Avon Longitudinal Study Of Parents Research Articles

Prenatal cannabis exposure is associated with alterations in offspring DNA methylation at genes involved in neurodevelopment, across the life course.

Prenatal cannabis exposure (PCE) is of increasing concern globally, due to the potential impact on offspring neurodevelopment, and its association with childhood and adolescent brain development and cognitive function. However, there is currently a lack of research addressing the molecular impact of PCE, that may help to clarify the association between PCE and neurodevelopment. To address this knowledge gap, here we present epigenome-wide association study data across multiple time points, examining the effect of PCE and co-exposure with tobacco using two longitudinal studies, the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Christchurch Health and Development Study (CHDS) at birth (0 y), 7 y and 15-17 y (ALSPAC), and ~27 y (CHDS). Our findings reveal genome-wide significant DNA methylation differences in offspring at 0 y, 7 y, 15-17 y, and 27 y associated with PCE alone, and co-exposure with tobacco. Importantly, we identified significantly differentially methylated CpG sites within the genes LZTS2, NPSR1, NT5E, CRIP2, DOCK8, COQ5, and LRP5 that are shared between different time points throughout development in offspring. Notably, functional pathway analysis showed enrichment for differential DNA methylation in neurodevelopment, neurotransmission, and neuronal structure pathways, and this was consistent across all timepoints in both cohorts. Given the increasing volume of epidemiological evidence that suggests a link between PCE and adverse neurodevelopmental outcomes in exposed offspring, this work highlights the need for further investigation into PCE, particularly in larger cohorts.

The importance of timing of socioeconomic disadvantage throughout development for depressive symptoms and brain structure

Prior studies have reported associations between socioeconomic disadvantage, brain structure and mental health outcomes, but the timing of these relations is not well understood. Using prospective longitudinal data from the Avon Longitudinal Study of Parents and Children (ALSPAC), this preregistered study examined whether socioeconomic disadvantage related differentially to depressive symptoms (n=3012–3530) and cortical and subcortical structures (n=460–733) in emerging adults, depending on the timing of exposure to socioeconomic disadvantage. Family income in early childhood and own income measured concurrently were both significantly related to depressive symptoms in emerging adulthood. Similar results were observed for perceived financial strain. In contrast, only family income in early childhood was associated with brain structure in emerging adulthood, with positive associations with intracranial volume and total and regional cortical surface area. The findings suggest that both objective and subjective aspects of one’s financial standing throughout development relate to depressive symptoms in adulthood, but that specifically early life family income is related to brain structural features in emerging adulthood. This suggests that associations between socioeconomic disadvantage and brain structure originate early in neurodevelopment, highlighting the role of timing of socioeconomic disadvantage.

Companion animals and child development outcomes: longitudinal and cross-sectional analysis of a UK birth cohort study

BackgroundResearch into the impact of social relationships on childhood and adolescent health and wellbeing has been largely limited to children’s relationships with other humans, while studies into the impact of pet ownership are sparse and have generally not adjusted for potential confounders. This study aimed to investigate the association between pet ownership and a range of developmental outcomes in childhood and adolescence.MethodsData were self-reports and direct assessments of approx. 14,000 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). Multivariable regression models adjusting for confounding factors examined associations between developmental outcome measures (emotional health, behavioural development, cognitive development, language development, educational attainment) and concurrent pet ownership, including species, and also longitudinal pet ownership history and pet-interaction where possible. Analyses model numbers using multiple imputation varied from n = 393–8963.ResultsIn cross-sectional analyses, owning a dog (b = 0.24, [0.06–0.41], p = .004) and owning other/miscellaneous pets (b = 0.18, [0.03–0.33], p = .021) at age 3 were associated with higher prosocial behaviour score. Owning a pet was associated with a higher non-verbal communication score at age 2 (cross-sectional, b = 0.18, [0.04–0.32], p = .014), and a higher language development score at age 5 (cross-sectional, b = 1.01, [0.18–1.83], p = .017). However, pet ownership was associated with lower educational attainment across a number of academic subjects and timepoints, in both cross-sectional and longitudinal analyses. It was also cross-sectionally linked to hyperactivity at age 3 and conduct problems at age 3 and 11. Furthermore, at age 8, cross-sectional analysis showed that children who owned any pets (OR [95% CI]: 0.85 [0.73–0.98], p= ·026) or cats (0.83, [0.73–0.95], p= ·006) had lower odds of high self-esteem (scholastic competence).ConclusionsUsing a large, well-designed longitudinal study and adjusting for key confounders, we found little evidence of cross-sectional or longitudinal associations between pet ownership and emotional health or cognitive outcomes in children. There may, however, be some cross-sectional and longitudinal association with poorer educational attainment and a positive impact on social interactions as seen through associations with enhanced language development and prosocial behaviour. This study demonstrates the importance of adjustment for confounding variables and suggests that, contrary to popular belief, positive impacts of pet ownership on childhood development may be mainly limited to social behaviour and language development.

