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Background and Hypothesis: Childhood adversity is often described as a potential cause of incident psychotic experiences, but the underlying mechanisms are not well understood. We aimed to examine the mediating role of cognitive and psychopathological factors in the relation between childhood adversity and incident psychotic experiences in early adulthood., Study Design: We analyzed data from the Avon Longitudinal Study of Parents and Children, a large population-based cohort study. Childhood adversity was measured prospectively from birth to age 11 years, mediators (anxiety, depression, external locus of control [LoC], negative symptoms) were assessed at approximately 16 years of age, and incident psychotic experiences were assessed at ages 18 and 24 years. Mediation was examined via the counterfactual g-computation formula., Study Results: In total, 7% of participants had incident suspected or definite psychotic experiences in early adulthood. Childhood adversity was related to more incident psychotic experiences (ORadjusted = 1.34, 95% CI = 1.21; 1.49), and this association was partially mediated via all mediators examined (proportion mediated: 19.9%). In separate analyses for each mediator, anxiety, depression, external LoC, and negative symptoms were all found to mediate the link between adversity and incident psychotic experiences. Accounting for potential confounders did not modify our results., Conclusions: Our study shows that cognitive biases as well as mood symptomatology may be on the causal pathway between early-life adversity and the development of psychotic experiences. Future studies should determine which mediating factors are most easily modifiable and most likely to reduce the risk of developing psychotic experiences., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Mediation analysis can be applied in medical research with the aim of understanding the pathways that operate between an exposure and its effects on an outcome. This method can help to improve our understanding of pathophysiologic mechanisms and may guide the choice of potential treatment strategies. Traditional mediation analysis decomposes the total effect of an intervention on the outcome into 2 effects: (1) an indirect effect, from exposure using a mediator to the outcome, and (2) a direct effect, directly from exposure to outcome. A limitation of this method is that it assumes no interaction between the exposure and the mediator, which can either lead to an over- or underestimation of clinically relevant effects. The "4-way decomposition" method has the advantage of overcoming this limitation. Specifically, the total effect of an exposure on the outcome is decomposed into 4 elements: (1) reference interaction (interaction only), (2) mediated interaction (mediation and interaction), (3) the pure indirect effect (mediation but not interaction), and (4) the direct effect (no mediation and no interaction). We provide a guide to select the most appropriate method to investigate and decompose any causal effect given the research question at hand. We explain the application of the 4-way decomposition and illustrate this with a real-world example of how aerobic exercise may influence motor function in persons with Parkinson disease.

Latent classes are a useful tool in developmental research, however there are challenges associated with embedding them within a counterfactual mediation model. We develop and test a new method "updated pseudo class draws (uPCD)" to examine the association between a latent class exposure and distal outcome that could easily be extended to allow the use of any counterfactual mediation method. UPCD extends an existing group of methods (based on pseudo class draws) that assume that the true values of the latent class variable are missing, and need to be multiply imputed using class membership probabilities. We simulate data based on the Avon Longitudinal Study of Parents and Children, examine performance for existing techniques to relate a latent class exposure to a distal outcome ("one-step," "bias-adjusted three-step," "modal class assignment," "non-inclusive pseudo class draws," and "inclusive pseudo class draws") and compare bias in parameter estimates and their precision to uPCD when estimating counterfactual mediation effects. We found that uPCD shows minimal bias when estimating counterfactual mediation effects across all levels of entropy. UPCD performs similarly to recommended methods (one-step and bias-adjusted three-step), but provides greater flexibility and scope for incorporating the latent grouping within any commonly-used counterfactual mediation approach.

This study aimed to investigate alternative approaches to a cumulative risk score in the relationship between adverse childhood experiences (ACEs) and crime. Using data from the 1993 Pelotas (Brazil) Birth Cohort (n = 3236), we measured 12 ACEs up to 15 years, and past-year violent and non-violent crime at 22 years. We used four analytical approaches: single adversities, cumulative risk, latent class analysis, and network analysis. When examined individually, physical abuse, emotional abuse, and domestic violence were associated with both crime outcomes, whereas maternal mental illness and discrimination were associated with violent crime only, and parental divorce and poverty with non-violent crime only. There was a cumulative effect of ACEs on crime. The class with child maltreatment and household challenges was associated with both crime outcomes; exposure to household challenges and social risks was associated with violent crime only. In network models, crime showed conditional associations with physical abuse, maternal mental illness, and parental divorce. Although cumulative ACEs did associate with crime, some individual and combinations of ACEs showed particularly strong and robust effects, which were not captured by the cumulative score. Many ACEs are closely connected and/or cluster together, and the usefulness of the ACE score needs to be further evaluated., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background: The negative impacts of maternal depression on child mental health outcomes are well-documented. However, some children show adaptive functioning following exposure to maternal depression, demonstrating resilience. In a large birth cohort from Brazil, a middle-income country, we examined direct and indirect pathways, considering socioeconomic, family, and individual factors, contributing to the development of resilience., Methods: Using data from the 2004 Pelotas Birth Cohort ( N  = 4231), we restricted the sample to those exposed to maternal depression up to age 6 years (depression present at ≥2 out of 5 assessment waves; n  = 1132; 50% boys). Resilience was defined as scoring below or equal to the mean of the unexposed group on all four problem subscales of the parent-report Strengths and Difficulties Questionnaire at age 11 years. We examined pathways from socioeconomic status (SES; measured at birth) to resilience via cognitive stimulation (CS) (at 24 and 48 months) and Intelligence quotient (IQ) (at 6 years), and from CS to resilience via IQ, using counterfactual mediation., Results: A minority of children exposed to maternal depression showed resilience (12.4%). There was evidence of indirect pathways from SES to resilience via CS (odds ratio (OR) = 1.76, 95% confidence interval (CI) 1.02-3.38) and IQ (OR = 1.19, 95% CI 1.01-1.42), such that higher SES was associated with resilience via both higher levels of CS and higher IQ, which, in turn, were each positively associated with resilience. Furthermore, there was evidence of a direct (OR = 1.86, 95% CI 1.01-3.76) and total effect (OR = 1.94, 95% CI 1.05-3.89) of CS on resilience, even after controlling for SES. However, these effects varied depending on how persistent and severe depression was defined., Conclusions: These findings suggest that CS in early childhood may represent a modifiable protective factor for children exposed to maternal depression and a promising intervention target to promote child resilience in the context of maternal depression exposure., Competing Interests: Graeme Fairchild is on the JCPP Advances Editorial Advisory Board. The remaining authors have declared that they have no competing or potential conflicts of interest., (© 2023 The Authors. JCPP Advances published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: The role of alcohol use in the development of depression is unclear. We aimed to investigate whether alcohol dependence, but not high frequency or quantity of consumption, during adolescence increased the risk of depression in young adulthood., Methods: In this prospective cohort study, we included adolescents who were born to women recruited to the Avon Longitudinal Study of Parents and Children in Avon, UK, with delivery dates between April 1, 1991, and Dec 31, 1992. Alcohol dependence and consumption were measured at about age 16 years, 18 years, 19 years, 21 years, and 23 years using the self-reported Alcohol Use Disorders Identification Test, and at about age 18 years, 21 years, and 23 years using items corresponding to DSM-IV symptoms. The primary outcome was depression at age 24 years, assessed using the Clinical Interview Schedule Revised. Analyses were probit regressions between growth factors for alcohol dependence and consumption and depression, before and after adjustments for confounders: sex, housing tenure, maternal education, maternal depressive symptoms, parents' alcohol use, conduct problems at age 4 years, being bullied from age 12-16 years, and frequency of smoking cigarettes or cannabis. Adolescents were included in analyses if they had data from at least one timepoint for alcohol use and confounders., Findings: We included 3902 adolescents (2264 [58·0%] female; 1638 [42·0%] male) in our analysis, and 3727 (96·7%) of 3853 participants with data on ethnicity were White. After adjustments, we found a positive association between alcohol dependence at 18 years of age (latent intercept) and depression at 24 years of age (probit coefficient 0·13 [95% CI 0·02 to 0·25]; p=0·019), but no association between rate of change (linear slope) and depression (0·10 [-0·82 to 1·01]; p=0·84). There was no evidence of an association between alcohol consumption and depression (latent intercept probit coefficient -0·01 [-0·06 to 0·03]; p=0·60; linear slope 0·01 [-0·40 to 0·42]; p=0·96) after adjustments., Interpretation: Psychosocial or behavioural interventions that reduce the risk of alcohol dependence during adolescence could contribute to preventing depression in young adulthood., Funding: UK Medical Research Council and Alcohol Research UK (grant number MR/L022206/1)., Competing Interests: Declaration of interests MH has served as Trustee of Society of Study of Addiction and Regional Editor of Addiction in the past 3 years. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Characterizing patterns of mental phenomena in epidemiological studies of adolescents can provide insight into the latent organization of psychiatric disorders. This avoids the biases of chronicity and selection inherent in clinical samples, guides models of shared aetiology within psychiatric disorders and informs the development and implementation of interventions. We applied Gaussian mixture modelling to measures of mental phenomena from two general population cohorts: the Avon Longitudinal Study of Parents and Children (ALSPAC, n = 3018) and the Neuroscience in Psychiatry Network (NSPN, n = 2023). We defined classes according to their patterns of both positive (e.g. wellbeing and self-esteem) and negative (e.g. depression, anxiety, and psychotic experiences) phenomena. Subsequently, we characterized classes by considering the distribution of diagnoses and sex split across classes. Four well-separated classes were identified within each cohort. Classes primarily differed by overall severity of transdiagnostic distress rather than particular patterns of phenomena akin to diagnoses. Further, as overall severity of distress increased, so did within-class variability, the proportion of individuals with operational psychiatric diagnoses. These results suggest that classes of mental phenomena in the general population of adolescents may not be the same as those found in clinical samples. Classes differentiated only by overall severity support the existence of a general, transdiagnostic mental distress factor and have important implications for intervention., (© 2021. The Author(s).)

