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Background: Depression and anxiety are the most common mental health problems in young people. Currently, clinicians are advised to wait before initiating treatment for young people with these disorders as many spontaneously remit. However, others develop recurrent disorder but this subgroup cannot be identified at the outset. We examined whether psychiatric polygenic scores (PGS) could help inform stratification efforts to predict those at higher risk of recurrence. Methods: Probable emotional disorder was examined in two UK population cohorts using the emotional symptoms subscale of the Strengths and Difficulties Questionnaire (SDQ). Those with emotional disorder at two or more time points between ages 5 and 25 years were classed as 'recurrent emotional disorder' (n = 1,643) and those with emotional disorder at one time point as having 'single episode emotional disorder' (n = 1,435, controls n = 8,715). We first examined the relationship between psychiatric PGS and emotional disorders in childhood and adolescence. Second, we tested whether psychiatric PGS added to predictor variables of known association with emotional disorder (neurodevelopmental comorbidity, special educational needs, family history of depression and socioeconomic status) when discriminating between single‐episode and recurrent emotional disorder. Analyses were conducted separately in individuals of European and South Asian ancestry. Results: Probable emotional disorder was associated with higher PGS for major depressive disorder (MDD), anxiety, broad depression, ADHD and autism spectrum disorder (ASD) in those of European ancestry. Higher MDD and broad depression PGS were associated with emotional disorder in people of South Asian ancestry. Recurrent, compared to single‐episode, emotional disorder was associated with ASD and parental psychiatric history. PGS were not associated with episode recurrence, and PGS did not improve discrimination of recurrence when combined with clinical predictors. Conclusions: Our findings do not support the use of PGS as a tool to assess the likelihood of recurrence in young people experiencing their first episode of emotional disorder. [ABSTRACT FROM AUTHOR]

Previous population-based studies have identified associations between childhood neurodevelopmental traits and depression in childhood, adolescence, and young adulthood. However, neurodevelopmental traits are highly correlated with each other, which could confound associations when traits are examined in isolation. The authors sought to identify unique associations between multiple neurodevelopmental traits in childhood and depressive symptoms across development, while taking into account co-occurring difficulties, in multivariate analyses. Data from two U.K. population-based cohorts, the Twins Early Development Study (TEDS) (N=4,407 independent twins) and the Avon Longitudinal Study of Parents and Children (ALSPAC) (N=10,351), were independently analyzed. Bayesian Gaussian graphical models were estimated to investigate pairwise conditional associations between neurodevelopmental traits (autism and ADHD symptoms and general cognitive, learning, and communication abilities), socioenvironmental stressors (academic performance and peer relations), and emotional dysregulation in childhood (ages 7–11) and depressive symptoms across development (ages 12, 16, and 21). In both cohorts, bivariate correlations indicated several associations between neurodevelopmental traits and depressive symptoms across development. However, based on replicated findings across cohorts, these pairs of variables were mostly conditionally independent, and none were conditionally associated, after accounting for socioenvironmental stressors and emotional dysregulation. In turn, socioenvironmental stressors and emotional dysregulation were conditionally associated with both neurodevelopmental traits and depressive symptoms. Based on replicated findings across cohorts, neurodevelopmental traits in childhood could be associated only indirectly with depressive symptoms across development. This study indicates that associations between childhood neurodevelopmental traits and depressive symptoms across development could be explained by socioenvironmental stressors and emotional dysregulation. The present findings could inform future research aimed at the prevention of depression in youths with neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

Emotional disorders are common in childhood, and their prevalence sharply increases during adolescence. The Strengths and Difficulties Questionnaire (SDQ) is widely used for screening emotional and behavioural difficulties in children and young people, but little is known about the accuracy of the emotional subscale (SDQ-E) in detecting emotional disorders, and whether this changes over development. Such knowledge is important in determining whether symptom changes across age are due to developmental or measurement differences. This study assessed the validity of the SDQ-E and two individual items (low mood and general worry) in differentiating between cases and non-cases of Major Depressive Disorder (MDD), Generalised Anxiety Disorder (GAD), and other anxiety disorders across ages 7, 10, 13, 15, and 25 years in a UK population cohort. Analyses showed moderate accuracy of the subscale in discriminating cases of MDD (AUC = 0.67–0.85), and high accuracy for discriminating cases of GAD (AUC = 0.80–0.93) and any anxiety disorder (AUC = 0.74–0.83) compared to non-cases. The SDQ-E performed well across ages and sex, and generally performed better than the two individual items. Together our findings validate the SDQ-E as a screen for emotional disorders during childhood, adolescence, and early adulthood, and as a tool for longitudinal research on depression and anxiety disorders. [ABSTRACT FROM AUTHOR]

Young people with neurodevelopmental disorders, such as attention‐deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), show high rates of mental health problems, of which depression is one of the most common. Given that depression in ASD and ADHD is linked with a range of poor outcomes, knowledge of how clinicians should assess, identify and treat depression in the context of these neurodevelopmental disorders is much needed. Here, we give an overview of the latest research on depression in young people with ADHD and ASD, including possible mechanisms underlying the link between ADHD/ASD and depression, as well as the presentation, assessment and treatment of depression in these neurodevelopmental disorders. We discuss the implications for clinicians and make recommendations for critical future research in this area. [ABSTRACT FROM AUTHOR]

Attention deficit/hyperactivity disorder (ADHD) is associated with friendship difficulties. This may partly account for the increasingly recognised association between ADHD and subsequent depression. Little is known about the types of friendship difficulties that could contribute to the association between ADHD and depressive symptoms and whether other relationships, such as parent–child relationships, can mitigate against potential adverse effects of friendship difficulties. In a representative UK school sample (n = 1712), three main features of friendship (presence of friends, friendship quality and characteristics of the individual's classroom friendship group) were assessed in a longitudinal study with two assessment waves (W1, W2) during the first year of secondary school (children aged 11-12 years). These friendship features (W1) were investigated as potential mediators of the prospective association between teacher-rated ADHD symptoms (W1) and self-rated depressive symptoms (W2) seven months later. Parent–child relationship quality (W1) was tested as a moderator of any indirect effects of ADHD on depression via friendship. ADHD symptoms were inversely associated with friendship presence, friendship quality and positive characteristics of classroom friendship groups. Depressive symptoms were inversely associated with presence and quality of friendships. Friendship quality had indirect effects in the association between ADHD and subsequent depressive symptoms. There was some evidence of moderated mediation, whereby indirect effects via friendship quality attenuated slightly as children reported warmer parent–child relationships. This highlights the importance of considering the quality of friendships and parent–child relationships in children with ADHD symptoms. Fostering good quality relationships may help disrupt the link between ADHD symptomology and subsequent depression risk. [ABSTRACT FROM AUTHOR]

Attention deficit/hyperactivity disorder (ADHD) demonstrates a high level of comorbidity with major depressive disorder (MDD). One possible contributor to this is that the two disorders show high genetic correlation. However, the specific regions of the genome that may be responsible for this overlap are unclear. To identify variants associated with both ADHD and MDD, we performed a meta-analysis of GWAS of ADHD and MDD. All genome wide significant (p < 5 × 10–8) SNPs in the meta-analysis that were also strongly associated (p < 5 × 10–4) independently with each disorder were followed up. These putatively pleiotropic SNPs were tested for additional associations across a broad range of phenotypes. Fourteen linkage disequilibrium-independent SNPs were associated with each disorder separately (p < 5 × 10–4) and in the cross-disorder meta-analysis (p < 5 × 10–8). Nine of these SNPs had not been highlighted previously in either individual GWAS. Evidence supported nine of the fourteen SNPs acting as eQTL and two as brain eQTL. Index SNPs and their genomic regions demonstrated associations with other mental health phenotypes. Through conducting meta-analysis on ADHD and MDD only, our results build upon the previously observed genetic correlation between ADHD and MDD and reveal novel genomic regions that may be implicated in this overlap. [ABSTRACT FROM AUTHOR]