A summary of pain and pain-related variables in the Avon Longitudinal Study of Parents and Children

A summary of pain and pain-related variables in the Avon Longitudinal Study of Parents and Children

An Examination of Sleep as a Protective Factor for Depression and Anxiety in the Perinatal Period: Novel Causal Analyses in a Prospective Pregnancy Cohort.

Sleep problems are common in the perinatal period. But the effects of sleep health on long-term postpartum depression and anxiety are underexamined. Using marginal structural models, we estimated the effect of sustained restful sleep quality, or adequate sleep quantity, or both, on clinically significant depression and anxiety at 23- and 32-weeks gestation, and 8-weeks, 8-, and 21-months postpartum. Women (n = 9,211) in the Avon Longitudinal Study of Parents and Children cohort reported on sleep quality (difficulty falling asleep, and early morning awakening), sleep quantity (< or > 5 hours and perceived sleep adequacy), depression (Edinburgh Postnatal Depression Scale), and anxiety (Crown-Crisp Experiential Index). Analyses adjusted for fixed (maternal education, age, body mass index, parity, marital status, smoking) and time varying (alcohol use, psychosocial adversities, depression, anxiety or sleep problems at prior time periods) covariates. Descriptive analyses suggest that sleep alterations persist beyond the immediate postpartum period. Estimates of counterfactual prevalences of outcomes under restful sleep quality and adequate sleep suggest a reduction of the population burden of clinically significant depression between 2.4% - 5.9%, and anxiety by 3.4% - 8.0% for the time points assessed. Interventions for perinatal sleep problems may reduce clinically significant depression and anxiety.

Generating synthetic identifiers to support development and evaluation of data linkage methods

We aimed to develop a framework for generating synthetic identifier datasets to support development and evaluation of data linkage methods. We evaluated whether replicating associations between attributes and identifiers improved the utility of the synthetic data for assessing linkage error. We determined the steps required to generate synthetic identifiers that replicate the properties of real-world data collection. We generated synthetic versions of a large United Kingdom cohort study (the Avon Longitudinal Study of Parents and Children), according to the quality and completeness of identifiers recorded over several waves of the cohort. We evaluated the utility of the synthetic identifier data in terms of assessing linkage quality (false matches and missed matches). Comparing data from two collection points in ALSPAC, we found within-person disagreement in identifiers (differences in recording due to both natural change and non-valid entries) in 18% of surnames and 12% of forenames. Rates of disagreement varied by maternal age and ethnic group. Synthetic data provided accurate estimates of linkage quality metrics compared with the original data (within 0.13-0.55% for missed matches and 0.00-0.04% for false matches). Incorporating associations between identifier errors and maternal age/ethnicity improved synthetic data utility. Replicating dependencies between attribute values (e.g. ethnicity), values of identifiers (e.g. name), identifier disagreements (e.g. missing values, errors or changes over time), and their patterns and distribution structure enables generation of realistic synthetic data that can be used for robust evaluation of linkage methods. Our framework provides a novel and generalisable mechanism for developing and benchmarking record linkage algorithms.

Does maternal education moderate the relationship between adolescent cannabis use and mental health in early adulthood?

