Avon Longitudinal Study Of Parents Research Articles

Metabolome-wide Mendelian randomization for age at menarche and age at natural menopause.

The role of metabolism in the variation of age at menarche (AAM) and age at natural menopause (ANM) in the female population is not entirely known. We aimed to investigate the causal role of circulating metabolites in AAM and ANM using Mendelian randomization (MR). We combined MR with genetic colocalization to investigate potential causal associations between 658 metabolites and AAM and between 684 metabolites and ANM. We extracted genetic instruments for our exposures from four genome-wide association studies (GWAS) on circulating metabolites and queried the effects of these variants on the outcomes in two large GWAS from the ReproGen consortium. Additionally, we assessed the mediating role of the body mass index (BMI) in these associations, identified metabolic pathways implicated in AAM and ANM, and sought validation for selected metabolites in the Avon Longitudinal Study of Parents and Children (ALSPAC). Our analysis identified 10 candidate metabolites for AAM, but none of them colocalized with AAM. For ANM, 76 metabolites were prioritized (FDR-adjusted MR P-value ≤ 0.05), with 17 colocalizing, primarily in the glycerophosphocholines class, including the omega-3 fatty acid and phosphatidylcholine (PC) categories. Pathway analyses and validation in ALSPAC mothers also highlighted the role of omega and polyunsaturated fatty acids levels in delaying age at menopause. Our study suggests that metabolites from the glycerophosphocholine and fatty acid families play a causal role in the timing of both menarche and menopause. This underscores the significance of specific metabolic pathways in the biology of female reproductive longevity.

The association between sexual orientation and psychotic like experiences during adolescence: a prospective cohort study.

Psychotic like experiences (PLEs) are relatively common during adolescence and associated with a range of negative outcomes. There is evidence that sexual minorities are at increased risk of mental health problems including depression, anxiety, self-harm and suicidality. However, no study has investigated the association between sexual orientation and psychotic experiences during adolescence. We compared trajectories of PLEs in sexual minority and heterosexual adolescents from 12 to 24years of age. We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants provided data on sexual orientation at age 16 and PLEs at ages 12, 17 and 24. We used multi-level logistic regression models to test associations between sexual orientation and PLEs, before and after adjusting for covariates. We investigated whether the association differed according to time-point and sex using interaction terms. We found evidence that the odds of PLEs were 2.35 times (95% Confidence Interval 1.79-3.06, p < 0.0001) higher among sexual minority compared with heterosexual adolescents, across all ages, after adjusting for covariates. There was no evidence that the association between sexual orientation and PLEs differed according to time-point (p = 0.50) or sex (p = 0.29). We found an increased risk of psychosis in sexual minorities compared with heterosexuals, which was present from around 12years of age and persisted until age 24. Early interventions to prevent this mental health inequality could include universal interventions to promote inclusivity and acceptance of diverse sexual orientations.

Emotional problems across development: examining measurement invariance across childhood, adolescence and early adulthood.

Emotional problems (anxiety, depression) are prevalent in children, adolescents and young adults with varying ages at onset. Studying developmental changes in emotional problems requires repeated assessments using the same or equivalent measures. The parent-rated Strengths and Difficulties Questionnaire is commonly used to assess emotional problems in childhood and adolescence, but there is limited research about whether it captures a similar construct across these developmental periods. Our study addressed this by investigating measurement invariance in the scales' emotional problems subscale (SDQ-EP) across childhood, adolescence and early adulthood. Data from two UK population cohorts were utilised: the Millennium Cohort Study (ages 3-17 years) and the Avon Longitudinal Study of Parents and Children (4-25 years). In both samples we observed weak (metric) measurement invariance by age, suggesting that the parent-rated SDQ-EP items contribute to the underlying construct of emotional problems similarly across age. This supports the validity of using the subscale to rank participants on their levels of emotional problems in childhood, adolescence and early adulthood. However strong (scalar) measurement invariance was not observed, suggesting that the same score may correspond to different levels of emotional problems across developmental periods. Comparisons of mean parent-rated SDQ-EP scores across age may therefore not be valid.

Disagreement concerning atopic dermatitis subtypes between an English prospective cohort (ALSPAC) and linked electronic health records.

