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OBJECTIVE: The role of negative parenting in the development of callous-unemotional (CU) traits remains unclear. Both negative parenting and CU traits are influenced by genetic and environmental factors. The authors used genetically informed longitudinal cross-lagged models to examine the extent to which reciprocal effects between negative parenting and children's CU traits in mid-to-late childhood are genetic versus environmental in origin. METHODS: In 9,260 twin pairs from the Twins Early Development Study, the authors estimated cross-lagged effects between negative parenting (discipline and feelings) and children's CU traits in mid (ages 7-9) and late (ages 9-12) childhood. RESULTS: CU traits were strongly heritable and stable. Stability was explained largely by genetic factors. The influence of negative parenting on the development of CU traits was small and driven mostly by genetic and shared environmental factors. In mid childhood, the influence of children's CU traits on subsequent negative parenting (i.e., evoked by children's CU traits) was also small and mostly genetic in origin. In late childhood, CU traits showed no effects on negative parental discipline and small effects on negative parental feelings, which reflected mostly shared environmental factors. CONCLUSIONS: In mid-to-late childhood, genetic factors strongly influenced the development of CU traits, whereas environmental effects of negative parenting were small. Negative parenting was also relatively unaffected by CU traits. The small reciprocal effects originated mostly from genetic and shared environmental factors. Therefore, repeated intensive interventions addressing multiple risk factors rather than negative parenting alone may be best positioned to support families of children with CU traits across development.
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Trastorno de la Conducta , Humanos , Niño , Trastorno de la Conducta/genética , Trastorno de la Conducta/psicología , Responsabilidad Parental/psicología , Trastorno de Personalidad Antisocial/etiología , Emociones/fisiología , Padres , EmpatíaRESUMEN
Several studies have examined the association of externalizing polygenic scores (PGS) with externalizing symptoms in samples of European ancestry. However, less is known about the associations of externalizing polygenic vulnerability in relation to phenotypic externalizing disorders among individuals of different ancestries, such as Mexican youth. Here, we leveraged the largest genome-wide association study on externalizing behaviors that included over 1 million individuals of European ancestry to examine associations of externalizing PGS with a range of externalizing disorders in Mexican adolescents, and investigated whether adversity exposure in childhood moderated these associations. Participants (N = 1064; age range 12-17 years old; 58.8% female) were adolescents recruited for a general population survey on adolescent mental health in the Mexico City Metropolitan region and were genotyped. Childhood adversity exposure and externalizing disorders, specifically attention-deficit hyperactivity disorder (ADHD), conduct disorder, oppositional defiant disorder, and substance use disorder, were assessed via the computer-assisted World Mental Health Composite International Diagnostic Interview for adolescents. A greater externalizing PGS was associated with a greater odds of any externalizing disorder (OR = 1.29 [1.12, 1.48]; p < 0.01) and ADHD (OR = 1.40 [1.15, 1.70]; p < 0.01) in the whole sample, and in females in particular. There were no main effects of the externalizing PGS on conduct disorder, oppositional defiant disorder, or substance use disorder, nor did adversity exposure moderate these associations. Our results suggest that greater genetic propensity for externalizing disorders is associated with increased odds of any externalizing disorders and ADHD among Mexican adolescents, furthering our understanding of externalizing disorder manifestation in this population.
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Trastorno por Déficit de Atención con Hiperactividad , Trastorno de la Conducta , Trastornos Relacionados con Sustancias , Humanos , Adolescente , Femenino , Niño , Masculino , Estudio de Asociación del Genoma Completo , México , Trastorno de la Conducta/epidemiología , Trastorno de la Conducta/genética , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/genética , Trastornos Relacionados con Sustancias/complicacionesRESUMEN
Externalizing behavioral problems in young children are associated with later delinquency and crime,1 which can cause burdens at both personal and socialeconomic levels. The heterogeneity of externalizing problems emphasizes the importance of examining the etiological mechanisms that underlie externalizing problems and related behaviors. The present study focuses on 2 risk factors for externalizing behavioral problems in early childhood: callous-unemotional traits (CU), characterized as a lack of guilt and empathy,2 and irritability, a tendency to show anger and frustration.3 Behavioral genetic studies find that externalizing problems, CU, and irritability are heritable,4,5 raising the possibility of common genetic effects linking the 3 behaviors, but this has not been previously explored. Neurological evidence suggests distinct pathways from CU and irritability to externalizing problems,6 implying that the genetic and environmental factors linking externalizing problems and CU may differ from those linking externalizing problems and irritability. We predict that there will be common genetic influences operating across externalizing problems, CU, and irritability; but we also predict unique genetic and environmental influences representing distinctive risks shared between externalizing problems and CU, and between externalizing problems and irritability, respectively.
