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Schizophrenia is a neurodevelopmental disorder associated with deficits in cognitive development and childhood psychopathology. Previous studies have focused on older children and the few studies of early childhood have yielded inconsistent findings. We studied cognitive development and psychopathology in children at familial high risk (FHR) of schizophrenia and matched controls from 1 to 6 years and hypothesized that FHR children would show consistent deficits across cognitive and behavioral measures in early childhood. STUDY DESIGN: Cognitive development in children at high familial risk for schizophrenia or schizoaffective disorder (n = 33) and matched healthy controls (n = 66) was assessed at 1 and 2 years with the Mullen Scales of Early Learning, and at 4 and 6 years with the Stanford Binet Intelligence Scales, BRIEF-P/BRIEF and CANTAB. Psychopathology was assessed at 4 and 6 years with the BASC-2. General linear models were used to examine differences on outcome scores, and chi-square analyses were used to explore differences in the proportion of "at risk" or "below average" score profiles. STUDY RESULTS: FHR children scored significantly lower than controls on Mullen Composite at age 2, and demonstrated broad deficits in IQ, executive function and working memory and 4 and 6 years. FHR children were also rated as significantly worse on most items of the BASC-2 at ages 4 and 6. CONCLUSIONS: Children at FHR for schizophrenia demonstrate abnormal cognitive development and psychopathology at younger ages than previously detected, suggesting that early detection and intervention needs to be targeted to very early childhood.
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Emotional regulation involves managing attention, affect, and behavior, and is essential for long-term health and well-being, including positive school adjustment. The purpose of this secondary data analysis from the Durham Child Health and Development Study was to explore how parent and teacher reported emotional regulation behaviors related to school adjustment outcomes (social skills, academic performance, and academic achievement) during early childhood. Parent and teacher reports on emotional regulation behaviors showed mixed concordance, however they correlated with critical aspects of school adjustment. Clinical and practical implications are discussed, including the role of psychiatric nurses in promoting positive emotional regulation and school adjustment outcomes across settings.
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Regulación Emocional , Instituciones Académicas , Ajuste Social , Humanos , Masculino , Femenino , Niño , Padres/psicología , Maestros/psicología , Preescolar , Habilidades Sociales , Éxito AcadémicoRESUMEN
INTRODUCTION: Existing evidence suggests that exposure to phthalates is higher among younger age groups. However, limited knowledge exists on how phthalate exposure, as well as exposure to replacement plasticizers, di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) and di-2-ethylhexyl terephthalate (DEHTP), change from infancy through early childhood. METHODS: Urine samples were collected across the first 5 years of life from typically developing infants and young children enrolled between 2017 and 2020 in the longitudinal UNC Baby Connectome Project. From 438 urine samples among 187 participants, we quantified concentrations of monobutyl phthalate (MnBP), mono-3-carboxypropyl phthalate (MCPP), monoisobutyl phthalate (MiBP), monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), and metabolites of di(2-ethylhexyl) phthalate (DEHP), diisonoyl phthalate (DiNP), DINCH and DEHTP. Specific gravity (SG) adjusted metabolite and molar sum concentrations were compared across age groups. Intraclass correlation coefficients (ICCs) were calculated among 122 participants with multiple urine specimens (373 samples). RESULTS: Most phthalate metabolites showed high detection frequencies (>80% of samples). Replacement plasticizers DINCH (58-60%) and DEHTP (>97%) were also commonly found. DiNP metabolites were less frequently detected (<10%). For some metabolites, SG-adjusted concentrations were inversely associated with age, with the highest concentrations found in the first year of life. ICCs revealed low to moderate reliability in metabolite measurements (ρ = 0.10-0.48) suggesting a high degree of within-individual variation in exposure among this age group. The first 6 months (compared to remaining age groups) showed an increased ratio of carboxylated metabolites of DEHP and DEHTP, compared to other common metabolites, but no clear age trends for DINCH metabolite ratios were observed. CONCLUSION: Metabolites of phthalates and replacements plasticizers were widely detected in infancy and early childhood, with the highest concentrations observed in the first year of life for several metabolites. Higher proportions of carboxylated metabolites of DEHP and DEHTP in younger age groups indicate potential differences in metabolism during infancy.