Importance: Adult mood disorders are often preceded by behavioral and emotional problems in childhood. It is yet unclear what explains the associations between childhood psychopathology and adult traits.Objective: To investigate whether genetic risk for adult mood disorders and associated traits is associated with childhood disorders.Design, Setting, and Participants: This meta-analysis examined data from 7 ongoing longitudinal birth and childhood cohorts from the UK, the Netherlands, Sweden, Norway, and Finland. Starting points of data collection ranged from July 1985 to April 2002. Participants were repeatedly assessed for childhood psychopathology from ages 6 to 17 years. Data analysis occurred from September 2017 to May 2019.Exposures: Individual polygenic scores (PGS) were constructed in children based on genome-wide association studies of adult major depression, bipolar disorder, subjective well-being, neuroticism, insomnia, educational attainment, and body mass index (BMI).Main Outcomes and Measures: Regression meta-analyses were used to test associations between PGS and attention-deficit/hyperactivity disorder (ADHD) symptoms and internalizing and social problems measured repeatedly across childhood and adolescence and whether these associations depended on childhood phenotype, age, and rater.Results: The sample included 42 998 participants aged 6 to 17 years. Male participants varied from 43.0% (1040 of 2417 participants) to 53.1% (2434 of 4583 participants) by age and across all cohorts. The PGS of adult major depression, neuroticism, BMI, and insomnia were positively associated with childhood psychopathology (β estimate range, 0.023-0.042 [95% CI, 0.017-0.049]), while associations with PGS of subjective well-being and educational attainment were negative (β, -0.026 to -0.046 [95% CI, -0.020 to -0.057]). There was no moderation of age, type of childhood phenotype, or rater with the associations. The exceptions were stronger associations between educational attainment PGS and ADHD compared with internalizing problems (Δβ, 0.0561 [Δ95% CI, 0.0318-0.0804]; ΔSE, 0.0124) and social problems (Δβ, 0.0528 [Δ95% CI, 0.0282-0.0775]; ΔSE, 0.0126), and between BMI PGS and ADHD and social problems (Δβ, -0.0001 [Δ95% CI, -0.0102 to 0.0100]; ΔSE, 0.0052), compared with internalizing problems (Δβ, -0.0310 [Δ95% CI, -0.0456 to -0.0164]; ΔSE, 0.0074). Furthermore, the association between educational attainment PGS and ADHD increased with age (Δβ, -0.0032 [Δ 95% CI, -0.0048 to -0.0017]; ΔSE, 0.0008).Conclusions and Relevance: Results from this study suggest the existence of a set of genetic factors influencing a range of traits across the life span with stable associations present throughout childhood. Knowledge of underlying mechanisms may affect treatment and long-term outcomes of individuals with psychopathology. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) and depression commonly co-occur. Identifying children with ADHD at risk for later depression may allow early intervention and prevention. Irritability is one possible mechanism linking these two disorders. It is common in ADHD and associated with later depression in the general population. Cross-sectional studies suggest an association between irritability and depression in ADHD, but longitudinal research is limited. This study followed up a clinical ADHD sample longitudinally to examine: (1) the association between childhood irritability and later depression symptoms, and (2) whether irritability persistence is important in this association. At baseline, parents (n = 696) completed semi-structured interviews about their child (mean age = 10.9), providing information on child psychopathology, including irritability. A subsample (n = 249) was followed up after a mean of 5.4 years. Parent-completed Mood and Feelings Questionnaires provided information on depressive symptoms at follow-up. Parent-rated structured diagnostic interviews provided information on ADHD diagnosis and irritability at follow-up. Regression analyses examined associations between (i) baseline irritability and depression symptoms at follow-up, and (ii) persistent (vs. remitted) irritability and depression symptoms at follow-up. Analyses controlled for age, gender, depression symptoms, anxiety, ADHD symptoms, and ADHD medication at baseline. Baseline irritability was associated with depression symptoms at follow-up, but the association attenuated after controlling for anxiety and ADHD symptoms. Persistent irritability was associated with depression symptoms at follow-up, after including all covariates. Children with ADHD with persistent irritability are at elevated risk of developing depression symptoms. They may be a target for early intervention and prevention of depression. [ABSTRACT FROM AUTHOR]

There is an enormous interest in identifying the causes of psychiatric disorders but there are considerable challenges in identifying which risks are genuinely causal. Traditionally risk factors have been inferred from observational designs. However, association with psychiatric outcome does not equate to causation. There are a number of threats that clinicians and researchers face in making causal inferences from traditional observational designs because adversities or exposures are not randomly allocated to individuals. Natural experiments provide an alternative strategy to randomized controlled trials as they take advantage of situations whereby links between exposure and other variables are separated by naturally occurring events or situations. In this review, we describe a growing range of different types of natural experiment and highlight that there is a greater confidence about findings where there is a convergence of findings across different designs. For example, exposure to hostile parenting is consistently found to be associated with conduct problems using different natural experiment designs providing support for this being a causal risk factor. Different genetically informative designs have repeatedly found that exposure to negative life events and being bullied are linked to later depression. However, for exposure to prenatal cigarette smoking, while findings from natural experiment designs are consistent with a causal effect on offspring lower birth weight, they do not support the hypothesis that intra-uterine cigarette smoking has a causal effect on attention-deficit/hyperactivity disorder and conduct problems and emerging findings highlight caution about inferring causal effects on bipolar disorder and schizophrenia. [ABSTRACT FROM AUTHOR]

Importance: Depression often first manifests in adolescence. Thereafter, individual trajectories vary substantially, but it is not known what shapes depression trajectories in youth. Adult studies suggest that genetic risk for schizophrenia, a psychiatric disorder with a neurodevelopmental component, may contribute to an earlier onset of depression.Objective: To test the hypothesis that there are distinct trajectories of depressive symptoms and that genetic liability for neurodevelopmental psychiatric disorders (eg, schizophrenia, attention deficit/hyperactivity disorder [ADHD]), as well as for major depressive disorder (MDD), contribute to early-onset depression.Design, Setting, and Participants: The Avon Longitudinal Study of Parents and Children is an ongoing, prospective, longitudinal, population-based cohort that has been collecting data since September 6, 1990, including data on 7543 adolescents with depressive symptoms at multiple time points. The present study was conducted between November 10, 2017, and August 14, 2018.Main Outcomes and Measures: Trajectories based on self-reported depressive symptoms dichotomized by the clinical cutpoint; MDD, schizophrenia, and ADHD polygenic risk score (PRS) were predictors.Results: In 7543 adolescents with depression data on more than 1 assessment point between a mean (SD) age of 10.64 (0.25) years and 18.65 (0.49) years (3568 [47.3%] male; 3975 [52.7%] female), 3 trajectory classes were identified: persistently low (73.7%), later-adolescence onset (17.3%), and early-adolescence onset (9.0%). The later-adolescence-onset class was associated with MDD genetic risk only (MDD PRS: odds ratio [OR], 1.27; 95% CI, 1.09-1.48; P = .003). The early-adolescence-onset class was also associated with MDD genetic risk (MDD PRS: OR, 1.24; 95% CI, 1.06-1.46; P = .007) but additionally with genetic risk for neurodevelopmental disorders (schizophrenia PRS: OR, 1.22; 95% CI, 1.04-1.43; P = .01; ADHD PRS: OR, 1.32; 95% CI, 1.13-1.54; P < .001) and childhood ADHD (χ21 = 6.837; P = .009) and neurodevelopmental traits (pragmatic language difficulties: OR, 1.31; P = .004; social communication difficulties: OR, 0.68; P < .001).Conclusions and Relevance: The findings of this study appear to demonstrate evidence of distinct depressive trajectories, primarily distinguished by age at onset. The more typical depression trajectory with onset of clinically significant symptoms at age 16 years was associated with MDD genetic risk. The less-common depression trajectory, with a very early onset, was particularly associated with ADHD and schizophrenia genetic risk and, phenotypically, with childhood ADHD and neurodevelopmental traits. Findings are consistent with emerging evidence for a neurodevelopmental component in some cases of depression and suggest that the presence of this component may be more likely when the onset of depression is very early. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) are two highly prevalent disorders that frequently co-occur. Prior evidence from genetic and cohort studies supports an association between ADHD and MDD. However, the direction and mechanisms underlying their association remain unclear. As onset of ADHD occurs in early life, it has been hypothesized that ADHD may cause MDD. We examined the association of ADHD with MDD using 3 different genetically informed methods to disentangle causality from confounding: 1) a nationwide longitudinal register-based full sibling comparison (N = 1,018,489) adjusting for shared familial confounding; 2) a prospective co-twin control study comprising 16,477 twins (5084 monozygotic and 11,393 dizygotic); and 3) a two-sample Mendelian randomization analysis using the largest available ADHD (N = 225,534) and MDD (N = 500,199) genome-wide association study summary statistics, adjusting for correlated and uncorrelated horizontal pleiotropy. Sibling and twin comparisons indicated that individuals with ADHD have an increased risk for subsequent development of MDD (hazard ratio = 4.12 [95% CI 3.62–4.69]) after adjusting for shared genetic and familial factors and that ADHD scores endorsed by parents are positively associated with subsequent MDD scores at ages 15 and 18 years (b = 0.07 [95% CI 0.05–0.08] and b = 0.09 [95% CI 0.08–0.11], respectively). Mendelian randomization analyses showed that genetic liability for ADHD is causally related to MDD (odds ratio = 1.15 [95% CI 1.08–1.23]). Our study provides consistent results across 3 different genetically informative approaches, strengthening the hypothesis that ADHD is causally related to MDD. [ABSTRACT FROM AUTHOR]

