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Depersonalisation (DP) and derealisation (DR) are dissociative experiences that disrupt an individual's perception of themself and their environment. Recent evidence suggests a potential role for inflammatory processes. This study examined longitudinal associations between interleukin-6 (IL-6), C-reactive protein (CRP), and DP and DR across development. Data were drawn from the Avon Longitudinal Study of Parents and Children. IL-6 was measured at age 9 (n = 2606) and CRP at ages 9, 15, and 24 (n = 3323). DP and DR symptoms were assessed at ages 12, 17, and 24. Generalised linear mixed models examined associations between inflammatory markers and DP and DR using both early-life and time-varying approaches. IL-6 at age 9 was not associated with DP or DR at any age. Higher CRP at age 9 was associated with increased odds of DR at age 12 but reduced odds of DR at ages 17 and 24. Higher CRP at age 9 was also associated with reduced odds of DP at age 24. Time-varying analyses differed: higher CRP at 24 was associated with reduced odds of DR at 24, but CRP measured in mid-adolescence was not associated with DR at 17, highlighting differences between fixed childhood and time-varying inflammatory models. Inflammatory processes may relate differently to DP and DR across development. Childhood CRP showed associations with later DP and DR, whereas contemporaneous CRP was associated only with DR, suggesting differing developmental patterns. These findings may reflect immune adaptation or cognitive mechanisms involved in the maintenance of symptoms.
Irritability is highly heterogeneous and a common challenge in youth clinical services. Albeit transdiagnostic, the diagnostic manuals conceptualize severe irritability differently: the ICD-11 primarily recognizes it as behavioral (oppositional defiant disorder specifier), and the DSM-5-TR, as depressive (core to disruptive mood dysregulation disorder). Irritability is also highly prevalent in, and genetically linked to, neurodevelopmental conditions. It is unclear whether irritability represents a unitary construct or multiple different types. We examined whether distinct behavioral, neurodevelopmental, and depressive irritability types, differentiated by their developmental course, sex-preponderance, clinical, genetic, and environmental covariates, could be observed. Using data from the Avon Longitudinal Study of Parents and Children (female participants: 5,085; male participants: 5,028), we explored sex-stratified irritability latent profiles across 5 time points (∼ages 7-25 years) for irritability measured with the Development and Well-Being Assessment. We investigated associations with various clinical, genetic, and environmental covariates typifying behavioral, neurodevelopmental, and depressive conditions. We identified 5 irritability profiles similar across sexes (low, child-limited, child/adolescent-limited moderate, child/adolescent-limited high, high-stable) and 2 sex-specific profiles: adolescent-onset (female participants) and fluctuating (male participants). Although most profiles were not distinguished by condition-specific covariates, 2 profiles showed some specificity with neurodevelopmental or depressive conditions: (1) the male high-stable profile was associated with attention-deficit/hyperactivity disorder diagnosis and genetic liability, and autism-like traits, and (2) the female adolescent-onset profile was associated with depression diagnosis and genetic liability, and adolescent/adult stressful life events. Irritability appears to be developmentally heterogeneous. Albeit often transdiagnostic, for some individuals irritability may align with neurodevelopmental or depressive conditions. This could have potential implications for classification and treatment. Exploring Possible Behavioural, Neurodevelopmental and Depressive Types of Irritability, Using a Developmental Approach; https://osf.io/av2s8/. Irritability is highly impairing and linked to different mental health conditions. Using data from the Avon Longitudinal Study of Parents and Children (n = 10,113), the authors characterized irritability in female and male youths. Five irritability profiles common to female and male youths were identified, as well as adolescent-onset irritability in female youths and fluctuating irritability in male youths. Irritability persisting from childhood to adulthood in male individuals was linked to attention-deficit/hyperactivity disorder and autism, whereas adolescent-onset irritability in female individuals was linked with depression.
Individuals with developmental language disorder (DLD) are disproportionately represented in the criminal justice system. The prospective associations between DLD and offending, and the educational and criminal justice pathways through which DLD might increase the risk of offending and reoffending, remain unclear. We analysed existing data from the Avon Longitudinal Study of Parents and Children (maximum N = 6,800; 51% female; 9% with DLD) with linked school data (national pupil database) and crime records (Avon and Somerset police records for offences committed between ages 13 and 29 years in the region). DLD was determined when the individuals were aged 7-9 years using direct assessments and parent reports. Regression and mediation models were fitted to the data. Individuals with DLD were more likely (odds ratio 1.74, 95% confidence intervals 1.25, 2.44) to have a recorded offence (i.e. charged or cautioned by the police) compared to those without DLD. School suspension was a significant mediator of the relationship between DLD and recorded offending. However, SEN identification was not associated with recorded offending for those with DLD. There was also no difference in the odds of being given an out of court disposal or reoffending for individuals with DLD compared to those without DLD. Individuals who have DLD are more likely to be cautioned or convicted for an offence by the police than those without DLD, and this may in part be because they are more likely than those without DLD to be suspended from school.
