY RESULTS: We analyzed 3171 adolescents; 151 reported psychotic experiences and 327 reported depression at age 16. Compared with the lowest tertile PIU group, the highest tertile PIU group at age 12 showed an increased adjusted risk of psychotic experiences (RD 3.3%, 95% CI 2.9%-3.7%; RR 1.65, 95% CI 1.55-1.73) and depression (RD 5.9%, 95% CI 5.5%-6.3%; RR 1.61, 95% CI 1.55-1.68) at age 16. PIU at age 16 showed analogous results, while PIU at age 10 suggested a smaller impact. Social withdrawal mediated 9.4%-29.0% of the association between PIU and psychotic experiences. CONCLUSIONS: PIU is longitudinally associated with psychotic experiences and depression in adolescents. Further longitudinal and intervention studies are warranted to provide robust public health implications and foster a safer digital future.

Macronutrient intake is associated with intelligence and neural development in adolescents.

Introduction: Macronutrient intake can be one of the most influential factors in cognitive and neural development in adolescents. Adolescence is a specific period of cognitive and neural development, and nutritional effects during this period could be life-long. Therefore, understanding the effects of macronutrient intake on cognitive and neural development in adolescents is crucially important. We thus examined the association across macronutrient intake, intelligence, and neural development using population-based cohort data. Methods: We conducted two studies. In study 1, we included a total of 1,734 participants (boys, 907, age [mean ± standard deviation] 171.9 ± 3.44 months; range 163.0-186.0 months) from the Tokyo TEEN Cohort (TTC) to examine the association between macronutrient intake and intelligence quotient (IQ). In study 2, we included a total of 63 participants (boys, 38, age 174.4 ± 7.7 months; range 160.7-191.6 months) to investigate the effect of nutrition intake on neural development using graph theory analysis for resting-state functional magnetic resonance imaging (rs-fMRI) derived from a subset of the TTC. Results: TTC data revealed that a higher IQ was associated in boys with increased protein intake (ß = 0.068, p = 0.031), and in girls, with reduced carbohydrate intake (ß = -0.076, p = 0.024). Graph theory analysis for rs-fMRI at approximately age 12 has shown that impaired local efficiency in the left inferior frontal gyrus was associated with higher carbohydrate and fat intake ([x, y, z] = [-51, 23, 8], pFDR-corrected = 0.00018 and 0.02290, respectively), whereas increased betweenness centrality in the left middle temporal gyrus was associated with higher carbohydrate, fat, and protein intake ([x, y, z] = [-61, -43, -13], pFDR-corrected = 0.0027, 0.0029, and 0.00075, respectively). Moreover, we identified a significant moderating effect of fat and protein intake on the relationship between change in betweenness centrality over a 2-year measurement gap in the left middle temporal gyrus and intelligence (ß = 12.41, p = 0.0457; ß = 12.12, p = 0.0401, respectively). Conclusion: Our study showed the association between macronutrient intake and neural development related to intelligence in early adolescents. Appropriate nutritional intake would be a key factor for healthy cognitive and neural development.

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.

Hippocampal Structures Among Japanese Adolescents Before and After the COVID-19 Pandemic.

Importance: Few studies have used a large-sample, longitudinal, population-based cohort study to examine whether the COVID-19 pandemic as a global major life event is associated with structural plasticity of the adolescent hippocampus. Objective: To examine whether Japan's first state of emergency (SoE) during the COVID-19 pandemic was associated with alterations in the macrostructures and microstructures of the hippocampus during its development. Design, Setting, and Participants: The population-neuroscience Tokyo TEEN Cohort study is a prospective cohort study with 4 consecutive waves in Tokyo, Japan. Due to the SoE, data collection was suspended between March 27, 2020, and July 30, 2020. Analyzed data, comprising 1149 brain structural scans obtained from 479 participants, of whom 336 participants had undergone 2 or more scans, were collected between October 2013 and November 2021. Data were analyzed from August 2022 to December 2023. Exposures: Japan's first SoE (April 7 to May 25, 2020). Main Outcomes and Measures: Hippocampal volume, 12 hippocampal subfield volumes, and 7 microstructural measures of the hippocampus. Results: A total of 1060 brain scans from 459 participants (214 female participants [47%]) including 246 participants from wave 1 (median [IQR] age, 11.3 [11.1-11.7] years), 358 from wave 2 (median [IQR] age, 13.8 [13.3-14.5] years), 304 from wave 3 (median [IQR] age, 15.9 [15.4-16.5] years), and 152 from wave 4 (median [IQR] age, 17.9 [17.5-18.4] years) were included in the final main analysis. The generalized additive mixed model showed a significant associations of the SoE with the mean hippocampal volume (ß = 102.19; 95% CI, 0.61-203.77; P = .049). The generalized linear mixed models showed the main associations of the SoE with hippocampal subfield volume (granule cell and molecular layer of the dentate gyrus: ß = 18.19; 95% CI, 2.97-33.41; uncorrected P = .02; CA4: ß = 12.75; 95% CI, 0.38-25.12; uncorrected P = .04; hippocampus-amygdala transition area: ß = 5.67; 95% CI, 1.18-10.17; uncorrected P = .01), and fractional anisotropy (ß = 0.03; 95% CI, 0.00-0.06; uncorrected P = .04). Conclusions and Relevance: After the first SoE, a volumetric increase in the hippocampus and trend increase in 3 subfield volumes and microstructural integration of the hippocampus were observed, suggesting that the transient plasticity of the adolescent hippocampus was affected by a major life event along with the typical developmental trajectory.

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.

Longitudinal trajectories of anterior cingulate glutamate and subclinical psychotic experiences in early adolescence: the impact of bullying victimization.

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.

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.

Longitudinal change in mismatch negativity (MMN) but not in gamma-band auditory steady-state response (ASSR) is associated with psychological difficulties in adolescence.

Adolescence is a critical period for psychological difficulties. Auditory mismatch negativity (MMN) and gamma-band auditory steady-state response (ASSR) are representative electrophysiological indices that mature during adolescence. However, the longitudinal association between MMN/ASSR and psychological difficulties among adolescents remains unclear. We measured MMN amplitude for duration and frequency changes and ASSR twice in a subsample (n = 67, mean age 13.4 and 16.1 years, respectively) from a large-scale population-based cohort. No significant longitudinal changes were observed in any of the electroencephalography indices. Changes in SDQ-TD were significantly associated with changes in duration MMN, but not frequency MMN and ASSR. Furthermore, the subgroup with higher SDQ-TD at follow-up showed a significant duration MMN decrease over time, whereas the subgroup with lower SDQ-TD did not. The results of our population neuroscience study suggest that insufficient changes in electroencephalography indices may have been because of the short follow-up period or non-monotonic change during adolescence, and indicated that the longitudinal association with psychological difficulties was specific to the duration MMN. These findings provide new insights that electrophysiological change may underlie the development of psychosocial difficulties emerging in adolescence.

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.

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.

Corrigendum: Being praised for prosocial behaviors longitudinally reduces depressive symptoms in early adolescents: a population-based cohort study.

[This corrects the article DOI: 10.3389/fpsyt.2022.865907.].

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.

Lower help-seeking intentions mediate subsequent depressive symptoms among adolescents with high autistic traits: a population-based cohort study.

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.

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.