Mice with reduced glutamate transporter GLT1 expression exhibit behaviors related to attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a common neuropsychiatric disorder in children. Although animal models and human brain imaging studies indicate a significant role for glutamatergic dysfunction in ADHD, there is no direct evidence that glutamatergic dysfunction is sufficient to induce ADHD-like symptoms. The glial glutamate transporter GLT1 plays a critical role in glutamatergic neurotransmission. We report here the generation of mice expressing only 20% of normal levels of the GLT1. Unlike conventional GLT1 knockout mice, these mice survive to adulthood and exhibit ADHD-like phenotypes, including hyperactivity, impulsivity and impaired memory. These findings indicate that glutamatergic dysfunction due to GLT1 deficiency, a mechanism distinct from the dopaminergic deficit hypothesis of ADHD, underlies ADHD-like symptoms.

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

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

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

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

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.].

Being Praised for Prosocial Behaviors Longitudinally Reduces Depressive Symptoms in Early Adolescents: A Population-Based Cohort Study.

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.