Subtypes of atopic dermatitis (AD) have been derived from the Avon Longitudinal Study of Parents and Children (ALSPAC) based on presence and severity of symptoms reported in questionnaires (Severe-Frequent, Moderate-Frequent, Moderate-Declining, Mild-Intermittent, Unaffected/Rare). Good agreement between ALSPAC and linked electronic health records (EHRs) would increase trust in the clinical validity of these subtypes and allow inferring subtypes from EHRs alone, which would enable their study in large primary care databases. 1. Explore if presence and number of AD records in EHRs agrees with AD symptom and severity reports from ALSPAC; 2. Explore if EHRs agree with ALSPAC-derived AD subtypes; 3. Construct models to classify ALSPAC-derived AD subtype using EHRs. We used data from the ALSPAC prospective cohort study from 11 timepoints until age 14 years (1991-2008), linked to local general practice EHRs. We assessed how far ALSPAC questionnaire responses and derived subtypes agreed with AD as established in EHRs using different AD definitions (e.g., diagnosis and/or prescription) and other AD-related records. We classified AD subtypes using EHRs, fitting multinomial logistic regression models tuning hyperparameters and evaluating performance in the testing set (ROC AUC, accuracy, sensitivity, and specificity). 8,828 individuals out of a total 13,898 had both been assigned an AD subtype and had linked EHRs. The number of AD-related codes in EHRs generally increased with severity of AD subtype, however not all with the Severe-Frequent subtypes had AD in EHRs, and many with the Unaffected/Rare subtype did have AD in EHRs. When predicting ALSPAC AD subtype using EHRs, the best tuned model had ROC AUC of 0.65, sensitivity of 0.29 and specificity of 0.83 (both macro averaged); when different sets of predictors were used, individuals with missing EHR coverage excluded, and subtypes combined, sensitivity was not considerably improved. ALSPAC and EHRs disagreed not just on AD subtypes, but also on whether children had AD or not. Researchers should be aware that individuals considered as having AD in one source may not be considered as having AD in another.

Genetic Architectures of Adolescent Depression Trajectories in 2 Longitudinal Population Cohorts

Adolescent depression is characterized by diverse symptom trajectories over time and has a strong genetic influence. Research has determined genetic overlap between depression and other psychiatric conditions; investigating the shared genetic architecture of heterogeneous depression trajectories is crucial for understanding disease etiology, prediction, and early intervention. To investigate univariate and multivariate genetic risk for adolescent depression trajectories and assess generalizability across ancestries. This cohort study entailed longitudinal growth modeling followed by polygenic risk score (PRS) association testing for individual and multitrait genetic models. Two longitudinal cohorts from the US and UK were used: the Adolescent Brain and Cognitive Development (ABCD; N = 11 876) study and the Avon Longitudinal Study of Parents and Children (ALSPAC; N = 8787) study. Included were adolescents with genetic information and depression measures at up to 8 and 4 occasions, respectively. Study data were analyzed January to July 2023. Trajectories were derived from growth mixture modeling of longitudinal depression symptoms. PRSs were computed for depression, anxiety, neuroticism, bipolar disorder, schizophrenia, attention-deficit/hyperactivity disorder, and autism in European ancestry. Genomic structural equation modeling was used to build multitrait genetic models of psychopathology followed by multitrait PRS. Depression PRSs were computed in African, East Asian, and Hispanic ancestries in the ABCD cohort only. Association testing was performed between all PRSs and trajectories for both cohorts. A total sample size of 14 112 adolescents (at baseline: mean [SD] age, 10.5 [0.5] years; 7269 male sex [52%]) from both cohorts were included in this analysis. Distinct depression trajectories (stable low, adolescent persistent, increasing, and decreasing) were replicated in the ALSPAC cohort (6096 participants; 3091 female [51%]) and ABCD cohort (8016 participants; 4274 male [53%]) between ages 10 and 17 years. Most univariate PRSs showed significant uniform associations with persistent trajectories, but fewer were significantly associated with intermediate (increasing and decreasing) trajectories. Multitrait PRSs-derived from a hierarchical factor model-showed the strongest associations for persistent trajectories (ABCD cohort: OR, 1.46; 95% CI, 1.26-1.68; ALSPAC cohort: OR, 1.34; 95% CI, 1.20-1.49), surpassing the effect size of univariate PRS in both cohorts. Multitrait PRSs were associated with intermediate trajectories but to a lesser extent (ABCD cohort: hierarchical increasing, OR, 1.27; 95% CI, 1.13-1.43; decreasing, OR, 1.23; 95% CI, 1.09-1.40; ALSPAC cohort: hierarchical increasing, OR, 1.16; 95% CI, 1.04-1.28; decreasing, OR, 1.32; 95% CI, 1.18-1.47). Transancestral genetic risk for depression showed no evidence for association with trajectories. Results of this cohort study revealed a high multitrait genetic loading of persistent symptom trajectories, consistent across traits and cohorts. Variability in univariate genetic association with intermediate trajectories may stem from environmental factors. Multitrait genetics may strengthen depression prediction models, but more diverse data are needed for generalizability.