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Background: Evidence for sex differences in cognition in childhood is established, but less is known about the underlying neural mechanisms for these differences. Recent findings suggest the existence of brain-behavior relationship heterogeneities during infancy; however, it remains unclear whether sex underlies these heterogeneities during this critical period when sex-related behavioral differences arise. Methods: A sample of 316 infants was included with resting-state functional magnetic resonance imaging scans at neonate (3 weeks), 1, and 2 years of age. We used multiple linear regression to test interactions between sex and resting-state functional connectivity on behavioral scores of working memory, inhibitory self-control, intelligence, and anxiety collected at 4 years of age. Results: We found six age-specific, intra-hemispheric connections showing significant and robust sex differences in functional connectivity-behavior relationships. All connections are either with the prefrontal cortex or the temporal pole, which has direct anatomical pathways to the prefrontal cortex. Sex differences in functional connectivity only emerge when associated with behavior, and not in functional connectivity alone. Furthermore, at neonate and 2 years of age, these age-specific connections displayed greater connectivity in males and lower connectivity in females in association with better behavioral scores. Conclusions: Taken together, we critically capture robust and conserved brain mechanisms that are distinct to sex and are defined by their relationship to behavioral outcomes. Our results establish brain-behavior mechanisms as an important feature in the search for sex differences during development.
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The human brain grows quickly during infancy and early childhood, but factors influencing brain maturation in this period remain poorly understood. To address this gap, we harmonized data from eight diverse cohorts, creating one of the largest pediatric neuroimaging datasets to date focused on birth to 6 years of age. We mapped the developmental trajectory of intracranial and subcortical volumes in â¼2,000 children and studied how sociodemographic factors and adverse birth outcomes influence brain structure and cognition. The amygdala was the first subcortical volume to mature, whereas the thalamus exhibited protracted development. Males had larger brain volumes than females, and children born preterm or with low birthweight showed catch-up growth with age. Socioeconomic factors exerted region- and time-specific effects. Regarding cognition, males scored lower than females; preterm birth affected all developmental areas tested, and socioeconomic factors affected visual reception and receptive language. Brain-cognition correlations revealed region-specific associations.
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Nacimiento Prematuro , Masculino , Femenino , Humanos , Recién Nacido , Preescolar , Niño , Cognición , Encéfalo/diagnóstico por imagen , Neuroimagen , Imagen por Resonancia MagnéticaRESUMEN
Amygdala function is implicated in the pathogenesis of autism spectrum disorder (ASD) and anxiety. We investigated associations between early trajectories of amygdala growth and anxiety and ASD outcomes at school age in two longitudinal studies: high- and low-familial likelihood for ASD, Infant Brain Imaging Study (IBIS, n = 257) and typically developing (TD) community sample, Early Brain Development Study (EBDS, n = 158). Infants underwent MRI scanning at up to 3 timepoints from neonate to 24 months. Anxiety was assessed at 6-12 years. Linear multilevel modeling tested whether amygdala volume growth was associated with anxiety symptoms at school age. In the IBIS sample, children with higher anxiety showed accelerated amygdala growth from 6 to 24 months. ASD diagnosis and ASD familial likelihood were not significant predictors. In the EBDS sample, amygdala growth from birth to 24 months was associated with anxiety. More anxious children had smaller amygdala volume and slower rates of amygdala growth. We explore reasons for the contrasting results between high-familial likelihood for ASD and TD samples, grounding results in the broader literature of variable associations between early amygdala volume and later anxiety. Results have the potential to identify mechanisms linking early amygdala growth to later anxiety in certain groups.
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Trastorno del Espectro Autista , Niño , Lactante , Recién Nacido , Humanos , Ansiedad , Trastornos de Ansiedad , Encéfalo , Imagen por Resonancia Magnética/métodos , Amígdala del CerebeloRESUMEN
There is strong evidence that the functional connectome is highly related to the white matter connectome in older children and adults, though little is known about structure-function relationships in early childhood. We investigated the development of cortical structure-function coupling in children longitudinally scanned at 1, 2, 4, and 6 years of age (N = 360) and in a comparison sample of adults (N = 89). We also applied a novel graph convolutional neural network-based deep learning model with a new loss function to better capture inter-subject heterogeneity and predict an individual's functional connectivity from the corresponding structural connectivity. We found regional patterns of structure-function coupling in early childhood that were consistent with adult patterns. In addition, our deep learning model improved the prediction of individual functional connectivity from its structural counterpart compared to existing models.