Importance: Early-onset major depressive disorder (MDD) is common in individuals at high familial risk of depression and is associated with poor long-term mental health, social, and educational outcomes.Objectives: To examine the developmental pathways that lead to first-episode adolescent-onset MDD (incident cases) in those at high familial risk and to postulate a theoretically informed model that enables simultaneous testing of different pathways to incident adolescent-onset MDD composed of contributions from familial/genetic and social risk factors, as well as effects via specific clinical antecedents.Design, Setting, and Participants: This investigation was a 4-year longitudinal study (April 2007 to March 2011) among offspring of depressed parents in the general community. Analyses were conducted between September 1, 2015, and May 27, 2016. Participants were 337 families in whom the index parent (315 mothers and 22 fathers) had experienced at least 2 episodes of MDD (recruited through primary care) and among whom there was a biologically related child in the age range of 9 to 17 years living with the index parent (197 girls and 140 boys with a mean [SD] age of 12.4 [2.0] years) at baseline. Offspring with MDD before the study or at baseline (n = 27), offspring with an episode of MDD that had remitted by follow-up (n = 4), and offspring with missing baseline MDD data (n = 2) were excluded. Ninety-two percent (279 of 304) of families completed the follow-up.Main Outcomes and Measures: The primary outcome was new-onset offspring MDD, and the secondary outcome was the total DSM-IV MDD symptom score.Results: On average, children and adolescents had a mean (SD) of 1.85 (1.74) (range, 0-8.5) DSM-IV symptoms of MDD at follow-up. Twenty (6 males and 14 females) had new-onset MDD, with a mean (SD) age at onset of 14.4 (2.0) years (range, 10-18 years). Irritability (β = 0.12, P = .03) and fear and/or anxiety (β = 0.38, P < .001) were significant independent clinical antecedents of new adolescent-onset MDD, but disruptive behavior (β = -0.08, P = .14) and low mood (β = -0.03, P = .65) were not. The results were similar for the DSM-IV symptom count at follow-up. All the measured familial/genetic and social risk indicators directly influenced risk for new-onset MDD rather than indirectly through acting on dimensional clinical antecedents.Conclusions and Relevance: There are multiple pathways to first-onset adolescent depression in individuals at familial risk. Irritability and fear/anxiety may be additional clinical phenomena to be included as targets in primary preventive interventions focusing on the child. In addition to targeting these phenomena in parents and children, depression prevention methods in high-risk groups may need to take into consideration social risks, such as poverty and psychosocial adversity. [ABSTRACT FROM AUTHOR]

Previous cross-sectional research has shown that parents of children with attention deficit hyperactivity disorder (ADHD) have high rates of psychopathology, especially ADHD and depression. However, it is not clear whether different types of parent psychopathology contribute to the course and persistence of ADHD in the child over time. The aim of this two wave study was to investigate if mother self-reported ADHD and depression influence persistence of offspring ADHD and conduct disorder symptom severity in adolescents diagnosed with ADHD in childhood. A sample of 143 males with a confirmed diagnosis of ADHD participated in this study. ADHD and conduct disorder symptoms were assessed at baseline and reassessed 4 years later. The boys in this sample had a mean age of 10.7 years at Time 1 (SD 2.14, range 6-15 years) and 13.73 years at Time 2 (SD 1.74, range 10-17 years). Questionnaire measures were used to assess ADHD and depression symptoms in mothers at Time 1. Mother self-reported ADHD was not associated with a change in child ADHD or conduct symptom severity over time. Mother self-reported depression was found to predict an increase in child conduct disorder symptoms, but did not contribute to ADHD symptom levels. This study provides the first evidence that concurrent depression in mothers may be a predictor of worsening conduct disorder symptoms in adolescents with ADHD. It may, therefore, be important to screen for depression in mothers of children with ADHD in clinical practice to tailor interventions accordingly. [ABSTRACT FROM AUTHOR]

Purpose: Childhood hyperactivity leads to mental health problems, but it is not known whether there are long-term risks for adult mood problems in unselected population cohorts that extend to mid-life. Aims were to examine links between childhood hyperactivity and mood problems up to age 50 years and to consider confounding factors and gender differences in associations.Methods: The National Child Development Study (NCDS) is a UK cohort of children born in 1958. Children with (N = 453) and without (N = 9192) pervasive and persistent hyperactivity were followed to age 50. Adult mood was assessed using the Malaise Inventory at ages 23, 33, 42, and 50 years and the CIS-R interview at 45 years.Results: Childhood hyperactivity predicted low mood at all adult assessments (ES = 0.27-0.45), including after covariate adjustment (childhood adversity, emotional and behavioural problems, and attainment).Conclusion: Hyperactivity has enduring risk effects on low mood throughout the life course that extend to middle age. [ABSTRACT FROM AUTHOR]

There is a renewed interest in better conceptualizing trajectories of attention-deficit/hyperactivity disorder (ADHD) from childhood to adulthood, driven by an increased recognition of long-term impairment and potential persistence beyond childhood and adolescence. This review addresses the following major issues relevant to the course of ADHD in light of current evidence from longitudinal studies: (1) conceptual and methodological issues related to measurement of persistence of ADHD, (2) estimates of persistence rate from childhood to adulthood and its predictors, (3) long-term negative outcomes of childhood ADHD and their early predictors, and (4) the recently proposed new adult-onset ADHD. Estimates of persistence vary widely in the literature, and diagnostic criteria, sample characteristics, and information source are the most important factors explaining variability among studies. Evidence indicates that ADHD severity, comorbid conduct disorder and major depressive disorder, and treatment for ADHD are the main predictors of ADHD persistence from childhood to adulthood. Comorbid conduct disorder and ADHD severity in childhood are the most important predictors of adverse outcomes in adulthood among children with ADHD. Three recent population studies suggested the existence of a significant proportion of individuals who report onset of ADHD symptoms and impairments after childhood. Finally, we highlight areas for improvement to increase our understanding of ADHD across the life span. [ABSTRACT FROM AUTHOR]