Sexual experiences, behaviours and attitudes in the parents in the Avon Longitudinal Study of Parents and Childhood (ALSPAC)

The aim of this data note is to describe the sexual experiences, behaviours, and attitudes data collected from the parent cohorts of the Avon Longitudinal Study of Parents and Children (ALSPAC) over a 30-year period. ALSPAC is an ongoing birth cohort which enrolled 14,541 pregnant women living in Avon, a county of southwest England, with expected dates of delivery between April 1991 and December 1992 inclusive and continues collecting data on these mothers (age range at delivery &lt;16–41 years), their partners (age range at delivery &lt;16–65), and their offspring, so far resulting in 100,000+ phenotype variables. During the index pregnancy the mothers were asked (and at 8 months post-delivery for partners) about their early sexual experiences to identify sexual abuse/assaults and the age at which an event first happened. Both parents were asked also about sexual abuse within a battery of questions identifying Adverse Childhood Events (ACE). Further longitudinal data described here includes satisfaction with sexual and non-sexual sides of their relationship; sexual functioning; and at seven years post-delivery, both parents were asked to describe their sexual orientation as well as the sex of their partners and cohabiting partners. These data provide the ability to compare generational differences between parental sexual behaviours and attitudes with those of their offspring, as well as allowing comparisons with other longitudinal surveys where similar (or identical) information has been collected such as the National Survey of Sexual Attitudes and Lifestyles (NATSAL-3). This paper forms a companion to another data note describing similar data collected on the offspring cohort.

Sexual experiences and behaviours in the offspring generation of the Avon Longitudinal Study of Parents and Childhood

Previous research on child/teenage sexual experiences has largely focussed on negative outcomes such as teen pregnancy or acquiring sexually transmitted infections and are mainly cross-sectional. Longitudinal research is required to assess normal sexual development and the attainment of psychologically healthy attitudes towards sexuality. The Avon Longitudinal Study of Parents and Children (ALSPAC) has administered questions on relationships and sexual experiences from the age of 11 years to the index children. This data note describes these data.

Role of Inflammation in Short Sleep Duration Across Childhood and Psychosis in Young Adulthood

Short sleep duration over a prolonged period in childhood could have a detrimental impact on long-term mental health, including the development of psychosis. Further, potential underlying mechanisms of these associations remain unknown. To examine the association between persistent shorter nighttime sleep duration throughout childhood with psychotic experiences (PEs) and/or psychotic disorder (PD) at age 24 years and whether inflammatory markers (C-reactive protein [CRP] and interleukin 6 [IL-6]) potentially mediate any association. This cohort study used data from the Avon Longitudinal Study of Parents and Children. Data analysis was conducted from January 30 to August 1, 2023. Nighttime sleep duration was collected at 6, 18, and 30 months and at 3.5, 4 to 5, 5 to 6, and 6 to 7 years. PEs and PD were assessed at age 24 years from the Psychosislike Symptoms Interview. CRP level at ages 9 and 15 years and IL-6 level at 9 years were used as mediators. Latent class growth analyses (LCGAs) were applied to detect trajectories of nighttime sleep duration, and logistic regressions were applied for the longitudinal associations between trajectories of nighttime sleep duration and psychotic outcomes at 24 years. Path analyses were applied to test CRP and IL-6 as potential mediators. Data were available on 12 394 children (6254 female [50.5%]) for the LCGA and on 3962 young adults (2429 female [61.3%]) for the logistic regression and path analyses. The LCGA identified a group of individuals with persistent shorter nighttime sleep duration across childhood. These individuals were more likely to develop PD (odds ratio [OR], 2.50; 95% CI, 1.51-4.15; P < .001) and PEs (OR, 3.64; 95% CI, 2.23-5.95; P < .001) at age 24 years. Increased levels of IL-6 at 9 years, but not CRP at 9 or 15 years, partially mediated the associations between persistent shorter sleep duration and PD (bias-corrected estimate = 0.003; 95% CI, 0.002-0.005; P = .007) and PEs (bias-corrected estimate = 0.002; 95% CI, 0-0.003; P = .03) in young adulthood. Findings of this cohort study highlight the necessity of addressing short sleep duration in children, as persistence of this sleep problem was associated with subsequent psychosis. This study also provides preliminary evidence for future targeted interventions in children addressing both sleep and inflammatory responses.

Behavioural, psychiatric, and cognitive phenotypes associated with numbers of repeats of the FRAXE allele on the FMR2 gene

Background The FRAXE site on the X-chromosome has a variable number of trinucleotide repeats. The rare condition Fragile XE has &gt;200 repeats, but most X chromosomes have &lt;60 such repeats, with evidence of a bimodal distribution. It is known that when the number of repeats is &lt;60, the repeat number can increase from mother to son, which raises the question as to whether there is an evolutionary advantage in the size of these repeats. This paper investigates whether the higher of the &lt;60 repeats are associated with neurocognitive differences among boys in a general population. We hypothesised that although there was previous evidence of a link between higher numbers of repeats in the boys in this population with maternal grandmothers with schizophrenia, there may be cognitive or behavioural advantages to their grandsons of increased levels of repeats. Methods We compared 1951 behavioural, psychiatric, and cognitive outcomes of 5060 boys from the Avon Longitudinal Study of Parents and Children (ALSPAC) using a phenome scan. Results We found that boys with relatively high levels of repeats (&gt;24) had a higher risk of certain neurocognitive outcomes (P&lt;0.01). Boys with &gt;24 repeats were more likely to report: (a) psychosis-like experiences; (b) increased ability to recognise facial signs of anger; (c) increased risk of eating disorders; (d) increased likelihood of smoking cigarettes and using illicit drugs during adolescence than would be expected by chance. There was no sign of associations with cognitive abilities. Conclusions We concluded that there was little evidence that higher levels of the normal range of FRAXE repeats were associated with a difference in cognitive abilities, but there was evidence of increased reports of psychotic-like experiences and other behaviour problems in this group. There was no evidence of evolutionary neurocognitive advantage.

Accelerometer-based sedentary time and physical activity from childhood through young adulthood with progressive cardiac changes: a 13-year longitudinal study.

Longitudinal evidence on the relationship of sedentary time (ST), light-intensity physical activity (LPA), and moderate-to-vigorous-intensity physical activity (MVPA) with changes in cardiac structure and function in the paediatric population is scarce. This evidence is clinically important due to the impact ST can have on the long-term prognosis of healthy young population in the lifetime continuum. This prospective observational study examined the relationships of cumulative ST, LPA, and MVPA from childhood with longitudinal changes in cardiac structure and function. This is a secondary analysis from the Avon Longitudinal Study of Parents and Children, UK birth cohort of 1682 children aged 11 years. Participants who had at least one follow-up timepoints accelerometer-measured ST, LPA, and MVPA over a period of 13 years and repeated echocardiography-measured cardiac structure and function at ages 17- and 24-year clinic visit were included. Left ventricular mass indexed for height2.7 (LVMI2.7) and left ventricular (LV) diastolic function from mitral E/A ratio (LVDF) were computed. Among 1682 children (mean [SD] age, 11.75 [0.24] years; 1054 [62.7%] females), the cumulative one-min/day increase in ST from ages 11 to 24 years was associated with progressively increased LVMI2.7 {effect estimate 0.002 g/m2.7 [confidence interval (CI) 0.001-0.003], P < 0.001}, irrespective of sex, obesity, and hypertensive status. Cumulative one-min/day increase in LPA was associated with a decreased LVMI2.7 (-0.005 g/m2.7 [-0.006 to -0.003], P < 0.0001) but an increased LVDF. Cumulative one-minute/day increase in MVPA was associated with progressively increased LVMI2.7 (0.003 g/m2.7 [0.001-0.006], P = 0.015). ST contributed +40% to the 7-year increase in cardiac mass, MVPA increased cardiac mass by +5%, but LPA reduced cardiac mass by -49%. Increased ST may have long-term pathologic effects on cardiac structure and function during growth from childhood through young adulthood; however, engaging in LPA may enhance cardiac health in the young population.

Shorter night-time sleep duration and later sleep timing from infancy to adolescence.

Here, we (a) examined the trajectories of night-time sleep duration, bedtime and midpoint of night-time sleep (MPS) from infancy to adolescence, and (b) explored perinatal risk factors for persistent poor sleep health. This study used data from 12,962 participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Parent or self-reported night-time sleep duration, bedtime and wake-up time were collected from questionnaires at 6, 18 and 30 months, and at 3.5, 4-5, 5-6, 6-7, 9, 11 and 15-16 years. Child's sex, birth weight, gestational age, health and temperament, together with mother's family adversity index (FAI), age at birth, prenatal socioeconomic status and postnatal anxiety and depression, were included as risk factors for persistent poor sleep health. Latent class growth analyses were applied first to detect trajectories of night-time sleep duration, bedtime and MPS, and we then applied logistic regressions for the longitudinal associations between risk factors and persistent poor sleep health domains. We obtained four trajectories for each of the three sleep domains. In particular, we identified a trajectory characterized by persistent shorter sleep, a trajectory of persistent later bedtime and a trajectory of persistent later MPS. Two risk factors were associated with the three poor sleep health domains: higher FAI with increased risk of persistent shorter sleep (OR = 1.20, 95% CI = 1.11-1.30, p < .001), persistent later bedtime (OR = 1.28, 95% CI = 1.19-1.39, p < .001) and persistent later MPS (OR = 1.30, 95% CI = 1.22-1.38, p < .001); and higher maternal socioeconomic status with reduced risk of persistent shorter sleep (OR = 0.99, 95% CI = 0.98-1.00, p = .048), persistent later bedtime (OR = 0.98, 95% CI = 0.97-0.99, p < .001) and persistent later MPS (OR = 0.99, 95% CI = 0.98-0.99, p < .001). We detected trajectories of persistent poor sleep health (i.e. shorter sleep duration, later bedtime and later MPS) from infancy to adolescence, and specific perinatal risk factors linked to persistent poor sleep health domains.

Air and Noise Pollution Exposure in Early Life and Mental Health From Adolescence to Young Adulthood.

Growing evidence associates air pollution exposure with various psychiatric disorders. However, the importance of early-life (eg, prenatal) air pollution exposure to mental health during youth is poorly understood, and few longitudinal studies have investigated the association of noise pollution with youth mental health. To examine the longitudinal associations of air and noise pollution exposure in pregnancy, childhood, and adolescence with psychotic experiences, depression, and anxiety in youths from ages 13 to 24 years. This cohort study used data from the Avon Longitudinal Study of Parents and Children, an ongoing longitudinal birth cohort founded in 1991 through 1993 in Southwest England, United Kingdom. The cohort includes over 14 000 infants with due dates between April 1, 1991, and December 31, 1992, who were subsequently followed up into adulthood. Data were analyzed October 29, 2021, to March 11, 2024. A novel linkage (completed in 2020) was performed to link high-resolution (100 m2) estimates of nitrogen dioxide (NO2), fine particulate matter under 2.5 μm (PM2.5), and noise pollution to home addresses from pregnancy to 12 years of age. Psychotic experiences, depression, and anxiety were measured at ages 13, 18, and 24 years. Logistic regression models controlled for key individual-, family-, and area-level confounders. This cohort study included 9065 participants who had any mental health data, of whom (with sample size varying by parameter) 51.4% (4657 of 9051) were female, 19.5% (1544 of 7910) reported psychotic experiences, 11.4% (947 of 8344) reported depression, and 9.7% (811 of 8398) reported anxiety. Mean (SD) age at follow-up was 24.5 (0.8) years. After covariate adjustment, IQR increases (0.72 μg/m3) in PM2.5 levels during pregnancy (adjusted odds ratio [AOR], 1.11 [95% CI, 1.04-1.19]; P = .002) and during childhood (AOR, 1.09 [95% CI, 1.00-1.10]; P = .04) were associated with elevated odds for psychotic experiences. Pregnancy PM2.5 exposure was also associated with depression (AOR, 1.10 [95% CI, 1.02-1.18]; P = .01). Higher noise pollution exposure in childhood (AOR, 1.19 [95% CI, 1.03-1.38]; P = .02) and adolescence (AOR, 1.22 [95% CI, 1.02-1.45]; P = .03) was associated with elevated odds for anxiety. In this longitudinal cohort study, early-life air and noise pollution exposure were prospectively associated with 3 common mental health problems from adolescence to young adulthood. There was a degree of specificity in terms of pollutant-timing-outcome associations. Interventions to reduce air and noise pollution exposure (eg, clean air zones) could potentially improve population mental health. Replication using quasi-experimental designs is now needed to shed further light on the underlying causes of these associations.

Blood-based epigenome-wide analyses of chronic low-grade inflammation across diverse population cohorts

Chronic inflammation is a hallmark of age-related disease states. The effectiveness of inflammatory proteins including C-reactive protein (CRP) in assessing long-term inflammation is hindered by their phasic nature. DNA methylation (DNAm) signatures of CRP may act as more reliable markers of chronic inflammation. We show that inter-individual differences in DNAm capture 50% of the variance in circulating CRP (N= 17,936, Generation Scotland). We develop a series of DNAm predictors of CRP using state-of-the-art algorithms. An elastic-net-regression-based predictor outperformed competing methods and explained 18% of phenotypic variance in the Lothian Birth Cohort of 1936 (LBC1936) cohort, doubling that of existing DNAm predictors. DNAm predictors performed comparably in four additional test cohorts (Avon Longitudinal Study of Parents and Children, Health for Life in Singapore, Southall and Brent Revisited, and LBC1921), including for individuals of diverse genetic ancestry and different age groups. The best-performing predictor surpassed assay-measured CRP and a genetic score in its associations with 26 health outcomes. Our findings forge new avenues for assessing chronic low-grade inflammation in diverse populations.

Mode of birth and DNA methylation at birth, in childhood, and in adolescence: Uncovering the relationship using ALSPAC data.

Mode of birth has been linked to offspring health. Changes in DNA methylation (DNAm) may represent a potential mechanism; however, findings are heterogeneous and limited to early infancy. This preregistered study examined whether mode of birth (vaginal birth compared with elective or emergency cesarean section) affects DNAm at birth, in childhood, and adolescence and whether these effects are modified by the postnatal care environment, specifically by breastfeeding and mother-infant bonding. Using data from 876 mother-infant dyads from the U.K. Avon Longitudinal Study of Parents and Children, we examined differentially methylated cytosine-phosphate-guanine dinucleotides and regions associated with mode of birth. DNAm was quantified using Illumina Infinium Human Methylation 450 K BeadChip in cord blood (at birth) and in peripheral blood (at 7 and 15-17 years). Analyses controlled for maternal age, education, smoking during pregnancy, child sex, gestational week at birth, and batch effects. We also examined interactions of mode of birth with breastfeeding practices and mother-infant bonding. In cord blood, two cytosine-phosphate-guanine dinucleotides (cg05230316; cg13230077) were linked to mode of birth (pFDR < .050). DNAm in childhood or adolescence was not statistically associated with mode of birth (pFDR > .050), and breastfeeding and mother-infant bonding were not moderators (p > .050). Overall, findings suggest mode of birth may have a small effect on cord blood DNAm, but these effects may not persist into later developmental stages. Other postnatal influences should be considered, and further investigation is needed to address study limitations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Genetics impact risk of Alzheimer’s disease through mechanisms modulating structural brain morphology in late life

BackgroundAlzheimer’s disease (AD)-related neuropathological changes can occur decades before clinical symptoms. We aimed to investigate whether neurodevelopment and/or neurodegeneration affects the risk of AD, through reducing structural brain reserve and/or...

Developmental epigenomic effects of maternal financial problems.

Early-life adversity as neglect or low socioeconomic status is associated with negative physical/mental health outcomes and plays an important role in health trajectories through life. The early-life environment has been shown to be encoded as changes in epigenetic markers that are retained for many years.We investigated the effect of maternal major financial problems (MFP) and material deprivation (MD) on their children's epigenome in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Epigenetic aging, measured with epigenetic clocks, was weakly accelerated with increased MFP. In subsequent EWAS, MFP, and MD showed strong, independent programing effects on children's genomes. MFP in the period from birth to age seven was associated with genome-wide epigenetic modifications on children's genome visible at age 7 and partially remaining at age 15.These results support the hypothesis that physiological processes at least partially explain associations between early-life adversity and health problems later in life. Both maternal stressors (MFP/MD) had similar effects on biological pathways, providing preliminary evidence for the mechanisms underlying the effects of low socioeconomic status in early life and disease outcomes later in life. Understanding these associations is essential to explain disease susceptibility, overall life trajectories and the transition from health to disease.

The relationship between type, timing and duration of exposure to adverse childhood experiences and adolescent self-harm and depression: findings from three UK prospective population-based cohorts.

Adverse childhood experiences (ACEs) are well-established risk factors for self-harm and depression. However, despite their high comorbidity, there has been little focus on the impact of developmental timing and the duration of exposure to ACEs on co-occurring self-harm and depression. Data were utilised from over 22,000 children and adolescents participating in three UK cohorts, followed up longitudinally for 14-18 years: the Avon Longitudinal Study of Parents and Children (ALSPAC), the Millennium Cohort Study (MCS) and the Environmental Risk (E-Risk) Longitudinal Twin Study. Multinomial logistic regression models estimated associations between each ACE type and a four-category outcome: no self-harm or depression, self-harm alone, depression alone and self-harm with co-occurring depression. A structured life course modelling approach was used to examine whether the accumulation (duration) of exposure to each ACE, or a critical period (timing of ACEs) had the strongest effects on self-harm and depression in adolescence. The majority of ACEs were associated with co-occurring self-harm and depression, with consistent findings across cohorts. The importance of timing and duration of ACEs differed across ACEs and across cohorts. For parental mental health problems, longer duration of exposure was strongly associated with co-occurring self-harm and depression in both ALSPAC (adjusted OR: 1.18, 95% CI: 1.10-1.25) and MCS (1.18, 1.11-1.26) cohorts. For other ACEs in ALSPAC, exposure in middle childhood was most strongly associated with co-occurring self-harm and depression, and ACE occurrence in early childhood and adolescence was more important in the MCS. Efforts to mitigate the impact of ACEs should start in early life with continued support throughout childhood, to prevent long-term exposure to ACEs contributing to risk of self-harm and depression in adolescence.

Spiritual and religious beliefs and behaviour: data collected from 27/28-year-old offspring in the Avon Longitudinal Study of Parents and Children, 2019-2020.

Religious/spiritual belief and practices have sometimes been demonstrated to have positive associations with outcomes such as coping with serious illness, anxiety, depression, negative life events and general well-being, and therefore warrants consideration in many facets of health research. For example, increasing secularisation evidenced, particularly in the West, may reflect increasing rates of depression and anxiety. Very few studies have charted the ways in which religious/spiritual beliefs and practices of parents and their offspring vary longitudinally or between generations. Avon Longitudinal Study of Parents and Children (ALSPAC) is one such study that can relate belief and practices with aspects of physical and mental health and/or distinguish the different facets of the environment that may influence the development, or inter-generational loss, of belief and behaviours. This paper describes the 2019–2020 data collection in the ALSPAC on the religious/spiritual beliefs and behaviours (RSBB) of the study offspring (born 1991/1992) at ages 27–28 years. Previously collected and new data on the offspring are described here and comparisons are made with identical data completed by their parents (mothers and their partners) in early 2020. The most striking observations are that in almost all aspects of RSBB the offspring of both sexes are more secular, especially when compared with their mothers. For example, 56.2% of offspring state that they do not believe in God, or a divine power compared with 26.6% of mothers and 45.3% of mothers’ partners. When asked about their type of religion, 65.4% of participants stated ‘none’, compared with 27.2% of mothers and 40.2% of partners. This confirms previous research reporting increasing secularisation from one generation to the next. As with the mothers and their partners, female offspring were more likely than males to believe in a divine power and to practice their beliefs.