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Conectoma , Sustancia Blanca , Adulto , Niño , Humanos , Preescolar , Encéfalo , Imagen por Resonancia Magnética , Red NerviosaRESUMEN
OBJECTIVE: Maternal psychological stress during pregnancy is a common risk factor for psychiatric disorders in offspring, but little is known about how heterogeneity of stress trajectories during pregnancy affect brain systems and behavioral phenotypes in infancy. This study was designed to address this gap in knowledge. METHODS: Maternal anxiety, stress, and depression were assessed at multiple time points during pregnancy in two independent low-risk mother-infant cohorts (N=115 and N=2,156). Trajectories in maternal stress levels in relation to infant negative affect were examined in both cohorts. Neonatal amygdala resting-state functional connectivity MRI was examined in a subset of one cohort (N=60) to explore the potential relationship between maternal stress trajectories and brain systems in infants relevant to negative affect. RESULTS: Four distinct trajectory clusters, characterized by changing patterns of stress over time, and two magnitude clusters, characterized by severity of stress, were identified in the original mother-infant cohort (N=115). The magnitude clusters were not associated with infant outcomes. The trajectory characterized by increasing stress in late pregnancy was associated with blunted development of infant negative affect. This relationship was replicated in the second, larger cohort (N=2,156). In addition, the trajectories that included increasing or peak maternal stress in late pregnancy were related to stronger neonatal amygdala functional connectivity to the anterior insula and the ventromedial prefrontal cortex in the exploratory analysis. CONCLUSIONS: The trajectory of maternal stress appears to be important for offspring brain and behavioral development. Understanding heterogeneity in trajectories of maternal stress and their influence on infant brain and behavioral development is critical to developing targeted interventions.
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Amígdala del Cerebelo , Corteza Prefrontal , Lactante , Recién Nacido , Femenino , Humanos , Embarazo , Amígdala del Cerebelo/diagnóstico por imagen , Corteza Prefrontal/diagnóstico por imagen , Madres/psicología , Imagen por Resonancia Magnética , AfectoRESUMEN
Prior work has shown that different functional brain networks exhibit different maturation rates, but little is known about whether and how different brain areas may differ in the exact shape of longitudinal functional connectivity growth trajectories during infancy. We used resting-state functional magnetic resonance imaging (fMRI) during natural sleep to characterize developmental trajectories of different regions using a longitudinal cohort of infants at 3 weeks (neonate), 1 year, and 2 years of age (n = 90; all with usable data at three time points). A novel whole brain heatmap analysis was performed with four mixed-effect models to determine the best fit of age-related changes for each functional connection: (i) growth effects: positive-linear-age, (ii) emergent effects: positive-log-age, (iii) pruning effects: negative-quadratic-age, and (iv) transient effects: positive-quadratic-age. Our results revealed that emergent (logarithmic) effects dominated developmental trajectory patterns, but significant pruning and transient effects were also observed, particularly in connections centered on inferior frontal and anterior cingulate areas that support social learning and conflict monitoring. Overall, unique global distribution patterns were observed for each growth model indicating that developmental trajectories for different connections are heterogeneous. All models showed significant effects concentrated in association areas, highlighting the dominance of higher-order social/cognitive development during the first 2 years of life.
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Conectoma , Imagen por Resonancia Magnética , Recién Nacido , Humanos , Lactante , Imagen por Resonancia Magnética/métodos , Encéfalo , Cognición , Giro del Cíngulo , Conectoma/métodosRESUMEN
Human brain undergoes rapid growth during the first few years of life. While previous research has employed graph theory to study early brain development, it has mostly focused on the topological attributes of the whole brain. However, examining regional graph-theory features may provide unique insights into the development of cognitive abilities. Utilizing a large and longitudinal rsfMRI dataset from the UNC/UMN Baby Connectome Project, we investigated the developmental trajectories of regional efficiency and evaluated the relationships between these changes and cognitive abilities using Mullen Scales of Early Learning during the first twenty-eight months of life. Our results revealed a complex and spatiotemporally heterogeneous development pattern of regional global and local efficiency during this age period. Furthermore, we found that the trajectories of the regional global efficiency at the left temporal occipital fusiform and bilateral occipital fusiform gyri were positively associated with cognitive abilities, including visual reception, expressive language, receptive language, and early learning composite scores (P < 0.05, FDR corrected). However, these associations were weakened with age. These findings offered new insights into the regional developmental features of brain topologies and their associations with cognition and provided evidence of ongoing optimization of brain networks at both whole-brain and regional levels.