Background Depression is typically more common in females and rates rise around puberty. However, studies of children and adolescents suggest that depression accompanied by conduct problems may represent a different subtype not characterised by a female preponderance, with differing risk factors and genetic architecture compared to pure-depression. This study aimed to identify aetiologically distinct profiles of depressive symptoms, distinguished by the presence or absence of co-occurring conduct problems. Methods Latent profile analysis was conducted on a school sample of 1648 children (11-12 years) and replicated in a sample of 2006 twins (8-17 years). Results In both samples pure-depressive and conduct-depressive profiles were identified. The pure-depressive profile was associated with female gender, while the conduct-depressive profile was associated with lower cognitive ability but not with gender. Twin analyses indicated possible differences in genetic aetiology. Conclusions There was evidence for aetiologically heterogeneous depression symptom profiles based on the presence or absence of co-occurring conduct problems. [ABSTRACT FROM AUTHOR]

Past research has identified maternal depression and family of origin maltreatment as precursors to adolescent depression and antisocial behavior. Caregiving experiences have been identified as a factor that may ameliorate or accentuate adolescent psychopathology trajectories. Using a multilevel approach that pools the unique attributes of two geographically diverse, yet complementary, longitudinal research designs, the present study examined the role of maternal caregiver involvement as a factor that promotes resilience-based trajectories related to depressive symptoms and antisocial behaviors among adolescent girls. The first sample comprises a group of US-based adolescent girls in foster care (n = 100; mean age = 11.50 years), each of whom had a history of childhood maltreatment and removal from their biological parent(s). The second sample comprises a group of UK-based adolescent girls at high familial risk for depression (n = 145; mean age = 11.70 years), with all girls having biological mothers who experienced recurrent depression. Analyses examined the role of maternal caregiving on girls' trajectories of depression and antisocial behavior, while controlling for levels of co-occurring psychopathology at each time point. Results suggest increasing levels of depressive symptoms for girls at familial risk for depression but decreasing levels of depression for girls in foster care. Foster girls' antisocial behavior also decreased over time. Maternal caregiver involvement was differentially related to intercept and slope parameters in both samples. Results are discussed with respect to the benefits of applying multilevel (multisample, multiple outcome) approaches to identifying family-level factors that can reduce negative developmental outcomes in high-risk youth. [ABSTRACT FROM PUBLISHER]

Identifying environmental risk factors in the pathway to depression is an important research goal. To extend prior research, designs that rule out alternative explanatory factors; genetic effects and reverse causation, and permit tests of both parent and child gender are required. The present study used two different samples to address these issues. A longitudinal community sample of 316 families (157 boys, 159 girls) aged 11-12 years (mean 11.7) at Time 1 and 12-13 years at Time 2 (mean 12.7) was used to test the direction of effects between parent hostility and child and adolescent depression symptoms. A genetically sensitive sample of 1,075 twin pairs; 653 dizygotic (135 male, 183 female, 335 opposite sex) and 422 monozygotic (180 male and 242 female) aged 12-20 years (mean 16.12) was used to test whether parent hostility had environmental effects. Analyses were conducted separately by parent and child gender. Using cross-lagged panel analyses, the association between mother-daughter hostility and depression symptoms was found to be longitudinal and bidirectional with reciprocal effects between mothers and daughters. Behavioural genetic analyses in the twin sample revealed a significant environmental link between mother hostility and symptoms of daughter depression independent of genetic factors. A significant pathway was found between daughter depressive symptoms and father hostility but not vice versa. This association was accounted for by genetic factors in behavioural genetic analyses. Findings provide evidence of an environmental risk pathway to depression symptoms and identify patterns of variation according to parent and child gender. Results are discussed in relation to underlying explanatory processes and clinical implications. [ABSTRACT FROM AUTHOR]

Background Disruption in the parent-child relationship is a commonly hypothesized risk factor through which maternal depression may increase risk for offspring psychopathology. However, maternal depression is commonly accompanied by other psychopathology, including antisocial behaviour. Few studies have examined the role of co-occurring psychopathology in depressed mothers. Using a longitudinal study of offspring of mothers with recurrent depression, we aimed to test whether maternal warmth/hostility mediated links between maternal depression severity and child outcomes, and how far direct and indirect pathways were robust to controls for co-occurring maternal antisocial behaviour. Methods Mothers with a history of recurrent major depressive disorder and their adolescent offspring (9-17 years at baseline) were assessed three times between 2007 and 2010. Mothers completed questionnaires assessing their own depression severity and antisocial behaviour at Time 1 (T1). The parent-child relationship was assessed using parent-rated questionnaire and interviewer-rated 5-min speech sample at Time 2 (T2). Offspring symptoms of depression and disruptive behaviours were assessed using the Child and Adolescent Psychiatric Assessment at Time 3 (T3). Results Maternal hostility and warmth, respectively, mediated the association between maternal depression severity and risk for offspring psychopathology. However, the effects were attenuated when maternal antisocial behaviour was included in the analysis. In tests of the full theoretical model, maternal antisocial behaviour predicted both maternal hostility and low warmth, maternal hostility predicted offspring disruptive behaviour disorder symptoms, but not depression, and maternal warmth was not associated with either child outcome. Conclusions Parenting interventions aimed at reducing hostility may be beneficial for preventing or reducing adolescent disruptive behaviours in offspring of depressed mothers, especially when depressed mothers report co-occurring antisocial behaviour. [ABSTRACT FROM AUTHOR]

An enduring tendency towards negative thinking is thought to increase vulnerability for future depression. However, it has not been possible to assess this tendency in non-depressed mood states. We examined if response latency to endorse dysfunctional attitudes is associated with depressive outcomes in a longitudinal study. A sample of young people at familial risk of depression ( N = 252, aged 10-19, 56.3 % female) completed a computer-administered dysfunctional attitude scale. The main outcome measure was the difference in reaction time to agree versus disagree with dysfunctional attitudes. Cross-sectional differences between current and previous depression and no psychiatric disorder groups as well as longitudinal associations with depressive symptoms were examined. Young people with current and previous depression were quicker to agree with dysfunctional attitudes than those without disorder. In young people free from depressive disorder, faster agreements with dysfunctional attitudes were specifically associated with increased depressive symptoms over time. Self-reported dysfunctional attitudes did not differentiate the formerly depressed and no disorder groups and showed a longitudinal association with depressive symptoms for older adolescents only. Reaction time to endorse dysfunctional attitudes may indicate changes in affective processing that represent an early risk for future depression that is not indexed by self-report measures of negative thought. [ABSTRACT FROM AUTHOR]

Background: Offspring of mothers with depression are at heightened risk of psychiatric disorder. Many mothers with depression have comorbid psychopathology. How these co-occurring problems affect child outcomes has rarely been considered.Aims: To consider whether the overall burden of co-occurring psychopathology in mothers with recurrent depression predicts new-onset psychopathology in offspring.Method: Mothers with recurrent depression and their adolescent offspring (9-17 years at baseline) were assessed in 2007 and on two further occasions up to 2011. Mothers completed questionnaires assessing depression severity, anxiety, alcohol problems and antisocial behaviour. Psychiatric disorder in offspring was assessed using the Child and Adolescent Psychiatric Assessment.Results: The number of co-occurring problems in mothers (0, 1 or 2+) predicted new-onset offspring disorder (odds ratio (OR) = 1.80, 95% CI 1.17-2.77, P = 0.007). Rates varied from 15.7 to 34.8% depending on the number of co-occurring clinical problems. This remained significant after controlling for maternal depression severity (OR = 1.73, 95% CI 1.03-2.89, P = 0.040).Conclusions: The burden of co-occurring psychopathology among mothers with recurrent depression indexes increased risk of future onset of psychiatric disorder for offspring. This knowledge can be used in targeting preventive measures in children at high risk of psychiatric disorder. [ABSTRACT FROM AUTHOR]