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Trastorno de la Conducta , Problema de Conducta , Niño , Humanos , Preescolar , Trastorno de la Conducta/genética , Trastorno de la Conducta/psicología , Genio Irritable , Empatía , Factores de Riesgo , EmocionesRESUMEN
The aetiology of conduct problems involves a combination of genetic and environmental factors, many of which are inherently linked to parental characteristics given parents' central role in children's lives across development. It is important to disentangle to what extent links between parental heritable characteristics and children's behaviour are due to transmission of genetic risk or due to parental indirect genetic influences via the environment (i.e., genetic nurture). We used 31,290 genotyped mother-father-child trios from the Norwegian Mother, Father and Child Cohort Study (MoBa), testing genetic transmission and genetic nurture effects on conduct problems using 13 polygenic scores (PGS) spanning psychiatric conditions, substance use, education-related factors, and other risk factors. Maternal or self-reports of conduct problems at ages 8 and 14 years were available for up to 15,477 children. We found significant genetic transmission effects on conduct problems for 12 out of 13 PGS at age 8 years (strongest association: PGS for smoking, ß = 0.07, 95% confidence interval = [0.05, 0.08]) and for 4 out of 13 PGS at age 14 years (strongest association: PGS for externalising problems, ß = 0.08, 95% confidence interval = [0.05, 0.11]). Conversely, we did not find genetic nurture effects for conduct problems using our selection of PGS. Our findings provide evidence for genetic transmission in the association between parental characteristics and child conduct problems. Our results may also indicate that genetic nurture via traits indexed by our polygenic scores is of limited aetiological importance for conduct problems-though effects of small magnitude or effects via parental traits not captured by the included PGS remain a possibility.
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Trastorno de la Conducta , Herencia Multifactorial , Humanos , Femenino , Niño , Noruega , Masculino , Adolescente , Factores de Riesgo , Herencia Multifactorial/genética , Estudios de Cohortes , Trastorno de la Conducta/genética , Trastorno de la Conducta/epidemiología , Adulto , Madres , Padre , Problema de Conducta , Predisposición Genética a la Enfermedad/genética , GenotipoRESUMEN
BACKGROUND: We used a polygenic score for externalizing behavior (extPGS) and structural MRI to examine potential pathways from genetic liability to conduct problems via the brain across the adolescent transition. METHODS: Three annual assessments of child conduct problems, attention-deficit/hyperactivity problems, and internalizing problems were conducted across across 9-13 years of age among 4,475 children of European ancestry in the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®). RESULTS: The extPGS predicted conduct problems in each wave (R2 = 2.0%-2.9%). Bifactor models revealed that the extPRS predicted variance specific to conduct problems (R2 = 1.7%-2.1%), but also variance that conduct problems shared with other measured problems (R2 = .8%-1.4%). Longitudinally, extPGS predicted levels of specific conduct problems (R2 = 2.0%), but not their slope of change across age. The extPGS was associated with total gray matter volume (TGMV; R2 = .4%) and lower TGMV predicted both specific conduct problems (R2 = 1.7%-2.1%) and the variance common to all problems in each wave (R2 = 1.6%-3.1%). A modest proportion of the polygenic liability specific to conduct problems in each wave was statistically mediated by TGMV. CONCLUSIONS: Across the adolescent transition, the extPGS predicted both variance specific to conduct problems and variance shared by all measured problems. The extPGS also was associated with TGMV, which robustly predicted conduct problems. Statistical mediation analyses suggested the hypothesis that polygenic variation influences individual differences in brain development that are related to the likelihood of conduct problems during the adolescent transition, justifying new research to test this causal hypothesis.