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Conectoma , Imagen por Resonancia Magnética , Humanos , Encéfalo , Cognición , Conectoma/métodos , Lenguaje , Mapeo EncefálicoRESUMEN
Objective: Longer sleep duration in infancy supports cognitive and affective functioning - likely through effects on brain development. From childhood through old age, there is evidence for a close link between sleep and brain volume. However, little is known about the association between sleep duration and brain volume in infancy, a developmental period of unprecedented brain maturation. This study aimed to close this gap by assessing sleep duration across the first year of life and gray and white matter volume at 12-mo age. Method: Infant sleep duration trajectories across the first year of life were based on maternal reports at 1, 3, 6, 9, and 12 months of age. Infant specific trajectories were generated by running a logarithmic regression for each infant and residualizing the resulting slopes for their intercept. Structural magnetic resonance imaging (MRI) scans were acquired at 12-mo age. Gray and white matter volume estimates were residualized for intracranial volume and age at scan. Results: Data to calculate sleep trajectories was available for 112 infants. Overall, sleep duration decreased over the course of the first year of life and was best described by a logarithmic function. Of these infants, data on brain volume was available for 45 infants at 12-mo age. Infants whose sleep duration decreased less during the first year of life relative to their intercept had, on average, greater white matter volume (ß = .36, p = .02). Furthermore, average sleep duration across the first year of life, and sleep duration specifically at 6 and 9 months were positively associated with white matter volume. Sleep duration during the first year of life was not significantly associated with gray matter volume at 12-mo age. Conclusion: Sufficient sleep duration may benefit infant white matter development - possibly by supporting myelination. The fact that sleep duration was not associated with gray matter volume is in line with preclinical studies suggesting that sleep may be crucial for the balance between synaptogenesis and synaptic pruning but not necessarily relate to a net increase in gray matter volume. Supporting sleep during periods of rapid brain development and intervening in case of sleep problems may have long-term benefits for cognitive function and mental health.
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Adult twin neuroimaging studies have revealed that cortical thickness (CT) and surface area (SA) are differentially influenced by genetic information, leading to their spatially distinct genetic patterning and topography. However, the postnatal origins of the genetic topography of CT and SA remain unclear, given the dramatic cortical development from neonates to adults. To fill this critical gap, this study unprecedentedly explored how genetic information differentially regulates the spatial topography of CT and SA in the neonatal brain by leveraging brain magnetic resonance (MR) images from 202 twin neonates with minimal influence by the complicated postnatal environmental factors. We capitalized on infant-dedicated computational tools and a data-driven spectral clustering method to parcellate the cerebral cortex into a set of distinct regions purely according to the genetic correlation of cortical vertices in terms of CT and SA, respectively, and accordingly created the first genetically informed cortical parcellation maps of neonatal brains. Both genetic parcellation maps exhibit bilaterally symmetric and hierarchical patterns, but distinct spatial layouts. For CT, regions with closer genetic relationships demonstrate an anterior-posterior (A-P) division, while for SA, regions with greater genetic proximity are typically within the same lobe. Certain genetically informed regions exhibit strong similarities between neonates and adults, with the most striking similarities in the medial surface in terms of SA, despite their overall substantial differences in genetic parcellation maps. These results greatly advance our understanding of the development of genetic influences on the spatial patterning of cortical morphology.SIGNIFICANCE STATEMENT Genetic influences on cortical thickness (CT) and surface area (SA) are complex and could evolve throughout the lifespan. However, studies revealing distinct genetic topography of CT and SA have been limited to adults. Using brain structural magnetic resonance (MR) images of twins, we unprecedentedly discovered the distinct genetically-informed parcellation maps of CT and SA in neonatal brains, respectively. Each genetic parcellation map comprises a distinct spatial layout of cortical regions, where vertices within the same region share high genetic correlation. These genetic parcellation maps of CT and SA of neonates largely differ from those of adults, despite their highly remarkable similarities in the medial cortex of SA. These discoveries provide important insights into the genetic organization of the early cerebral cortex development.
