BACKGROUND:Although obesity and mental health problems represent two of the most pressing public health challenges, their developmental interplay remains insufficiently understood. Thus, we examined how depressive and anxiety symptoms, self-esteem, and psychological resilience are associated with weight development during adolescence. METHODS:We included 1280 11-year-old children from the Finnish Health in Teens cohort, following 814 of them for 4.3 years. Mental health was assessed with validated self-administered scales at age 11. Psychological resilience was determined by complete mental health after exposure to stressful life events. Body mass index z-score (BMIz) and waist-to-height ratio (WtHr) were calculated at ages 11 and 16. RESULTS:In models adjusted for sex, age, physical activity, dietary pattern, puberty status, caregivers' BMI and education level, depressive symptoms were associated with higher baseline BMIz but smaller increases in mean BMIz thereafter (p = 0.030). High self-esteem was associated with lower baseline BMIz, yet with steeper increases over follow-up (adjusted model, p = 0.021). Anxiety symptoms and resilience were not associated with BMIz after adjustments. Similar patterns were observed for WtHr. CONCLUSION:Findings highlight that mental health is associated with physical growth in adolescence, emphasizing the need to consider mental health in understanding and addressing patterns of weight development and their underlying dynamics. IMPACT:This study provides up-to-date, longitudinal evidence on how mental health shapes subsequent weight development during the critical and rapid growth period of adolescence. Both positive and negative dimensions of mental health play a role in shaping adolescent weight development, with evidence that some youths experiencing mental health difficulties exhibited smaller increases in BMI z-score, even when starting from a higher baseline BMI. It should be acknowledged that in contemporary society, adolescents with mental health difficulties may not necessarily present immediate excessive weight gain but instead follow stable or even declining weight trajectories.

Background: The impact of parental mental wellbeing on adolescent physical activity, digital media use, and body mass index (BMI) remains understudied. We aimed to identify parental mental wellbeing profiles when adolescents were 11 years old and to examine whether parental mental wellbeing, both as profiles and continuous variables, is associated with adolescents' physical activity, digital media use, and BMI at ages 11 and 14. Methods: The study included 5839 parent-adolescent pairs in a 3-year follow-up. At baseline (mean adolescent age 11 years), parents completed the Short Form Beck Depression Inventory, the Sense of Coherence (SOC) Scale, and the RAND-36 Mental Component Summary. Adolescents reported physical activity and sedentary digital media use via questionnaire, and their height and weight were measured to calculate BMI z-scores at baseline and follow-up (mean age 14 years). Results: Latent profile analysis identified three parental mental wellbeing profiles: balanced (82 %), somewhat balanced (13 %), and unbalanced (5 %). Better parental mental wellbeing, analysed as a continuous latent variable rather than profiles, was associated with higher adolescent physical activity and lower digital media use at age 11. These associations were still observed at age 14, more strongly for physical activity. Among individual mental wellbeing indicators, greater parental depressive symptoms were associated with lower physical activity, while higher SOC was associated with less digital media use. We observed no associations between parental mental wellbeing and adolescent BMI. Conclusions: These findings highlight the association of better parental mental wellbeing with higher adolescent physical activity and lower digital media use.

Background University students’ mental health problems are prevalent globally, which underlines the need for accessible and cost-effective mental health services in universities. Loneliness is a key risk factor for mental health problems, and it disproportionately affects students from minority backgrounds. Therefore, addressing loneliness and fostering inclusion and equality can be crucial strategies for enhancing students’ well-being. Objective The aim of this study is to investigate a social-identity group intervention called Groups 4 Health (G4H) for university students’ well-being using both quantitative and qualitative methods. Here, we present the research protocol and report preliminary descriptive findings from the study cohort. Methods The quantitative part of the study is a 4 parallel-arm nonrandomized controlled trial aiming to recruit 600 student participants from the University of Helsinki. The experimental group, which receives the G4H intervention, includes 5 group meetings held over a 7-week period. The experimental group will be compared with 2 active comparators: groups organized by the University of Helsinki study psychologists and a 7-week online intervention course focused on well-being and study skills, and to a no-intervention control group. The primary quantitative outcomes of the study are loneliness and depression; secondary outcomes include several measures of students’ well-being, academic performance, and cost-effectiveness of the intervention. Quantitative data are collected before the intervention, during the intervention (at week 3), immediately post intervention (at week 7 after baseline), and at 1- and 3-month follow-ups. The qualitative part of the study explores the challenges and opportunities related to inclusion and equality identified in the G4H intervention using observations, interviews, and focus group discussions. Results In the preliminary findings based on the first data freeze in March 2025, we observed differences in the background characteristics between the trial arms, highlighting the need to address group selection bias. First results from the study are expected in 2026. Conclusions If proven effective, these interventions have significant potential to improve students’ well-being in both short and long term, fostering mental health and supporting academic success and future career paths. Trial Registration ClinicalTrials.gov NCT06542029; https://clinicaltrials.gov/study/NCT06542029 International Registered Report Identifier (IRRID) DERR1-10.2196/79319

There is currently a lack of empirical studies investigating whether specific personality traits moderate the effects of mindfulness-based interventions (MBIs) on distinct adolescent mental health outcomes. This study examined how personality traits from a five-factor model (agreeableness, conscientiousness, emotional stability, extraversion, and openness to experience) moderate the effects of an MBI in schools on adolescents’ depression, socio-emotional functioning, and resilience. A total of 2773 Finnish students aged 12–15 years participated in a cluster randomized controlled trial with three arms: a 9-week MBI (the.b program), a 9-week active control condition (a relaxation program), and an inactive control condition (the routine school curriculum). Personality traits were assessed before the MBI (T0). Mental health was evaluated before (T0) and after (T9) the intervention, as well as at a 26-week follow-up (T26), using scores for depressive symptoms, socio-emotional functioning difficulties, and resilience. When compared with both control groups, personality traits did not moderate the effects of the MBI on resilience or socio-emotional functioning. Most of the moderation analyses were also nonsignificant on depressive symptoms. Only, at the 26-week follow-up, the analyses indicated a small moderating effect on the change in depressive symptoms between the MBI and active control groups (β = 0.31, 95 http://rdcu.be/t57S .

BACKGROUND:Depression and anxiety are among the most prevalent mental health problems globally, with psychotherapy serving as a first-line treatment. Initial symptom severity, prior treatment history, waiting time, and session frequency may influence treatment effectiveness in routine care. METHODS:We analyzed session-by-session data from clients receiving a seven-session cognitive-behavioral therapy (CBT) program for depression (N = 2627) or anxiety (N = 3929) in primary care. Symptoms were assessed using the PHQ-9 and GAD-7 at each session. The magnitude and rate of change were examined using pre-post comparisons and linear mixed models. RESULTS:Clients showed significant reductions in both depressive (mean change -4.45 PHQ-9 points, 95% CI -4.69, -4.22) and anxiety symptoms (mean change -4.36 GAD-7 points, 95% CI -4.54, -4.17). Higher initial symptom severity was associated with faster reductions, while prior psychiatric care or previous very long-term psychotherapy were associated with smaller pre-post gains. Waiting time and session frequency were not consistently related to outcomes. CONCLUSIONS:In routine CBT, clients with higher baseline severity benefited substantially, supporting equitable access to CBT regardless of initial symptom level. Clinical improvement was driven by the total number of attended treatment sessions rather than by the rate of attendance (i.e., the number of sessions per unit of time). This supports flexible scheduling without compromising outcomes. Longer waiting times did not systematically predict poorer results, suggesting that client- versus system-driven delays may have distinct implications. Considering prior treatment history may help tailor interventions for individuals with more persistent or treatment-resistant symptom patterns.

This cluster randomized controlled trial (RCT) study conducted in Southern Finland investigates the effectiveness of a universal mindfulness-based intervention (MBI) in classrooms in improving emotional well-being and regulation among adolescents with elevated inattentiveness and/or hyperactivity-impulsivity. The study comprised 342 students, divided into an MBI group, a relaxation control group, and an inactive control group. Positive affect (PA) and negative affect (NA) and emotion regulation strategies (rumination, acceptance, catastrophizing, positive reappraisal, and self-kindness) were measured at pre- (T0), postintervention (T9), and 26-week follow-up (T26). The intervention effects were analyzed among all participants and by gender and symptom type. Compared to the controls, there was a beneficial effect for the MBI group in relation to acceptance at T9; acceptance remained at the baseline level in the MBI group but decreased in the inactive control group. Conversely, in the inactive control group, rumination decreased at T9, and positive reappraisal increased at T26 compared to the MBI group. The MBI had no other detectable effects. The results on emotion regulation strategies varied by gender. These findings do not provide convincing evidence that universal MBIs improve emotional well-being among students with elevated inattentiveness and/or hyperactivity-impulsivity. More research is needed to determine whether the programs are beneficial for all adolescents, regardless of mental health status.