Parental depression is associated with disruptions in the parent–child relationship, exposure to stressful family life events, and offspring depressive symptoms. Evidence suggests that intergenerational transmission of depression involves environmental and inherited contributions. We sought to evaluate the role of passive gene–environment correlation (rGE) in relation to depression, family life events that were due to parental behavior, and parental positivity in a sample where children varied in genetic relatedness to their rearing parents. Our study included 865 families with children born through assisted conception (444 related to both parents, 210 related to the mother only, 175 related to the father only, and 36 related to neither parent). Consistent with previous studies, the intergenerational transmission of depressive symptoms was largely due to environmental factors, although parent and child gender influenced results. Maternal and paternal depressive symptoms were associated with reduced positivity and increased parentally imposed life events regardless of parent–child relatedness. Results of path analysis were consistent with passive rGE for both maternal and paternal positivity in that positivity partially mediated the link between maternal/paternal depression and child depression only in genetically related parent–child pairs. Results also suggested passive rGE involving parentally imposed life events for mothers and fathers although passive rGE effects were smaller than for positivity. [ABSTRACT FROM AUTHOR]

This study investigated moderation of the association between recurrent maternal depression and offspring depression symptoms by a selection of biologically relevant gene variants. 271 children/adolescents (aged 9.00 to 16.00 years) whose mothers had experienced at least two episodes of DSM-IV major depression and 165 controls (aged 12.25 to 16.67 years) drawn from a population-based twin register were used. Seven single nucleotide polymorphisms (SNPs) from three genes were genotyped in children. The genes were the Corticotropin Receptor Type 1 gene ( CRHR1), the gene coding for the FK506 binding protein 5 ( FKBP5) and the Glucocorticoid receptor gene ( NR3c1) along with a haplotype formed by the SNPs in CRHR1. A significant association was found between recurrent maternal depression and depression symptoms in offspring. None of the SNPs were associated with offspring depression symptoms and associations did not differ according to the presence of recurrent maternal depression. However, caution is required due to a relatively small sample size. [ABSTRACT FROM AUTHOR]

The article discusses a clinical review of managing and preventing depression in adolescents. It examines the importance of identifying adolescent depression based on evidence from prospective community studies. It identifies adolescents who are most at risk of developing a depressive disorder, including ones whose parents have a history of depression. The article also describes ways in which adolescent depression is diagnosed, as well as preventive options and treatments that are effective for adolescent depression.

The study of gene–environment interaction (G × E) constitutes an area of significant social and clinical significance. Different types of research study designs are being used to investigate the contribution of G × E to psychopathology, although the term G × E has also been used and interpreted in different ways. Despite mixed evidence that G × E contributes to psychopathology, some promising and consistent findings are emerging. Evidence is reviewed in relation to depression, antisocial behavior, schizophrenia, and attention-deficit/hyperactivity disorder. Although findings from various research designs have different meaning, interestingly much of the evidence with regard to the contribution of G × E that has arisen from twin and adoption studies has been for antisocial behavior and depression. It is for these same forms of psychopathology that molecular genetic evidence of G × E has also been most convincing. Finally, current and anticipated methodological challenges and implications for future research in this area are considered. [ABSTRACT FROM PUBLISHER]

Low birth-weight has been associated with depression and related outcomes in adults, and with problem behaviours in children. This study aimed to examine the association between low birth-weight for gestation and depressive symptoms in children and adolescents and to examine whether the relationship is moderated by genetic risk for depression. An epidemiological, genetically sensitive design was used including 2,046 twins aged 8–17 years (1,023 families). Data were obtained by parental report and analysed using regression analysis. A small but significant association between birth-weight for gestation and early depressive symptoms was observed. The unit increase in depressive symptoms per unit decrease in birth-weight for gestation was greater for individuals at genetic or familial risk for depression. For low birth-weight children, genetic risk for depression moderated the influence of birth-weight for gestation in predicting early depressive symptoms. Birth-weight for gestation is moderated by genetic and familial risk for depression in influencing early depression symptoms. These observations have clinical implications in that the impact of being small for gestational age on depressive symptoms is greater in children at familial/genetic risk although the association between birth weight and depression does not imply causality. [ABSTRACT FROM AUTHOR]

Background: Medically unexplained disabling fatigue in young people is familial and frequently associated with depressed mood.Aims: To examine the degree of sharing of genetic and environmental influences on the symptoms of depression and fatigue in this age group.Method: The parents of twins aged 8-17 years, derived from a population-based register, completed a questionnaire regarding lifetime-ever disabling fatigue in both twins. Twins aged 11 years or over completed the Mood and Feelings Questionnaire. The genetic and environmental influences on fatigue and the relationship with depression were examined using bivariate genetic analysis.Results: Parent-rated data were obtained for 1468 twin pairs (65%) and self-rated data from 930 older twin pairs (58%). Bivariate analysis of fatigue and depression suggested that genetic and environmental influences on disabling fatigue were mainly specific to fatigue.Conclusions: Unexplained disabling fatigue in childhood is substantially familial and has mainly an independent aetiology from depression. [ABSTRACT FROM AUTHOR]

Background: The epidemiology of chronic fatiguing illnesses in young people is poorly understood.Aims: To estimate the lifetime prevalence of different definitions of chronic fatigue in 8- to 17-year-olds.Method: Participants came from two population-based twin series. Parents completed self-report questionnaires that inquired whether either child had ever experienced more than a few days of disabling fatigue. Telephone interviews were undertaken for individuals who had experienced such an episode.Results: Questionnaires were returned by 1468 families (65% response rate) and telephone interviews were undertaken regarding 99 of the 129 subjects (77%) who had experienced fatigue. The lifetime prevalence estimates ranged from 2.34% (95% CI 1.75-2.94) for disabling fatigue lasting 3 months to 1.29% (95% CI 0.87-1.71) for a disorder resembling adult operationally defined chronic fatigue syndrome.Conclusions: From the age of 11 years, young people have similar rates and types of chronic fatiguing illnesses to adults. [ABSTRACT FROM AUTHOR]

Background: Anxiety and depression co-occur in children and adolescents with anxiety commonly preceding depression. Although there is some evidence to suggest that the association between early anxiety and later depression is explained by a shared genetic aetiology, the contribution of environmental factors is less well examined and it is unknown whether anxiety itself is a phenotypic risk factor for later depression. These explanations of the association between early anxiety and later depression were evaluated. Methods: Anxiety and depressive symptoms were assessed longitudinally in a U.K. population-based sample of 676 twins aged 5-17 at baseline. At baseline, anxiety and depression were assessed by parental questionnaire. Depression was assessed three years later by parental and adolescent questionnaire. Results: Shared genetic effects between early anxiety and later depression were found. A model of a phenotypic risk effect from early anxiety on later depression provided a poor fit to the data. However, there were significant genetic effects specific to later depression, showing that early anxiety and later depression do not index entirely the same genetic risk. Conclusions: Anxiety and depression are associated over time because they share a partly common genetic aetiology rather than because the anxiety phenotype leads to later depression. [ABSTRACT FROM AUTHOR]

Background: Although depression in childhood appears to be familial, transmission of symptoms could be genetic or environmental. Twin studies enable us to separate these effects. Our aim was to assess the importance of genetic and environmental factors on depressive symptoms during childhood and adolescence in an epidemiological sample of twins.Method: Questionnaires (including the Mood and Feelings questionnaire) were mailed to a systematically ascertained sample (411 twin pairs) aged between 8 and 16 years. The overall response rate was 77%.Results: Data for the whole sample were best explained by an additive genetic model, with heritability of depressive symptom scores estimated at 79%. However, on splitting the sample, symptoms in children (aged 8 to 11) could be explained by shared environmental factors only, while symptoms in adolescents (aged 11 to 16) remained highly heritable.Conclusions: The results suggest that although depressive symptoms appear to be largely heritable, the influence of genetic and environmental factors may vary with age. [ABSTRACT FROM AUTHOR]

The author discusses a cohort study by George Patton and colleagues to assess how often depression and anxiety persist from adolescence to adulthood and identify which demographic, behavioural and disorder characteristics predict this persistence. The study centered on the course and prognosis of depression and anxiety which are the most prevalent in the age group.