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Encéfalo , Corteza Cerebral , Humanos , Adulto , Lactante , Recién Nacido , Encéfalo/diagnóstico por imagen , Encéfalo/anatomía & histología , Gemelos/genética , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , Mapeo EncefálicoRESUMEN
PURPOSE: The purpose of this study was to investigate if social adversity is associated with mother reported emotional dysregulation behaviors and trajectories during infancy and early childhood. DESIGN & METHODS: A secondary data analysis from the Durham Child Health and Development study study included 206 child-mother dyads. Three models were used to explore the relationship between social adversity and mother reported emotional dysregulation during infancy (Infant Behavior Questionnaire-Revised) and early childhood (Child Behavior Checklist - Dysregulation Profile). Linear mixed effects models were adopted to investigate if social adversity was associated with mother reported emotional dysregulation longitudinally. Regression analysis was conducted to explore if social adversity was associated with maternal reported emotional dysregulation trajectory slope scores and maternal reported emotional dysregulation trajectory class. Maternal psychological distress and the child's sex assigned at birth were included as covariates in each analysis. RESULTS: Infants with greater social adversity scores had significantly higher maternal reported fear responses across the first year of life. Social adversity was associated with maternal reported distress to limitations trajectory, dysregulated recovery class, and dysregulated distress to limitations class. During early childhood social adversity was significantly associated with maternal reported emotional dysregulation but not trajectories which showed little variability. CONCLUSION & PRACTICAL IMPLICATIONS: Our results indicate that social adversity is associated with maternal reported emotional dysregulation during infancy and early childhood. Nursing and other professionals can participate in early screening to determine risk and provide intervention.
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Regulación Emocional , Emociones , Determinantes Sociales de la Salud , Preescolar , Humanos , Lactante , Recién Nacido , MadresRESUMEN
Imaging genetics provides an opportunity to discern associations between genetic variants and brain imaging phenotypes. Historically, the field has focused on adults and adolescents; very few imaging genetics studies have focused on brain development in infancy and early childhood (from birth to age 6 years). This is an important knowledge gap because developmental changes in the brain during the prenatal and early postnatal period are regulated by dynamic gene expression patterns that likely play an important role in establishing an individual's risk for later psychiatric illness and neurodevelopmental disabilities. In this review, we summarize findings from imaging genetics studies spanning from early infancy to early childhood, with a focus on studies examining genetic risk for neuropsychiatric disorders. We also introduce the Organization for Imaging Genomics in Infancy (ORIGINs), a working group of the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium, which was established to facilitate large-scale imaging genetics studies in infancy and early childhood.
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Encéfalo , Trastornos Mentales , Femenino , Embarazo , Preescolar , Humanos , Encéfalo/diagnóstico por imagen , Trastornos Mentales/genética , Neuroimagen/métodos , FenotipoRESUMEN
Sex differences in behavior have been reported from infancy through adulthood, but little is known about sex effects on functional circuitry in early infancy. Moreover, the relationship between early sex effects on the functional architecture of the brain and later behavioral performance remains to be elucidated. In this study, we used resting-state fMRI and a novel heatmap analysis to examine sex differences in functional connectivity with cross-sectional and longitudinal mixed models in a large cohort of infants (n = 319 neonates, 1-, and 2-year-olds). An adult dataset (n = 92) was also included for comparison. We investigated the relationship between sex differences in functional circuitry and later measures of language (collected in 1- and 2-year-olds) as well as indices of anxiety, executive function, and intelligence (collected in 4-year-olds). Brain areas showing the most significant sex differences were age-specific across infancy, with two temporal regions demonstrating consistent differences. Measures of functional connectivity showing sex differences in infancy were significantly associated with subsequent behavioral scores of language, executive function, and intelligence. Our findings provide insights into the effects of sex on dynamic neurodevelopmental trajectories during infancy and lay an important foundation for understanding the mechanisms underlying sex differences in health and disease.