Socioeconomic disadvantage has been associated with cannabis use and poor mental health. It is therefore hypothesised that lower maternal education, a proxy for socioeconomic disadvantage, may increase the risk of cannabis-related mental health and substance use consequences. A total of 5099 participants from the Avon Longitudinal Study of Parents and Children reported cannabis use via questionnaires at 16 or 18. Logistic regression was used to examine the relationship between any and regular (weekly or more) adolescent cannabis use with depression, anxiety, psychotic experiences, and problematic cannabis use at age 24. Maternal education was included as an effect modifier. Missing data were addressed through multiple imputation using chained equations. In total, 36.5% of participants reported adolescent cannabis use and, of these, 14% reported regular use. Adolescent cannabis use was associated with an increased likelihood of anxiety and problematic cannabis use; however, there was little evidence of moderation by maternal education. Regular cannabis use was associated with an increased likelihood of problematic cannabis use, with little evidence of moderation by maternal education. There was weak evidence that the association between regular cannabis use and depression (interaction p-value = 0.024) and anxiety (interaction p-value = 0.056) was stronger in people with high maternal education. Adolescent cannabis use is associated with increased risk of anxiety and cannabis use disorder, but there was insufficient evidence that childhood socioeconomic position (proxied by maternal education) modifies this relationship. Improved public health messages for all adolescents about these risks may be warranted.

The association between poverty and longitudinal patterns of adverse childhood experiences across childhood and adolescence: Findings from a prospective population-based cohort study in the UK

BackgroundAdverse childhood experiences (ACEs) affect up to half the general population, they are known to co-occur, and are particularly common among those experiencing poverty. Yet, there are limited studies examining specific patterns of ACE co-occurrence considering their developmental timing. ObjectiveTo examine the longitudinal co-occurrence patterns of ACEs across childhood and adolescence, and to examine the role of poverty in predicting these. Participants and settingThe sample was 8859 children from the Avon Longitudinal Study of Parents and Children, a longitudinal prospective population-based UK birth cohort. MethodsRepeated measures of ten ACEs were available, occurring in early childhood (birth-5 years), mid-childhood (6–10 years), and adolescence (11–16 years). Latent class analysis was used to identify groups of children with similar developmental patterns of ACEs. Multinomial regression was used to examine the association between poverty during pregnancy and ACE classes. ResultsSixteen percent of parents experienced poverty. A five-class latent model was selected: “Low ACEs” (72·0 %), “Early and mid-childhood household disharmony” (10·6 %), “Persistent parental mental health problems” (9·7 %), “Early childhood abuse and parental mental health problems” (5·0 %), and “Mid-childhood and adolescence ACEs” (2·6 %). Poverty was associated with a higher likelihood of being in each of the ACE classes compared to the low ACEs reference class. The largest effect size was seen for the “Early and mid-childhood household disharmony” class (OR 4·70, 95 % CI 3·68–6·00). ConclusionsA multifactorial approach to preventing ACEs is needed – including support for parents facing financial and material hardship, at-risk families, and timely interventions for those experiencing ACEs.

Inflammation Proteomic Profiling of Psychosis in Young Adults: Findings from the ALSPAC Birth Cohort

Psychotic disorder is associated with altered levels of various inflammatory markers in blood, but existing studies have typically focused on a few selected biomarkers, have not examined specific symptom domains notably negative symptoms, and are based on individuals with established/chronic illness. Based on data from young people aged 24 years from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK birth cohort, we have examined the associations of 67 plasma immune/inflammatory proteins assayed using the Olink Target 96 Inflammation panel with psychotic disorder, positive (any psychotic experiences and definite psychotic experiences) and negative symptoms, using linear models with empirical Bayes estimation. The analyses included between 2317 and 2854 individuals. After adjustment for age, sex, body mass index and smoking and correction for multiple testing, positive symptoms and psychotic disorder were consistently associated with upregulation of CDCP1 and IL-6, and psychotic disorder was additionally associated with upregulation of MMP-10. Negative symptoms were associated with upregulation of CDCP1 and TRAIL. CDCP1 and MMP-10 are novel markers of psychosis identified in this study, and are involved in immune regulation, immune cell activation/migration, blood-brain barrier disruption, and extracellular matrix abnormalities. Our findings highlight psychosis symptom domains have overlapping and distinct immune associations, and support a role of inflammation and immune dysfunction in the pathogenesis of psychosis.

