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A growing body of literature highlights the important role of paternal health and socioemotional characteristics in child development, from preconception through adolescence. Much of this research addresses the indirect effects of fathers, for instance, their influence on maternal behaviors during the prenatal period or via the relationship with their partner. However, emerging evidence also recognizes the direct role of paternal health and behavior for child health and adjustment across development. This critical review presents evidence of biological and sociocultural influences of fathers on preconception, prenatal, and postnatal contributions to child development. The National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) program incorporates in its central conceptualization the impact of fathers on family and child outcomes. This critical synthesis of the literature focuses on three specific child outcomes in the ECHO program: health outcomes (e.g., obesity), neurodevelopmental outcomes (e.g., emotional, behavioral, psychopathological development), and positive health. We highlight the unique insights gained from the literature to date and provide next steps for future studies on paternal influences.
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Desenvolvimento Infantil , Pai , Masculino , Criança , Gravidez , Feminino , Adolescente , Humanos , Pai/psicologia , Emoções , Avaliação de Resultados em Cuidados de SaúdeRESUMO
The multifactorial nature of psychopathology, whereby both genetic and environmental factors contribute risk, has long been established. In this paper, we provide an update on genetically informative designs that are utilized to disentangle genetic and environmental contributions to psychopathology. We provide a brief reminder of quantitative behavioral genetic research designs that have been used to identify potentially causal environmental processes, accounting for genetic contributions. We also provide an overview of recent molecular genetic approaches that utilize genome-wide association study data which are increasingly being applied to questions relevant to psychopathology research. While genetically informative designs typically have been applied to investigate the origins of psychopathology, we highlight how these approaches can also be used to elucidate potential causal environmental processes that contribute to developmental course and outcomes. We highlight the need to use genetically sensitive designs that align with intervention and prevention science efforts, by considering strengths-based environments to investigate how positive environments can mitigate risk and promote children's strengths.
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Adolescence is a period when both mental health (MH) and wellbeing start deteriorating, which raises the question of how the two phenomena are linked and whether deterioration in one might be used to flag problematic developments in the other. While research shows that wellbeing and MH are associated, the direction of the association is not clear and longitudinal analyses, that might help disentangle the cause and effect, are scarce. Moreover, few studies have investigated the directional relation between MH and wellbeing early in the life course. In emerging adulthood, evidence indicates reciprocal associations and no gender differences, whereas, in early and middle adolescence, results are mixed and differ across gender. Thus, we investigated the relationship between MH and wellbeing and the moderating effect of gender in the crucial developmental transition from middle adolescence to emerging adulthood. We undertake a cross-lagged longitudinal data analysis from a pooled sample of six pseudo-cohorts, including information from 661 young people who participated in the UK Household Longitudinal Study at ages 17, 19, and 21. Using a 7-points overall life satisfaction (LS) scale as an index of wellbeing and the 12-item General Health Questionnaire as a measure of MH, we found no associations between LS and MH in the 17-19 transition and bidirectional associations in the 19-21 transition. There were no substantial gender differences in either transition. We conclude that LS and MH predict each other in the transition from late adolescence (age 19) to emerging adulthood (age 21) for both males and females.
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Although genetic factors may contribute to initial liability for ADHD onset, there is growing evidence of the potential importance of the rearing environment on the developmental course of ADHD symptomatology. However, associations between family-level variables (maternal hostility, maternal depressive symptoms) and child behaviors (developmental course of ADHD and aggression) may be explained by genes that are shared by biologically related parents and children. Furthermore, ADHD symptoms and aggression commonly co-occur: it is important to consider both simultaneously to have a better understanding of processes underlying the developmental course of ADHD and aggression. To addresses these issues, we employed a longitudinal genetically sensitive parent-offspring adoption design. Analyses were conducted using Cohort I (n = 340) of the Early Growth and Development Study with cross-validation analyses conducted with Cohort II (n = 178). Adoptive mother hostility, but not depression, was associated with later child ADHD symptoms and aggression. Mothers and their adopted children were genetically unrelated, removing passive rGE as a possible explanation. Early child impulsivity/activation was associated with later ADHD symptoms and aggression. Child impulsivity/activation was also associated with maternal hostility, with some evidence for evocative gene-environment correlation processes on adoptive mother depressive symptoms. This study provides novel insights into family-based environmental influences on child ADHD and aggression symptoms, independent of shared parental genetic factors, implications of which are further explicated in the discussion.