Smoking during pregnancy and its effect on placental weight: a Mendelian randomization study

BackgroundThe causal relationship between maternal smoking in pregnancy and reduced offspring birth weight is well established and is likely due to impaired placental function. However, observational studies have given conflicting results on the association between smoking and placental weight. We aimed to estimate the causal effect of newly pregnant mothers quitting smoking on their placental weight at the time of delivery.MethodsWe used one-sample Mendelian randomization, drawing data from the Avon Longitudinal Study of Parents and Children (ALSPAC) (N = 690 to 804) and the Norwegian Mother, Father and Child Cohort Study (MoBa) (N = 4267 to 4606). The sample size depends on the smoking definition used for different analyses. The analysis was performed in pre-pregnancy smokers only, due to the specific role of the single-nucleotide polymorphism (SNP) rs1051730 (CHRNA5 – CHRNA3 – CHRNB4) in affecting smoking cessation but not initiation.ResultsFixed effect meta-analysis showed a 182 g [95%CI: 29,335] higher placental weight for pre-pregnancy smoking mothers who continued smoking at the beginning of pregnancy, compared with those who stopped smoking. Using the number of cigarettes smoked per day in the first trimester as the exposure, the causal effect on placental weight was 11 g [95%CI: 1,21] per cigarette per day. Similarly, smoking at the end of pregnancy was causally associated with higher placental weight. Using the residuals of birth weight regressed on placental weight as the outcome, we showed evidence of lower offspring birth weight relative to the placental weight, both for continuing smoking at the start of pregnancy as well as continuing smoking throughout pregnancy (change in z-score birth weight adjusted for z-score placental weight: -0.8 [95%CI: -1.6,-0.1]).ConclusionOur results suggest that continued smoking during pregnancy causes higher placental weights.

Longitudinal trajectories of plasma polyunsaturated fatty acids and associations with psychosis-spectrum outcomes in early adulthood

Evidence supports associations between polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and psychosis. However, PUFA trajectories in the general population have not been characterised and associations with psychosis-spectrum outcomes in early adulthood are unknown. background METHODS: Plasma omega-6:omega-3 ratio and DHA %total fatty acids were measured by nuclear magnetic spectroscopy at 7,15,17 and 24years in the Avon Longitudinal Study of Parents and Children. Curvilinear growth mixture modelling evaluated BMI-adjusted trajectories of both measures. Outcomes were assessed at 24years. Psychotic experiences (PEs), At-Risk-Mental-State status, psychotic disorder and number of PEs were assessed using the Psychosis-Like Symptoms interview PLIKSi (n=3635, 2247 [61.8%]female). Negative symptoms score was measured using the Community Assessment of Psychic Experiences (n=3484, 2161 [62.0%]female). Associations were adjusted for sex, ethnicity, parental social class, cumulative smoking and alcohol use. Relative to stable average, the persistently high omega-6:omega-3 ratio trajectory was associated with increased odds of PEs and psychotic disorder, but attenuated on adjustment for covariates (PEs adjusted odds ratio[aOR] 1.63, 95% confidence interval[CI] 0.92-2.89; psychotic disorder aOR 1.69, 95%CI 0.71-4.07). This was also the case for persistently low DHA (PEs aOR 1.42, 95%CI 0.84-2.37; psychotic disorder aOR 1.14, 95%CI 0.49-2.67). Following adjustment, persistently high omega-6:omega-3 ratio was associated with increased number of PEs (β0.41, 95%CI 0.05-0.78) and negative symptoms score (β0.43, 95%CI 0.14-0.72), as was persistently low DHA (number of PEs:β 0.45, 95%CI 0.14-0.76; negative symptoms:β 0.35, 95%CI 0.12-0.58). Optimisation of PUFA status during development warrants further investigation in relation to psychotic symptoms in early adulthood.