Background: Emotional dysregulation may be a risk factor for disordered eating and self-harm in young people, but few prospective studies have assessed these associations long-term, or considered potential mediators. We examined prospective relationships between childhood emotional dysregulation and disordered eating and self-harm in adolescence; and social cognition, emotional recognition, and being bullied as mediators., Methods: We analysed Avon Longitudinal Study of Parents and Children data on 3,453 males and 3,481 females. We examined associations between emotional dysregulation at 7 years and any disordered eating and any self-harm at 16 years with probit regression models. We also assessed whether social cognition (7 years), emotional recognition (8 years) and bullying victimisation (11 years) mediated these relationships., Results: Emotional dysregulation at age 7 years was associated with disordered eating [fully adjusted probit B (95% CI) = 0.082 (0.029, 0.134)] and self-harm [fully adjusted probit B (95% CI) = 0.093 (0.036, 0.150)] at age 16 years. There was no evidence of sex interactions or difference in effects between self-harm and disordered eating. Mediation models found social cognition was a key pathway to disordered eating (females 51.2%; males 27.0% of total effect) and self-harm (females 15.7%; males 10.8% of total effect). Bullying victimisation was an important pathway to disordered eating (females 17.1%; males 10.0% of total effect), but only to self-harm in females (15.7% of total effect). Indirect effects were stronger for disordered eating than self-harm., Conclusions: In males and females, emotional dysregulation in early childhood is associated with disordered eating and self-harm in adolescence and may be a useful target for prevention and treatment. Mediating pathways appeared to differ by sex and outcome, but social cognition was a key mediating pathway for both disordered eating and self-harm., (© 2022 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

There is considerable variability in developmental outcomes of children whose mothers experience depression. Few longitudinal studies have examined contributions of paternal involvement in the association between maternal postnatal depression (PND) and offspring development. We examined pathways from maternal PND at 8 weeks (Edinburgh Postnatal Depression Scale; total score) to offspring emotional and behavioral development at 7 years (Strengths and Difficulties Questionnaire; total score) through behavioral, affective, and cognitive dimensions of paternal involvement in a U.K.-based birth cohort (Avon Longitudinal Study of Parents and Children; n = 3,434). Analyses were adjusted for baseline confounders and paternal PND (Edinburgh Postnatal Depression Scale; total score) as an intermediate confounder. Maternal PND was strongly associated with offspring development, but this association was not mediated by the combination of all indirect pathways through various dimensions of paternal involvement. Only father-child conflict emerged as a risk factor for adverse offspring development and as a mediator in the association between maternal PND and offspring development (albeit the effect size was small). If found causal, interventions that reduce father-child conflict may reduce the risk of adverse development in offspring of mothers with PND. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Little is known on whether associations between childhood autistic traits and psychotic experiences persist into adulthood and whether genetic confounding and childhood trauma influence them. Here we investigate the associations between childhood autistic traits and psychotic experiences until young adulthood and assess the influence of schizophrenia polygenic risk and childhood traumatic experiences, using the Avon Longitudinal Study of Parents and Children (ALSPAC) population-based birth cohort., Study Design: We used a measure of broad autistic traits (autism factor mean score), and four dichotomised measures of autistic traits capturing social communication difficulties (age 7), repetitive behaviours (age 5), sociability (age 3), and pragmatic language (age 9). Psychotic experiences were assessed at ages 18 and 24 using the semi-structured Psychosis-Like Symptoms interview (PLIKSi). Traumatic experiences between ages 5 and 11 were assessed with questionnaires and interviews administered to children and parents at multiple ages., Study Results: Broad autistic traits, as well as social communication difficulties, were associated with psychotic experiences that were distressing and/or frequent until age 24 (autism factor mean score, n = 3707: OR 1.19, 95%CI 1.01-1.39; social communication difficulties, n = 3384: OR 1.54, 95%CI 0.97-2.45). Childhood trauma mediated a substantial proportion of the identified associations (~28% and 36% respectively, maximum n = 3577). Schizophrenia polygenic risk did not appear to confound the associations. Multiple imputation analyses (maximum n = 13 105) yielded comparable results., Conclusions: Childhood trauma may be an important, potentially modifiable pathway between autistic features and later onset of psychotic psychopathology., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background: Childhood trauma is a proposed transdiagnostic risk factor for psychopathology, but epidemiological evidence from low-income and middle-income countries (LMICs) is scarce. We investigated associations between trauma and child psychiatric disorders in a birth cohort in Brazil., Methods: The 2004 Pelotas Birth Cohort is an ongoing, population-based, prospective birth cohort, including all hospital births occurring between Jan 1 and Dec 31, 2004, in the city of Pelotas, Brazil. When the children were aged 6 and 11 years, trained psychologists administered the Development and Well-Being Assessment clinical interview to caregivers to assess current child psychiatric disorders (anxiety disorders, mood disorders, ADHD and hyperactivity disorders, and conduct and oppositional disorders), and lifetime trauma exposure (ie, experiencing or witnessing life-threatening events) including interpersonal and non-interpersonal events. Analyses used multiple imputation and logistic regression models., Outcomes: Of 4263 live births, 4231 children were included in the study sample, and 4229 (2195 [51·9%] boys and 2034 [48·1%] girls; 2581 [61·7%] with White mothers and 1600 [38·3%] with Black or mixed race mothers) were included in the imputed analyses. 1154 (34·3%) of 3367 children with complete data at age 11 years had been exposed to trauma by that age. After adjusting for confounders, at age 6 years, trauma was associated with increased odds of anxiety disorders (adjusted odds ratio 1·79 [95% CI 1·33-2·42]) and any psychiatric disorder (1·59 [1·22-2·06]), and at age 11 years, with any psychiatric disorder (1·45 [1·17-1·79]) and all four specific diagnostic classes of anxiety disorders (1·47 [1·04-2·09]), mood disorders (1·66 [1·08-2·55]), ADHD and hyperactivity disorders (1·47 [1·01-2·13]), and conduct and oppositional disorders (1·76 [1·19-2·61]). Interpersonal trauma and non-interpersonal trauma were each associated with increased odds of multiple psychiatric disorders, even when adjusting for their co-occurrence., Interpretation: A considerable mental health burden associated with childhood trauma is already evident by middle childhood in this sample from Brazil. Evidence-based efforts to reduce the incidence of childhood trauma in Brazil and address its consequences are urgently needed., Funding: Children's Pastorate, WHO, National Support Program for Centres of Excellence, Brazilian National Research Council, Brazilian Ministry of Health, São Paulo Research Foundation, University of Bath, Wellcome Trust., Translation: For the Portuguese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Maternal postnatal depression (PND) is a risk factor for offspring depression in adulthood. However, few longitudinal studies have examined the role of maternal nurturing parenting behaviours in the association between maternal PND and offspring depression in adulthood. Methods: We examined pathways from maternal PND measured using self-reported Edinburgh Postnatal Depression Scale at 8 weeks to offspring ICD-10 depression diagnosed using the Clinical Interview Schedule-Revised computerised assessment at 24 years through maternal-reported nurturing behaviours concerning feeding, sleeping and crying measured from pregnancy to age 3 years 6 months in 5,881 members of the UK-based birth cohort study, the Avon Longitudinal Study of Parents and Children.   Results: The fully adjusted model revealed an indirect effect from PND to adult offspring depression through the combination of all parenting factors (probit regression coefficient [ B ]=0.038, 95% confidence interval [CI] 0.005, 0.071); however, there was no evidence of a direct effect from early maternal PND to offspring depression once the indirect effect via parenting factors was accounted for ( B =0.009, 95%CI -0.075, 0.093). Specificity analyses revealed indirect effects through maternal worries about feeding ( B =0.019, 95%CI 0.003, 0.035, p=0.010) and maternal perceptions and responses to crying ( B =0.018, 95%CI 0.004, 0.032, p=0.012). Conclusions: The adverse impact of maternal PND on offspring depression in early adulthood was explained by maternal nurturing behaviours concerning feeding, crying and sleeping in early childhood. Residual confounding and measurement error likely limit reliable conclusions. If found causal, interventions providing support to reduce worries around maternal nurturing behaviours and treating depression could reduce adverse outcomes in adult offspring of depressed mothers., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Culpin I et al.)