Gestational diabetes mellitus (GDM) affects ~14% of pregnancies and increases maternal type 2 diabetes mellitus (T2DM) risk. The GenDiP Consortium presents trans-generational, multi-ancestry genome-wide association study meta-analyses of GDM and pregnancy glycemic traits in up to 38,305 GDM cases and 776,145 controls. We identify 37 GDM-associated loci (7 novel) and five novel loci for pregnancy glycemic traits, all operating through the maternal genome. We classify 12 GDM variants with stronger effects in GDM than T2DM into five biologically informed categories, revealing pleiotropy patterns, pregnancy-dependent effect modification, and diagnostic heterogeneity. While all these loci overlap with T2DM and/or non-pregnant glycaemic traits, four (G6PC2, CAST-PCSK1, HKDC1, FOXA2) lack genome-wide-significant T2DM associations; GCK shows distinct causal variants for GDM, and MTNR1B exhibits pregnancy-amplified effects. Our findings provide new genetic insights into GDM and highlight the need for larger, ancestrally diverse studies of GDM and glycaemic traits during pregnancy to understand potential pregnancy-specific effects.

Background Perinatal depression is common: on average, more than 13% of women suffer from physician-diagnosed disorder and 20% report symptoms bearing clinical relevance. Maternal depression not only significantly impacts women’s quality of life but also increases the offspring’s risk of negative developmental outcomes, including mental disorders, through a combination of maternal alterations in in-utero biology and postnatal rearing factors during the early period of life. The HappyMums project aims to improve our understanding of perinatal depression by identifying the factors that robustly predict risk and resilience in mothers and their offspring, determining underlying neurobiological mechanisms, and, finally, testing the efficacy of potential interventions. Methods HappyMums will use data from a large collection of cohorts and registries containing biological, clinical, socio-demographic, environmental, and lifestyle data. It will pool unique human samples of maternal blood, placenta, chorionic villi and amniotic fluid, analyzing these data alongside pre-clinical samples of brain, blood and placental tissue from models of prenatal stress in mice and livebearing fish for correlative analyses. HappyMums will develop a mobile application (App) to collect multiple data types from women for early screening and monitoring of depressive symptoms. Conclusion The findings generated by HappyMums will be clinically relevant as they will increase the knowledge on perinatal depression, with unprecedented benefits for the offspring and the society as a whole.

BACKGROUND:Autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and schizophrenia (SCZ) are highly heritable and linked to disruptions in fetal neurodevelopment. Epigenetic processes, such as DNA methylation (DNAm), are considered a key pathway of interest. However, it is unclear whether 1) genetic susceptibility to neurodevelopmental conditions (NDCs) is associated with DNAm patterns already at birth, 2) DNAm patterns are unique or shared across conditions, and 3) neonatal DNAm patterns can be leveraged to enhance genetic prediction of neurodevelopmental outcomes. METHODS:We conducted epigenome-wide meta-analyses of genetic susceptibility to ASD, ADHD, and SCZ (measured with polygenic scores [PGSs]) and cord blood DNAm in 4 European population-based cohorts (npooled = 5802; 50.2% female). We estimated DNAm pattern overlap between PGSs using heterogeneity statistics. Furthermore, we built methylation profile scores for each PGS to test incremental variance explained over genetic data alone in 130 developmental outcomes from birth to 14 years. RESULTS:In probe-level analyses, the SCZ PGS was associated with neonatal DNAm at 246 loci (p < 9 × 10-8), predominantly in the major histocompatibility complex, supporting an early-origins perspective on SCZ. Functional characterization confirmed strong genetic effects, blood-brain concordance, and enrichment for immune-related pathways. Eight loci were identified for the ASD PGS (mapping to FDFT1 and MFHAS1) and none for the ADHD PGS. Differentially methylated regions were detected across PGSs (130-166 regions). Overall, DNAm signals were largely distinct between conditions. Incorporating neonatal DNAm data in genetic prediction models nominally increased the explained variance for several cognitive and motor outcomes. CONCLUSIONS:Genetic susceptibility to NDCs, particularly SCZ, is detectable in cord blood DNAm in the general population.

Personality traits describe stable differences in how individuals think, feel, and behave and how they interact with and experience their social and physical environments. We assemble data from 46 cohorts including 611K-1.14M participants with European-like and African-like genomes for genome-wide association studies (GWAS) of the Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism, and openness to experience), and data from 51K participants for within-family GWAS. We identify 1,257 lead genetic variants associated with personality, including 823 novel variants. Common genetic variants explain 4.8%-9.3% of the variance in each trait, and 10.5%-16.2% accounting for measurement unreliability. Genetic effects on personality are highly consistent across geography, reporter (self vs. close other), age group, and measurement instrument, and we find minimal spousal assortment for personality in recent history. In stark contrast to many other social and behavioral traits, within-family GWAS and polygenic index analyses indicate little to no shared environmental confounding in genetic associations with personality. Polygenic prediction, genetic correlation, and Mendelian randomization analyses indicate that personality genetics have widespread, potentially causal associations with a wide range of consequential behaviors and life outcomes. The genetic architecture of personality is robust and fundamental to being a human.

Background: Major depressive episodes (MDEs) are phenomenologically heterogeneous. The Multidimensional Assessment of Thymic States (MAThyS) scale was developed to estimate activation/inhibition, emotional reactivity, and to differentiate types of depression in bipolar disorder (BD). Their role in diagnosis or other depressions remains unclear. Methods: We assessed validity of Finnish translation of the MAThyS in 94 patients with Major Depressive Disorder (MDD), MDE/BD, or MDE/BPD (MDE comorbid with Borderline Personality Disorder), and 29 healthy controls. We examined the associations of MAThyS total score with depression severity (MADRS), (hypo)manic symptoms (YMRS, MIXMDE), and BPD severity (BPDSI), assessed internal consistency, and conducted confirmatory factor analysis to test the postulated two-factor structure. Results: MAThyS demonstrated good internal consistency in patient subcohorts (Cronbach’s α = 0.78–0.88), but not in controls (α = 0.19). In hierarchical regression model (adjusted R² = 0.34), MAThyS total score was negatively associated with depression severity (MADRS) (β = –0.316, p = 0.003), but positively with mixed symptoms (MIXMDE; β = 0.319, p = 0.017), borderline severity (BPDSI; β = 0.195, p = 0.13) and momentary (hypo)manic symptoms (YMRS; β = 0.171, p = 0.15). The two-factor model had poor fit (CFI = 0.687; RMSEA = 0.125). Conclusions: The Finnish MAThyS translation retains good internal consistency, for total scores assessed in MDE patient subgroups, but validity of the scale in assessing activation and emotional reactivity specifically remains unclear. MAThyS may aid in detecting signs of increased activation and mixed features. Further studies are needed to evaluate its validity and clinical utility.

Chronic and increased levels of stress during adolescence are associated with academic performance, school dropout, and mental health challenges. This study investigated the effectiveness of the universal mindfulness-based intervention (MBI) on adolescents' stress symptoms in schools through a cluster randomised controlled trial (cRCT) design. In addition, we examined the effectiveness of MBI on self-kindness. Finally, we explored how age, gender, and an independent mindfulness practice moderated the effects on outcomes. A total of 3519 Finnish students aged 12-15 were randomised to a MBI group (n = 1646), an active relaxation control group (n = 1488), and an inactive control group that followed a routine school curriculum (n = 385). Outcomes were measured at baseline (T0), 9 weeks post-intervention (T9), and 26 weeks following the intervention (T26). Overall, those belonging to the MBI group reported a greater reduction in stress symptoms compared with the active control group at T9 and T26. Furthermore, students in the MBI group who carried out their mindfulness home practice regularly showed a greater decrease in stress symptoms compared with those who practiced less regularly. There were no MBI effects on self-kindness. These results indicate that a universal MBI in schools may potentially support stress management among students.

To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.

Sleep duration has been linked with obesity in population-based studies. Less is known about bedtimes and, especially, if discrepancy between bedtimes on school and non-school days associate with adiposity in children. The associations of self-reported bedtimes with the body mass index z-score (BMIz) and waist-to-height ratio (WtHr) were examined among children with a mean (SD) age of 11.2 (0.85) years in cross-sectional (n = 10,245) and longitudinal (n = 5085) study settings. The causal relationship of whether BMIz contributes to bedtimes, was further examined in a subset of 1064 participants by exploiting Mendelian randomisation (MR). After adjusting for sleep duration and other confounders, every 0.5 h later bedtime on non-school nights and a delay in bedtime in non-school nights compared with school nights associated with 0.048 (95% CI 0.027; 0.069) and 0.08 (95% CI 0.056; 0.105) higher BMIz as well as 0.001 (95% CI 0; 0.002) and 0.004 (95% CI 0.003; 0.005) with higher WtHr, respectively. Moreover, every 0.5-h delay in bedtime in non-school nights compared with school nights associated with 0.001 (95% CI 0; 0.002) greater increase in WtHr in the 2.5 years follow-up. Thus, a 2-h delay in bedtime at the age of 11 years corresponds with a 0.6 cm increase in waist circumference. The MR analysis did not indicate an opposite causal relationship: higher BMIz was not causing delayed bedtimes. Later bedtime on non-school days and discrepancy in bedtimes associated with increased BMIz and WtHr, while longitudinally these predicted higher WtHr, independently of sleep duration. Promoting early bedtimes, especially on weekends, should be considered in obesity prevention among school-aged children.

Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P < 0.05) and 1107 regions. Forty CpGs were located within known quantitative trait loci for gene expression traits in blood, and trait enrichment analysis suggested a strong association with immune-related, transcriptional control, and blood pressure regulation phenotypes. Decreasing fertility rates worldwide with the concomitant increased proportion of first-born children highlights a potential reflection of birth order-related epigenomic states on changing disease incidence trends.

OBJECTIVE:To investigate longitudinal associations between variations in the co-expression-based brain insulin receptor polygenic risk score and frailty, as well as change in frailty across follow-up. METHODS:This longitudinal study included 1605 participants from the Helsinki Birth Cohort Study. Biologically informed expression-based polygenic risk scores for the insulin receptor gene network, which measure genetic variation in the function of the insulin receptor, were calculated for the hippocampal (hePRS-IR) and the mesocorticolimbic (mePRS-IR) regions. Frailty was assessed in at baseline in 2001-2004, 2011-2013 and 2017-2018 by applying a deficit accumulation-based frailty index. Analyses were carried out by applying linear mixed models and logistical regression models adjusted for adult socioeconomic status, birthweight, smoking and their interactions with age. RESULTS:The FI levels of women were 1.19%-points (95% CI 0.12-2.26, P = 0.029) higher than in men. Both categorical and continuous hePRS-IR in women were associated with higher FI levels than in men at baseline (P < 0.05). In women with high hePRS-IR, the rate of change was steeper with increasing age compared to those with low or moderate hePRS-IR (P < 0.05). No associations were detected between mePRS-IR and frailty at baseline, nor between mePRS-IR and the increase in mean FI levels per year in either sex (P > 0.43). CONCLUSIONS:Higher variation in the function of the insulin receptor gene network in the hippocampus is associated with increasing frailty in women. This could potentially offer novel targets for future drug development aimed at frailty and ageing.

AbstractBackgroundMaternal psychological distress during pregnancy is associated with infant temperament. Whether associations persist into late childhood, whether maternal distress is associated with temperament change from infancy to late childhood, whether associations are independent of maternal concurrent distress, and whether maternal distress has sensitive exposure periods on child temperament remain unclear.MethodsOur study includes mother‐child dyads from Finnish, prospective Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study. The mothers completed the Center for Epidemiologic Studies Depression Scale, State Anxiety Inventory and Perceived Stress Scale: biweekly up to 14 times during pregnancy; once in infancy (at child age 4–12 months); and once in late childhood (at child age 7–11 years). They also completed the Infant Behavior Questionnaire Revised at the infancy (n = 2538) and Temperament in Middle Childhood Questionnaire at the late childhood (n = 2004; 1693 children had data at both follow‐ups) follow‐up on child negative affectivity, extraversion and effortful control. We examined the associations of maternal distress with child temperament with linear regression, linear mixed and Bayesian relevant lifecourse exposure models.ResultsMaternal distress during pregnancy was associated with higher negative affectivity and lower effortful control in children in infancy and late childhood. Maternal distress during pregnancy was also associated with increases in negative affectivity, decreases in effortful Control, and smaller decreases in extraversion from infancy to late childhood. The associations with late childhood temperament and temperament change were independent of maternal concurrent distress. Late childhood was a sensitive period for lifetime‐to‐date effects of maternal distress on late childhood negative affectivity and effortful control. Distress during pregnancy and infancy had smaller contributions.ConclusionsMaternal psychological distress during pregnancy is associated with individual differences and change in child temperament from infancy to late childhood. However, distress during pregnancy has a smaller effect on late childhood temperament than maternal concurrent distress.

Childhood adversity is a potent determinant of mental health, especially when exposure occurs during sensitive periods. Importantly, recent studies suggest DNA methylation (DNAm) may capture these time-dependent effects of adversity. Here, we present results from the first meta-analysis of time-varying exposures to childhood adversity and DNAm.