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Trastorno de la Conducta , Imagen por Resonancia Magnética , Herencia Multifactorial , Humanos , Adolescente , Niño , Masculino , Femenino , Trastorno de la Conducta/genética , Trastorno de la Conducta/diagnóstico por imagen , Trastorno de la Conducta/fisiopatología , Estudios Longitudinales , Desarrollo del Adolescente/fisiología , Encéfalo/diagnóstico por imagen , Trastorno por Déficit de Atención con Hiperactividad/genética , Conducta del Adolescente/fisiología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patologíaRESUMEN
Conduct disorder (CD), a common mental disorder in children and adolescents, is characterized by antisocial behavior. Despite similarities with antisocial personality disorder (ASPD) and possible diagnostic continuity, CD has been shown to precede a range of adult-onset mental disorders. Additionally, little is known about the putative shared genetic liability between CD and adult-onset mental disorders and the underlying gene-environment interplay. Here, we interrogated comorbidity between CD and other mental disorders from the Norwegian Mother, Father and Child Cohort Study (n = 114 500) and investigated how polygenic risk scores (PRS) for mental health traits were associated with CD/CD traits in childhood and adolescence. Gene-environment interplay patterns for CD was explored with data on bullying and parental education. We found CD to be comorbid with several child and adult-onset mental disorders. This phenotypic overlap corresponded with associations between PRS for mental disorders and CD. Additionally, our findings support an additive gene-environment model. Previously conceptualized as a precursor of ASPD, we found that CD was associated with polygenic risk for several child- and adult-onset mental disorders. High comorbidity of CD with other psychiatric disorders reflected on the genetic level should inform research studies, diagnostic assessments and clinical follow-up of this heterogenous group.
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Trastorno de la Conducta , Adulto , Femenino , Adolescente , Humanos , Trastorno de la Conducta/epidemiología , Trastorno de la Conducta/genética , Trastorno de la Conducta/diagnóstico , Estudios de Cohortes , Trastorno de Personalidad Antisocial/epidemiología , Trastorno de Personalidad Antisocial/genética , Trastorno de Personalidad Antisocial/diagnóstico , Comorbilidad , Factores de RiesgoRESUMEN
If Cleckley1,2 and Robins3 were alive today, it is conceivable that they may argue about whether conduct disorder (CD) should be measured primarily with personality traits or behavioral characteristics. However, these strict demarcations may not be needed, or most helpful, for understanding youth with conduct problems. Recently, I proposed that CD might be best specified with 3 personality dimensions including grandiose-manipulative (GM), callous-unemotional (CU), and daring-impulsive (DI) traits.4 These traits are observable from an early age, appear to have a genetic basis, and have distinct correlates suggesting potentially differing etiologies relevant to understanding CD. Importantly, each domain is also related to conduct problems and delinquency.5.
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Trastorno de la Conducta , Problema de Conducta , Adolescente , Humanos , Trastorno de la Conducta/genética , Trastorno de la Conducta/psicología , Conducta ImpulsivaRESUMEN
A systematic understanding of the aetiology of neurodevelopmental disorders (NDDs) and their co-occurrence with other conditions during childhood and adolescence remains incomplete. In the current meta-analysis, we synthesized the literature on (1) the contribution of genetic and environmental factors to NDDs, (2) the genetic and environmental overlap between different NDDs, and (3) the co-occurrence between NDDs and disruptive, impulse control and conduct disorders (DICCs). Searches were conducted across three platforms: Web of Science, Ovid Medline and Ovid Embase. Studies were included only if 75% or more of the sample consisted of children and/or adolescents and the studies had measured the aetiology of NDDs and DICCs using single-generation family designs or genomic methods. Studies that had selected participants on the basis of unrelated diagnoses or injuries were excluded. We performed multilevel, random-effects meta-analyses on 296 independent studies, including over four million (partly overlapping) individuals. We further explored developmental trajectories and the moderating roles of gender, measurement, geography and ancestry. We found all NDDs to be substantially heritable (family-based heritability, 0.66 (s.e. = 0.03); SNP heritability, 0.19 (s.e. = 0.03)). Meta-analytic genetic correlations between NDDs were moderate (grand family-based genetic correlation, 0.36 (s.e. = 0.12); grand SNP-based genetic correlation, 0.39 (s.e. = 0.19)) but differed substantially between pairs of disorders. The genetic overlap between NDDs and DICCs was strong (grand family-based genetic correlation, 0.62 (s.e. = 0.20)). While our work provides evidence to inform and potentially guide clinical and educational diagnostic procedures and practice, it also highlights the imbalance in the research effort that has characterized developmental genetics research.