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Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Interação Gene-Ambiente , Adoção , Adulto , Agressão/psicologia , Transtorno da Personalidade Antissocial/genética , Transtorno do Deficit de Atenção com Hiperatividade/genética , Criança , Comportamento Infantil , Criança Adotada/psicologia , Estudos de Coortes , Pai , Feminino , Hostilidade , Humanos , Comportamento Impulsivo , Estudos Longitudinais , Masculino , Mães , Poder Familiar , Pais , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Studies involving clinically recruited samples show that genetic liability to schizophrenia overlaps with that for several psychiatric disorders including bipolar disorder, major depression and, in a population study, anxiety disorder and negative symptoms in adolescence.AimsWe examined whether, at a population level, association between schizophrenia liability and anxiety disorders continues into adulthood, for specific anxiety disorders and as a group. We explored in an epidemiologically based cohort the nature of adult psychopathology sharing liability to schizophrenia. METHOD: Schizophrenia polygenic risk scores (PRSs) were calculated for 590 European-descent individuals from the Christchurch Health and Development Study. Logistic regression was used to examine associations between schizophrenia PRS and four anxiety disorders (social phobia, specific phobia, panic disorder and generalised anxiety disorder), schizophrenia/schizophreniform disorder, manic/hypomanic episode, alcohol dependence, major depression, and - using linear regression - total number of anxiety disorders. A novel population-level association with hypomania was tested in a UK birth cohort (Avon Longitudinal Study of Parents and Children). RESULTS: Schizophrenia PRS was associated with total number of anxiety disorders and with generalised anxiety disorder and panic disorder. We show a novel population-level association between schizophrenia PRS and manic/hypomanic episode. CONCLUSIONS: The relationship between schizophrenia liability and anxiety disorders is not restricted to psychopathology in adolescence but is present in adulthood and specifically linked to generalised anxiety disorder and panic disorder. We suggest that the association between schizophrenia liability and hypomanic/manic episodes found in clinical samples may not be due to bias.Declarations of interestNone.
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Alcoolismo/epidemiologia , Transtornos de Ansiedade/epidemiologia , Transtorno Bipolar/epidemiologia , Transtorno Depressivo Maior/epidemiologia , Herança Multifatorial , Esquizofrenia/epidemiologia , Adolescente , Adulto , Comorbidade , Feminino , Humanos , Estudos Longitudinais , Masculino , Nova Zelândia/epidemiologia , Fatores de Risco , Reino Unido/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Child mental health problems are common. Previous studies have examined secular changes in their prevalence but have not assessed whether later outcomes have changed. We therefore aimed to test whether outcomes of child mental health problems have changed over a 40-year period. METHODS: Three cohorts were utilized: The National Child Development Study (NCDS: N = 14,544, aged 7 in 1965), the Avon Longitudinal Study of Parents and Children (ALSPAC: N = 8,188, aged 7 in 1998), and the Millennium Cohort Study (MCS: N = 13,192, aged 7 in 2008). Mental health problems at age 7 were identified using the parent-reported Rutter-A scale (NCDS) and Strengths and Difficulties Questionnaire (ALSPAC and MCS). Associated outcomes were compared across cohorts: age 11 social functioning, age 16 exam attainment and age 16 mental health. RESULTS: Child mental health problems were common in each cohort (boys: 7.0%-9.7%; girls: 5.4%-8.4%). Child mental health problems became more strongly associated with social functioning problems (boys: NCDS OR = 1.95 (1.50, 2.53), MCS OR = 3.77 (2.89, 4.92); interaction p < .001; girls: NCDS OR = 1.69 (1.22, 2.33), MCS OR = 3.99 (3.04, 5.25), interaction p < .001), lower academic attainment for boys (NCDS OR = 0.49 (0.31, 0.78), ALSPAC OR = 0.30 (0.22, 0.41), interaction p = .009), and age 16 mental health problems (boys: NCDS d' = 0.55 (0.38, 0.72), ALSPAC d' = 0.95 (0.73, 1.16); interaction p = .004; girls: NCDS d' = 0.50 (0.34, 0.65), ALSPAC d' = 0.99 (0.78, 1.20); interaction p < .001). CONCLUSIONS: Child mental health problems have become more strongly associated with negative social, educational and mental health outcomes in recent generations.
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Escolaridade , Transtornos Mentais/epidemiologia , Comportamento Social , Adolescente , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Fatores SexuaisRESUMO
There are substantial health disparities between children from low and higher income families. The study aimed to test changes in child mental health inequalities across three large UK population cohorts of 11-year-old children assessed in 1999, 2004 and 2012 as part of the British Child and Adolescent Mental Health Surveys and Millennium Cohort Study. Child mental health was assessed using parent and teacher versions of the Strengths and Difficulties Questionnaire. There were substantial differences in parent and teacher reported symptom scores between children from low and higher income families in each cohort. Differences in parent-reported symptoms increased over time (ES 0.35 [95% CI 0.20, 0.49] in 1999, ES 0.39 [95% CI 0.17, 0.61] in 2004, ES 0.54 [95% CI 0.49, 0.58] in 2012); cohort interaction: p = 0.01). This study found that marked child mental health inequalities exist. The mental health gap between advantaged and disadvantaged children has not reduced over the last 20 years and may be getting worse.
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Disparidades nos Níveis de Saúde , Saúde Mental/normas , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Fatores Socioeconômicos , Inquéritos e Questionários , Reino Unido/epidemiologiaRESUMO
The quality of the interparental relationship is recognized as an important influence on child and adolescent psychopathology. Historically, clinically oriented research on this topic has focused on the impacts of parental divorce and domestic violence as primary interparental relationship influences on child outcomes, to the relative neglect of dimensional or qualitative features of the couple/interparental relationship for youth (child and adolescent) psychopathology. Recent research has highlighted that children are affected by attributes of interparental conflict, specifically how parents express and manage conflicts in their relationship, across a continuum of expressed severity and negativity - ranging from silence to violence. Furthermore, new evidence highlights that children's emotional, behavioral, social, academic outcomes, and future interpersonal relationships are adversely affected by conflict between parents/carers whether adults are living together or not (i.e. married or separated), or where children are or are not genetically related to their rearing parents (e.g. adoption). We review evidence and present an integrated theoretical model, highlighting how children are affected by interparental conflict and what this evidence base means for effective intervention and prevention program development, as well as the development of possible cost-benefit models. Additionally, we review policy implications of this research and highlight some very recent examples of UK-based policy focusing on addressing the interparental relationship and its impact on youth psychopathology.
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Experiências Adversas da Infância , Conflito Familiar/psicologia , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia , Saúde Mental , Relações Pais-Filho , Adolescente , Adulto , Criança , Pré-Escolar , Divórcio , Violência Doméstica/psicologia , Ajustamento Emocional , Feminino , Humanos , Lactente , Relações Interpessoais , Masculino , Fatores de Risco , Comportamento SocialRESUMO
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 (ßâ¯=â¯-.21, 95% CI [-.34, -.08]; pâ¯=â¯.002) which in turn predicted adolescent depression (ßâ¯=â¯-.18, 95% CI [-.33, -.04]; pâ¯=â¯.02), but not disruptive behaviours (ßâ¯=â¯-.08, 95% CI [-.22, .07]; pâ¯=â¯.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.
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Filho de Pais com Deficiência/psicologia , Transtorno Depressivo/psicologia , Relações Pai-Filho , Pai/psicologia , Mães/psicologia , Adolescente , Criança , Feminino , Humanos , Masculino , Casamento/psicologia , Resiliência Psicológica , Estudos Retrospectivos , País de GalesRESUMO
There is robust evidence that the interparental relationship and parenting behaviors each have a significant influence on children's risk for emotional (internalizing) and behavioral (externalizing) problems. Indeed, interventions targeting the interparental relationship and parenting processes show significant intervention-related reductions in child internalizing and externalizing problems. However, most evidence-based parenting- and couple-focused interventions result in small to medium effects on children's emotional and behavior problems. It is proposed that there is opportunity to improve upon these interventions through incorporation of knowledge from quantitative genetic research. Three core recommendations are provided for practitioners engaging in intervention work with children and families. These recommendations are contextualized relative to what quantitative genetic studies can tell us about the role of the interparental relationship and parenting behaviors on child outcomes.
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Comportamento Infantil/psicologia , Desenvolvimento Infantil/fisiologia , Conflito Familiar/psicologia , Terapia Familiar/métodos , Hereditariedade/genética , Poder Familiar/psicologia , Criança , HumanosRESUMO
Stress has been shown to have a causal effect on risk for depression. We investigated the role of cognitive ability as a moderator of the effect of stressful life events on depressive symptoms and whether this varied by gender. Data were analyzed in two adolescent data sets: one representative community sample aged 11-12 years (n = 460) and one at increased familial risk of depression aged 9-17 years (n = 335). In both data sets, a three-way interaction was found whereby for girls, but not boys, higher cognitive ability buffered the association between stress and greater depressive symptoms. The interaction was replicated when the outcome was a diagnosis of major depressive disorder. This buffering effect in girls was not attributable to coping efficacy. However, a small proportion of the variance was accounted for by sensitivity to environmental stressors. Results suggest that this moderating effect of cognitive ability in girls is largely attributable to greater available resources for cognitive operations that offer protection against stress-induced reductions in cognitive processing and cognitive control which in turn reduces the likelihood of depressive symptomatology.
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Aptidão , Cognição , Depressão/psicologia , Transtorno Depressivo Maior/psicologia , Estresse Psicológico/psicologia , Adaptação Psicológica , Adolescente , Criança , Feminino , Humanos , Masculino , Fatores SexuaisRESUMO
BACKGROUND: Evidence from Western countries indicates marked increases in diagnosis and treatment of childhood psychiatric disorders in recent years. These could reflect changes in prevalence of mental health problems, changes in their impact or increased clinical recognition and help-seeking. Epidemiological cross-cohort comparisons are required to test possible changes in prevalence, but are lacking for pre-adolescent children in Great Britain. METHODS: Parent and teacher Strength and Difficulties Questionnaire (SDQ) ratings were used to compare rates of emotional, conduct and hyperactivity problems in 7-year-old children across three nationally representative British samples assessed in 1999 (n = 1033), 2004 (n = 648) and 2008 (n = 13,857). The SDQ impact supplement was used to assess associated distress, social, and educational impairment. Stratified analyses examined trends by gender and socio-economic group. RESULTS: There was a decline in mean problem scores and a fall in the percentages scoring in the 'abnormal' range for all symptom types across the period of study. This decline was observed for all demographic groups, for parent and teacher reports, and was more marked for boys than girls. Both parent- and teacher-rated impact scores differed across the three cohorts for boys. Teacher-rated impact scores differed across cohorts for girls. CONCLUSIONS: The first decade of the 21st Century saw a reduction in perceived levels of emotional and behaviour problems in pre-adolescent children in Great Britain. The threshold at which mental health problems have an impact on children's distress and classroom learning has changed over time. Continued monitoring of child mental health remains a priority.
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Sintomas Afetivos/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtornos do Comportamento Infantil/epidemiologia , Transtorno da Conduta/epidemiologia , Criança , Docentes , Humanos , Pais , Prevalência , Fatores Sexuais , Reino Unido/epidemiologiaRESUMO
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.
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Transtorno da Personalidade Antissocial/psicologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/etiologia , Filho de Pais com Deficiência/psicologia , Depressão/etiologia , Transtorno Depressivo Maior/psicologia , Hostilidade , Relações Mãe-Filho , Mães/psicologia , Adolescente , Adulto , Criança , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Recidiva , Índice de Gravidade de DoençaRESUMO
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.
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Filho de Pais com Deficiência/estatística & dados numéricos , Transtornos Mentais/epidemiologia , Mães/psicologia , Adolescente , Adulto , Criança , Filho de Pais com Deficiência/psicologia , Comorbidade , Transtorno Depressivo/epidemiologia , Métodos Epidemiológicos , Feminino , Humanos , Entrevista Psicológica , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Recidiva , Fatores SocioeconômicosRESUMO
BACKGROUND: Over the past three decades, the prevalence of adolescent emotional problems (ie, anxiety and depression) has risen. Although the onset and developmental course of emotional symptoms shows high variability, no study has directly tested secular differences across development. Our aim was to investigate whether and how developmental trajectories of emotional problems have changed across generations. METHODS: We used data from two UK prospective cohorts assessed 10 years apart: the Avon Longitudinal Study of Parents and Children (ALSPAC) including individuals born in 1991-92, and the Millennium Cohort Study (MCS) with individuals born in 2000-02. Our outcome was emotional problems, assessed using the parent-rated emotional subscale of the Strengths and Difficulties Questionnaire (SDQ-E) at approximate ages 4, 7, 8, 10, 11, 13, and 17 years in ALSPAC and ages 3, 5, 7, 11, 14, and 17 years in MCS. Participants were included if the SDQ-E was completed at least once in childhood and at least once in adolescence. Trajectories were generated using multilevel growth curve models using the repeated assessments of the SDQ-E in children aged 3-17 years. FINDINGS: Data were available for 19 418 participants (7012 from ALSPAC and 12 406 from the MCS), of whom 9678 (49·8%) were female and 9740 (50·2%) were male, and 17 572 (90·5%) had White mothers. Individuals born between 2000 and 2002 had higher emotional problem scores from around 9 years (intercept statistic ß 1·75, 95% CI 1·71-1·79) than did individuals born in 1991-92 (1·55, 1·51-1·59). The later cohort had an earlier onset of problems than the earlier cohort, and sustained higher average trajectories from around 11 years, with female adolescents showing the steepest trajectories of emotional problems. Differences between cohorts peaked overall at age 14 years. INTERPRETATION: Our comparison of two cohorts of young people provides evidence that compared with a cohort assessed 10 years prior, emotional problems emerge earlier in development in the more recent cohort, and these are especially pronounced for females during mid-adolescence. Such findings have implications for public health planning and service provision. FUNDING: Wolfson Centre for Young People's Mental Health, Wolfson Foundation.
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Pais , Criança , Humanos , Masculino , Adolescente , Feminino , Adulto , Estudos Longitudinais , Estudos de Coortes , Estudos Prospectivos , Reino Unido/epidemiologiaRESUMO
Importance: Understanding the origins of clinical heterogeneity in bipolar disorder (BD) will inform new approaches to stratification and studies of underlying mechanisms. Objective: To identify components of genetic liability that are shared between BD, schizophrenia, and major depressive disorder (MDD) and those that differentiate each disorder from the others and to examine associations between heterogeneity for key BD symptoms and each component. Design, Setting, and Participants: Using data from the Bipolar Disorder Research Network in the United Kingdom, components of liability were identified by applying genomic structural equation modeling to genome-wide association studies of schizophrenia, BD, and MDD. Polygenic risk scores (PRS) representing each component were tested for association with symptoms in an independent BD data set. Adults with DSM-IV BD or schizoaffective disorder, bipolar type, were included. Data were collected from January 2000 to December 2013, and data were analyzed from June 2020 to February 2022. Main Outcomes and Measures: PRS representing the components of liability were tested for association with mania and depression, psychosis, and mood incongruence of psychosis in participants with BD, measured using the Bipolar Affective Disorder Dimensional Scale. Results: Of 4429 included participants, 3012 (68.0%) were female, and the mean (SD) age was 46.2 (12.3) years. Mania and psychosis were associated with the shared liability component (mania ß = 0.29; 95% CI, 0.23-0.34; P = 3.04 × 10-25; psychosis ß = 0.05; 95% CI, 0.04-0.07; P = 2.33 × 10-13) and the components that differentiate each of schizophrenia (mania ß = 0.08; 95% CI, 0.03-0.14; P = .002; psychosis ß = 0.03; 95% CI, 0.01-0.04; P = 1.0 × 10-4) and BD (mania ß = 0.14; 95% CI, 0.09-0.20; P = 1.99 × 10-7; psychosis ß = 0.02; 95% CI, 0.01-0.03; P = .006) from the other disorders. The BD differentiating component was associated with mania independently of effects on psychosis (ß = 0.14; 95% CI, 0.08-0.20; P = 4.32 × 10-6) but not with psychosis independently of mania. Conversely, the schizophrenia differentiating component was associated with psychosis independently of effects on mania (ß = 0.01; 95% CI, 0.003-0.03; P = .02), but not with mania independently of psychosis. Mood incongruence of psychosis was associated only with the schizophrenia differentiating component (ß = 0.03; 95% CI, 0.01-0.05; P = .005). Depression was associated with higher MDD differentiating component (ß = 0.07; 95% CI, 0.01-0.12; P = .01) but lower BD differentiating component (ß = -0.11; 95% CI, -0.17 to -0.06; P = 7.06 × 10-5). Conclusions and Relevance: In this study of BD, clinical heterogeneity reflected the burden of liability to BD and the contribution of alleles that have differentiating effects on risk for other disorders; mania, psychosis, and depression were associated with the components of genetic liability differentiating BD, MDD, and schizophrenia, respectively. Understanding the basis of this etiological heterogeneity will be critical for identifying the different pathophysiological processes underlying BD, stratifying patients, and developing precision therapeutics.
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Transtorno Bipolar , Transtorno Depressivo Maior , Esquizofrenia , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/genética , Transtorno Bipolar/psicologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Mania , Pessoa de Meia-Idade , Esquizofrenia/diagnóstico , Esquizofrenia/genéticaRESUMO
BACKGROUND: Maternal smoking in pregnancy is associated with low birth weight (LBW), child conduct problems, hyperactivity and lower cognitive attainment, but associations may reflect measured and unmeasured confounding. Cross-cohort designs can aid causal inference through comparison of associations across populations with different confounding structures. We compared associations between maternal smoking in pregnancy and child conduct and hyperactivity problems, cognition and LBW across two cohorts born four decades apart. METHODS: Two national UK cohorts born in 1958 (n = 12 415) and 2000/01 (n = 11 800) were compared. Maternal smoking in pregnancy and child birth weight was assessed at or shortly after birth. Parents rated children's conduct problems and hyperactivity, and children completed standardized tests of reading and mathematics. RESULTS: Maternal smoking in pregnancy was less common and more strongly associated with social disadvantage in 2000/01 compared with 1958 (interactions P < 0.001). Maternal smoking in pregnancy was robustly and equivalently associated with infant LBW in both cohorts [interactions: boys odds ratio (OR) = 1.01 (0.89, 1.16), P = 0.838; girls OR = 1.01 (0.91, 1.17), P = 0.633]. Maternal smoking was more strongly associated with conduct problems, hyperactivity and reading in the 2000/01 cohort (interactions P < 0.001). CONCLUSIONS: Marked cross-cohort change in associations between maternal smoking and child conduct problems, hyperactivity and reading highlights the likely role of confounding factors. In contrast, association with LBW was unaffected by change in prevalence of maternal smoking and patterns of confounding. The study highlights the utility of cross-cohort designs in helping triangulate conclusions about the role of putative causal risk factors in observational epidemiology.
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Efeitos Tardios da Exposição Pré-Natal , Fumar , Criança , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Aprendizagem , Masculino , Saúde Mental , Pessoa de Meia-Idade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/efeitos adversos , Reino Unido/epidemiologiaRESUMO
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 (ß = 0.12, P = .03) and fear and/or anxiety (ß = 0.38, P < .001) were significant independent clinical antecedents of new adolescent-onset MDD, but disruptive behavior (ß = -0.08, P = .14) and low mood (ß = -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.
Assuntos
Transtorno Depressivo Maior/genética , Predisposição Genética para Doença/genética , Adolescente , Criança , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pobreza/psicologia , Estudos Prospectivos , Carência Psicossocial , RiscoRESUMO
Adolescent offspring of depressed parents are at particularly heightened risk of developing early onset Major Depressive Disorder (MDD) yet are unlikely to access services. We therefore aimed to identify a parsimonious combination of parent-reported symptoms that accurately detected offspring MDD. We used a multi-sample study comprising a development sample of 335 offspring of adults with recurrent MDD assessed on three occasions (mean age 12.4-14.8 years) and an independent validation sub-sample of 807 adolescents from a general population cohort (mean age 13.1 years). Parent ratings of psychiatric symptoms in adolescent offspring were assessed using established questionnaires. The best performing four-item combination of symptoms was identified. Accuracy in detecting concurrent DSM-IV MDD diagnosis, assessed by direct adolescent and parent interviews, was compared to the well-established 13-item short Moods and Feelings Questionnaire (sMFQ) using ROC curve analysis. The combination identified (concentration problems, anhedonia, worrying excessively and feeling unloved) performed equivalently to the sMFQ both in the development dataset and in the validation dataset. We concluded that a combination of four parent-reported mental health items performs equivalently to an established, longer depression questionnaire measure in detecting a diagnosis of adolescent major depressive disorder among offspring of parents with recurrent MDD and needs further evaluation.