The article offers an overview on the meta-analysis conducted by Neil Risch and colleagues on the interaction between serotonin transporter gene 5-HTTLPR, stressful life events on depression. It mentions that the study puts serious doubt on the assumption that gene-environment interaction (G×E) was a real phenomenon by basing on the meta-analysis. It stresses that they failed to ask why they find no significant G×E while several studies did find significant G×E.

Parental depression is a common and potent risk factor for depression in offspring. However, the developmental course of depression from childhood to early-adulthood has not been characterized in this high-risk group. Using longitudinal data from 337 young people who had a parent with a history of recurrent major depressive disorder (MDD), we characterized trajectories of broadly defined depressive disorder using latent class growth analysis. We used clinical descriptions to further characterise trajectory classes. Two trajectory classes were identified: childhood-emerging (25 %) and adulthood-emerging (75 %). The childhood-emerging class showed high rates of depressive disorder from age 12.5, which persisted through the study period. The adulthood-emerging class showed low rates of depressive disorder until age 26. Individual factors (IQ and ADHD symptoms) and parent depression severity (comorbidity, persistence and impairment) differentiated the classes but there were no differences in family history score or polygenic scores associated with psychiatric disorder. Clinical descriptions indicated functional impairment in both classes, but more severe symptomatology and impairment in the childhood-emerging class. Attrition particularly affected participation in young adulthood. Factors associated with attrition were low family income, single parent household status and low parental education. The developmental course of depressive disorder in children of depressed parents is variable. When followed up to adult life, most individuals exhibited some functional impairment. An earlier age-of-onset was associated with a more persistent and impairing course of depression. Access to effective prevention strategies is particularly warranted for at-risk young people showing early-onsetting and persistent depressive symptoms. • Adulthood-emerging and childhood-emerging trajectory classes were identified. • The childhood-emerging class showed a severe and persistent course of depression. • Most individuals in both classes experienced some functional impairment. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic negatively impacted mental health globally. Individuals with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), are at elevated risk of mental health difficulties. We investigated the impact of the pandemic on anxiety, depression and mental wellbeing in adults with NDDs using data from the Avon Longitudinal Study of Parents and Children (n = 3058). Mental health data were collected pre-pandemic (age 21–25) and at three timepoints during the pandemic (ages 27–28) using the Short Mood and Feelings Questionnaire, Generalized Anxiety Disorder Assessment-7, and Warwick Edinburgh Mental Wellbeing Scale. ADHD and ASD were defined using validated cut-points of the Strengths and Difficulties Questionnaire and Autism Spectrum Quotient, self-reported at age 25. We used multi-level mixed-effects models to investigate changes in mental health in those with elevated ADHD/ASD traits compared to those without. Prevalences of depression, anxiety and poor mental wellbeing were higher at all timepoints (pre-pandemic and during pandemic) in those with ADHD and ASD compared to those without. Anxiety increased to a greater extent in those with ADHD (β = 0.8 [0.2,1.4], p = 0.01) and ASD (β = 1.2 [-0.1,2.5], p = 0.07), while depression symptoms decreased, particularly in females with ASD (β = −3.1 [-4.6,-1.5], p = 0.0001). On average, mental wellbeing decreased in all, but to a lesser extent in those with ADHD (β = 1.3 [0.2,2.5], p = 0.03) and females with ASD (β = 3.0 [0.2,5.9], p = 0.04). To conclude, anxiety disproportionately increased in adults with NDDs during the pandemic, however, the related lockdowns may have provided a protective environment for depressive symptoms in the same individuals. [ABSTRACT FROM AUTHOR]

Background: Depression is highly heterogeneous in its clinical presentation. Those with attention deficit/hyperactivity disorder (ADHD) may be at risk of a more chronic and impairing depression compared to those with depression alone according to studies of young people. However, no studies to date have examined ADHD in recurrently depressed adults in mid-life.Method: In a sample of women in mid-life (n=148) taken from a UK based prospective cohort of adults with a history of recurrent depression, we investigated the prevalence of ADHD and the association of ADHD with clinical features of depression.Results: 12.8% of the recurrently depressed women had elevated ADHD symptoms and 3.4% met DSM-5 diagnostic criteria for ADHD. None of the women reported having a diagnosis of ADHD from a medical professional. ADHD symptoms were associated with earlier age of depression onset, higher depression associated impairment, a greater recurrence of depressive episodes and increased persistence of subthreshold depression symptoms over the study period, higher levels of irritability and increased risk of self-harm or suicide attempt. ADHD symptoms were associated with increased risk of hospitalisation and receiving non-first-line antidepressant medication.Limitations: ADHD was measured using a questionnaire measure. We focussed on mothers in a longitudinal study of recurrent depression, so the findings may not apply to males or other groups.Conclusions: Higher ADHD symptoms appear to index a worse clinical presentation for depression. Clinical implications include that in women with early onset, impairing and recurrent depression, the possibility of underlying ADHD masked by depression needs to be considered. [ABSTRACT FROM AUTHOR]

Background: Depression often onsets in adolescence and is associated with recurrence in adulthood. There is a need to identify and monitor depression symptoms across adolescence and into young adulthood. The short Mood and Feelings Questionnaire (sMFQ) is commonly used to measure depression symptoms in adolescence but has not been validated in young adulthood. This study aimed to (1) examine whether the sMFQ is valid in young adulthood, and (2) identify cut-points best capturing DSM-5 depression diagnosis at age 25 METHODS: The sample included participants in the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 25 (n = 4098). Receiver Operating Characteristic analyses examined how well the self-rated sMFQ discriminates between cases and non-cases of DSM-5 Major Depressive Disorder (MDD) classified using the self-rated Development and Well Being Assessment. Sensitivity and specificity values were used to identify cut-points on the sMFQ RESULTS: The sMFQ had high accuracy for discriminating MDD cases from non-cases at age 25. The commonly used cut-point in adolescence (≥12) performed well at this age, best balancing sensitivity and specificity. However, a lower cut-point (≥10) may be appropriate when favouring sensitivity over specificity e.g., in context of screening. Sensitivity analyses suggested similar results for males and females LIMITATIONS: ALSPAC is a longitudinal population cohort that suffers from non-random attrition CONCLUSIONS: The sMFQ is a valid measure of depression in young adults in the general population. It can be used to screen for and monitor depression across adolescence and early adulthood. [ABSTRACT FROM AUTHOR]

