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BACKGROUND: Autism and different neurodevelopmental conditions frequently co-occur, as do their symptoms at sub-diagnostic threshold levels. Overlapping traits and shared genetic liability are potential explanations. METHODS: In the population-based Norwegian Mother, Father, and Child Cohort study (MoBa), we leverage item-level data to explore the phenotypic factor structure and genetic architecture underlying neurodevelopmental traits at age 3 years (N = 41,708-58,630) using maternal reports on 76 items assessing children's motor and language development, social functioning, communication, attention, activity regulation, and flexibility of behaviors and interests. RESULTS: We identified 11 latent factors at the phenotypic level. These factors showed associations with diagnoses of autism and other neurodevelopmental conditions. Most shared genetic liabilities with autism, ADHD, and/or schizophrenia. Item-level GWAS revealed trait-specific genetic correlations with autism (items rg range = - 0.27-0.78), ADHD (items rg range = - 0.40-1), and schizophrenia (items rg range = - 0.24-0.34). We find little evidence of common genetic liability across all neurodevelopmental traits but more so for several genetic factors across more specific areas of neurodevelopment, particularly social and communication traits. Some of these factors, such as one capturing prosocial behavior, overlap with factors found in the phenotypic analyses. Other areas, such as motor development, seemed to have more heterogenous etiology, with specific traits showing a less consistent pattern of genetic correlations with each other. CONCLUSIONS: These exploratory findings emphasize the etiological complexity of neurodevelopmental traits at this early age. In particular, diverse associations with neurodevelopmental conditions and genetic heterogeneity could inform follow-up work to identify shared and differentiating factors in the early manifestations of neurodevelopmental traits and their relation to autism and other neurodevelopmental conditions. This in turn could have implications for clinical screening tools and programs.
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Fenotipo , Humanos , Noruega , Femenino , Masculino , Preescolar , Estudios de Cohortes , Trastornos del Neurodesarrollo/genética , Trastornos del Neurodesarrollo/diagnóstico , Madres , Trastorno Autístico/genética , Predisposición Genética a la Enfermedad , Adulto , Padre , Estudio de Asociación del Genoma Completo , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Esquizofrenia/genética , Heterogeneidad GenéticaRESUMEN
LAY ABSTRACT: Using questionnaires in research relies on the expectation that they measure the same things across different groups of individuals. If this is not true, then interpretations of results can be misleading when researchers compare responses across different groups of individuals or use in it a group that differs from that in which the questionnaire was developed. For the questionnaire we investigated, the Social Communication Questionnaire (SCQ), we found that parents of boys and girls responded to questionnaire items in largely the same way but that the SCQ measured traits and behaviors slightly differently depending on whether the children had autism. Based on these results, we concluded that researchers using this questionnaire should carefully consider these differences when deciding how to interpret findings. SCQ scores as a reflection of "autism-associated traits" in samples that are mostly or entirely made up of individuals without an autism diagnosis may be misleading and we encourage a more precise interpretation of scores as a broader indication of social-communicative and behavioral traits.
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Trastorno Autístico , Comunicación , Humanos , Masculino , Femenino , Encuestas y Cuestionarios , Trastorno Autístico/psicología , Trastorno Autístico/diagnóstico , Niño , Factores Sexuales , Conducta Social , Adolescente , Análisis Factorial , Adulto , Padres/psicología , PreescolarRESUMEN
Background: Adolescent self-reported psychotic experiences are associated with mental illness and could help guide prevention strategies. The Community Assessment of Psychic Experiences (CAPE) was developed over 20 years ago. In a rapidly changing society, where new generations of adolescents are growing up in an increasingly digital world, it is crucial to ensure high reliability and validity of the questionnaire. Methods: In this observational validation study, we used unique transgenerational questionnaire and health registry data from the Norwegian Mother, Father, and Child Cohort, a population-based pregnancy cohort. Adolescents, aged ~14 years, responded to the CAPE-16 (n = 18,835) and fathers to the CAPE-9 questionnaire (n = 28,793). We investigated the psychometric properties of CAPE-16 through factor analyses, measurement invariance testing across biological sex, response before/ during the COVID-19 pandemic, and generations (comparison with fathers), and examined associations with later psychiatric diagnoses. Outcomes: One third (33·4%) of adolescents reported lifetime psychotic experiences. We confirmed a three-factor structure (paranoia, bizarre thoughts, and hallucinations) of CAPE-16, and observed good scale reliability of the distress and frequency subscales (ω = ·86 and ·90). CAPE-16 measured psychotic experiences were invariant to biological sex and pandemic status. CAPE-9 was non-invariant across generations, with items related to understanding of the digital world (electrical influences) prone to bias. CAPE-16 sum scores were associated with a subsequent psychiatric diagnosis, particularly psychotic disorders (frequency: OR = 2·06; 97·5% CI = 1·70-2·46; distress: OR = 1·93; 97·5% CI = 1·63-2·26). Interpretation: CAPE-16 showed robust psychometric properties across sex and pandemic status, and sum scores were associated with subsequent psychiatric diagnoses, particularly psychotic disorders. These findings suggest that with certain adjustments, CAPE-16 could have value as a screening tool for adolescents in the modern, digital world. Funding: European Union's Horizon 2020 Programme, Research Council of Norway, South-Eastern Norway Regional Health Authority, NIMH, and the KG Jebsen Stiftelsen.
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There is growing recognition that earliest signs of autism need not clearly manifest in the first three years of life. To what extent is this variation in developmental trajectories associated with age at autism diagnosis? Does the genetic profile of autism vary with age at autism diagnosis? Using longitudinal data from four birth cohorts, we demonstrate that two different trajectories of socio-emotional behaviours are associated with age at diagnosis. We further demonstrate that the age at autism diagnosis is partly heritable (h2 SNP = 0.12, s.e.m = 0.01), and is associated with two moderately correlated (rg = 0.38, s.e.m = 0.07) autism polygenic factors. One of these factors is associated with earlier diagnosis of autism, lower social and communication abilities in early childhood. The second factor is associated with later autism diagnosis, increased socio-emotional difficulties in adolescence, and has moderate to high positive genetic correlations with Attention-Deficit/Hyperactivity Disorder, mental health conditions, and trauma. Overall, our research identifies an axis of heterogeneity in autism, indexed by age at diagnosis, which partly explains heterogeneity in autism and the profiles of co-occurring neurodevelopmental and mental health profiles. Our findings have important implications for how we conceptualise autism and provide one model to explain some of the diversity within autism.