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Trastorno de la Conducta , Trastornos del Neurodesarrollo , Niño , Humanos , Adolescente , Trastornos del Neurodesarrollo/epidemiología , Trastornos del Neurodesarrollo/genética , Trastornos del Neurodesarrollo/diagnóstico , Genoma , Familia , Trastorno de la Conducta/genéticaRESUMEN
INTRODUCTION: The co-occurrence between major depression disorder (MDD) and conduct disorder (CD) is common across development and represents a significant risk factor for future psychiatric problems and long-term impairment. Large-scale quantitative genetic studies suggest that the MDD-CD co-occurrence may be partly explained by shared genetic vulnerability factors, in line with transdiagnostic models of psychopathology, but no systematic synthesis of the literature is currently available. METHODS: We therefore conducted a systematic review of the available genetic literature on the co-occurrence between MDD and CD in children and adolescents. We identified 10 eligible studies, including 5 cross-sectional bivariate/multivariate twin studies, 3 longitudinal bivariate/multivariate twin studies, and 2 latent profile/trajectory twin studies. RESULTS: Most of the reviewed studies found a strong contribution of shared genetic factors on the covariation between depression and conduct problems, in line with the prominent effect of a common genetic liability across development. LIMITATIONS: The scientific literature on this psychiatric comorbidity is still limited, as it solely consists of twin studies from high income countries. CONCLUSION: Considering the joint burden of MDD and CD on youth, families and society worldwide, future studies are needed to better investigate the shared risk processes of these frequently co-occurring conditions, in order to inform new treatments through personalized medicine.
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Trastorno de la Conducta , Trastorno Depresivo Mayor , Niño , Adolescente , Humanos , Trastorno de la Conducta/epidemiología , Trastorno de la Conducta/genética , Depresión/psicología , Estudios Transversales , Enfermedades en Gemelos/genética , Comorbilidad , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/genéticaRESUMEN
Despite the substantial heritability of antisocial behavior (ASB), specific genetic variants robustly associated with the trait have not been identified. The present study by the Broad Antisocial Behavior Consortium (BroadABC) meta-analyzed data from 28 discovery samples (N = 85,359) and five independent replication samples (N = 8058) with genotypic data and broad measures of ASB. We identified the first significant genetic associations with broad ASB, involving common intronic variants in the forkhead box protein P2 (FOXP2) gene (lead SNP rs12536335, p = 6.32 × 10-10). Furthermore, we observed intronic variation in Foxp2 and one of its targets (Cntnap2) distinguishing a mouse model of pathological aggression (BALB/cJ strain) from controls (BALB/cByJ strain). Polygenic risk score (PRS) analyses in independent samples revealed that the genetic risk for ASB was associated with several antisocial outcomes across the lifespan, including diagnosis of conduct disorder, official criminal convictions, and trajectories of antisocial development. We found substantial genetic correlations of ASB with mental health (depression rg = 0.63, insomnia rg = 0.47), physical health (overweight rg = 0.19, waist-to-hip ratio rg = 0.32), smoking (rg = 0.54), cognitive ability (intelligence rg = -0.40), educational attainment (years of schooling rg = -0.46) and reproductive traits (age at first birth rg = -0.58, father's age at death rg = -0.54). Our findings provide a starting point toward identifying critical biosocial risk mechanisms for the development of ASB.