Externalising behaviours are among the most common childhood mental health problems and have been linked to numerous adverse psychosocial outcomes including antisocial behaviour and depression. Parental negativity (PNeg) and child behaviours have been shown to mutually influence each other, leading to coercive cycles of negative behaviour over time. Interrupting these negative cycles is a common target for clinical intervention but little is known about what factors moderate these cycles over time in the general population. Using data on 9943 families from The Avon Longitudinal Study of Parents and Children across ages 4, 7 and 8, we explored the reciprocal associations between PNeg and externalising behaviour and tested whether they differed as a function of high versus low parent-reported interpersonal social support and neighbourhood social cohesion. Using random-intercept cross-lagged panel models, we found bidirectional associations between PNeg and child externalising behaviour across ages 7 to 8 (βs = 0.13-0.15) but not ages 4 to 7 (βs = 0.01-0.03). Moreover, we did not find evidence of moderation of any of the cross-lagged paths by social support or neighbourhood cohesion. Parent-reported interpersonal social support and neighbourhood social cohesion do not appear to play a role in interrupting negative parent-child interaction cycles in the general population.
Mendelian randomization (MR) is increasingly used to strengthen causal inference in nutritional epidemiology. However, dietary MR studies often rely on instruments selected from genome-wide association studies of self-reported intake based solely on statistical significance, increasing vulnerability to pleiotropy and reverse causation and potentially violating key MR assumptions. We aimed to develop and evaluate a biologically informed framework for selecting valid genetic instruments for dietary exposures, leveraging genes encoding taste and olfactory receptors that influence chemosensory perception and shape food preferences and dietary behaviour. We prioritised 1,214 nonsynonymous variants (minor allele frequency ≥ 1%) across 30 taste and 295 olfactory receptor genes. Associations with 140 food-liking traits were tested in UK Biobank participants aged 37 to 73 years. Candidate variants were evaluated using a multi-stage filtering pipeline comprising replication in an independent younger cohort (Avon Longitudinal Study of Parents and Children, age 25), concordance between food liking and intake, exclusion of associations with socioeconomic status, assessment of food specificity accounting for linkage disequilibrium and co-consumption, and directionality testing to reduce reverse causation. Retained variants were used as instruments in MR analyses of cardiometabolic outcomes. We identified 268 variants within 101 olfactory and 16 taste receptor genes associated with 96 food-liking traits. Filtering yielded 24 candidate instruments for 20 foods. The instrument for onion liking satisfied all pre-defined criteria for classification as high confidence. As an illustrative MR application, genetically proxied onion liking was associated with lower systolic and diastolic blood pressure and reduced risk of type 2 diabetes, with no evidence of effects on body mass index, glycaemic traits, or serum lipid levels. Instrument selection guided by chemosensory genetics provides a scalable strategy for dietary MR that can improve instrument credibility and reduce susceptibility to pleiotropy and reverse causation. However, this approach prioritises biological specificity at the cost of fewer available instruments. This framework supports more robust causal evaluation of diet-disease relationships and strengthens inference in nutritional epidemiology and public health research.
Depression is a major global health challenge, with onset commonly occurring in youth. There is an urgent need to better understand the epidemiology of depression to facilitate better interventions and preventions that are person-specific and time-specific. Long-term depression trajectories and ecological momentary assessment (EMA) can help address this need. Embedding EMA designs within established longitudinal cohorts offers a uniquely powerful approach to examine depression in both long- and short-term settings and to identify distal and proximal modifiable risk factors for depression. Our study will include ~450 participants from the Twins Early Development Study and ~250 participants from the Avon Longitudinal Study of Parents and Children (ALSPAC) who have depression trajectories data previously collected between late childhood and early adulthood. Participants will be recruited from four different depression trajectories in each cohort based on participants' prior symptoms. They will undertake EMA surveys of depression, sleep, physical activity, substance use, diet, recent activities and social interactions three times a day for 6 weeks, with more detailed questionnaires at baseline, 2, 4 and 6 weeks. We will use descriptive analysis, mixed effects models and dynamic structural equation modelling to examine how depression occurs over this time, how potentially modifiable factors affect depression and vice versa and how these effects vary by different life-course trajectories. This study is designed to identify people at heightened risk of depression and/or identify modifiable targets that could inform more effective prevention and intervention strategies. Favourable ethical opinions were given by the Edinburgh Medical School Research Ethics Committee (REC References: 25-EMREC-001 and 25-EMREC-030) and the ALSPAC Law and Ethics Committee (Ref: 0027 B4792). The results will be disseminated through journal publications, conferences and seminar presentations and to relevant stakeholders, such as those with a history of depression, policy makers and clinicians.