Very early-onset depression (i.e. onset by 15 years) is a rare form of depression that may differ in genetic aetiology to later-onset depression. Very early-onset depression is associated with higher ADHD polygenic scores, higher prevalence of ADHD and autism, and is more common in males. In contrast, later-adolescent onset depression is more common in females and shows other similarities to adult depression. One hypothesis is that very early-onset depression may be neurodevelopmental in nature. Neurodevelopmental conditions including autism, ADHD and schizophrenia are associated with a higher rate of neurodevelopmental copy number variants (NDD CNVs), and evidence suggests providing a genetic aetiology for a neurodevelopmental diagnosis is perceived as highly positive and valuable information for patients. Although CNV burden is increased in those with depression, the role of CNVs in early-onset depression has not previously been examined and may help better understand the heterogeneity of depression. NDD CNVs were called in the Millennium Cohort Study, a cohort of children born in the UK in 2000-2001 (n=156 carriers, n=6621 noncarriers). Early-onset depression was defined as scoring >4 at either age 11 or 14 on the parent-reported Strengths and Difficulties Questionnaire emotional subscale (cases n=2096, controls n=10828; with CNV data: cases n=1215, controls n=5550). Neurodevelopmental disorders were defined by parent-report of ADHD, autism, epilepsy and reading impairment up to age 14. Special education needs were defined by parent-report up to age 11, and IQ was measured at age 5 using the British Ability Scales. Logistic regressions measured associations between early-onset depression, compared to later-onset or no depression, and neurodevelopmental phenotypes and NDD CNV carrier status. We will extend this analysis to two additional cohorts (n=20000) prior to WCPG 2023, and meta-analyse the findings across cohorts. Individuals with a neurodevelopmental disorder were significantly more likely to experience early-onset depression (OR=3.44 [3.08-3.83], p=8.2 × 10-109), with autistic individuals experiencing the highest odds (OR=6.34 [5.08–7.92], p=5.7 × 10-60). Early-onset depression was also associated with special educational needs (OR=3.05 [2.67-3.48], p=1.5 × 10-62), lower IQ (OR=0.72 [0.69-0.76], p=9.1 × 10-40), and having a parent with autism (OR=2.71 [1.84-3.98], p=4.6 × 10-7). Carrying an NDD CNV was associated with increased risk of ADHD (OR=2.03, [1.42-2.92], p=1.1 × 10-4), but not with autism (OR=1.68 [0.73-3.85], p=0.22). 3.0% of people with early-onset depression carried an NDD CNV, compared to 2.1% of controls. NDD CNV carrier status was not significantly associated with early-onset depression (OR=1.42 [0.97-2.07], p=0.07). Early-onset depression was associated with substantially increased likelihood of having a neurodevelopmental disorder. NDD CNVs increased risk of ADHD, but were not significantly associated with autism or early-onset depression. Given the small number of NDD CNV carriers in our sample, larger samples may be needed to detect a significant effect. Nevertheless, the proportion of individuals with early-onset depression that carried an NDD CNV was small, indicating that screening for CNVs in this group is unlikely to be useful. However, our findings suggest that it may be valuable for clinicians to screen patients with early-onset depression for potential comorbid neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

Children with chronic physical illnesses, such as asthma, diabetes and migraine, have a higher rate of mental disorders, including depression and anxiety, than their physically healthy counterparts. With chronic illnesses estimated to affect around 25% of children, it is important to consider how these conditions contribute to early-onset mental disorders. Whilst previous studies have indicated associations between chronic illness and mental ill-health, causality has not been determined and cannot be concluded due to the potential of reverse causality or confounding factors (e.g. poverty, preterm birth). Therefore, we aim to use genetic approaches to investigate causal links between childhood chronic physical illness and major depressive and anxiety disorders in youth. Using data from the Norwegian Mother, Father and Child cohort study (MoBa) and the Norwegian National Patient Registry, we first investigated epidemiological associations between maternal reports of child chronic illnesses by 14 years (arthritis, asthma, cerebral palsy, chronic fatigue syndrome (CF), coeliac disease, diabetes, epilepsy, migraine and hearing loss) with a depression diagnosis (ICD-10: F32/F33) and anxiety disorder diagnosis (ICD-10: F40/41) prior to 18 years, including birth year and sex as covariates where appropriate. Two-sample Mendelian randomisation (MR) analysis was conducted using SNPs associated with common childhood chronic physical illnesses from existing GWAS. Initial analyses using outcome data from the largest depression and anxiety GWASs were undertaken. We will extend this analysis using outcome data from a GWAS of child/adolescent-onset depression (Childhood arthritis (OR = 3.1 [1.1-7.1], p=0.02), cerebral palsy (OR = 3.1 [1.1-6.9], p = 0.02), CF (OR = 2.7 [0.9-6.3], p=0.03), epilepsy (OR = 2.9 [1.6-5.0], p=3 × 10-4) and migraine (OR = 1.4 [1.0-1.8], p=0.02) were associated with a diagnosis of anxiety disorder by 18 years. CF was the only illness also associated with a depression diagnosis (OR = 6.2 [2.5-13.0], p=1 × 10-5). Initial MR results did not indicate causal associations between juvenile arthritis, childhood-onset asthma, type 1 diabetes and eczema and major depressive disorder (MDD). However, migraine genetic liability was associated with MDD (b=2.0 ±0.99, p=0.04). For anxiety disorders, genetic liability to type 1 diabetes had a weak protective effect (b=-0.04 ±0.02, p=0.03), but there was no causal association for juvenile arthritis, childhood-onset asthma, eczema, nor migraine. Having a chronic physical health condition is associated with mental ill-health in young people, however, initial MR analysis indicates the majority of these conditions are not causally associated with depression nor anxiety disorders. However current GWAS do not focus on early-onset depression so MR findings using these data will also be presented. [ABSTRACT FROM AUTHOR]

Background: Irritability and the new DSM-5 diagnostic category of Disruptive Mood Dysregulation Disorder (DMDD) have been conceptualised as related to mood disorder. Irritability is common in Attention Deficit Hyperactivity Disorder (ADHD) but little is known about its association with depression risk in this group. This study aims to establish levels of irritability and prevalence of DMDD in a clinical sample of children with ADHD, and examine their association with anxiety, depression and family history of depression.Methods: The sample consisted of 696 children (mean age 10.9 years) with a diagnosis of ADHD, recruited from UK child psychiatry and paediatric clinics. Parents completed the Child and Adolescent Psychiatric Assessment, a semi-structured diagnostic interview, about their child. This was used to establish prevalence of DMDD, anxiety disorder and depressive disorder, as well as obtain symptom scores for irritability, anxiety and depression. Questionnaires assessed current parental depression, and family history of depression.Result: Irritability was common, with 91% endorsing at least one irritable symptom. 3-month DMDD prevalence was 31%. Children with higher levels of irritability or DMDD were more likely to have comorbid symptoms of anxiety, depression and a family history of depression.Limitations: Results are based on a clinical sample, so may not be generalizable to children with ADHD in the general population.Conclusions: Irritability and DMDD were common, and were associated with markers of depression liability. Longitudinal studies are needed to examine the association between irritability and depression in youth with ADHD as they get older. [ABSTRACT FROM AUTHOR]

Depression is known to be influenced by psychosocial stressors. For mothers with recurrent depressive illness, the presence of psychopathology in their children may have important effects on their own mental health. Although the impact of maternal depression on child mental health is well-established, no study to date, as far as we are aware, has examined the extent to which offspring psychopathology influences the course of depression in mothers with a history of recurrent depressive illness, what types of child psychopathology impact maternal mental health, or whether risks vary by child gender. Aims were to (a) Use a longitudinal design to examine whether adolescent psychopathology (depression, disruptive behavior disorder; DBD) predicts recurrence of a depressive episode and depression symptom course in women with a history of recurrent depression; and (b) To test if observed effects vary by child gender. 299 mothers with recurrent major depressive disorder and their adolescent offspring were assessed on 2 occasions, 29 months apart. Maternal depression and offspring psychopathology were assessed using semistructured interview measures. Cross-generational links across time were assessed using structural equation modeling. Analyses were adjusted for past severity of maternal depression. Offspring depression symptoms but not DBD symptoms at baseline predicted future episode recurrence in mothers. Depression symptoms in daughters (β = .16, p = .039) but not sons (β = -.07, p = .461), predicted an increase in maternal depression symptoms across time. Psychopathology in daughters is associated with long-term depressive symptoms in women (mothers) with a history of recurrent depression. Findings highlight the importance of careful assessment and management of mental health problems in adolescents for more effective management of maternal depression. This study suggests that offspring symptoms of depression may be important for the recurrence of maternal depression episodes. Girls' symptoms of depression may be a particularly important psychosocial stressor for the development of depressive symptoms in mothers with a history of recurrent depression. [ABSTRACT FROM AUTHOR]