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Trastorno de Personalidad Antisocial , Trastorno de la Conducta , Animales , Ratones , Trastorno de Personalidad Antisocial/genética , Estudio de Asociación del Genoma Completo , Trastorno de la Conducta/genética , Trastorno de la Conducta/psicología , Agresión/psicología , Herencia Multifactorial/genética , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genéticaRESUMEN
In childhood and adolescence, overt antisocial and aggressive manifestations are typically diagnosed as conduct disorder (CD). Given that the emerging research has pointed to the influence of 5-HT2A receptors in the ontogeny of aggression, we aimed to analyze the association of its genetic polymorphisms with CD. The study included 228 male adolescent subjects (120 with and 108 without CD). CD was diagnosed according to Structured Clinical Interview for DSM-IV criteria, while evaluations of aggressive/dissociative behaviors were performed using psychometric questionnaires including the PCL-YV, OAS-M, KADS, and CBCL. Platelet 5-HT concentration was determined by spectrophotofluorometry. Genotyping of 5-HT2A receptor polymorphisms rs2070040, rs9534511, rs4142900, rs9534512 was performed using TaqMan SNP Genotyping Assays. Subjective irritability, physical aggression toward others, and antisocial behavior were strongly associated with the G allele of rs2070040 and rs4142900, and the C allele of rs9534511 and rs9534512. A significantly increased platelet 5-HT concentration in CD subjects, compared to controls, was lost after the correction according to the smoking status. Our results indicate an association of the studied HTR2A polymorphisms and their haplotypes with irritability and impulsivity traits, which may contribute to the aggressive and antisocial behavior in male adolescents with CD.
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Trastorno de la Conducta , Receptor de Serotonina 5-HT2A , Adolescente , Agresión , Plaquetas/metabolismo , Trastorno de la Conducta/sangre , Trastorno de la Conducta/genética , Humanos , Masculino , Polimorfismo Genético , Receptor de Serotonina 5-HT2A/sangre , Receptor de Serotonina 5-HT2A/genéticaRESUMEN
This study systematically reviewed available evidence regarding associations between polymorphisms of the oxytocin receptor (OXTR) gene and socio-emotional and behavioral functioning in children and adolescents. The search yielded 69 articles, which were grouped into nine categories: depression, anxiety, and internalizing symptoms, alcohol abuse, borderline personality disorder, conduct disorder symptoms or diagnosis, autism spectrum disorder, attention deficit hyperactivity disorder, early childhood attachment and behavior, pro-social skills, and resilience. Direct and/or gene x environment interactions were identified in over half of the studies. ASD and conduct disorder (including callous unemotional traits) were the diagnoses that were most studied and for which there was the strongest evidence of direct links with OXTR polymorphisms. In most studies identifying gene x environment interactions, the candidate OXTR polymorphism was rs53576. Results suggest that OXTR polymorphisms are associated with social, emotional or behavioural functioning in children and adolescents. The mixed findings do, however, highlight the need for further research.
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Emociones , Receptores de Oxitocina , Adolescente , Trastorno del Espectro Autista/genética , Niño , Preescolar , Trastorno de la Conducta/genética , Humanos , Oxitocina , Polimorfismo de Nucleótido Simple , Receptores de Oxitocina/genética , Conducta SocialRESUMEN
Conduct Disorder (CD) is an impairing psychiatric disorder of childhood and adolescence characterized by aggressive and dissocial behavior. Environmental factors such as maternal smoking during pregnancy, socio-economic status, trauma, or early life stress are associated with CD. Although the number of females with CD is rising in Western societies, CD is under-researched in female cohorts. We aimed at exploring the epigenetic signature of females with CD and its relation to psychosocial and environmental risk factors. We performed HpaII sensitive genome-wide methylation sequencing of 49 CD girls and 50 matched typically developing controls and linear regression models to identify differentially methylated CpG loci (tags) and regions. Significant tags and regions were mapped to the respective genes and tested for enrichment in pathways and brain developmental processes. Finally, epigenetic signatures were tested as mediators for CD-associated risk factors. We identified a 12% increased methylation 5' of the neurite modulator SLITRK5 (FDR = 0.0046) in cases within a glucocorticoid receptor binding site. Functionally, methylation positively correlated with gene expression in lymphoblastoid cell lines. At systems-level, genes (uncorr. P < 0.01) were associated with development of neurons, neurite outgrowth or neuronal developmental processes. At gene expression level, the associated gene-networks are activated perinatally and during early childhood in neocortical regions, thalamus and striatum, and expressed in amygdala and hippocampus. Specifically, the epigenetic signatures of the gene network activated in the thalamus during early childhood correlated with the effect of parental education on CD status possibly mediating its protective effect. The differential methylation patterns identified in females with CD are likely to affect genes that are expressed in brain regions previously indicated in CD. We provide suggestive evidence that protective effects are likely mediated by epigenetic mechanisms impairing specific brain developmental networks and therefore exerting a long-term effect on neural functions in CD. Our results are exploratory and thus, further replication is needed.
