Mitsuhiro Miyashita

Background: Adolescent and young adult (AYA) mothers often experience unmet psychosocial needs, and those under 25 years of age are at increased risk of perinatal depression. Although home visiting programmes may be beneficial, no controlled trial has evaluated a programme co-designed with first-time AYA mothers and grounded in their lived experiences. Objective: We evaluated the effect of the co-designed Early Partnership programme on perceived fulfilment of psychosocial needs and postnatal depressive symptoms among first-time AYA mothers. Methods: We emulated a target trial using data from a pragmatic historically controlled study in four Tokyo municipalities. Participants were primiparous women aged 16–25 years. The intervention group included 151 participants and the control group included 158 participants. The intervention group received intensive tailored home visits by multi-professional family support workers from pregnancy to 12 months postnatally, and the historical control group received publicly funded health and social services. Findings: Retention at 12 months was high in both groups (intervention group, 82.1%; control group, 82.9%). For the primary outcome analysis, the intervention group had greater improvement in perceived fulfilment of psychosocial needs at 6 months postnatally (difference in mean changes 4.16, 95% CI 1.35 to 6.97, Cohen’s d 0.40, 95% CI 0.13 to 0.67) and 12 months postnatally (difference in mean changes 3.93, 95% CI 0.63 to 7.23, Cohen’s d 0.39, 95% CI 0.06 to 0.72) than the control group. Postnatal depressive symptoms were lower in the intervention group at 6 months postnatally (mean difference −1.54, 95% CI −2.70 to −0.38, Cohen’s d −0.34, 95% CI −0.59 to −0.08) and 12 months postnatally (mean difference −1.55, 95% CI −2.74 to −0.36, Cohen’s d −0.34, 95% CI −0.61 to −0.07). Well-being also improved at each time point, but estimates were imprecise. Conclusions: The Early Partnership programme, co-designed with young mothers and delivered by multi-professional teams, was acceptable and effective in improving perceived fulfilment of psychosocial needs and postnatal depressive symptoms. Clinical implications: These findings suggest that a person-centred and relationship-based home visiting model, delivered through a non-stigmatising design, may represent a plausible model of maternal care.

Background: Mental health encompasses subjective well-being (SWB) as well as psychopathology (PP). SWB and PP are related but separate domains: some individuals experience high SWB despite high PP, and others experience low SWB despite minimal PP. Given substantial and heterogeneous developmental changes in both domains during adolescence, examining their co-developmental trajectories may clarify how they integrate across this period. Methods: Using data from the Tokyo Teen Cohort ( N = 2994), a population-based prospective birth cohort study, we conducted parallel process latent class growth analysis to cluster SWB–PP trajectories at ages 10, 12, 14, and 16 years. We then investigated various sociodemographic, individual, familial, and socioenvironmental correlates for each class. Results: We identified four distinct classes: high SWB–low PP (55.0%), high SWB–mid PP (20.2%), low SWB–mid PP (17.0%), and mid SWB–high PP (7.7%). SWB declined from ages 10 to 16 years across all four classes. Lower PP did not necessarily correspond to higher SWB, and in some pairs of classes, the relationship between SWB and PP levels was reversed. When comparing the two classes with moderate PP, higher aspirations, more prosocial behavior, and better interpersonal relationships were associated with the high SWB class. In contrast, being female and having a higher household income were associated with the low SWB class. Conclusions: Discrepant SWB–PP trajectories suggest characteristic patterns of developmental integration between these domains during adolescence. Considering their interplay may complement domain-specific approaches and inform psychosocial supports aimed at maintaining SWB even in the presence of PP.

Bullying is a critical social stressor with long-lasting adverse impacts on mental health throughout life. Identifying biological mediators between bullying and subsequent mental health problems could help mitigate the long-term negative impact of bullying. However, such biological mediators have yet to be identified. This study assessed the mediating role of pentosidine, a representative glycation biomarker (i.e., pro-inflammatory aging compounds), between bullying and mental health problems among adolescents. This prospective, population-based cohort study (Tokyo Teen Cohort) included 3,158 participants. Causal mediation analysis was performed to test whether pentosidine at age 14 mediates the association between bullying at age 12 and subsequent mental health problems including psychotic experiences and depressive symptoms at age 16. Among the 3,158 adolescents aged 12 years (female, 46.9%), 473 (15.0%) were classified as being bullied. Bullying was associated with higher pentosidine levels (adjusted β [95% confidence interval], 0.27 [0.14–0.41]: P < 0.001) at age 14, and pentosidine at age 14 was associated with psychotic experiences (adjusted β [95% confidence interval], 0.02 [0.001–0.03]: P < 0.01) and depressive symptoms (adjusted β [95% confidence interval], 0.21 [0.09–0.32]; P < 0.001) at age 16. Pentosidine mediated 28.0% and 19.2% of the association between bullying and psychotic experiences and depressive symptoms, respectively. The mediating role of pentosidine was consistent across sexes. Higher levels of pentosidine possibly caused by bullying suggest that accelerated aging may begin from adolescence partly due to social stress. Future research should explore whether reducing pentosidine mitigates the adverse impact of bullying on subsequent mental health problems.

MicroRNAs (miRNAs) are critical regulators of neurodevelopment and are implicated in the pathogenesis of schizophrenia. Schizophrenia is increasingly recognized as a neurodevelopmental disorder, with most cases emerging during late adolescence and early adulthood, which is a critical period of brain maturation. However, the study of miRNAs during this phase has been limited by the challenges of postmortem brain analysis. Neuron-derived extracellular vesicles (NEVs) have recently been proposed for investigating brain-derived molecular profiles. In this study, NEVs were enriched from plasma using the L1CAM antibody in patients with recent-onset schizophrenia (ROS) within 5 years of onsets and chronic-phase schizophrenia (CS). The miRNA profiles of these NEVs in patients with ROS and CS were compared with those of age-and sex-matched healthy controls. Differential expression analysis revealed miRNA changes specific to the recent-onset phase as well as possible pathophysiological mechanisms transitioning from the recent-onset to the chronic phases. These findings provide novel insights into the role of miRNAs in neurodevelopmental abnormalities associated with schizophrenia onset. This study highlights the utility of NEVs as a tool for accessing brain-derived miRNA profiles and diagnostic biomarkers and underscores the importance of an onset period as a critical window for understanding the molecular underpinnings of schizophrenia.

Aim: Prediction of future psychosis in individuals with obsessive and compulsive (OC) symptoms is crucial for treatment choice, but only a few predictors have been revealed. Although OC symptoms and psychotic experiences (PEs) are common in adolescence, no studies have revealed the predictors of subsequent PEs in adolescents with OC symptoms. We aimed to explore the predictors for subsequent PEs among adolescents with OC symptoms, using a data‐driven machine‐learning approach on an adolescent cohort.Methods: We used data from a cohort study on the general population of adolescents in Tokyo (n = 3171 at age 10). Data were collected at age 10, 12, 14, and 16. We focused on a subgroup of participants who had OC symptoms at age 12. Participants who had PEs at age 10 were excluded. A machine learning method was utilized to explore over 600 potential predictors at baseline, distinguishing between those who had an onset of PEs after age 14 (n = 45) and those who never had PEs (n = 99).Results: The predicting model demonstrated a good performance (test area under the curve = 0.80 ± 0.05). Other than known risk factors for PEs, novel predictors of subsequent PEs among adolescents with OC symptoms included: lack of interaction with people of different ages, desire to be like their father in the future, and nonworking of primary caregiver when they were 5 years old. Not sharing their belongings readily with other children was a strong predictor of having no PEs.Conclusion: Close‐knit family bonds and limited social connections outside the family predict the later PEs among adolescents with OC symptoms.

INTRODUCTION: Evidence is scarce regarding the role of menopause in age‐related cognitive function trajectories associated with increased depressive symptoms. We examined the longitudinal association among sex and age at menopause, depressive symptoms, and 2‐year follow‐up cognitive function.METHODS: We used data from the English Longitudinal Study of Ageing, classifying age at menopause into three categories: < 40, 40 to 49, and ≥ 50 years. The study included 4726 women and 4286 men, using multilevel panel data regression to depict age trajectories.RESULTS: Later menopause (≥ 50 years) was significantly associated with fewer depressive symptoms and better cognition than earlier menopause (< 40 years). Men showed significantly fewer depressive symptoms and worse cognition than women with later menopause.DISCUSSION: Earlier menopause was significantly associated with worse 2‐year follow‐up cognition after adjusting for baseline depressive symptoms, cognition, and lifestyle factors. Dementia risk‐reduction strategies should consider women who undergo early menopause as a sex‐specific high‐risk group.Highlights: Early menopause is associated with worse depressive symptoms and cognitive function. Early menopause is a high‐risk factor for cognitive decline and depressive symptoms. Menopause at < 40 years is linked to worse orientation and immediate and delayed recall. Men exhibit worse cognitive function than women experiencing late menopause.

Background: Glucuronic acid (GlcA) is crucial in the glucuronidation pathway, facilitating the metabolism and elimination of various substances and drugs. Recent studies have noted elevated GlcA levels in patients with schizophrenia (SCZ) compared with healthy individuals. However, it remains unclear whether this elevation contributes to SCZ pathophysiology or results from medication effects. Aims: This study investigated the relationship between peripheral GlcA levels and clinical characteristics in patients with SCZ and assess whether these associations persist independently of psychotropic medication effects to provide insight into the potential role of GlcA in the pathophysiology of SCZ. Methods: Plasma GlcA levels were analysed in 218 patients with SCZ, examining their association with clinical features. The correlation between GlcA levels and symptom severity, assessed using the Positive and Negative Syndrome Scale (PANSS), was analysed in 35 patients. In addition, multiple regression analysis was conducted to adjust for age and psychotropic medication effects. Results: Significant correlations were observed between GlcA levels and PANSS scores for negative symptoms, general psychopathology and total scores. After adjustment for age and psychotropic medications, significant correlations between GlcA levels and PANSS scores persisted for negative symptoms (adjusted β [95% CI], 13.926 [2.369, 25.483]) and general psychopathology (adjusted β [95% CI], 19.437 [3.884, 34.990]), while the total score was no longer significant (adjusted β [95% CI], 34.054 [–0.517, 68.626]). Conclusions: Elevated GlcA levels in patients with SCZ are associated with specific symptom severity irrespective of the medication dose, suggesting a potential role of GlcA in SCZ pathophysiology.