Chronic inflammation may be a key mechanism driving social to biological transitions across the lifecourse. We investigated the effect of early-life socioeconomic position (SEP) on inflammatory biomarkers in childhood and adolescence and assessed mediation by body mass index (BMI). We conducted cohort-specific analysis in five birth cohorts: the Barwon Infant Study (BIS, Australia, n = 708, 4-5 years); Born in Bradford (BiB, United Kingdom, n = 4576, 7-11 years); the Longitudinal Study of Australian Children's Child Health CheckPoint (LSAC-CP, Australia, n = 1874, 11-12 years); the Northern Finland Birth Cohort 1986 (NFBC1986, Finland, n = 9467, 15-16 years); and the Avon Longitudinal Study of Parents and Children (ALSPAC, United Kingdom, n = 4875, 17-18 years). Exposures were neighbourhood disadvantage, household economic conditions, and maternal education, in pregnancy or infancy. Outcomes were log-transformed high sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls (GlycA) levels. We conducted confounder-adjusted linear regression to estimate the effect of exposures on outcomes, and mediation analysis using interventional effects to assess mediation by BMI. Lower early-life SEP, particularly neighbourhood disadvantage and lower maternal education, was associated with higher inflammation from the age of 7-11 years. Effects were most apparent for GlycA (e.g., mean GlycA difference between BiB children in most and least disadvantaged neighbourhoods: 0.1 SD [95% CI 0.03-0.2]; between NFBC1986 adolescents with most and least educated mothers: 0.2 SD [0.02, 0.3]). BMI partially mediated many of these effects (20-100%). Neighbourhood disadvantage and lower maternal education may increase inflammation in children and adolescents, in part through higher adiposity. This underscores the importance of addressing socioeconomic conditions in early life and of preventing excess BMI.
OBJECTIVES : Lead and mercury are recognised as critical determinants of population health, especially for children and pregnant women. Few UK cohorts have measured lead or mercury in pregnant women since 1990. The aims of this study are to: (1) quantify lead and mercury exposures in a sample of pregnant women in the UK; (2) document concentrations over time in pregnant women in the UK; and (3) compare concentrations with international data. Whole blood samples were obtained from pregnant women in a quantitative arm of the Pregnancy, the Environment And nutRition Study in a cross-sectional observational study design. The samples were analysed by inductively coupled plasma mass spectrometry (Health and Safety Executive, Buxton, UK). SETTING : Community-based with recruitment through a hospital antenatal clinic in south-west England. PARTICIPANTS : Women ≥18 years old and ≥11 weeks pregnant by last menstrual period. Whole blood lead and speciated mercury concentrations. RESULTS : The whole blood lead concentration was: mean 5.8 (SD 6.2), median 4.6 (IQR 3.5, 5.9), range 1.7-78.1 µg/L (n=262; gestational age range by scan 8.3-15.9 weeks). These values are about 84% lower than in pregnant women in the UK Avon Longitudinal Study of Parents and Children (ALSPAC; 1991-1992), about 47% lower than in the UK Born in Bradford (BiB) study (2007-2011) and about 34% lower than in White women in the UK Mother's and Baby's Exposure to Lead study (MaBEL; 2011). Blood total mercury concentration was: mean 0.83 (SD 0.64), median 0.69 (IQR 0.34, 1.19), range 0.07-3.40 (about 60% lower than in pregnant women in ALSPAC and about 37% lower than in BiB). These results are similar to contemporary concentrations found in Europe and the USA. Blood concentrations of lead and mercury in pregnant women in the UK have declined considerably since the early 1990s. However, no safe levels have previously been identified for adverse effects on cognition, preterm birth rate or coronary heart disease prevalence. These data will contribute to the ongoing development of public health advice. ISTCTN92638336.