Background: Traumatic experiences are associated with a higher risk of psychotic illnesses, but little is known about potentially modifiable mechanisms underlying this relationship. This study aims to examine whether post-traumatic stress disorder (PTSD) symptoms mediate the relationship between trauma and psychotic experiences (PEs)., Methods: We used data from the Avon Longitudinal Study of Parents and Children to examine whether: PTSD symptoms mediate the relationships between (a) childhood trauma and adolescent PEs (study of adolescent PEs; n = 2952), and (b) childhood/adolescent trauma and PEs in early adulthood (study of adult PEs; n = 2492). We examined associations between variables using logistic regression, and mediation using the parametric g-computation formula., Results: Exposure to trauma was associated with increased odds of PEs (adolescent PEs: OR adjusted 1.48, 95% CI 1.23-1.78; adult PEs: OR adjusted 1.57, 95% CI 1.25-1.98) and PTSD symptoms (adolescent PTSD: OR adjusted 1.59, 95% CI 1.31-1.93; adult PTSD: OR adjusted 1.50, 95% CI 1.36-1.65). The association between PTSD symptoms and PE was stronger in adolescence (OR adjusted 4.63, 95% CI 2.34-9.17) than in adulthood (OR adjusted 1.62, 95% CI 0.80-3.25). There was some evidence that PTSD symptoms mediated the relationship between childhood trauma and adolescent PEs (proportion mediated 14%), though evidence of mediation was weaker for adult PEs (proportion mediated 8%)., Conclusions: These findings are consistent with the hypothesis that PTSD symptoms partly mediate the association between trauma exposure and PEs. Targeting PTSD symptoms might help prevent the onset of psychotic outcomes.

Background: Parental depression is associated with a range of mental health conditions and other difficulties in the offspring. Nevertheless, some offspring exposed to parental depression do not develop mental health problems, indicating the presence of protective factors that may buffer parental depression-related risk effects. However, evidence of protective factors that might explain good sustained mental health in offspring of depressed parents is limited and systematic synthesis of these factors is still needed. Therefore, as far as we are aware, this will be the first systematic review that will identify parent, family, child, social, and lifestyle factors associated with mental health resilience in offspring of depressed parents, examine evidence for sex-, developmental stage-, and outcome-specific factors and define mental health resilience in the parental depression context., Methods: This protocol has been developed according to the PRISMA-P guidelines. Electronic searches will be performed for articles published up to 2022 in PsycINFO, Embase, MEDLINE, Web of Science Core Collection, and Cochrane Library. Two reviewers will independently screen titles/abstracts and full-texts against eligibility criteria, extract the data, and assess the overall quality of evidence. Both observational and RCT studies will be eligible for inclusion if they report offspring mental health resilience/outcome and depressive symptoms or depressive disorder in at least one of the parents/caregivers. Risk of bias will be assessed using The Joanna Briggs Institute (JBI) critical appraisal checklists and The Revised Cochrane risk of bias tool for randomised trials (RoB 2). It is expected that studies will be heterogeneous; therefore, meta-analysis will not be attempted. Studies will be systematically retrieved and collated using numerical, graphical, tabular, and narrative summaries and grouped by their design, scope, or overall quality. Further sub-group analyses will be performed to examine sex-, developmental stage-, and outcome-specific protective factors., Discussion: The proposed systematic review will be the first to summarise and critically assess quality and strength of evidence of protective factors associated with mental health resilience in offspring of depressed parents. Directions and effect sizes of the protective factors will be discussed as well as differences between the studies, their limitations, and research gaps and future directions. Strengths and limitations of the proposed systematic review will be also discussed. The proposed systematic review findings are expected to help better understand mental health resilience and identify targets for evidence-based prevention and intervention strategies for those in need., Systematic Review Registration: A previous version of this systematic review protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO) database ( www.crd.york.ac.uk/PROSPERO , CRD42021229955)., (© 2022. The Author(s).)

In high-income countries, links between harsh and abusive parenting and child conduct and emotional problems are well-documented. However, less is known about these relationships in low- and middle-income countries, where harsh parenting may be more widely accepted and higher rates of conduct or emotional problems may exist which could influence the strength of these associations. We sought to investigate these relationships in a large population-based, prospective longitudinal study from Brazil, which also allowed us to test for sex differences. Using data from the 2004 Pelotas Birth Cohort Study (N = 4231) at ages 6 and 11 years, we applied cross-lagged path analysis to examine the relationships between harsh parenting (Conflict Tactics Scale Parent-Child version), and child conduct and emotional problems (Strengths and Difficulties Questionnaire). We found reciprocal relationships between harsh parenting and child conduct problems, with harsh parenting at age 6 predicting child conduct problems at age 11, and vice versa, even after adjusting for initial levels of conduct problems and harsh parenting, respectively. For child emotional problems, only unidirectional effects were found, with harsh parenting at age 6 predicting child emotional problems at age 11, after adjusting for initial levels of emotional problems, but not vice versa. No significant sex differences were observed in these relationships. These observations based on a middle-income country birth cohort highlight the potential universality of detrimental effects of harsh parenting on child conduct and emotional problems and affirm the importance of addressing parent- and child-effects in preventive and treatment interventions, especially those targeting conduct problems., (© 2021. The Author(s).)