Associations between early experiences of thought interference and auditory-verbal hallucinations with first-rank symptoms and suicidality in adulthood

Background Suicide is one of the major causes of premature death in patients diagnosed with a schizophrenia-spectrum psychotic disorder. However, associations between psychotic-like experiences in youth and suicidality in later life remain under-researched. Aims We aimed to investigate any associations between early experiences of thought interference and auditory-verbal hallucinations (AVHs) with first-rank symptoms of schizophrenia and suicidal thoughts and behaviours in adulthood. Method This study used data from the Avon Longitudinal Study of Parents and Children (ALSPAC). We calculated combined thought interference score at ages 11 years 8 months, 13 years 1 month, 14 years 1 month and 16 years 6 months. We also assessed AVHs at the same age points. For outcome variables, we used specific variables measuring delusions of control, AVHs and suicidality at 24 years of age. We carried out logistic regressions and mediation analyses to assess the relationships among these variables. Results Thought interference and AVHs at all ages throughout childhood and adolescence were associated with suicidal thoughts and behaviours, and also with clinically more significant symptoms of delusions of control and AVHs at age 24. Substance use-induced psychotic-like experiences mediated a large proportion of the relationship between early psychotic-like experiences and suicidality in later life. Conclusions Thought interference and AVHs in childhood and adolescence are associated with first-rank symptoms and suicidality in adulthood. Mental health interventions in children and adolescents need to take into account the impact of specific psychotic-like experiences and allow for the early detection of thought interference and AVH-related symptoms.

Exploring the importance of family socio-economic position on the association between parental BMI and offspring BMI trajectories

PurposeWe aimed to investigate the associations between parental BMI and offspring BMI trajectories and to explore whether the parent-offspring BMI growth trajectory association differed according to family SEP or social mobility. MethodsWe used data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Children’s weight and height were collected from 1 to 18 years. Parents’ height and weight were reported pre-pregnancy. We assessed family SEP by measuring parents’ and grandparents’ educational attainment, social class, and social mobility by changes in education attainment across generations. Multilevel models were used to develop trajectories and assess patterns of change in offspring BMI, to associate parental BMI with these trajectories, and explore whether these associations differed by family SEP and social mobility. Results13,612 children were included in the analyses. The average BMI of offspring whose parents were overweight or obese was higher throughout childhood and adolescence, compared to those with parents of normal BMI. Parental and grandparental low SEP were associated with higher child BMI, but there was little evidence of modification of parent-offspring associations. For example, at age 15 years the predicted mean BMI difference between children of overweight or obese mothers versus normal-weight mothers was 12.5 % (95 %CI: 10.1 % to 14.7 %) and 12.2 % (95 %CI: 10.3 % to 13.7 %) for high and low grandparental SEP, respectively. DiscussionThese findings strengthen the evidence that higher parental BMI and lower family SEP were associated with higher offspring BMI, but we did not observe strong evidence that family SEP modifies the parental-offspring BMI association.

Analyses Using Multiple Imputation Need to Consider Missing Data in Auxiliary Variables.

Auxiliary variables are used in multiple imputation (MI) to reduce bias and increase efficiency. These variables may often themselves be incomplete. We explored how missing data in auxiliary variables influenced estimates obtained from MI. We implemented a simulation study with three different missing data mechanisms for the outcome. We then examined the impact of increasing proportions of missing data and different missingness mechanisms for the auxiliary variable on bias of an unadjusted linear regression coefficient and the fraction of missing information. We illustrate our findings with an applied example in the Avon Longitudinal Study of Parents and Children. We found that where complete records analyses were biased, increasing proportions of missing data in auxiliary variables, under any missing data mechanism, reduced the ability of MI including the auxiliary variable to mitigate this bias. Where there was no bias in the complete records analysis, inclusion of a missing not at random auxiliary variable in MI introduced bias of potentially important magnitude (up to 17% of the effect size in our simulation). Careful consideration of the quantity and nature of missing data in auxiliary variables needs to be made when selecting them for use in MI models.

Longitudinal relationships between early-life homelessness and school-aged asthma and wheezing

BackgroundHomelessness is a disruptive life event with profound impacts on children’s health. It remains unclear, however, whether homelessness in early life has an enduring association with asthma and wheezing among...