Little is known about the provision of diagnoses to young people with mental health disorders. We investigated diagnosis provision by NHS mental health services, focusing on 17-year-olds in South London between 2009-2024, and compared with estimated disorder prevalence. To examine diagnosis provision in the population, we extracted diagnosis data from records of the NHS mental healthcare provider serving South London, using the Maudsley Biomedical Research Centre Clinical Record Interactive Search application; we then compared these data with the corresponding population size, obtained from the Office for National Statistics. To assess diagnosis provision in those with mental health disorders, we compared diagnosis data with the number of young people estimated to have met criteria for a disorder, derived from epidemiological interview data collected in the Environmental Risk (E-Risk) Longitudinal Twin Study and weighted according to characteristics of 17-year-old South Londoners. To assess diagnosis provision in those with mental health disorders within health services, we compared diagnosis data with the number estimated to have met criteria for a disorder and used any health service for their mental health, again derived from weighted E-Risk Study data. Of 17-year-olds from South London in 2009-2024, 4.0% (n=8,958/223,404) had a diagnosis in mental health records during the previous year. This diagnosis provision covered <1 in 16 of those estimated to have had a mental health disorder, and <1 in 4 of those estimated to have also used health services. Diagnosis provision was lower in girls than boys and in young people with Black/Asian/Mixed/Other ethnicity than those with White ethnicity, in those estimated to have had a mental health disorder and used health services. These findings demonstrate gaps and biases in mental health diagnosis provision for young people, including within health services, and reveal the imperative need to strengthen young people's mental healthcare. National Institute for Health Research, Medical Research Council, National Institute of Child Health and Development, Jacobs Foundation, National Society for Prevention of Cruelty to Children, Economic and Social Research Council, Prudence Trust, Wellcome Trust. Evidence before this study: Epidemiological research has found that less than half of young people with a mental health disorder report seeing a health professional for their symptoms and only a quarter to a third have seen a mental health specialist, and these findings are fairly consistent across high-income countries where this research has been conducted. For young people who see health professionals, there are likely to be barriers to the recognition and treatment of mental health disorders. We focused on the recognition of mental health disorders in young people, which is operationalised in clinical practice as provision of diagnoses. To identify studies examining mental health diagnosis provision in young people accessing health services, we searched MEDLINE with the terms "diagnos*" AND ("mental" OR "psychiatr*" OR [various terms for individual disorders]) AND ("young" OR "youth*" OR "child*" OR "adolescen*" OR "paedatric*" OR "pedatric*" OR "juvenile") AND ("clinical" OR "healthcare" OR "health care" OR "service*"). This search was supplemented by reviewing reference lists and forward citations of relevant articles. We identified several studies that found diagnosis provision varied by sociodemographic characteristics and has increased over the past two decades in young people across multiple countries for several disorders, including depression, anxiety disorders, eating disorders, autism, and attention-deficit/hyperactivity disorder (ADHD). Only a small number of studies investigated diagnosis provision within young people who met criteria for a disorder. In the Avon Longitudinal Study of Parents and Children in the UK, of 18-year-olds who met criteria for depression, only 7.0% had a diagnosis of depression documented in their primary care records. In the Child and Adolescent Twin Study in Sweden, of 9-year-olds who met criteria for ADHD, only 18.5% of boys and 12.1% of girls had a diagnosis of ADHD noted in their health records. Within an Irish child and adolescent mental health service, of 12-15-year-olds who met criteria for depressive disorder, only 28.4% received a depressive disorder diagnosis after their usual clinical assessment. These studies suggest large gaps in diagnosis provision, including within health services, and highlight possible bias by sociodemographic characteristics. A better understanding of this topic is needed to enable more effective service planning, commissioning, and policymaking.Added value of this study: This study investigated mental health diagnosis provision in 17-year-olds from South London. We examined diagnosis provision for several mental health disorders in NHS mental healthcare records. We compared these data with population and epidemiological data to calculate diagnosis provision rates in the general population, in those estimated to have met criteria for a disorder, and in those estimated to have also seen a health professional. We found that diagnosis provision substantially increased during our study period of 2009-2024, demonstrating an increase in the number of young people whose mental health needs were recognised in specialist services. However, we estimated that diagnoses were only provided to a small proportion of young people with a mental health disorder, including those within health services. Estimated diagnosis gaps were largest for those with generalised anxiety disorder and multiple disorders. We also found evidence of biases in diagnosis provision, based on gender, neighbourhood deprivation, and ethnicity.Implications of all the available evidence: Barriers to mental healthcare access for young people should be reduced by policymakers and commissioners, including through investment in adequately staffed services with skilled clinicians, enabling more young people with mental health disorders to receive cost-effective evidence-based healthcare that has long-term benefits. Greater awareness among clinicians of the under-diagnosis and bias in diagnosis of young people's mental health disorders, alongside strategies to address these problems, could improve young people's mental healthcare. Innovative scalable interventions that can reach many more young people need to be developed, evaluated, and implemented by researchers. Prevention strategies are also required, including addressing risk factors for young people's mental health disorders, and intervening early for those with symptoms before disorders develop, to reduce the future burden of mental health disorders in young people.