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Trastorno de la Conducta , Metilación de ADN , Epigénesis Genética , Epigenoma , Redes Reguladoras de Genes , Hipocampo/metabolismo , Adolescente , Línea Celular , Trastorno de la Conducta/genética , Trastorno de la Conducta/metabolismo , Trastorno de la Conducta/psicología , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Factores de RiesgoRESUMEN
BACKGROUND: Callous-unemotional (CU) traits are associated with chronic and escalating trajectories of antisocial behavior. Extant etiologic studies suggest that heritability estimates for CU traits vary substantially, while also pointing to an environmental association between parenting and CU traits. METHODS: We used twin modeling to estimate additive genetic (A), shared environmental (C), and nonshared environmental (E) influences on CU traits, measured with the Inventory of Callous-Unemotional Traits (ICU) and its subscales. Our sample included 600 twin pairs (age 6-11, 230 monozygotic) from neighborhoods with above-average levels of family poverty, a risk factor for antisocial behavior. We examined the extent to which correlations between parenting, measured via parent and child report on the Parental Environment Questionnaire, and CU traits reflected genetic versus environmental factors. Then, we tested whether parenting moderated the heritability of CU traits. RESULTS: In the context of lower-income neighborhoods, CU traits were moderately to highly heritable (A = 54%) with similar moderate-to-high nonshared environmental influences (E = 46%). Bivariate models revealed that associations between CU traits and warm parenting were genetic (rA = .22) and environmental (rE = .19) in origin, whereas associations between CU traits and harsh parenting were largely genetic in origin (rA = .70). The heritability of CU traits decreased with increasing parental warmth and decreasing harshness. CONCLUSIONS: Callous-unemotional traits are both genetic and environmental in origin during middle childhood, but genetic influences are moderated by parenting quality. Parenting may be an important target for interventions, particularly among youth with greater genetic risk.
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Trastorno de la Conducta , Adolescente , Trastorno de Personalidad Antisocial/genética , Trastorno de Personalidad Antisocial/psicología , Niño , Trastorno de la Conducta/genética , Trastorno de la Conducta/psicología , Emociones , Empatía , Humanos , Responsabilidad Parental/psicologíaRESUMEN
Conduct disorder (CD), a psychiatric disorder characterized by a repetitive pattern of antisocial behaviors, results from a complex interplay between genetic and environmental factors. The clinical presentation of CD varies both according to the individual's sex and level of callous-unemotional (CU) traits, but it remains unclear how genetic and environmental factors interact at the molecular level to produce these differences. Emerging evidence in males implicates methylation of genes associated with socio-affective processes. Here, we combined an epigenome-wide association study with structural neuroimaging in 51 females with CD and 59 typically developing (TD) females to examine DNA methylation in relation to CD, CU traits, and gray matter volume (GMV). We demonstrate an inverse pattern of correlation between CU traits and methylation of a chromosome 1 region in CD females (positive) as compared to TD females (negative). The identified region spans exon 1 of the SLC25A24 gene, central to energy metabolism due to its role in mitochondrial function. Increased SLC25A24 methylation was also related to lower GMV in multiple brain regions in the overall cohort. These included the superior frontal gyrus, prefrontal cortex, and supramarginal gyrus, secondary visual cortex and ventral posterior cingulate cortex, which are regions that have previously been implicated in CD and CU traits. While our findings are preliminary and need to be replicated in larger samples, they provide novel evidence that CU traits in females are associated with methylation levels in a fundamentally different way in CD and TD, which in turn may relate to observable variations in GMV across the brain.
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Antiportadores/genética , Proteínas de Unión al Calcio/genética , Trastorno de la Conducta , Metilación de ADN , Proteínas Mitocondriales/genética , Trastorno de la Conducta/diagnóstico por imagen , Trastorno de la Conducta/genética , Epigénesis Genética , Femenino , Sustancia Gris/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , NeuroimagenRESUMEN
Antisocial behavior and psychopathic traits are subject to complex patterns of inheritance, gene--environment interactive effects, and powerful environmental influences. Yet genetic factors are important in the etiology of antisocial behavior and psychopathic traits, and identifying youth with an elevated genetic risk may lead to improved interventions and preventive efforts. Additionally, research revealing the importance of gene--environment interactions in the development of antisocial behavior and psychopathic traits should be harnessed to promote more rehabilitative, developmentally appropriate policies to benefit youth in the juvenile justice and social welfare systems.
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Trastorno de Personalidad Antisocial/genética , Trastorno de la Conducta/genética , Interacción Gen-Ambiente , Adolescente , Adulto , Humanos , PolíticasRESUMEN
Dimensions of irritability and defiant behavior, though correlated within the structure of ODD, convey separable developmental risks through adolescence and adulthood. Irritability predicts depression and anxiety, whereas defiant behavior is a precursor to antisocial outcomes. Previously we demonstrated that a bifactor model comprising irritability and defiant behavior dimensions, in addition to a general factor, provided the best-fitting structure of ODD symptoms in five large datasets. Herein we extend our previous work by externally validating the bifactor model of ODD using multiple regression and multivariate behavior genetic analyses. We used parent ratings of DSM IV ODD symptoms, and symptom dimensions for ADHD (i.e., inattention and hyperactivity-impulsivity), conduct disorder (CD), depression/dysthymia, and generalized anxiety disorder (GAD) from 846 6-18-year-old twin pairs. We found that the ODD irritability factor was associated only with depression/dysthymia and GAD and the ODD defiant behavior factor was associated only with inattention, hyperactivity-impulsivity, and CD, whereas the ODD general factor was associated with all five symptom dimensions. Multivariate behavior genetic analyses found all five symptom dimensions shared genetic influences in common with the ODD general, irritability, and defiant behavior factors. In contrast, the defiant behavior factor shared genetic influences uniquely with inattention and hyperactivity-impulsivity, whereas the irritability factor shared genetic influences uniquely with depression/dysthymia and GAD, but not vice versa. This suggests that genes that influence irritability in early childhood also predispose to depression and anxiety in adolescence and adulthood. These multivariate genetic findings also support the external validity of the three ODD dimensions at the etiological level. Our study provides additional support for subtyping ODD based on these symptom dimensions, as in the revisions in the ICD-11, and suggests potential mechanisms underlying the development from ODD to behavioral or affective disorders.
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Trastorno por Déficit de Atención con Hiperactividad , Trastorno de la Conducta , Adolescente , Adulto , Ansiedad/genética , Trastorno por Déficit de Atención con Hiperactividad/genética , Déficit de la Atención y Trastornos de Conducta Disruptiva/genética , Preescolar , Cognición , Trastorno de la Conducta/genética , HumanosRESUMEN
Depression, conduct, and hyperactivity symptoms are chronic and frequently co-occur in adolescence. Common genetic and environmental vulnerability to these conditions have previously been demonstrated, however, the manner in which common versus disorder-specific etiological influences operate across development and maintain symptom co-occurrence is unclear. Thus, the current study investigated the role of common genetic and environmental influences in the comorbidity of depression, conduct, and hyperactivity across adolescence. Over 10,000 twins and their parents reported adolescents' symptoms at mean ages 11 and 16 years. Biometric independent pathway models were fitted to estimate genetic and environmental contributions to the continuity of symptom co-occurrence over time, as well as time- and symptom-specific influences. Results found that a common stable genetic factor accounted for the concurrent and longitudinal co-occurrence of depression, conduct, and hyperactivity symptoms. New genetic influences common to these three symptom scales emerged at 16 years, and further contributed to symptom co-occurrence. Conversely, environmental influences largely contributed to the time-specific associations. The findings were generally consistent for self- and parent-reported symptoms. Overall, the results suggest that stable, overlapping genetic influences contribute to the co-occurrence of depression, conduct, and hyperactivity symptoms across adolescence. The results are in line with hierarchical causal models of psychopathology, which posit that much of the developmental co-occurrence between different symptoms is due to common liability. Specifically, current findings indicate that only genetic influences constitute common liability over time. Future studies should identify genetically influenced transdiagnostic risk and maintenance factors to inform prevention and treatment of comorbid internalizing and externalizing symptoms in adolescence.
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Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno de la Conducta/genética , Depresión/genética , Interacción Gen-Ambiente , Adolescente , Niño , Comorbilidad , Femenino , Humanos , Masculino , Gemelos/genéticaRESUMEN
Takahashi et al. (2020) showed that CU traits at age 7 were highly heritable, that the genetic influences underlying the course of CU traits from age 7 to 16 were largely independent from those underlying the initial level, and that the genetic influences on CU traits in early childhood were substantially different from the genetic influences on these traits in adolescence. This commentary on these important and provocative findings focuses on their implications for future research. Specifically, it notes that future studies attempting to find genetic loci related to CU traits need to consider that such loci may differ depending on the age of the sample and this research needs to consider several important considerations when measuring CU traits that can influence the results. Further, the results of Takahashi et al highlight the importance of environmental influences on the stability of CU traits that could play an important role in treatment.
Asunto(s)
Trastorno de la Conducta , Adolescente , Niño , Preescolar , Trastorno de la Conducta/genética , Emociones , HumanosRESUMEN
BACKGROUND: Conduct disorder (CD), a serious behavioral and emotional disorder in childhood and adolescence, characterized by disruptive behavior and breaking societal rules. Studies have explored the overlap of CD with neurodevelopmental problems (NDP). The somatic health of children with NDP has been investigated; however, the prevalence of these problems in children with CD has not been sufficiently studied. Holistic assessment of children with CD is required for establishing effective treatment strategies. AIMS: (1) Define the prevalence of selected neurological problems (migraine and epilepsy) and gastrointestinal problems (celiac disease, lactose intolerance, diarrhea, and constipation) in a population of twins aged 9 or 12; (2) Compare the prevalence of somatic problems in three subpopulations: (a) children without CD or NDP, (b) children with CD, and (c) children with both CD and NDP; (3) Select twin pairs where at least one child screened positive for CD but not NDP (proband) and map both children's neurological and gastrointestinal problems. METHOD: Telephone interviews with parents of 20,302 twins in a cross-sectional, nationwide, ongoing study. According to their scores on the Autism-Tics, AD/HD, and Comorbidities inventory, screen-positive children were selected and divided into two groups: (1) children with CD Only, (2) children with CD and at least one NDP. RESULTS: Children with CD had an increased prevalence of each neurological and gastrointestinal problem (except celiac disease), and the prevalence of somatic problems was further increased among children with comorbid CD and NDP. The presence of CD (without NDP) increased the odds of constipation for girls and the odds of epilepsy for boys. Girls with CD generally had more coexisting gastrointestinal problems than boys with CD. Female co-twins of probands with CD were strongly affected by gastrointestinal problems. Concordance analyses suggested genetic background factors in neurological and gastrointestinal problems, but no common etiology with CD could be concluded. CONCLUSION: Co-occurring NDP could explain most of the increased prevalence of somatic problems in CD. Our results raise a new perspective on CD in children and adolescents; their CD seems to be linked to a number of other health problems, ranging from neurodevelopmental and psychiatric disorders to somatic complaints.