Longitudinal characterization of impulsivity phenotypes boosts signal for genomic correlates and heritability.

Genomic correlates of impulsivity have been identified in several genome-wide association studies (GWAS) using cross-sectional designs, but no studies have investigated the molecular genetic correlates of impulsivity phenotypes using longitudinally constructed traits. In 3860 unrelated European participants in the Avon Longitudinal Study of Parents and Children (ALSPAC), we constructed longitudinal phenotypes for delay discounting and impulsive personality traits (as measured by the UPPS-P impulsive behavior scales) via assessment at ages 24, 26, and 28. We conducted GWASs of impulsivity using both cross-sectional and longitudinal phenotypes, estimated heritability and their phenotypic and genetic correlations, and evaluated their association with recently-developed polygenic risk scores (PRSs) for the impulsivity indicators themselves and also related psychiatric conditions. Latent growth curve modeling revealed a stable intercept over time for all impulsivity phenotypes. High genetic correlation of cross-sectional measures over time suggested a stable genetic component for delay discounting (rg = 0.53-0.99) and sensation seeking (rg = 0.99). Heritability estimates of the stable longitudinal phenotypes substantively improved as compared to their cross-sectional counterparts, revealing a significant SNP-heritability for delay discounting (0.22; p = 0.03) and sensation seeking (0.35; p = 0.0007). Consistent with previous reports, GWAS and gene-based analyses revealed associations between specific longitudinal impulsivity indicators and CADM2 and NCAM1 genes. The PRSs for the impulsivity indicators and disorders related to self-regulation were also significantly associated with longitudinal impulsivity traits. Finally, we validated the associations between longitudinal impulsivity phenotypes and their PRSs in an independent 13-wave longitudinal study (n = 1019) and the benefit of longitudinal phenotypes in simulation studies. In this first longitudinal genetic study of impulsivity traits, the results revealed stable genomic correlates of delay discounting and sensation seeking over time and further validated the utility of recently-developed PRSs, both in relation to the observed traits and in connecting them to psychiatric disorders. More generally, these findings support using latent intercepts as novel longitudinal phenotypes to boost signal for heritability and genomic correlates of mechanisms contributing to psychiatric disease liability.

The Chain Mediation Effect of Victimization and Neuroticism on the Association Between Sexual Orientation and Depressive Symptoms: A Prospective Birth Cohort Study.

This study tested whether sexual orientation differences in depressive symptoms were partially explained by the chain mediation effect of neuroticism and victimization. Using the Avon Longitudinal Study of Parents and Children from the UK (N = 4647, 36.52% men, 88% White), self-reported neuroticism, sexual orientation, and depressive symptoms were measured at age 13.5, 21, and 22years, respectively. Childhood abuse between birth and age 11years and the individuals' experiences of being bullied at age 17.5years were measured as the components of victimization. Structural equation modeling was used to analyze the data. Non-heterosexual individuals reported higher depressive symptoms than heterosexual individuals, with a total effect (standardized path coefficient) of 0.590 and 0.768 for men and women, respectively. This association was partially explained by childhood abuse (indirect effect = 0.043 and 0.046 for men and women, respectively) and neuroticism directly (indirect effect = 0.036 and 0.056 for men and women, respectively). Sexual orientation differences in depressive symptoms were also partially explained by a path through increased risk of experiencing childhood abuse leading to higher levels of neuroticism (indirect effect = 0.004 and 0.009 for men and women, respectively) and by a path through higher levels of neuroticism leading to increased risk of being bullied (indirect effect = 0.004 and 0.002 for men and women, respectively). The findings suggest that while some of the association between sexual orientation and depression might be explained by neuroticism and experiences of victimization measured prospectively, these factors do not account for most of this relationship.

Later eating rhythm measured in children at 7 years of age in the ALSPAC cohort.