Digital devices have become a major aspect of children's lives. Associations between screen time and mental health have been observed, but the causality remains unclear. This study aimed to investigate the associations between screen time and later depressive symptoms, and to test the robustness of these associations when accounting for genetic confounding. This study used data from the Avon Longitudinal Study of Parents and Children-a prospective cohort of children born between 1991 and 1992 in the UK. Different forms of screen time and depressive symptoms at ages 16, 22, and 26 years were assessed through self-completion questionnaires. The average daily screen time was calculated. Depressive symptoms were measured by using the Short Mood and Feelings Questionnaire (SMFQ). Polygenic scores (PGSs) for depression were calculated. Linear regression models were used to examine the associations between standardized screen time at ages 16, 22, and 26 years, and standardized depressive symptoms at age 26 years, adjusting for sociodemographic confounders and PGSs. Genetic sensitivity analysis (Gsens) was used to test for genetic confounding in these associations. A total of 3003 participants were included in the analysis. Some, but not all, forms of screen time were associated with higher SMFQ scores, e.g. time spent using a phone, tablet, or e-book at age 22 years [β: 0.10, 95% confidence interval (CI) 0.07, 0.14 for weekdays; β: 0.08, 95% CI 0.04, 0.11 for weekends] and television time at age 26 years (β: 0.10, 95% CI 0.06, 0.14 for weekdays; β: 0.09, 95% CI 0.06, 0.13 for weekends). These associations persisted after adjustment for sociodemographic confounders and PGSs, but were attenuated in the Gsens (β = 0.03, 95% CI -0.01, 0.07 for the association with time spent using a phone, tablet, or e-book at age 22 years on weekends; β = 0.06, 95% CI 0.01, 0.10 for television time at age 26 years on weekends). For some measures of screen time, there were no associations with depressive symptoms. Where associations were seen, they were attenuated in the Gsens, implying that genetic confounding is present in the relationship between screen time and depressive symptoms in adolescents and young adults.
Attention-deficit/hyperactivity disorder (ADHD) may lead to depression, but little is known about its underlying mechanisms. We examined whether clinical factors (irritability, anxiety), cognitive-affective processes (emotion recognition, response inhibition, working memory, sustained attention), and negative thought patterns (external locus of control, negative cognitive style) mediated ADHD-depression associations across development and whether these pathways differ by sex. Analyses were performed in the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Twins Early Development Study (TEDS). In both samples, ADHD was assessed using the Strengths and Difficulties Questionnaire (SDQ) hyperactivity/inattention subscale at ages 7, 12/13, and 16/17 years. Depressive symptoms were assessed using the short Mood and Feelings Questionnaire at ages 12, 18/21, and 26/27. Mediators were assessed at ages 8-11, 16-17, and 21-25 years with counterfactual mediation models. Clinical factors were assessed and mediated the ADHD-depression effect in both cohorts across development. In ALSPAC, clinical mediators contributed most in childhood (30%) and young adulthood (25%), whereas in TEDS, they contributed most in adolescence (46%). In ALSPAC, negative thought patterns mostly contributed in adolescence (39%), whereas cognitive-affective factors did not show consistent evidence of mediating effects across development. All mediators combined explained 30%, 48%, and 29% of the total effect of ADHD on depression in childhood, adolescence, and young adulthood, respectively. In sex-stratified models, the relative contribution of mediators varied by sex and developmental stage. In childhood, mediators accounted for a greater proportion of the total effect in male (37%) than in female (25%) individuals, whereas a similar proportion of mediated effects was observed across sexes during adolescence (48% in female and 45% in male individuals). In young adulthood, the indirect effect via all mediators was evident only in female individuals (36%). Mechanisms linking ADHD and depression are developmental stage and sex specific. Irritability and anxiety in childhood and young adulthood (particularly for female individuals), and external locus of control and negative cognitive style in adolescence, might represent promising intervention targets for preventing depression in youth with ADHD. Study Preregistration: Clinical and Cognitive Mediators Underlying Subsequent Depression in Individuals With Attention-Deficit/Hyperactivity Disorder: A Developmental Approach; https://www.jaacap.org/article/S0890-8567(25)00171-6/fulltext.
Mental health difficulties in childhood are increasing. Prevention is the only sustainable and ethical public health approach. However, predicting which children are most at-risk of mental health difficulties prior to symptoms emerging remains elusive. We developed and internally validated a perinatal multivariable model, predicting 7-year-olds mental health, using the Avon Longitudinal Study of Parents and Children (N = 6021, 51.2% male, 98.6% White). Perinatal predictors were reported by the mother prospectively in pregnancy and the Strengths and Difficulties Questionnaire (SDQ) was completed by the mother at 7-years-old. This was dichotomised at recommended clinical cut-off (total>16) Building on our previous model in a French cohort, 15 perinatal parameters spanning maternal pre-pregnancy health, biological and psychosocial pregnancy-specific-experiences, maternal health behaviours in pregnancy and sociodemographic factors were entered into a logistic regression using the least absolute selection and shrinkage operator. Optimism-adjusted estimates were achieved using bootstrapping. Model performance was stratified by sex, sociodemographic risk and admission to a special-care baby unit. Combining eight variables predicted poor mental health, with a C-statistic of 0.66; 95% Confidence-Interval (0.64-0.68). It accurately predicted 85.6% of the participants mental health at 7-years in the perinatal period. Model performance was similar across groups of interest. Applying this model leads to a higher benefit than serving 'all' or 'no' children, that is, using the model, 30.9% of children who later had poor mental health would have been identified in the perinatal period. It is possible to predict childhood mental health at birth with moderate accuracy. Similar patterns of model performance were observed in this English cohort compared to a previous French cohort. At population-level, the model is most useful for ruling-out babies who are not predicted to be high-risk. In addition to improving its positive predictive value and external validation, future research should examine the model's performance at service-delivery level before implementation.