Background: Childhood maltreatment has been consistently associated with cardiovascular disease (CVD). However, the mechanisms of this relationship are not yet fully understood. We explored the relative contribution of anxiety/depression, smoking, body mass index (BMI) and inflammation (C-reactive protein, CRP) to the association between childhood maltreatment and CVD in men and women aged 40-69 years in the UK., Methods: We used data from 40 596 men and 59 511 women from UK Biobank. To estimate the indirect effects of childhood maltreatment (physical, sexual and emotional abuse, and emotional and physical neglect) on incident CVD via each of the mediators, we applied a sequential mediation approach., Results: All forms of maltreatment were associated with increased CVD risk [hazard ratios (HRs) ranging from 1.09 to 1.27]. Together, anxiety/depression, smoking, BMI and inflammation (indexed by CRP) mediated 26-90% of the association between childhood maltreatment and CVD, and the contribution of these mediators differed by type of maltreatment and sex. Anxiety/depression mediated the largest proportion of the association of sexual abuse, emotional abuse and emotional neglect with CVD (accounting for 16-43% of the total effect), especially in women. In men, BMI contributed the most to the indirect effect of associations of physical abuse and physical neglect with CVD; in women, anxiety/depression and BMI had similar contributions., Conclusions: These findings add to the understanding of how childhood maltreatment affects CVD risk and identify modifiable mediating factors that could potentially reduce the burden of CVD in people exposed to maltreatment in early life., (© The Author(s) 2021. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Neighbourhood collective efficacy has been proposed as a protective factor against family violence and youth antisocial behaviour. However, little is known about its impact on parent and child behaviour in non-Western countries. Using data from two population-based prospective cohorts from South Korea, including primary school students aged 10-12 years (N = 2844) and secondary school students aged 15-17 years (N = 3449), we examined the interplay between collective efficacy, family violence, and youth antisocial behaviour, and whether effects vary by SES. In a first series of models, in both samples, higher levels of collective efficacy were associated with lower levels of family violence, whereas higher levels of family violence were associated with higher levels of youth antisocial behaviour. There was no direct effect of collective efficacy on youth antisocial behaviour; however, there was an indirect effect via family violence. Although these effects were more pronounced in low SES children, there was no evidence of moderation by SES. In a second series of models, in primary school students, collective efficacy was not associated with youth antisocial behaviour. However, there was a direct effect of collective efficacy on family violence, even after adjusting for youth antisocial behaviour. Again, there was no evidence of moderation by SES. In secondary school students, the pattern of results was less consistent, however, again, suggesting more pronounced effects of collective efficacy in low SES children. The findings suggest that collective efficacy may influence family violence more directly, whereas youth antisocial behaviour may be affected more indirectly through the family environment., (© 2021. The Author(s).)

Background: The negative impact of trauma work has been well documented in mental health professionals. There are three main phenomena used to describe these effects: Secondary Traumatic Stress (STS), Vicarious Trauma (VT) and Compassion Fatigue (CF). To date, the majority of research has focused on the contribution of individual level factors. However, it is imperative to also understand the role of organizational factors., Objectives: This review examines the role of organizational factors in ameliorating or preventing STS, VT, and CF in mental health professionals. We further aimed to identify specific elements of these factors which are perceived to be beneficial and/or detrimental in mitigating against the effects of STS, VT, and CF., Method: Studies were identified by searching the electronic databases Medline, PsycINFO, Embase, Web of Science and SCOPUS with final searches taking place on 10 March 2021., Results: Twenty-three quantitative studies, eight qualitative studies, and five mixed methods studies were included in the final review. A narrative synthesis was conducted to analyse the findings. The results of the review highlight the importance of regular supervision within supportive supervisory relationships, strong peer support networks, and balanced and diverse caseloads. The value of having an organizational culture which acknowledges and validates the existence of STS was also imperative., Conclusions: Organizations have an ethical responsibility to support the mental health professionals they employ and provide a supportive environment which protects them against STS. This review provides preliminary evidence for the types of support that should be offered and highlights the gaps in the literature and where future research should be directed. Further research is needed to evaluate which strategies - and under what conditions - best ameliorate and prevent STS., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Adverse childhood experiences (ACEs) have been found to predict many negative life outcomes. However, very little evidence exists on Intimate Partner Violence (IPV) and Child Maltreatment (CM). We investigated the impact of maternal ACEs on IPV and CM in three different: cumulative risk, individual adversities and particular groupings of ACEs. The 2015 Pelotas Birth Cohort, Southern Brazil, has followed a population-based sample mothers and children repeatedly until children were aged 4 years, when mothers provided data on ACEs, and current IPV and CM. ACEs were examined in three different ways: (i) as a cumulative risk score; (ii) individual adversities; and (iii) patterns of ACEs (Latent Class Analysis: LCA). One quarter (25.4%) of mothers reported having 5+ ACEs in childhood. Compared to mothers with no ACEs, those who reported 5+ ACEs, had 4.9 (95%CI 3.5; 6.7) times the risk of experiencing IPV and 3.8 (95%CI 2.5; 5.6) times the risk of reporting child maltreatment. LCA results also highlighted the major influence of multiple ACEs on later IPV and CM. However, individual ACEs related to violence (exposure to abuse or domestic violence) showed some specificity for both later IPV and CM, over and above the influence of cumulative childhood adversity. This is the first large study to demonstrate a strong link between maternal ACEs and both IPV and CM. Cumulative ACE exposure and some specificity in effects of childhood violence are important for later IPV and CM. Integrated prevention is essential for reducing the intergenerational transmission of adversity and violence., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies., Methods: Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes., Results: The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses., Conclusions: Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.

Background: Psychotic experiences are reported by 5-10% of young people, although only a minority persist and develop into psychotic disorders. It is unclear what characteristics differentiate those with transient psychotic experiences from those with persistent psychotic experiences that are more likely to be of clinical relevance., Aims: To investigate how longitudinal profiles of psychotic experiences, created from assessments at three different time points, are influenced by early life and co-occurring factors., Method: Using data from 8045 individuals from a birth cohort study, longitudinal profiles of psychotic experiences based on semi-structured interviews conducted at 12, 18 and 24 years were defined. Environmental, cognitive, psychopathological and genetic determinants of these profiles were investigated, along with concurrent changes in psychopathology and cognition., Results: Following multiple imputations, the distribution of longitudinal profiles of psychotic experiences was none (65.7%), transient (24.1%), low-frequency persistent (8.4%) and high-frequency persistent (1.7%). Individuals with high-frequency persistent psychotic experiences were more likely to report traumatic experiences, other psychopathology, a more externalised locus of control, reduced emotional stability and conscientious personality traits in childhood, compared with those with transient psychotic experiences. These characteristics also differed between those who had any psychotic experiences and those who did not., Conclusions: These findings indicate that the same risk factors are associated with incidence as with persistence of psychotic experiences. Thus, it might be that the severity of exposure, rather than the presence of specific disease-modifying factors, is most likely to determine whether psychotic experiences are transient or persist, and potentially develop into a clinical disorder over time.

Background: Maternal postnatal depression (PND) is a risk factor for offspring depression in adulthood. However, few longitudinal studies have examined the role of maternal nurturing parenting behaviours in the association between maternal PND and offspring depression in adulthood. Methods: We examined pathways from maternal PND measured using self-reported Edinburgh Postnatal Depression Scale at 8 weeks to offspring ICD-10 depression diagnosed using the Clinical Interview Schedule-Revised computerised assessment at 24 years through maternal-reported nurturing behaviours concerning feeding, sleeping and crying measured from pregnancy to age 3 years 6 months in 5,881 members of the UK-based birth cohort study, the Avon Longitudinal Study of Parents and Children.   Results: The fully adjusted model revealed an indirect effect from PND to adult offspring depression through the combination of all parenting factors (probit regression coefficient [ B ]=0.038, 95% confidence interval [CI] 0.005, 0.071); however, there was no evidence of a direct effect from early maternal PND to offspring depression once the indirect effect via parenting factors was accounted for ( B =0.009, 95%CI -0.075, 0.093). Specificity analyses revealed indirect effects through maternal worries about feeding ( B =0.019, 95%CI 0.003, 0.035, p=0.010) and maternal perceptions and responses to crying ( B =0.018, 95%CI 0.004, 0.032, p=0.012). Conclusions: The adverse impact of maternal PND on offspring depression in early adulthood was explained by maternal nurturing behaviours concerning feeding, crying and sleeping in early childhood. Residual confounding and measurement error likely limit reliable conclusions. If found causal, interventions providing support to reduce worries around maternal nurturing behaviours and treating depression could reduce adverse outcomes in adult offspring of depressed mothers., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Culpin I et al.)

Mediation analysis seeks to explain the pathway(s) through which an exposure affects an outcome. Traditional, non-instrumental variable methods for mediation analysis experience a number of methodological difficulties, including bias due to confounding between an exposure, mediator and outcome and measurement error. Mendelian randomisation (MR) can be used to improve causal inference for mediation analysis. We describe two approaches that can be used for estimating mediation analysis with MR: multivariable MR (MVMR) and two-step MR. We outline the approaches and provide code to demonstrate how they can be used in mediation analysis. We review issues that can affect analyses, including confounding, measurement error, weak instrument bias, interactions between exposures and mediators and analysis of multiple mediators. Description of the methods is supplemented by simulated and real data examples. Although MR relies on large sample sizes and strong assumptions, such as having strong instruments and no horizontally pleiotropic pathways, our simulations demonstrate that these methods are unaffected by confounders of the exposure or mediator and the outcome and non-differential measurement error of the exposure or mediator. Both MVMR and two-step MR can be implemented in both individual-level MR and summary data MR. MR mediation methods require different assumptions to be made, compared with non-instrumental variable mediation methods. Where these assumptions are more plausible, MR can be used to improve causal inference in mediation analysis.

Experimental studies support the conventional belief that people behave more aggressively whilst under the influence of alcohol. To examine how these experimental findings manifest in real life situations, this study uses a method for estimating evidence for causality with observational data-'situational decomposition' to examine the association between alcohol consumption and crime in young adults from the Avon Longitudinal Study of Parents and Children. Self-report questionnaires were completed at age 24 years to assess typical alcohol consumption and frequency, participation in fighting, shoplifting and vandalism in the previous year, and whether these crimes were committed under the influence of alcohol. Situational decomposition compares the strength of two associations, (1) the total association between alcohol consumption and crime (sober or intoxicated) versus (2) the association between alcohol consumption and crime committed while sober. There was an association between typical alcohol consumption and total crime for fighting [OR (95% CI): 1.47 (1.29, 1.67)], shoplifting [OR (95% CI): 1.25 (1.12, 1.40)], and vandalism [OR (95% CI): 1.33 (1.12, 1.57)]. The associations for both fighting and shoplifting had a small causal component (with the association for sober crime slightly smaller than the association for total crime). However, the association for vandalism had a larger causal component.

Background: Although there is strong evidence for a relationship between child abuse and neglect and conduct problems, associations between child abuse experienced at different developmental stages and developmental trajectories of conduct problems have not been examined. We sought to investigate effects of timing of child abuse on conduct problem trajectories in a large UK birth cohort study., Methods: We applied latent class growth analysis to identify conduct problem trajectories in the Avon Longitudinal Study of Parents and Children, using parent-rated conduct problems from ages 4-17 years (N = 10,648). Childhood-only and adolescence-only abuse, in addition to abuse in both developmental periods ('persistent' abuse), were assessed by retrospective self-report at age 22 years (N = 3172)., Results: We identified four developmental trajectories: early-onset persistent (4.8%), adolescence-onset (4.5%), childhood-limited (15.4%), and low (75.3%) conduct problems. Childhood-only abuse and 'persistent' abuse were associated with increased odds of being on the early-onset persistent and adolescence-onset conduct problem trajectories compared to the low conduct problems trajectory. Adolescence-only abuse was not predictive of trajectory membership. There were no associations between abuse and childhood-limited trajectory membership., Conclusions: Early-onset persistent and adolescence-onset conduct problems showed similar patterns of association with abuse exposure, challenging developmental theories that propose qualitative, as opposed to quantitative, differences in environmental risk factors between these trajectories. The results also highlight that childhood-only and 'persistent' abuse were more strongly linked to elevated conduct problem trajectories than adolescence-only abuse, and that 'persistent' abuse is particularly detrimental.

Introduction: Depression and harmful alcohol consumption contribute significantly to the global health burden, but in young adults, this relationship is under-researched and conflicted. The aim of this study was to determine the sex-based prevalence and the association between internalising disorders such as depression and alcohol use disorders., Method: Using the Avon Longitudinal Study of Parents and Children, we assessed the sex-specific prevalence of International Classification of Diseases,Tenth Revision diagnosed generalised anxiety disorder (GAD), depression and fear-based anxieties (FBA) at 24 years (n=3572). We examined the association between internalising disorders and alcohol consumption using the Alcohol Use Disorder Identification Test for Consumption 5+ threshold and Diagnostic and Statistical Manual on Mental Disorders defined criteria for alcohol dependence., Results: Women reported more GAD (11.6% vs 6.5%), depression (13.4% vs 6.9%) and FBA (1.3% vs 0.5%) than men (p<0.001). Harmful drinking, after adjustment for sex and socioeconomic status, was associated with a higher prevalence of depression (OR 1.8, 95% CI 1.3 to 2.4, p<0.001), anxiety (OR 1.4, 95% CI 1.0 to 2.0, p<0.001) and FBA (OR 2.4, 95% CI 1.04 to 5.56, p=0.009) compared with lower-risk drinkers. In contrast, hazardous drinking was associated with a lower prevalence of GAD (OR 0.69, 95% CI 0.54 to 0.88) and depression (OR 0.68, 95% CI 0.54 to 0.86) compared with lower-risk drinkers., Conclusions: Young adults in the UK who drink harmfully are more likely to have depression and other internalising disorders. Further research should test whether there is a J-shaped relationship between alcohol consumption and mental health in young people and whether this varies across the life course., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

There is increasing evidence that childhood Attention-Deficit Hyperactivity Disorder (ADHD) elevates risk of later depression, but the mechanisms behind this association are unclear. We investigated the relationship between childhood ADHD symptoms and late-adolescent depressive symptoms in a population cohort, and examined whether academic attainment and peer problems mediated this association. ALSPAC (Avon Longitudinal Study of Parents and Children) is an ongoing prospective longitudinal population-based UK cohort that has collected data since September 1990. 2950 individuals with data on parent-reported ADHD symptoms in childhood (7.5 years) and self-reported depressive symptoms in late adolescence (17.5 years) were included in analyses. 2161 individuals with additional data at age 16 years on parent-reported peer problems as an indicator of peer relationships and formal examination results (General Certificate of Secondary Education; GCSE) as an indicator of academic attainment were included in mediation analyses. Childhood ADHD symptoms were associated with higher depressive symptoms (b = 0.49, SE = 0.11, p < 0.001) and an increased odds of clinically significant depressive symptoms in adolescence (OR = 1.27, 95% CI 1.15-1.41, p < 0.001). The association with depressive symptoms was mediated in part by peer problems and academic attainment which accounted for 14.68% and 20.13% of the total effect, respectively. Childhood ADHD is associated with increased risk of later depression. The relationship is mediated in part by peer relationships and academic attainment. This highlights peer relationships and academic attainment as potential targets of depression prevention and intervention in those with ADHD. Future research should investigate which aspects of peer relationships are important in conferring later risk for depression.

Objectives: To assess and compare associations between childhood maltreatment and cardiovascular disease (CVD) in men and women in the UK. In secondary analyses, we also explored possible age differences and associations with early onset CVD (<50 years)., Methods: We included 157 311 participants from the UK Biobank who had information on physical, sexual or emotional abuse, emotional or physical neglect. CVD outcomes were defined as any CVD, hypertensive disease, ischaemic heart disease (IHD) and cerebrovascular disease. These were extracted from self-report, blood pressure measurements, hospital register and death register. The associations between maltreatment and CVD were assessed using Poisson regression with robust variance to estimate risk ratios, stratified by sex and adjusted for socioeconomic and demographic factors., Results: All types of maltreatment were associated with increased risk of CVD and IHD in both sexes. Additionally, in women all types of maltreatment were associated with higher risk of hypertensive disease, and all, except emotional neglect, were associated with cerebrovascular disease. In men, all but sexual abuse, were associated with higher risk of hypertensive disease, and all, except physical and sexual abuse, were associated with cerebrovascular disease. Associations were generally stronger in women, and individuals who were younger at baseline had stronger associations of childhood maltreatment with any CVD and IHD, but age differences were less evident when only early onset CVD was considered., Conclusions: Childhood maltreatment was consistently associated with CVD and stronger associations were generally observed in women and seemed to be stronger for early onset CVD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: Both 'early-onset persistent' and 'adolescent-onset' conduct problems (CPs) are associated with alcohol-related problems in emerging adulthood. The escalation of early CPs into criminal behaviour and heavy alcohol consumption prior to emerging adulthood are both likely to be important pathways., Methods: Data were analysed from 3,038 young people in a UK birth cohort, the Avon Longitudinal Study of Parents and Children. The exposure was developmental trajectories of CPs ('low', 'childhood-limited', 'adolescent-onset' and 'early-onset persistent') between ages 4 and 13 years. The mediator was latent classes representing heavy alcohol consumption and/ or criminal behaviour at age 15 years. For the outcome, a quadratic latent growth curve was estimated to capture nonlinear change in alcohol-related problems between ages 18 and 23 years., Results: Those with 'early-onset persistent' [b(95% CI) = 1.16 (0.17, 2.14)] and 'adolescent-onset' CPs [b(95% CI) = 1.31 (0.17, 2.45)] had higher levels of alcohol-related problems at age 18 years compared to those with 'low' CPs', but there was little evidence of an association with alcohol-related problems after age 19 years. There was evidence for an indirect effect of 'early-onset persistent' CPs [b(95% CI) = 1.12 (0.52, 1.72)] on alcohol-related problems at age 18 years via the latent classes of alcohol and criminal behaviour in adolescence. This was not found for 'adolescent-onset' CPs [b(95% CI) = 0.35 (-0.36, 1.07)]., Conclusions: Strong associations exist between early CPs, adolescent alcohol consumption and criminal behaviour and alcohol-related problems at age 18 years. Associations between early CPs and alcohol-related problems weakened considerably across emerging adulthood., (© 2019 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: The estimated worldwide prevalence of non-alcoholic fatty liver disease (NAFLD) in adults is 25%; however, prevalence in young adults remains unclear. We aimed to identify the prevalence of steatosis and fibrosis in young adults in a sample of participants recruited through the Avon Longitudinal Study of Parents and Children (ALSPAC), based on transient elastography and controlled attenuation parameter (CAP) score., Methods: In this population-based study, we invited active participants of the ALSPAC cohort to our Focus@24+ clinic at the University of Bristol (Bristol, UK) between June 5, 2015, and Oct 31, 2017, for assessment by transient elastography with FibroScan, to determine the prevalence of steatosis and fibrosis. FibroScan data were collected on histologically equivalent fibrosis stage (F0-F4) and steatosis grade (S0-S3); results with an IQR to median ratio of 30% or greater were excluded for median fibrosis results greater than 7·1 kPa, and CAP scores for steatosis were excluded if less than ten valid readings could be obtained. Results were collated with data on serology (including alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transferase) and exposures of interest: alcohol consumption (via the Alcohol Use Disorder Identification Test for Consumption [AUDIT-C] and the Diagnostic and Statistical Manual of Mental Disorders-5 criteria for alcohol use disorder), body-mass index (BMI), waist-to-height ratio, socioeconomic status (based on predefined ALSPAC markers), and sex. We used logistic regression models to calculate odds ratios (ORs) for the effect of exposures of interest on risk of steatosis and fibrosis, after dichotomising the prevalences of fibrosis and steatosis and adjusting for covariates (excessive alcohol intake [hazardous drinking, AUDIT-C score ≥5; or harmful drinking, evidence of alcohol use disorder], social class, smoking, and BMI)., Findings: 10 018 active ALSPAC participants were invited to our Focus@24+ clinic, and 4021 attended (1507 men and 2514 women), with a mean age of 24·0 years (IQR 23·0-25·0). 3768 CAP scores were eligible for analysis. 780 (20·7% [95% CI 19·4-22·0]) participants had suspected steatosis (S1-S3; ≥248 dB/m), with 377 (10·0%) presenting with S3 (severe) steatosis (≥280 dB/m). A BMI in the overweight or obese range was positively associated with steatosis when adjusted for excessive alcohol consumption, social class, and smoking (overweight BMI: OR 5·17 [95% CI 4·11-6·50], p<0·0001; obese BMI: 27·27 [20·54-36·19], p<0·0001). 3600 participants had valid transient elastography results for fibrosis analysis. 96 participants (2·7% [95% CI 2·2-3·2]) had transient elastography values equivalent to suspected fibrosis (F2-F4; ≥7·9 kPa), nine of whom had values equivalent to F4 fibrosis (≥11·7 kPa). Individuals with alcohol use disorder and steatosis had an increased risk of fibrosis when adjusted for smoking and social class (4·02 [1·24-13·02]; p=0·02)., Interpretation: One in five young people had steatosis and one in 40 had fibrosis around the age of 24 years. The risk of fibrosis appears to be greatest in young adults who have harmful drinking patterns and steatosis. A holistic approach to the UK obesity epidemic and excessive drinking patterns is required to prevent an increasing health-care burden of adults with advanced liver disease in later life., Funding: Medical Research Council UK, Alcohol Change UK, David Telling Charitable Trust., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Depressive symptoms show different trajectories throughout childhood and adolescence that may have different consequences for adult outcomes., Aims: To examine trajectories of childhood depressive symptoms and their association with education and employment outcomes in early adulthood., Method: We estimated latent trajectory classes from participants with repeated measures of self-reported depressive symptoms between 11 and 24 years of age and examined their association with two distal outcomes: university degree and those not in employment, education or training at age 24., Results: Our main analyses (n = 9399) yielded five heterogenous trajectories of depressive symptoms. The largest group found (70.5% of participants) had a stable trajectory of low depressive symptoms (stable-low). The other four groups had symptom profiles that reached full-threshold levels at different developmental stages and for different durations. We identified the following groups: childhood-limited (5.1% of participants) with full-threshold symptoms at ages 11-13; childhood-persistent (3.5%) with full-threshold symptoms at ages 13-24; adolescent onset (9.4%) with full-threshold symptoms at ages 17-19; and early-adult onset (11.6%) with full-threshold symptoms at ages 22-24. Relative to the majority 'stable-low' group, the other four groups all exhibited higher risks of one or both adult outcomes., Conclusions: Accurate identification of depressive symptom trajectories requires data spanning the period from early adolescence to early adulthood. Consideration of changes in, as well as levels of, depressive symptoms could improve the targeting of preventative interventions in early-to-mid adolescence.

Importance: Less favorable trajectories of depressive mood from adolescence to early adulthood are associated with current and later psychopathology, impaired educational attainment, and social dysfunction, yet the genetic and environmental risk factors associated with these trajectories are not fully established. Examining what risk factors are associated with different trajectories of depressive mood could help identify the nature of depression symptoms and improve preventive interventions for those at most risk., Objective: To examine the differential associations of genetic and environmental risk factors with trajectories of depression symptoms among individuals observed from ages 10 to 24 years., Design, Setting, and Participants: In a longitudinal cohort study established in 1990 and currently ongoing (the Avon Longitudinal Study of Parents and Children [ALSPAC]), growth mixture modeling was used to identify trajectories of depression symptoms in 9394 individuals in the United Kingdom. Associations of different risk factors with these trajectories were then examined. Analysis was conducted between August 2018 and January 2019., Main Outcomes and Measures: Trajectories were composed from depression symptoms measured using the Short Mood and Feelings Questionnaire at 9 occasions from ages 10 to 24 years. Risk factors included sex, a polygenic risk score taken from a recent genome-wide association study of depression symptoms, maternal postnatal depression, partner cruelty to the offspring's mother when the child was aged 2 to 4 years, childhood anxiety at age 8 years, and being bullied at age 10 years., Results: Data on all risk factors, confounders, and the outcome were available for 3525 individuals, including 1771 (50.2%) who were female. Trajectories were assessed between the mean (SD) age of 10.7 (0.3) years and mean (SD) age of 23.8 (0.5) years. Overall, 5 distinct trajectories of depression symptoms were identified: (1) stable low (2506 individuals [71.1%]), (2) adolescent limited (325 individuals [9.2%]), (3) childhood limited (203 individuals [5.8%]), (4) early-adult onset (393 individuals [11.1%]), and (5) childhood persistent (98 individuals [2.8%]). Of all the associations of risk factors with trajectories, sex (odds ratio [OR], 6.45; 95% CI, 2.89-14.38), the polygenic risk score for depression symptoms (OR, 1.47; 95% CI, 1.10-1.96), and childhood anxiety (OR, 1.30; 95% CI, 1.16-1.45) showed the strongest association with the childhood-persistent trajectory of depression symptoms compared with the stable-low trajectory. Maternal postnatal depression (OR, 2.39; 95% CI, 1.41-4.07) had the strongest association with the early-adult-onset trajectory, while partner cruelty to mother (OR, 2.30; 95% CI, 1.36-3.90) had the strongest association with the adolescent-limited trajectory. Bullying (OR, 8.08; 95% CI, 4.92-13.26) showed the strongest association with the childhood-limited trajectory., Conclusions and Relevance: The least favorable trajectories of depression symptoms (childhood persistent and early-adult onset) were associated with both genetic and environmental risk factors, but the 2 trajectories of limited duration that had resolved by early adulthood (childhood limited and adolescent limited) were not associated with the polygenic risk score or maternal postnatal depression. Bullying was strongly associated with both the childhood-persistent and childhood-limited trajectories, suggesting that this risk factor may have a time-specific effect. These findings suggest that examining genetic and multiple time-specific environmental antecedents could help identify trajectories of varying onset and chronicity.

Purpose: Examine associations between childhood behavioural problems with criminal behaviour, emotional disorders, substance use and unemployment in early adulthood in two birth cohorts from a middle- and high-income country., Methods: Data were utilised from large, prospective birth cohorts in Brazil (1993 Pelotas Birth Cohort; N  = 3939) and the UK (Avon Longitudinal Study of Parents and Children; ALSPAC; N  = 5079). Behavioural problems were reported on by parents at age 11 years (including disobeys, temper, lies, fights, steals). Outcomes (assessed with youth between ages 22 and 24 years) included criminal behaviour, emotional disorders, substance use and NEET (not in education, employment or training)., Results: In both cohorts, children with 'conduct problems' (those with increased probability of all five behaviours at age 11), were at higher risk of criminal behaviour, emotional disorders and NEET in adulthood compared to those with 'low problems'. Associations for 'conduct problems' were stronger in Pelotas compared to ALSPAC for hazardous alcohol use [Pelotas: risk ratio = 1.39, 95% CI = 1.14-1.70; ALSPAC: risk ratio = 0.76, 95% CI = 0.57-1.02] and illegal drug use [Pelotas: risk ratio = 1.32, 95% CI = 1.16-1.50; ALSPAC: risk ratio = 1.05, 95% CI = 0.91-1.20], whereas associations for criminal behaviour [Pelotas: risk ratio = 1.92, 95% CI = 1.29-2.86; ALSPAC: risk ratio = 2.75, 95% CI = 2.04-3.73] and NEET [Pelotas: risk ratio = 1.38, 95% CI = 1.13-1.70; ALSPAC: risk ratio = 3.04, 95% CI = 1.99-4.65] were stronger in ALSPAC., Conclusions: Childhood conduct problems were associated with criminal behaviour, emotional disorders and unemployment in adulthood in both Brazil and the UK. Additional associations were found for substance use in Brazil., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© The Author(s) 2019.)

Smoking usually begins in adolescence, and early onset of smoking has been linked to increased risk of later life disease. There is a need to better understand the biological impact of cigarette smoking behaviours in adolescence. DNA methylation profiles related to smoking behaviours and cessation in adulthood have been previously identified, but alterations arising from smoking initiation have not been thoroughly investigated. We aimed to investigate DNA methylation in the Avon Longitudinal Study of Parents and Children in relation to (1) different smoking measures, (2) time since smoking initiation and frequency of smoke exposure and (3) latent classes of smoking behaviour. Using 2620 CpG sites previously associated with cigarette smoking, we investigated DNA methylation change in relation to own smoking measures, smoke exposure duration and frequency, and using longitudinal latent class analysis of different smoking behaviour patterns in 968 adolescents. Eleven CpG sites located in seven gene regions were differentially methylated in relation to smoking in adolescence. While only AHRR (cg05575921) showed a robust pattern of methylation in relation to weekly smoking, several CpGs showed differences in methylation among individuals who had tried smoking compared with non-smokers. In relation to smoke exposure duration and frequency, cg05575921 showed a strong dose-response relationship, while there was evidence for more immediate methylation change at other sites. Our findings illustrate the impact of cigarette smoking behaviours on DNA methylation at some smoking-responsive CpG sites, even among individuals with a short smoking history.

Objective: Twin studies suggest that genetic factors contribute to continuity in mental health problems and that environmental factors are the major contributor to developmental change. The authors investigated the influence of psychiatric risk alleles on early-onset mental health trajectories and whether the trajectories were subsequently modified by exposure to childhood victimization., Methods: The sample was a prospective U.K. population-based cohort, the Avon Longitudinal Study of Parents and Children. The developmental trajectories of emotional problems were estimated in childhood (approximately ages 4-8 years) and adolescence (approximately ages 12-17 years). Psychiatric risk alleles were indexed by polygenic risk scores (PRS) for schizophrenia using genome-wide association study results from the Psychiatric Genomics Consortium. Chronic peer victimization in late childhood (ages 8.5 and 10.5 years) was assessed as an index of environmental exposure. Individuals with sufficient data on emotional problems, the PRS, and victimization were included in the main analyses (N=3,988)., Results: Higher schizophrenia PRSs were associated with a trajectory of early-onset increasing emotional problems (odds ratio=1.18, 95% CI=1.02-1.36) compared with a trajectory of low-stable emotional problems. Subsequent exposure to victimization increased the likelihood of transitioning from a trajectory of low-stable emotional problems during childhood (before exposure) to an increasing trajectory in adolescence (after exposure) (odds ratio=2.59, 95% CI=1.48-4.53)., Conclusions: While the early development of emotional problems was associated with genetic risk (schizophrenia risk alleles), the subsequent course of emotional problems for those who might otherwise have remained on a more favorable trajectory was altered by exposure to peer victimization, which is a potentially modifiable environmental exposure.