Later eating rhythm (LER) refers to later timing, greater energy intake (EI), and higher frequency of eating occasions (meal/snack) in the evening. The significance of LER in child health is becoming increasingly recognised. However, the lack of consensus regarding definitions of LER make it challenging to fully comprehend its role. This data note describes LER variables derived in the Avon Longitudinal Study of Parents and Children (ALSPAC), an ongoing birth cohort which enrolled 14,541 pregnant women living in Avon, UK, with an expected date of delivery between April 1991 - December 1992. When children were 7 years, parents completed a structured 3-day food diary, recording all foods/drinks consumed over 3 days (preferably 1 weekend day and 2 weekdays). Data was available for 7,285 children (50.1% response rate). A subsample of 4,869 children had exact time of eating occasions added to the existing database, which only included broad indications of eating timing based on 2-7 hour long meal slots. 13 LER variables were derived for the entire week and weekdays/weekend days separately. These comprise: 1) eating around individual bedtime (number days); 2) eating around average bedtime (number days); 3) time of evening main meal (hrs:mins); 4) time of last eating occasion (hrs:mins); 5) EI in the evening (percentage of total daily energy intake, %TDEI); 6) EI within 2hrs before bedtime (%TDEI); 7) EI for evening main meal (%TDEI); 8) EI for evening snacks (%TDEI); 9) Night eating1 (NE1): eating over 30% of total daily energy intake after 18:00 (number days); 10) NE2: eating over 25% of total daily energy intake within 2hrs before bedtime (number days); 11) eating frequency after 17:00 (number of eating occasions); 12) regularity of dinner (number of days); 13) frequency of evening snacks (number days). We describe the derivation, prevalence and inter-corelations between LER variables.

Trajectories of Inflammation in Youth and Risk of Mental and Cardiometabolic Disorders in Adulthood

Research suggests that low-grade, nonresolving inflammation may predate adult mental and physical illness. However, evidence to date is largely cross-sectional or focuses on single disorder outcomes. To examine trajectories of inflammation as measured by C-reactive protein (CRP) levels in a large sample of children and adolescents, and to explore associations between different identified trajectories and mental and related cardiometabolic health outcomes in early adulthood. In a longitudinal cohort study using data from the large UK-based Avon Longitudinal Study of Parents and Children (ALSPAC), latent class growth analysis (LCGA) was used to explore different trajectories of inflammation, with logistic regression exploring association with mental and physical health outcomes. Participants with measurable CRP data and associated mental and cardiometabolic health outcomes recorded were included in the analysis. Data analysis was performed from May 1, 2023, to March 30, 2024. Inflammation was assessed via CRP levels at ages 9, 15, and 17 years. LCGA was used to identify different trajectories of inflammation. Outcomes assessed at age 24 years included psychotic disorders, depressive disorders, anxiety disorders, hypomania, and, as a measure of insulin resistance, Homeostasis Model Assessment (HOMA2) score. A total of 6556 participants (3303 [50.4%] female) were included. Three classes of inflammation were identified: persistently low CRP levels (reference class, n = 6109); persistently raised CRP levels, peaking at age 9 years (early peak, n = 197); and persistently raised CRP levels, peaking at age 17 years (late peak, n = 250). Participants in the early peak group were associated with a higher risk of psychotic disorder (odds ratio [OR], 4.60; 95% CI, 1.81-11.70; P = .008), a higher risk of severe depression (OR, 4.37; 95% CI, 1.64-11.63; P = .02), and higher HOMA2 scores (β = 0.05; 95% CI, 0.01-0.62, P = .04) compared with participants with persistently low CRP. The late peak group was not associated with any outcomes at age 24 years. Low-grade systemic inflammation peaking in midchildhood was associated with specific mental and cardiometabolic disorders in young adulthood. These findings suggest that low-grade persistent inflammation in early life may be an important shared common factor for mental-physical comorbidity and so could be relevant to future efforts of patient stratification and risk profiling.

Mapping associations of polygenic scores with autistic and ADHD traits in a single city region.

The genetic and environmental aetiology of autistic and Attention Deficit Hyperactivity Disorder (ADHD) traits is known to vary spatially, but does this translate into variation in the association of specific common genetic variants? We mapped associations between polygenic scores for autism and ADHD and their respective traits in the Avon Longitudinal Study of Parents and Children (N = 4,255-6,165) across the area surrounding Bristol, UK, and compared them to maps of environments associated with the prevalence of autism and ADHD. Our results suggest genetic associations vary spatially, with consistent patterns for autistic traits across polygenic scores constructed at different p-value thresholds. Patterns for ADHD traits were more variable across thresholds. We found that the spatial distributions often correlated with known environmental influences. These findings shed light on the factors that contribute to the complex interplay between the environment and genetic influences in autistic and ADHD traits.

Adolescent Psychotic Experiences and Adverse Mental Health Outcomes in Adulthood in a General Population Sample.

This study estimated risk of incident mental disorders in adulthood associated with both transient and persistent adolescent psychotic experiences (PEs). A nested case-control design was used within the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth cohort study which recruited expectant mothers from 1991-1992. Participants consisted of 8822 offspring of ALSPAC mothers who completed the Psychosis-like Symptoms Interview Questionnaire (PLIKSi-Q). PEs were assessed using the PLIKSi-Q. Depressive disorders were assessed using the Short Mood and Feelings Questionnaire (SMFQ), anxiety disorders using the General Anxiety Disorder Assessment and the Clinical Interview Schedule-Revised, and psychotic disorder using the PLIKSi. Risk of incident depressive disorder, GAD, psychotic disorder, and past-year suicide attempts were compared amongst participants who had ever versus never reported a PE and those who reported persistent versus transient PEs. Adolescent PEs were associated with increased risk for incident depressive disorder (adjusted hazard ratio (aHR) = 1.62, 95% CI = 1.42, 1.84), GAD (aHR 1.23, 95% CI = 1.03, 1.47), psychotic disorder (adjusted odds ratio (aOR) = 5.08, 95% CI = 2.02, 12.79), and past-year suicide attempts (aHR = 2.56, 95% CI = 1.97, 3.25). Persistent PEs were associated with increased risk for depressive disorder (aHR = 1.81, 95% CI = 1.55, 2.12), generalized anxiety disorder (aHR = 1.34, 95% CI = 1.07, 1.68), and psychotic disorder (aOR = 7.39, 95% CI = 2.43, 22.19) but not past-year suicide attempts. Adolescent PEs are a risk factor for multiple mental disorders and suicide attempts, with persistent PEs conferring greater risk. Identifying interventions for adolescents who report PEs, particularly persistent PEs, could lessen the burden of multiple mental health disorders and suicide attempts.

The role of body image dissatisfaction in the relationship between body size and disordered eating and self-harm: complimentary Mendelian randomization and mediation analyses.

Disordered eating and self-harm commonly co-occur in young people suggesting potential for shared underlying causes. Body image dissatisfaction (BID) has been recognised as a psychological correlate of body size, associated with both disordered eating and self-harm. However, the investigation into etiological pathways early in the lifecourse to provide detail on how body size and BID may foster disordered eating and self-harm remains largely unexplored. Employing data from two large population-based cohorts, the UK Biobank and the Avon Longitudinal Study of Parents And Children (ALSPAC), we conducted bidirectional Mendelian randomization (MR) to determine the causal direction of effect between genetically predicted prepubertal body size and two measures of BID indicating (i) desire to be smaller, and (ii) desire to be larger. We then used multivariable regression followed by counterfactual mediation analyses. Bidirectional MR indicated robust evidence that increased genetically predicted prepubertal body size increased desire to be smaller and decreased desire to be larger. Evidence for the reverse causal direction was negligible. These findings remained very similar across sensitivity analyses. In females and males, multivariable regression analyses demonstrated that being overweight increased the risk of disordered eating (risk ratio (RR), 95% confidence interval (CI): 1.19, 1.01 to 1.40 and 1.98, 1.28 to 3.05, respectively) and self-harm (RR, 95% CI: 1.35, 1.04 to 1.77 and 1.55, 0.86 to 2.81, respectively), while being underweight was protective against disordered eating (RR, 95% CI: 0.57, 0.40 to 0.81 and 0.81, 0.38 to 1.73, respectively). There was weak evidence of an increase in the risk of self-harm among underweight individuals. Mediation analyses indicated that the relationship between being overweight and subsequent disordered eating was largely mediated by the desire to be smaller. Our research carries important public health implications, suggesting distinct risk profiles for self-harm and disordered eating in relation to weight and body image. In addition, a better understanding of genetically predicted prepubertal BID may be valuable in the prevention and treatment of disordered eating and self-harm in adolescence.