Prenatal alcohol exposure (PAE) is associated with lasting cognitive and neurodevelopmental deficits and can quadruple risk for depression later in life. However, it remains unknown whether there are specific trimesters when PAE is more strongly associated with longitudinal trajectories of internalizing symptoms - an indicator of depression risk - across childhood and adolescence. To investigate how PAE timing and dosage are associated with internalizing symptom trajectories from ages 4 to 16.5 years. We analyzed prospective data from the Avon Longitudinal Study of Parents and Children (ALSPAC), an ongoing longitudinal birth cohort from the United Kingdom. Internalizing symptom trajectories were estimated for 6,409 participants. Primary analyses were conducted on 2,254 participants with complete data on PAE in all three trimesters, covariates, and trajectories. We used growth mixture modelling to identify latent trajectories of depressive symptoms measured using the internalizing symptom scale from the Strengths and Difficulties Questionnaire (SDQ) at seven occasions between ages 4 to 16.5 years. Prospective alcohol consumption during each trimester were categorized into three PAE dosages: unexposed (0 drinks/week), low (1-7 drinks/week) and high (7+ drinks/week). We identified five distinct depressive symptom trajectories: stable low (75.9% of participants), moderate childhood peak (11.2%), progressive increase (5.57%), high early childhood (4.73%), and early adolescent peak (2.61%). PAE in the second (relative risk [RR]=2.08, 95% CI=1.15-3.76) and third trimesters (RR=1.83, 95% CI=1.05-3.21), as well as total PAE burden across pregnancy (RR=1.33, 95% CI=1.06-1.68) increased risk for the progressive increase trajectory, versus the stable low trajectory. High PAE in the second (RR=2.71, 95% CI=1.41-5.21) and third (RR=2.27, 95% CI=1.27-4.05) trimesters drove elevated risk for this trajectory. PAE in the first trimester or at low dosages showed no associations with depressive symptom trajectories. Negative control analyses of paternal drinking also found no associations. Our results highlight the second and third trimesters as potential sensitive periods for the impact of PAE on rising depressive symptoms from childhood to adolescence. Ultimately, these findings could inform the design of prevention programs, and facilitate targeted interventions to youth at elevated risk for depression.
Patterns of parent-child interactions are commonly cited as being predictive of later psychiatric disorders but precisely which elements of these interactions are important is rarely clear, potentially affecting the effective targeting of interventions in young children. The current study aimed to examine the relationship between timely vocal response during parent-child interactions (i.e., the probability of mothers responding to their child within a specified time period and vice versa), and later psychiatric diagnosis. Drawing on data from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort, a case control study was conducted based on infant-mother video observations of children assessed for neuropsychiatric disorders using the parent-reported Development and Wellbeing Assessment (DAWBA) at seven years of age (103 controls and 55 cases). Empirical examination suggested that 1 second represented the optimal threshold for maternal responses and 8 seconds for child responses. Only the maternal measure was found to predict later psychiatric disorders, with evidence of associations limited to hyperactivity and conduct disorders. These associations were not sensitive to either maternal education or child sex. The results are discussed in terms of the value of precise interpretation of early mother/child interaction and for the potential for providing targeted intervention to the population concerned.
Multi-system impacts of long COVID remain unknown. We aimed to compare multi-system deficits between people with long COVID and controls. We conducted a case-control study and recruited participants from two UK population-based cohorts: the Avon Longitudinal Study of Parents and Children (ALSPAC) and TwinsUK. Participants provided samples for SARS-CoV-2 serology between 2020 and 2021 and were asked about duration of COVID-19 symptoms between July and December 2021. Cases had long COVID (evidence of COVID-19 infection and persistent symptoms ≥4 weeks post infection); controls comprised 3 groups: acute COVID-19 only (symptoms reported for <4 weeks) and serological evidence of infection; self-reported long COVID-like symptoms but without wild-type SARS-CoV-2 virus antibodies; no symptoms or history of COVID-19 infection. People who were severely unwell or pregnant were excluded. Participants attended a clinic follow-up visit between 2021 and 2023 and underwent multi-system MRI, (cardiac, brain, lung, kidney), measurement of blood pressure and autonomic function, spirometry, renal function, exercise tests, strength and physical capability. Severity of deficit was then scored for each system as 0 (none) to 3 (severe). Primary outcome was a single composite multi-domain score summing each of nine domains: autonomic, brain, exercise capacity, heart, lungs, physical, renal, strength and vascular, with a maximum score of 27. In total, 349 participants, 141 with long COVID (40%) and 208 (60%) controls were recruited. Overall deficit score in cases was 0.22 (95% CI -0.44, 0.88) units greater than controls, adjusted for age, sex, ethnicity, cohort membership and relatedness. This estimate was little changed (0.32 (-0.34, 0.98)) when additionally adjusted for educational status, index of multiple deprivation, physical activity, smoking and co-morbidity. Restricting cases to those reporting symptoms including fatigue (n = 46) increased the excess deficit score to 0.81 (-0.19, 1.81) units in the minimally adjusted model. A difference was only observed in the vascular domain, largely attributable to elevated blood pressure, showing a 1.76 (1.04, 2.97) multivariable adjusted odds ratio excess in cases, and 3.04 (1.36, 6.80) when restricted to cases with fatigue. There was no evidence of marked residual subclinical deficits in most systems in people with long-COVID, although there was evidence of persistent deficits in the vascular system, largely related to elevated blood pressure. Mechanisms unrelated to organ dysfunction may contribute to symptoms. Blood pressure measurement and control should be included in clinical follow-up. Jointly funded by the National Institute for Health and Care Research and UK Research and Innovation (CONVALESCENCE, COV-LT-0009, MC_PC_20051).