Background and Aims: Evidence demonstrating an association between parental alcohol use and offspring alcohol use from robust prospective studies is lacking. We tested the direct and indirect associations between parental and young adult alcohol use via early alcohol initiation, parental monitoring and associating with deviant peers., Design: Prospective birth cohort study. Path analysis was used to assess the possible association between parental alcohol use (assessed at 12 years) and alcohol use in young adults (assessed at 18 years) via potential mediators (assessed at 14 and 15.5 years, respectively)., Setting: South West England., Participants: Data were available on 3785 adolescents and their parents from the Avon Longitudinal Study of Parents and Children., Measurements: The continuous Alcohol Use Disorders Identification Test (AUDIT) score was used as the primary outcome measure. Maternal alcohol use was defined as light (< 4 units on any day), moderate (≥ 4 units on 1-3 days) and high-risk (≥ 4 units on ≥ 4 days in 1 week). Partner alcohol use was also defined as light, moderate and high risk. Socio-economic variables were included as covariates., Findings: There was strong evidence of a total effect from maternal alcohol use to young adult alcohol use [moderate: b = 1.07, 95% confidence interval (CI) = 0.64, 1.49, P < 0.001; high risk: b = 1.71, 95% CI = 1.07, 2.35, P < 0.001]. The majority of this association was explained through early alcohol initiation (moderate: b = 0.14, 95% CI = 0.04, 0.25, P = 0.01; high risk: b = 0.24, 95% CI = 0.07, 0.40, P < 0.01) and early alcohol initiation/associating with deviant peers (moderate: b = 0.06, 95% CI = 0.02, 0.10, P < 0.01; high risk: b = 0.10, 95% CI = 0.03, 0.16, P < 0.01). There was strong evidence of a remaining direct effect (moderate: b = 0.81, 95% CI = 0.39, 1.22, P < 0.001; high risk: b = 1.28, 95% CI = 0.65, 1.91, P < 0.001). A similar pattern of results was evident for partner alcohol use., Conclusions: Young adults whose parents have moderate or high-risk alcohol consumption are more likely to consume alcohol than those with parents with lower alcohol consumption. This association appears to be partly accounted for by earlier alcohol use initiation and higher prevalence of association with deviant peers., (© 2018 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Low resting heart rate (RHR) is a consistent biological correlate of antisocial behaviour (ASB), however potential mechanisms have been largely unexplored. We hypothesise that lower RHR will be associated with higher ASB levels in mid-adolescence and persistence into adulthood, and that these associations will be explained, in part, by sensation seeking and callous-unemotional traits., Methods: ASB was assessed repeatedly with young people from ages 15 to 21 years in a population-based birth cohort (ALSPAC). A longitudinal trajectory was derived and showed ASB decreasing across adolescence before stabilising in early adulthood. RHR was recorded at age 12 years, and mediators were assessed at age 14 years., Results: After adjusting for socio-demographic confounders, there was evidence for a total effect of RHR on ASB levels in mid-adolescence [b(95% CI) = -0.08 (-0.14 to -0.02)], reflecting 0.08 more types of antisocial activity in the last year per 10 fewer heart beats per minute. This effect was almost entirely explained through sensation seeking [b(95% CI) = -0.06 (-0.08 to -0.04)]. After additionally adjusting for child and parent-related confounders, all effects weakened; however, there was still evidence of an indirect effect of RHR, via sensation seeking, on ASB levels in mid-adolescence [b(95% CI) = -0.01 (-0.03 to -0.003)]. There was no evidence for a total effect of RHR on ASB levels in early adulthood, and weak evidence of an indirect effect, via sensation seeking [b(95% CI) = -0.01 (-0.01 to -0.00)]., Conclusions: Lower RHR in childhood was associated with higher ASB levels in mid-adolescence, indirectly via sensation seeking.

Background: Adult ADHD has been assumed to be a continuation of childhood-onset ADHD. However, recent studies have identified individuals with ADHD in adulthood who have not had ADHD in childhood. Whether or not these individuals have a 'typical' neurodevelopmental profile is not clear., Methods: We tested two explanations for the emergence of apparent late-onset ADHD symptomatology using the ALSPAC epidemiological cohort, by grouping individuals according to their scores on the Strengths and Difficulties Questionnaire (SDQ) hyperactivity subscale at ages 12 and 17 years. First, we tested whether some of those with apparent late-onset ADHD symptoms had been potentially misclassified on the basis of earlier SDQ hyperactivity scores (ages 7, 8 and 9 years) or of subthreshold symptoms at age 12 years. Second, we investigated the possibility that those with 'genuine' late-onset ADHD symptoms had a delayed manifestation of the same liability that underlies childhood-onset symptoms, by investigating whether they had a similar profile of neurodevelopmental impairments (in the domains of autistic symptomatology, language, reading, spelling, executive functioning and IQ) as those with typical childhood-onset ADHD., Results: N = 56/75 (75%) of those with apparent late-onset ADHD had had high ADHD scores at least one point in childhood, suggesting that they may have been misclassified on the basis of their score at age 12 years. The remaining 19 individuals (25%) with genuine late-onset ADHD symptoms did not show a profile of neurodevelopmental impairment typically seen in ADHD, instead showing similar levels of autistic symptoms, language skills, executive functioning ability and IQ to those without ADHD symptoms. The only exceptions were that this group showed reading and spelling problems at age 9 years., Conclusions: Our work suggests that this small number of individuals with genuine late-onset symptoms may not be most appropriately considered as having a typical neurodevelopmental disorder., (© 2018 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Whilst associations between polygenic risk scores (PRSs) for schizophrenia and various phenotypic outcomes have been reported, an understanding of developmental pathways can only be gained by modelling comorbidity across psychopathology. We examine how genetic risk for schizophrenia relates to adolescent psychosis-related and internalizing psychopathology using a latent modelling approach, and compare this to genetic risk for other psychiatric disorders, to gain a more comprehensive understanding of the developmental pathways at this age. PRSs for schizophrenia, major depressive disorder, neuroticism and bipolar disorder were generated for individuals in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Multivariate linear regression was used to examine the relationships of these PRSs with psychopathology factors modelled within (i) a correlated factors structure and (ii) a bifactor structure. The schizophrenia PRS was associated with an increase in factors describing psychotic experiences, negative dimension, depression and anxiety, but, when modelling a general psychopathology factor based on these measures, specific effects above this persisted only for the negative dimension. Similar factor relationships were observed for the neuroticism PRS, with a (weak) specific effect only for anxiety once modelling general psychopathology. Psychopathology during adolescence can be described by a general psychopathology construct that captures common variance as well as by specific constructs capturing remaining non-shared variance. Schizophrenia risk genetic variants identified through genome-wide association studies mainly index negative rather than positive symptom psychopathology during adolescence. This has potentially important implications both for research and risk prediction in high-risk samples.

This study examines the role of paternal emotional support as a resilience promoter in offspring of mothers with depression by considering the role of fathers' mental health and the quality of the couple relationship. Two hundred and sixty-five mothers with recurrent unipolar depression, partners and adolescents from Wales were assessed. Paternal emotional support, couple relationship quality, and paternal depression were assessed at baseline; adolescent mental health symptoms were assessed using the Child and Adolescent Psychiatric Assessment at follow-up. Results showed evidence of an indirect pathway whereby couple relationship quality predicted paternal emotional support (β = -.21, 95% CI [-.34, -.08]; p = .002) which in turn predicted adolescent depression (β = -.18, 95% CI [-.33, -.04]; p = .02), but not disruptive behaviours (β = -.08, 95% CI [-.22, .07]; p = .30), after controlling for relevant confounders. The findings highlight that fathers and the broader family system play an important role in enhancing resilience to depression symptoms in at-risk adolescents., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)