Objective: Fundamental questions in biological psychiatry concern the mechanisms that mediate between genetic liability and psychiatric symptoms. Genetic liability for many common psychiatric disorders often confers transdiagnostic risk to develop a wide variety of psychopathological symptoms through yet unknown pathways. This study examined the psychological and cognitive pathways that might mediate the relationship between genetic liability (indexed by polygenic scores; PS) and broad psychopathology (indexed by p factor and its underlying dimensions).Method: First, which of the common psychiatric PSs (major depressive disorder [MDD], attention-deficit/hyperactivity disorder [ADHD], anxiety, bipolar disorder, schizophrenia, autism) that were associated with p factor were identified. Then focused was shifted to 3 pathways: punishment sensitivity (reflected by behavioral inhibition system), reward sensitivity (reflected by behavioral activation system), and cognitive abilities (reflected by g factor based on 10 neurocognitive tasks). We applied structural equation modeling on the Adolescent Brain Cognitive Development (ABCD) Study dataset (n = 4,814; 2,263 girls; 9-10 years old).Results: MDD and ADHD PSs were associated with p factor. The association between MDD PS and psychopathology was partially mediated by punishment sensitivity and cognitive abilities (proportion mediated = 22.35%). Conversely, the influence of ADHD PS on psychopathology was partially mediated by reward sensitivity and cognitive abilities (proportion mediated = 30.04%). The mediating role of punishment sensitivity was specific to emotional/internalizing. The mediating role of both reward sensitivity and cognitive abilities was specific to behavioral/externalizing and neurodevelopmental dimensions of psychopathology.Conclusion: This study provides a better understanding of how genetic risks for MDD and ADHD confer risks for psychopathology and suggests potential prevention/intervention targets for children at risk. [ABSTRACT FROM AUTHOR]

Objective: Links between maternal and offspring depression symptoms could arise from inherited factors, direct environmental exposure, or shared adversity. A novel genetically sensitive design was used to test the extent of environmental links between maternal depression symptoms and child depression/anxiety symptoms, accounting for inherited effects, shared adversity, and child age and gender. Method: Eight hundred fifty-two families with a child born by assisted conception provided questionnaire data. Mothers and fathers were genetically related or unrelated to the child depending on conception method. Parental depression symptoms were assessed using the Hospital Anxiety and Depression Scale. Child depression/anxiety symptoms were assessed using the Short Mood and Feelings questionnaire and six items tapping generalized anxiety disorder symptoms. Associations between maternal and child symptoms were examined separately for genetically unrelated and related mother-child pairs, adjusting for three measurements of shared adversity: negative life events, family income, and socioeconomic status. Analyses were then run separately for boys and girls and for children and adolescents, and the role of paternal depression symptoms was also examined. Results: Significant associations between parent and child symptoms were found for genetically unrelated mother-child (r = 0.32, p < .001) and father-child (r = 0.17, p < .05) pairs and genetically related mother-child (r = 0.31, p < .001) and father-child (r = 0.23, p < .001) pairs and were not explained by the shared adversity measurements. Environmental links were present for children and adolescents and were stronger for girls. Conclusions: The transmission of depression symptoms is due in part to environmental processes independent of inherited effects and is not accounted for by shared adversity measurements. Girls may be more sensitive to the negative effects of maternal depression symptoms than boys through environmental processes. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(5): 451-459. Key Words: depression, anxiety, transmission, environmental, genetic [ABSTRACT FROM AUTHOR]

Objective: To assess the value of maternal and self-ratings of adolescent depression by investigating the extent to which these reports predicted a range of mental health and functional outcomes 4 years later. The potential influence of mother's own depressed mood on her ratings of adolescent depression and suicidal ideation on adolescent outcome was also tested.Method: A longitudinal population-based study of 842 adolescents ages 11 to 16 at the baseline assessment and 15 to 20 at follow-up (62% retention).Results: Both mother- and adolescent-rated depressive symptoms predicted future depression, antisocial behavior, impairment, health service use, and regular tobacco use in the adolescent. The odds ratios obtained for maternal and adolescent ratings of depressive symptoms as predictors of future psychopathology were not significantly different. Mothers' own depressive symptoms were not significantly associated with adolescent depression, health service use, or substance use at follow-up. Depression that was accompanied by adolescent-rated suicidal thoughts was significantly more strongly associated with impairment at follow-up than depression alone.Conclusions: It is possible to obtain clinically useful information on adolescent depression from the child's mother. However, information on suicidal ideation was rarely endorsed by mothers, suggesting that maternal report of adolescent suicidal thoughts shows less sensitivity than adolescent report. [ABSTRACT FROM AUTHOR]

Objective: To test for gene-environment interaction with depressive symptoms and family conflict. Specifically, to first examine whether the influence of family conflict in predicting depressive symptoms is increased in individuals at genetic risk of depression. Second, to test whether the genetic component of variance in depressive symptoms increases as levels of family conflict increase.Method: A longitudinal twin design was used. Children ages 5 to 16 were reassessed approximately 3 years later to test whether the influence of family conflict in predicting depressive symptoms varied according to genetic liability. The conflict subscale of the Family Environment Scale was used to assess family conflict and the Mood and Feelings Questionnaire was used to assess depressive symptoms. The response rate to the questionnaire at time 1 was 73% and 65% at time 2. Controlling for initial symptoms levels (i.e., internalizing at time 1), primary analyses were conducted using ordinary least-squares multiple regression. Structural equation models, using raw score maximum likelihood estimation, were also fit to the data for the purpose of model fit comparison.Results: Results suggested significant gene-environment interaction specifically with depressive symptoms and family conflict. Genetic factors were of greater importance in the etiology of depressive symptoms where levels of family conflict were high. The effects of family conflict on depressive symptoms were greater in children and adolescents at genetic risk of depression.Conclusions: The present results suggest that children with a family history of depression may be at an increased risk of developing depressive symptoms in response to family conflict. Intervention programs that incorporate one or more family systems may be of benefit in alleviating the adverse effect of negative family factors on children. [ABSTRACT FROM AUTHOR]

Most psychiatric disorders are thought to have their origins at least in part in childhood, even if early manifestations of liability are quite different from the later full-blown clinical picture. This work aims to identify traits relevant to risk for psychiatric disorders early in development by investigating which "neurodevelopmental domains" are associated with psychiatric disorder risk alleles during childhood. Findings will be presented testing the hypothesis that psychiatric disorder risk alleles, as measured by polygenic risk scores, affect normative, dimensional childhood characteristics in the general population. Specifically, this work investigates associations between polygenic risk scores for schizophrenia, bipolar disorder, major depressive disorder and Attention Deficit Hyperactivity Disorder and primarily pre-pubertal neurodevelopmental traits using longitudinal general population samples. [ABSTRACT FROM AUTHOR]

Highlights from the article: Su93the contribution of psychiatric risk alleles to a general liability to psychopathology in early life: investigating one explanation for pleiotropy In this study we examine the structure of psychopathology in childhood and early adolescence in a population-based birth cohort, including autistic and ADHD symptoms as well as emotional and behavioral items that have been used in previous studies. PRS were derived from the largest available published genome-wide association studies of schizophrenia, major depressive disorder (MDD), autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD).