RESUMEN
Both common and rare genetic variants (minor allele frequency >1% and <0.1% respectively) have been implicated in the aetiology of schizophrenia. In this study, we integrate single-cell gene expression data with publicly available Genome-Wide Association Study (GWAS) and exome sequenced data in order to investigate in parallel, the enrichment of common and (ultra-)rare variants related to schizophrenia in several functionally relevant gene-sets. Four types of gene-sets were constructed 1) protein-truncating variant (PTV)-intolerant (PI) genes 2) genes expressed in brain cell types and neurons ascertained from mouse and human brain tissue 3) genes defined by synaptic function and location and 4) intersection genes, i.e., PI genes that are expressed in the human and mouse brain cell gene-sets. We show that common as well as ultra-rare schizophrenia-associated variants are overrepresented in PI genes, in excitatory neurons from the prefrontal cortex and hippocampus, medium spiny neurons, and genes enriched for synaptic processes. We also observed stronger enrichment in the intersection genes. Our findings suggest that across the allele frequency spectrum, genes and genetic variants likely to be under stringent selection, and those expressed in particular brain cell types, are involved in the same biological pathways influencing the risk for schizophrenia.
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Esquizofrenia , Humanos , Ratones , Animales , Esquizofrenia/genética , Estudio de Asociación del Genoma Completo , Predisposición Genética a la Enfermedad/genética , Secuenciación del Exoma , Exoma/genética , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
OBJECTIVE: Understanding the unmet needs of healthcare consumers with attention-deficit/hyperactivity disorder (ADHD) (individuals with ADHD and their caregivers) provides critical insight into gaps in services, education and research that require focus and funding to improve outcomes. This review examines the unmet needs of ADHD consumers from a consumer perspective. METHODS: A standardised search protocol identified peer-reviewed studies published between December 2011 and December 2021 focusing on consumer-identified needs relating to ADHD clinical care or research priorities. RESULTS: 1,624 articles were screened with 23 studies that reviewed examining the needs of ADHD consumers from Europe, the U.K., Hong Kong, Iran, Australia, the U.S.A. and Canada. Consumer-identified needs related to: treatment that goes beyond medication (12 studies); improved ADHD-related education/training (17 studies); improved access to clinical services, carer support and financial assistance (14 studies); school accommodations/support (6 studies); and ongoing treatment efficacy research (1 study). CONCLUSION: ADHD consumers have substantial unmet needs in clinical, psychosocial and research contexts. Recommendations to address these needs include: improving access to and quality of multimodal care provision; incorporating recovery principles into care provision; fostering ADHD health literacy; and increasing consumer participation in research, service development and ADHD-related training/education.
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Trastorno por Déficit de Atención con Hiperactividad , Humanos , Trastorno por Déficit de Atención con Hiperactividad/psicología , Cuidadores , Europa (Continente) , Instituciones Académicas , AustraliaRESUMEN
Parents can be essential change-agents in their children's lives. To support parents in their parenting role, a range of programs have been developed and evaluated. In this paper, we provide an overview of the evidence for the effectiveness of parenting interventions for parents and children across a range of outcomes, including child and adolescent mental and physical health, child and adolescent competencies and academic outcomes, parental skills and competencies, parental wellbeing and mental health, and prevention of child maltreatment and family violence. Although there is extensive research showing the effectiveness of evidence-based parenting programs, these are not yet widely available at a population level and many parents are unable to access support. We outline how to achieve increased reach of evidence-based parenting supports, highlighting the policy imperative to adequately support the use of these supports as a way to address high priority mental health, physical health, and social problems.
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Maltrato a los Niños , Responsabilidad Parental , Adolescente , Niño , Humanos , Responsabilidad Parental/psicología , Padres/psicología , Maltrato a los Niños/prevención & control , Salud Mental , PolíticasRESUMEN
BACKGROUND: To explore changes in child and youth mental health service (CYMHS) demand in Brisbane, Australia, following the COVID pandemic. METHODS: The number of monthly presentations and referrals to respectively the emergency department (ED) and community CYMHS were compared among 2018, 2019 and 2020. RESULTS: The study shows a marked increase in referrals to ED starting from July and in the community from May 2020. In the population referred to as community teams, the proportions of Indigenous children and those from lower socio-economic areas decreased. CONCLUSIONS: The COVID-19 pandemic has aggravated the supply and demand disparity in CYMHS, with the largest effect on the most vulnerable families.
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COVID-19 , Servicios de Salud Mental , Humanos , Niño , Adolescente , Pandemias , Australia , Servicio de Urgencia en HospitalRESUMEN
Ubiquitous associations have been detected between different types of childhood psychopathology and polygenic risk scores based on adult psychiatric disorders and related adult outcomes, indicating that genetic factors partly explain the association between childhood psychopathology and adult outcomes. However, these analyses in general do not take into account the correlations between the adult trait and disorder polygenic risk scores. This study aimed to further clarify the influence of genetic factors on associations between childhood psychopathology and adult outcomes by accounting for these correlations. Using a multivariate multivariable regression, we analyzed associations of childhood attention-deficit/hyperactivity disorder (ADHD), internalizing, and social problems, with polygenic scores (PGS) of adult disorders and traits including major depression, bipolar disorder, subjective well-being, neuroticism, insomnia, educational attainment, and body mass index (BMI), derived for 20,539 children aged 8.5-10.5 years. After correcting for correlations between the adult phenotypes, major depression PGS were associated with all three childhood traits, that is, ADHD, internalizing, and social problems. In addition, BMI PGS were associated with ADHD symptoms and social problems, while neuroticism PGS were only associated with internalizing problems and educational attainment PGS were only associated with ADHD symptoms. PGS of bipolar disorder, subjective well-being, and insomnia were not associated with any childhood traits. Our findings suggest that associations between childhood psychopathology and adult traits like insomnia and subjective well-being may be primarily driven by genetic factors that influence adult major depression. Additionally, specific childhood phenotypes are genetically associated with educational attainment, BMI and neuroticism.
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Trastorno por Déficit de Atención con Hiperactividad , Trastorno Depresivo Mayor , Humanos , Estudio de Asociación del Genoma Completo , Herencia Multifactorial/genética , Psicopatología , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno por Déficit de Atención con Hiperactividad/psicología , Análisis Multivariante , Trastorno Depresivo Mayor/genética , Biología MolecularRESUMEN
The Roadmap for Mental Health and Wellbeing Research in Europe (ROAMER) identified child and adolescent mental illness as a priority area for research. CAPICE (Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe) is a European Union (EU) funded training network aimed at investigating the causes of individual differences in common childhood and adolescent psychopathology, especially depression, anxiety, and attention deficit hyperactivity disorder. CAPICE brings together eight birth and childhood cohorts as well as other cohorts from the EArly Genetics and Life course Epidemiology (EAGLE) consortium, including twin cohorts, with unique longitudinal data on environmental exposures and mental health problems, and genetic data on participants. Here we describe the objectives, summarize the methodological approaches and initial results, and present the dissemination strategy of the CAPICE network. Besides identifying genetic and epigenetic variants associated with these phenotypes, analyses have been performed to shed light on the role of genetic factors and the interplay with the environment in influencing the persistence of symptoms across the lifespan. Data harmonization and building an advanced data catalogue are also part of the work plan. Findings will be disseminated to non-academic parties, in close collaboration with the Global Alliance of Mental Illness Advocacy Networks-Europe (GAMIAN-Europe).
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Trastornos de Ansiedad , Trastorno por Déficit de Atención con Hiperactividad , Adolescente , Ansiedad , Trastornos de Ansiedad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/psicología , Niño , Unión Europea , Humanos , Estudios LongitudinalesRESUMEN
BACKGROUND: There is concern that rates of mental disorders may be increasing although findings disagree. Using an innovative design with a daughter-mother data set we assess whether there has been a generational increase in lifetime ever rates of major depressive disorder, generalised anxiety disorder, panic disorder, and post-traumatic stress disorder (PTSD) experienced prior to 30 years of age. METHODS: Pregnant women were recruited during 1981-1983 and administered the Composite International Diagnostic Interview (CIDI) at the 27-year follow-up (2008-11). Offspring were administered the CIDI at the 30-year follow-up (2010-2014). Comparisons for onset of diagnosis are restricted to daughter and mother dyads up to 30 years of age. To address recall bias, disorders were stratified into more (≥12 months duration) and less persistent episodes (< 12 months duration) for the purposes of comparison. Sensitivity analyses with inflation were used to account for possible maternal failure to differentially recall past episodes. RESULTS: When comparing life time ever diagnoses before 30 years, daughters had higher rates of persistent generalised anxiety disorder, and less persistent major depressive disorder, generalised anxiety disorder and PTSD. CONCLUSIONS: In the context of conflicting findings concerning generational changes in mental disorders we find an increase in generational rates of persistent generalised anxiety disorders and a range of less persistent disorders. It is not clear whether this finding reflects actual changes in symptom levels over a generation or whether there has been a generational change in recognition of and willingness to report symptoms of mental illness.
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Trastorno Depresivo Mayor , Trastorno de Pánico , Trastornos por Estrés Postraumático , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/epidemiología , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/epidemiología , Femenino , Humanos , Madres , Embarazo , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/epidemiologíaRESUMEN
People affected by mental illness often come from families with patterns of mental illness that span across generations. Hence, child and adolescent mental health services (CAMHS) likely provide treatment to many children with parents who also experience mental illness. The aim of this scoping review was to: (1) identify the prevalence of mental illness among parents of children in CAMHS; (2) identify and appraise the methodologies that have been implemented to assess the prevalence of parental mental illness in CAMHS; (3) identify additional circumstances associated with families where both parent and child experience mental illness; and (4) present recommendations that have been made for CAMHS practice based on these findings. English language, peer-reviewed studies (2010-2018) that had investigated the mental health of parents in CAMHS were included in the review. Literature searching yielded 18 studies which were found to have utilised diverse methodologies to assess parental mental health. Overall, reported prevalence of parental mental illness ranged from 16 to 79%; however, a single study that was deemed to be comprehensive reported prevalence rates of 36% for mothers and 33% for fathers. Across studies, parent and child mental illness was found to be associated with additional adversities impacting family functioning and wellbeing. For children who receive treatment for mental illness, having a parent who also experiences mental illness is a frequent family circumstance that has implications for their prospects for recovery. Accordingly, the mental health of parents should be an important consideration within the mental health care CAMHS provide to children.
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Hijo de Padres Discapacitados/psicología , Trastornos Mentales/epidemiología , Trastornos Mentales/terapia , Padres/psicología , Adolescente , Servicios de Salud del Adolescente/estadística & datos numéricos , Niño , Servicios de Salud del Niño/estadística & datos numéricos , Hijo de Padres Discapacitados/estadística & datos numéricos , Humanos , Servicios de Salud Mental/estadística & datos numéricos , Prevalencia , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Mounting evidence shows genetic overlap between multiple psychiatric disorders. However, the biological underpinnings of shared risk for psychiatric disorders are not yet fully uncovered. The identification of underlying biological mechanisms is crucial for the progress in the treatment of these disorders. METHODS: We applied gene-set analysis including 7372 gene sets, and 53 tissue-type specific gene-expression profiles to identify sets of genes that are involved in the etiology of multiple psychiatric disorders. We included genome-wide meta-association data of the five psychiatric disorders schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, and attention-deficit/hyperactivity disorder. The total dataset contained 159 219 cases and 262 481 controls. RESULTS: We identified 19 gene sets that were significantly associated with the five psychiatric disorders combined, of which we excluded five sets because their associations were likely driven by schizophrenia only. Conditional analyses showed independent effects of several gene sets that in particular relate to the synapse. In addition, we found independent effects of gene expression levels in the cerebellum and frontal cortex. CONCLUSIONS: We obtained novel evidence for shared biological mechanisms that act across psychiatric disorders and we showed that several gene sets that have been related to individual disorders play a role in a broader range of psychiatric disorders.
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Alelos , Genes Sobrepuestos , Heterogeneidad Genética , Pruebas Genéticas , Trastornos Mentales/genética , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno del Espectro Autista/genética , Trastorno Bipolar/genética , Estudios de Casos y Controles , Trastorno Depresivo Mayor/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Polimorfismo de Nucleótido Simple , Análisis de Regresión , Factores de Riesgo , Esquizofrenia/genética , Población Blanca/genéticaRESUMEN
Nick Martin is a pioneer in recognizing the need for large sample size to study the complex, heterogeneous and polygenic disorders of common mental disorders. In the predigital era, questionnaires were mailed to thousands of twin pairs around Australia. Always quick to adopt new technology, Nick's studies progressed to phone interviews and then online. Moreover, Nick was early to recognize the value of collecting DNA samples. As genotyping technologies improved over the years, these twin and family cohorts were used for linkage, candidate gene and genome-wide association studies. These cohorts have underpinned many analyses to disentangle the complex web of genetic and lifestyle factors associated with mental health. With characteristic foresight, Nick is chief investigator of our Australian Genetics of Depression Study, which has recruited 16,000 people with self-reported depression (plus DNA samples) over a time frame of a few months - analyses are currently ongoing. The mantra of sample size, sample size, sample size has guided Nick's research over the last 30 years and continues to do so.
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Depresión/genética , Trastornos Mentales/genética , Herencia Multifactorial/genética , Australia/epidemiología , Depresión/historia , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Trastornos Mentales/historia , Gemelos/genética , Gemelos/historiaRESUMEN
It is unclear to what extent parental influences on the development of internalizing problems in offspring are explained by indirect genetic effects, reflected in the environment provided by the parent, in addition to the genes transmitted from parent to child. In this study, these effects were investigated using two innovative methods in a large birth cohort. Using maternal-effects genome complex trait analysis (M-GCTA), the effects of offspring genotype, maternal or paternal genotypes, and their covariance on offspring internalizing problems were estimated in 3,801 mother-father-child genotyped trios. Next, estimated genetic correlations within pedigree data, including 10,688 children, were used to estimate additive genetic effects, maternal and paternal genetic effects, and a shared family effect using linear mixed effects modeling. There were no significant maternal or paternal genetic effects on offspring anxiety or depressive symptoms at age 8, beyond the effects transmitted via the genetic pathway between parents and children. However, indirect maternal genetic effects explained a small, but nonsignificant, proportion of variance in childhood depressive symptoms in both the M-GCTA (~4%) and pedigree (~8%) analyses. Our results suggest that parental effects on offspring internalizing problems are predominantly due to transmitted genetic variants, rather than the indirect effect of parental genes via the environment.
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Trastornos de Ansiedad/genética , Herencia Materna , Relaciones Padres-Hijo , Herencia Paterna , Ansiedad/genética , Bases de Datos Factuales , Depresión/genética , Variación Genética , Genotipo , Humanos , Noruega , Responsabilidad Parental , Padres/psicología , Linaje , FenotipoRESUMEN
The development of problem behavior in children is associated with exposure to environmental factors, including the maternal environment. Both are influenced by genetic factors, which may also be correlated, that is, environmental risk and problem behavior in children might be influenced by partly the same genetic factors. In addition, environmental and genetic factors could interact with each other increasing the risk of problem behavior in children. To date, limited research investigated these mechanisms in a genome-wide approach. Therefore, the goal of this study was to investigate the association between genetic risk for psychiatric and related traits, as indicated by polygenetic risk scores (PRSs), exposure to previously identified maternal risk factors, and problem behavior in a sample of 1,154 children from the Amsterdam Born Children and their Development study at ages 5-6 and 11-12 years old. The PRSs were derived from genome-wide association studies (GWASs) on schizophrenia, major depressive disorder, neuroticism, and wellbeing. Regression analysis showed that the PRSs were associated with exposure to multiple environmental risk factors, suggesting passive gene-environment correlation. In addition, the PRS based on the schizophrenia GWAS was associated with externalizing behavior problems in children at age 5-6. We did not find any association with problem behavior for the other PRSs. Our results indicate that genetic predispositions for psychiatric disorders and wellbeing are associated with early environmental risk factors for children's problem behavior.
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Trastornos de la Conducta Infantil/psicología , Trastornos Mentales/etiología , Madres/psicología , Niño , Preescolar , Trastorno Depresivo Mayor/etiología , Trastorno Depresivo Mayor/genética , Femenino , Estudios de Asociación Genética/métodos , Estudio de Asociación del Genoma Completo/métodos , Salud , Humanos , Masculino , Trastornos Mentales/genética , Herencia Multifactorial/genética , Neuroticismo/fisiología , Escalas de Valoración Psiquiátrica , Análisis de Regresión , Factores de Riesgo , Esquizofrenia/etiología , Esquizofrenia/genéticaRESUMEN
The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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Estudios de Cohortes , Enfermedad/genética , Predisposición Genética a la Enfermedad , Adolescente , Adulto , Niño , Preescolar , Femenino , Predicción , Humanos , Lactante , Recién Nacido , Masculino , Fenotipo , Embarazo , Proyectos de Investigación , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Anxiety disorders in adolescence have been associated with several psychiatric outcomes. We sought to describe the prospective relationship between various levels of adolescent anxiety and psychiatric diagnoses (anxiety-, bipolar/psychotic-, depressive-, and alcohol and drug misuse disorders) and suicidal ideation in early adulthood while adjusting for childhood attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and developmental coordination disorder (DCD). Furthermore, we aimed to estimate the proportion attributable to the various anxiety levels for the outcomes. METHODS: We used a nation-wide population-based Swedish twin study comprising 14,106 fifteen-year-old twins born in Sweden between 1994 and 2002 and a replication sample consisting of 9211 Dutch twins, born between 1985 and 1999. Adolescent anxiety was measured with parental and self-report. Psychiatric diagnoses and suicidal ideation were retrieved from the Swedish National Patient Register and via self-report. RESULTS: Adolescent anxiety, of various levels, predicted, in the Swedish National Patient Register, anxiety disorders: hazard ratio (HR) = 4.92 (CI 3.33-7.28); depressive disorders: HR = 4.79 (3.23-7.08), and any psychiatric outcome: HR = 3.40 (2.58-4.48), when adjusting for ADHD, ASD, and DCD. The results were replicated in the Dutch data. The proportion of psychiatric outcome attributable to adolescent anxiety over time (age 15-21) was 29% for any psychiatric outcome, 43-40% for anxiety disorders, and 39-38% for depressive disorders. CONCLUSION: Anxiety in adolescence constitutes an important risk factor in the development of psychiatric outcomes, revealing unique predictions for the different levels of anxiety, and beyond the risk conferred by childhood ADHD, ASD, and DCD. Developmental trajectories leading into psychiatric outcomes should further empirically investigated.
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Ansiedad/psicología , Enfermedades en Gemelos/psicología , Ideación Suicida , Gemelos/psicología , Adolescente , Ansiedad/diagnóstico , Ansiedad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/psicología , Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/epidemiología , Trastorno del Espectro Autista/psicología , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/epidemiología , Trastorno Depresivo/psicología , Enfermedades en Gemelos/diagnóstico , Enfermedades en Gemelos/epidemiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Riesgo , Autoinforme , Suecia/epidemiología , Adulto JovenRESUMEN
Conduct problems in children and adolescents can predict antisocial personality disorder and related problems, such as crime and conviction. We sought an explanation for such predictions by performing a genetic longitudinal analysis. We estimated the effects of genetic, shared environmental, and unique environmental factors on variation in conduct problems measured at childhood and adolescence and antisocial personality problems measured at adulthood and on the covariation across ages. We also tested whether these estimates differed by sex. Longitudinal data were collected in the Netherlands Twin Register over a period of 27 years. Age appropriate and comparable measures of conduct and antisocial personality problems, assessed with the Achenbach System of Empirically Based Assessment, were available for 9783 9-10-year-old, 6839 13-18-year-old, and 7909 19-65-year-old twin pairs, respectively; 5114 twins have two or more assessments. At all ages, men scored higher than women. There were no sex differences in the estimates of the genetic and environmental influences. During childhood, genetic and environmental factors shared by children in families explained 43 and 44% of the variance of conduct problems, with the remaining variance due to unique environment. During adolescence and adulthood, genetic and unique environmental factors equally explained the variation. Longitudinal correlations across age varied between 0.20 and 0.38 and were mainly due to stable genetic factors. We conclude that shared environment is mainly of importance during childhood, while genetic factors contribute to variation in conduct and antisocial personality problems at all ages, and also underlie its stability over age.
Asunto(s)
Trastorno de Personalidad Antisocial/genética , Trastorno de la Conducta/genética , Enfermedades en Gemelos/genética , Exposición a Riesgos Ambientales/efectos adversos , Adolescente , Adulto , Anciano , Trastorno de Personalidad Antisocial/patología , Niño , Trastorno de la Conducta/patología , Enfermedades en Gemelos/patología , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
In studies of child psychopathology, phenotypes of interest are often obtained by parental ratings. When behavioral ratings are obtained in the context of a twin study, this allows for the decomposition of the phenotypic variance, into a genetic and a non-genetic part. If a phenotype is assessed by a single rater, heritability is based on the child's behavior as expressed in the presence of that particular rater, whereas heritability based on assessments by multiple raters allows for the estimation of the heritability of the phenotype based on rater agreement, as well as the heritability of the rater specific view of the behavior. The aim of this twin study was to quantify the rater common and rater specific contributions to the variation in children's behavioral problems. We estimated the heritability of maternal and paternal ratings of the Child Behavior Checklist (CBCL) 6-18 empirical emotional and behavioral problem scales in a large sample of 12,310 7-year old Dutch twin pairs. Between 30 and 59% of variation in the part of the phenotype parents agree upon was explained by genetic effects. Common environmental effects that make children in the same family similar explained less variance, ranging between 0 and 32%. For unique views of their children's behavioral problems, heritability ranged between 0 and 20% for maternal and between 0 and 22% for paternal views. Between 7 and 24% of the variance was accounted for by common environmental factors specific to mother and father's views. The proportion of rater shared and rater specific heritability can be translated into genetic correlations between parental views and inform the design and interpretation of results of molecular genetic studies. Genetic correlations were nearly or above 0.7 for all CBCL based psychopathology scales. Such large genetic correlations suggest two practical guidelines for genome-wide association studies (GWAS): when studies have collected data from either fathers or mothers, the shared genetic aetiology in parental ratings indicates that is possible to analyze paternal and maternal assessments in a single GWAS or meta-analysis. Secondly, if a study has collected information from both parents, a gain in statistical power may be realized in GWAS by the simultaneous analysis of the data.
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Trastornos de la Conducta Infantil/genética , Psicometría/métodos , Niño , Conducta Infantil/psicología , Trastornos de la Conducta Infantil/psicología , Padre/psicología , Femenino , Humanos , Masculino , Modelos Genéticos , Madres/psicología , Países Bajos , Padres/psicología , Problema de Conducta/psicología , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Gemelos/genética , Gemelos/psicologíaRESUMEN
This study sought to identify trajectories of DSM-IV based internalizing (INT) and externalizing (EXT) problem scores across childhood and adolescence and to provide insight into the comorbidity by modeling the co-occurrence of INT and EXT trajectories. INT and EXT were measured repeatedly between age 7 and age 15 years in over 7,000 children and analyzed using growth mixture models. Five trajectories were identified for both INT and EXT, including very low, low, decreasing, and increasing trajectories. In addition, an adolescent onset trajectory was identified for INT and a stable high trajectory was identified for EXT. Multinomial regression showed that similar EXT and INT trajectories were associated. However, the adolescent onset INT trajectory was independent of high EXT trajectories, and persisting EXT was mainly associated with decreasing INT. Sex and early life environmental risk factors predicted EXT and, to a lesser extent, INT trajectories. The association between trajectories indicates the need to consider comorbidity when a child presents with INT or EXT disorders, particularly when symptoms start early. This is less necessary when INT symptoms start at adolescence. Future studies should investigate the etiology of co-occurring INT and EXT and the specific treatment needs of these severely affected children.
Asunto(s)
Ansiedad/diagnóstico , Desarrollo Infantil/fisiología , Mecanismos de Defensa , Depresión/diagnóstico , Trastornos Mentales/diagnóstico , Adolescente , Ansiedad/psicología , Niño , Depresión/psicología , Femenino , Humanos , Masculino , Edad Materna , Trastornos Mentales/psicologíaRESUMEN
The assessment of children's psychopathology is often based on parental report. Earlier studies have suggested that rater bias can affect the estimates of genetic, shared environmental and unique environmental influences on differences between children. The availability of a large dataset of maternal as well as paternal ratings of psychopathology in 7-year old children enabled (i) the analysis of informant effects on these assessments, and (ii) to obtain more reliable estimates of the genetic and non-genetic effects. DSM-oriented measures of affective, anxiety, somatic, attention-deficit/hyperactivity, oppositional-defiant, conduct, and obsessive-compulsive problems were rated for 12,310 twin pairs from the Netherlands Twin Register by mothers (N = 12,085) and fathers (N = 8,516). The effects of genetic and non-genetic effects were estimated on the common and rater-specific variance. For all scales, mean scores on maternal ratings exceeded paternal ratings. Parents largely agreed on the ranking of their child's problems (r 0.60-0.75). The heritability was estimated over 55% for maternal and paternal ratings for all scales, except for conduct problems (44-46%). Unbiased shared environmental influences, i.e., on the common variance, were significant for affective (13%), oppositional (13%), and conduct problems (37%). In clinical settings, different cutoffs for (sub)clinical scores could be applied to paternal and maternal ratings of their child's psychopathology. Only for conduct problems, shared environmental and genetic influences explain an equal amount in differences between children. For the other scales, genetic factors explain the majority of the variance, especially for the common part that is free of rater bias. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.
Asunto(s)
Sesgo , Psicología Infantil/métodos , Niño , Padre , Femenino , Humanos , Masculino , Trastornos Mentales/epidemiología , Epidemiología Molecular/métodos , Madres , Países Bajos , Padres , Psicopatología/métodos , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Gemelos/psicologíaRESUMEN
Little is known about genes regulating male puberty. Further, while many identified pubertal timing variants associate with age at menarche, a late manifestation of puberty, and body mass, little is known about these variants' relationship to pubertal initiation or tempo. To address these questions, we performed genome-wide association meta-analysis in over 11 000 European samples with data on early pubertal traits, male genital and female breast development, measured by the Tanner scale. We report the first genome-wide significant locus for male sexual development upstream of myocardin-like 2 (MKL2) (P = 8.9 × 10(-9)), a menarche locus tagging a developmental pathway linking earlier puberty with reduced pubertal growth (P = 4.6 × 10(-5)) and short adult stature (p = 7.5 × 10(-6)) in both males and females. Furthermore, our results indicate that a proportion of menarche loci are important for pubertal initiation in both sexes. Consistent with epidemiological correlations between increased prepubertal body mass and earlier pubertal timing in girls, body mass index (BMI)-increasing alleles correlated with earlier breast development. In boys, some BMI-increasing alleles associated with earlier, and others with delayed, sexual development; these genetic results mimic the controversy in epidemiological studies, some of which show opposing correlations between prepubertal BMI and male puberty. Our results contribute to our understanding of the pubertal initiation program in both sexes and indicate that although mechanisms regulating pubertal onset in males and females may largely be shared, the relationship between body mass and pubertal timing in boys may be complex and requires further genetic studies.
Asunto(s)
Índice de Masa Corporal , Sitios Genéticos , Menarquia/fisiología , Pubertad/genética , Maduración Sexual/genética , Adiposidad/genética , Adolescente , Mama/crecimiento & desarrollo , Niño , Cromosomas Humanos Par 16 , Femenino , Genitales Masculinos/crecimiento & desarrollo , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Masculino , Menarquia/genética , Polimorfismo de Nucleótido Simple , Factores Sexuales , Factores de Transcripción/genética , Población BlancaRESUMEN
Depression in adults is heritable with about 40 % of the phenotypic variance due to additive genetic effects and the remaining phenotypic variance due to unique (unshared) environmental effects. Common environmental effects shared by family members are rarely found in adults. One possible explanation for this finding is that there is an interaction between genes and the environment which may mask effects of the common environment. To test this hypothesis, we investigated genotype by environment interaction in a large sample of female and male adult twins aged 18-70 years. The anxious depression subscale of the Adult Self Report from the Achenbach System of Empirically Based Assessment (Achenbach and Rescorla in Manual for the ASEBA adult: forms and profiles, 2003) was completed by 13,022 twins who participate in longitudinal studies of the Netherlands Twin Register. In a single group analysis, we found genotype by unique environment interaction, but no genotype by common environment interaction. However, when conditioning on gender, we observed genotype by common environment interaction in men, with larger common environmental variance in men who are genetically less at risk to develop depression. Although the effect size of the interaction is characterized by large uncertainty, the results show that there is at least some variance due to the common environment in adult depression in men.