Lower birthweight, a marker of prenatal adversity, is associated with adverse health outcomes, including psychopathology and immune-metabolic alterations. This study tests whether longitudinal trajectories of chronic immune-metabolic alteration across adolescence, a period of rapid physiological changes, are predicted by birthweight and associated with subsequent depression risk, notably the atypical subtype. We aim to clarify pathways linking prenatal adversity to psychopathology. We derived a latent immune-metabolic factor at ages 15, 17, and 24 from standardized C-reactive protein and Homeostatic measurement of insulin resistance in participants from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (N = 3000). We used latent class mixed modeling to identify immune-metabolic trajectory classes. Depression at 24 was measured on the International Classification of Diseases-10 criteria; atypical features were operationalized as the presence of neurovegetative symptoms (e.g. hypersomnia, hyperphagia). Inverse-probability weighting was used to mitigate selection bias. Here we show that a four-class quadratic model best fits the data. Membership in the late-adolescence-peaking trajectory is associated with higher odds of depression at 24 (Weighted-Beta=0.767, p = 0.047, OR = 2.15, 95%CI:1.20-3.88), and, notably, of depression with atypical symptoms (Weighted-Beta=1.25, p = 0.0035, OR = 3.50, 95%CI:1.50-8.11). Birthweight is inversely associated with odds of experiencing an unfavourable late-peak trajectory group (Weighted-Beta = -1.99, robust p = 0.0313, OR = 0.14, 95%CI:0.02-0.84). Sex demonstrates a marginal moderating effect (p = 0.050), with the association between birthweight and late-peak trajectory membership being more pronounced in females. Findings provide longitudinal evidence that prenatal adversity, indexed by lower birthweight, predicts individuals experiencing unfavourable adolescent immune-metabolic trajectories that are associated with adult depression, particularly with atypical features. Results suggest that developmental immune-metabolic trajectories could eventually inform patient clinical stratification and point to late adolescence as a possible intervention window. In this study, through longitudinal data modeling, we investigated how fluctuations in immune-metabolic biomarkers during adolescence and early adulthood contribute to depression, specifically the atypical subtype characterized by oversleeping, increased appetite, and low energy. We also examined whether prenatal adversity, indexed by lower birthweight, could predict an unfavorable biomarker trajectory. We found that a trajectory marked by a surge in immune-metabolic biomarkers during late adolescence is predicted by lower birthweight, especially in women, and increases the risk of atypical depression. These findings suggest that tracking these biological changes can help identify individuals at higher risk for depression. Ultimately, this highlights late adolescence as a critical window for early intervention and emphasizes the lifelong impact of the prenatal environment on both mental and physical health.
Relationships between maternal mental health and breastfeeding outcomes are complex, with evidence of bi-directional effects complicated by culturally specific residual confounding and selection bias. This study aimed to examine, for the first time, associations between maternal genetic liability for neuroticism and breastfeeding intention, initiation and maintenance. We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective birth cohort. Maternal genotype data were used to create polygenic scores (PGS) for neuroticism. Mothers self-reported breastfeeding intentions at 32 weeks gestation, breastfeeding initiation within the first week after birth and maintenance of breastfeeding to 6 months after birth. We examined associations between maternal genetic liability for neuroticism and breastfeeding outcomes by using unadjusted logistic regression models (n = 4611). We also examined associations between paternal genetic liability for neuroticism and breastfeeding outcomes as a negative control (n = 1446). There was evidence that genetic liability for neuroticism was associated with lower odds for breastfeeding maintenance (odds ratio 0.86, 95% CI 0.83-0.94, p < 0.001), with no evidence for associations with intention or initiation. That is, mothers with higher genetic liability for neuroticism were less likely to maintain breastfeeding to 6 months postpartum. There were no associations between paternal PGS for neuroticism and breastfeeding outcomes. The specificity of links between neuroticism and maintenance of breastfeeding could direct targeting of efforts to support women with emotional difficulties in maintaining breastfeeding. This is important because currently, most efforts to support breastfeeding women focus on intention and initiation.
Observational studies have suggested that a younger age at menarche is associated with increased risks of adverse pregnancy and perinatal outcomes. However, it is unclear whether these relationships are causal. We estimated the associations between age at menarche and 13 pre-specified pregnancy outcomes by using two approaches. We estimated observational associations in the Avon Longitudinal Study of Parents and Children (N = 9441) using multivariable regression accounting for educational attainment, ethnicity, maternal age, parity, offspring sex, and adiposity. We conducted two-sample Mendelian randomization (MR) using data from the Mendelian Randomization in Pregnancy (MR-PREG) collaboration (77 683-707 797 pregnancies) and multivariable MR (MVMR) accounting for genetically-proxied adiposity. Older age at menarche was associated with lower risks of hypertensive disorders of pregnancy, gestational hypertension, and preeclampsia, but accounting for adiposity attenuated these effects across approaches. For example, per 1-year older age at menarche, the odds ratio (OR) for hypertensive disorders of pregnancy was 0.88 (95% confidence interval (CI) : 0.84, 0.93) in inverse variance weighted MR and 0.95 (95% CI: 0.90, 1.01) in MVMR, while the observational association attenuated from OR = 0.91 (95% CI: 0.87, 0.94) to OR = 0.97 (95% CI: 0.93, 1.01). No clear evidence was found for the effects of age at menarche on small-for-gestational-age, low birthweight, post-term birth, or perinatal depression from either approach. For other outcomes evidence was limited by imprecision (very preterm birth, gestational diabetes) or inconsistent effects in sensitivity analyses (offspring birthweight, large-for-gestational-age, high birthweight, preterm birth). We find little robust evidence for causal effects of age at menarche on pregnancy outcomes. Effects of younger menarche on increased risks of hypertensive disorders of pregnancy may be driven by adiposity.
Adverse childhood experiences (ACEs) negatively impact children's psychological development and subsequent mental health. However, life-course trajectories of ACEs on common mental health outcomes in adulthood have not been explored in depth. We analysed longitudinal data from the Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK to determine the best-fitting life-course models between ACEs and mental health outcomes (depression and anxiety) at 17 and 24 years, using a Structured Life Course Modelling Approach. Six ACEs related to interpersonal trauma were integrated into life-course hypotheses, including: critical periods (at ages 0-5, 5-11 and 11-17), ACE accumulation, ever-experiencing ACEs and persistent ACE exposure. ACEs during late childhood/early adolescence (11-17 years) had the strongest association with depression and anxiety at age 24, with any ACEs at this time-point approximately doubling the odds of diagnoses. A weaker association with ACEs in middle childhood (5-11 years) on depression was also observed (approx. 50 per cent increase in odds). Results at age 17 were similar, with a consistent relationship between ACE exposure in late childhood/early adolescence on depression and anxiety, potentially combined with weaker exposure effects in middle childhood and/or accumulation effects. Life-course trajectories for analyses of the individual ACEs were more inconsistent, potentially due to the relative rarity of these events and their correlation over time, but often also indicated strongest relationships during late childhood/early adolescence. In sum, traumatic ACEs during late childhood/early adolescence may have the strongest effect on subsequent mental health in early adulthood, although we cannot distinguish 'critical period' and 'recency' effects.
This study examined whether the age of nap cessation (the transition from daytime napping to sleeping exclusively at night) is associated with screen-positive Autism Spectrum Disorder (ASD) traits or an Attention-Deficit Hyperactivity Disorder (ADHD) diagnosis in children. This retrospective cohort study used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based birth cohort recruited between 1991 and 1992. The analytic sample included 6,424 children with available nap cessation and covariate data. Parents reported children's nap patterns at 6, 18, 30, 42, 57, 69, and 81 months. Binary logistic regression examined associations between age of nap cessation and later ASD traits or ADHD diagnosis. Models adjusted for gestational age, birth weight, maternal age, child sex, maternal ethnicity, older siblings, social class, and maternal alcohol use during pregnancy. Children who ceased napping by 18 months had higher odds of an ADHD diagnosis at age seven than those who ceased at 30 months (OR = 5.54, 95% CI [2.52, 11.20], p < .001). Nap cessation at 18 months was also associated with increased odds of ASD traits, although the estimate was less precise (OR = 1.81, 95% CI [0.96, 3.16], p = .051). Early nap cessation may be associated with later ADHD diagnosis and could reflect differences in sleep regulation. A possible association with elevated ASD traits was also observed but remains uncertain and should be considered exploratory pending replication. Nap cessation timing should not be interpreted as an early screening or diagnostic marker.