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Encéfalo , Caracteres Sexuales , Lactante , Recién Nacido , Adulto , Humanos , Masculino , Femenino , Preescolar , Estudios Transversales , Lóbulo Temporal , Mapeo Encefálico , Imagen por Resonancia Magnética , Vías NerviosasRESUMEN
BACKGROUND: The white matter (WM) connectome is important for cognitive development and intelligence and is altered in neuropsychiatric illnesses. Little is known about how the WM connectome develops or its relationship to IQ in early childhood. METHODS: The development of node centrality in the WM connectome was studied in a longitudinal cohort of 226 (123 female) children from the University of North Carolina Early Brain Development Study. Structural and diffusion-weighted images were acquired after birth and at 1, 2, 4, and 6 years, and IQ was assessed at 6 years. Eigenvector centrality, betweenness centrality, and the global graph metrics of global efficiency, small worldness, and modularity were determined at each age. RESULTS: The greatest developmental change in eigenvector centrality and betweenness centrality occurred during the first year of life, with relative stability between ages 1 and 6 years. Most of the high-centrality hubs at age 6 were also high-centrality hubs at 1 year, and many were already high-centrality hubs at birth. There were generally small but significant changes in global efficiency and modularity from birth to 6 years, while small worldness increased between 2 and 4 years. Individual node centrality was not significantly correlated with IQ at 6 years. CONCLUSIONS: Node centrality in the WM connectome is established very early in childhood and is relatively stable from age 1 to 6 years. Many high-centrality hubs are established before birth, and most are present by age 1.
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Conectoma , Sustancia Blanca , Niño , Recién Nacido , Humanos , Preescolar , Femenino , Lactante , Encéfalo , Conectoma/métodos , Cognición , InteligenciaRESUMEN
Functional magnetic resonance imaging has been used to identify complex brain networks by examining the correlation of blood-oxygen-level-dependent signals between brain regions during the resting state. Many of the brain networks identified in adults are detectable at birth, but genetic and environmental influences governing connectivity within and between these networks in early infancy have yet to be explored. We investigated genetic influences on neonatal resting-state connectivity phenotypes by generating intraclass correlations and performing mixed effects modeling to estimate narrow-sense heritability on measures of within network and between-network connectivity in a large cohort of neonate twins. We also used backwards elimination regression and mixed linear modeling to identify specific demographic and medical history variables influencing within and between network connectivity in a large cohort of typically developing twins and singletons. Of the 36 connectivity phenotypes examined, only 6 showed narrow-sense heritability estimates greater than 0.10, with none being statistically significant. Demographic and obstetric history variables contributed to between- and within-network connectivity. Our results suggest that in early infancy, genetic factors minimally influence brain connectivity. However, specific demographic and medical history variables, such as gestational age at birth and maternal psychiatric history, may influence resting-state connectivity measures.
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Mapeo Encefálico , Encéfalo , Embarazo , Femenino , Humanos , Encéfalo/diagnóstico por imagen , Fenotipo , Descanso , Imagen por Resonancia Magnética , Vías Nerviosas/diagnóstico por imagenRESUMEN
Background: A large body of research supports the deleterious effects of adverse childhood experiences (ACEs) on disease susceptibility and health for both the exposed individual and the next generation. It is likely that there is an intergenerational transmission of risk from mother to child; however, the mechanisms through which such risk is conferred remain unknown. The current study evaluated the association between maternal ACEs, neonatal brain development of the amygdala and hippocampus, and later infant negative emotionality at six months of age. Methods: The sample included 85 mother-infant dyads (44 female infants) from a longitudinal study. Maternal ACEs were assessed with the Adverse Childhood Experiences Questionnaire (ACE-Q) and neonatal hippocampal and amygdala volume was assessed using structural magnetic resonance imaging (MRI). Infant negative emotionality was assessed at 6 months using the Infant Behavior Questionnaire (IBQ). Results: Multivariate analyses demonstrated that maternal ACEs were associated with bilateral amygdala volume (F(2,78) = 3.697,p = .029). Specifically, higher maternal ACEs were associated with smaller left (ß = -0.220, t(79) = -2.661, p = .009, R2 = 0.494, and right (ß = -0.167, t(79) = -2.043, p = .044, R2 = 0.501) amygdala volume. No significant association between maternal ACEs and bilateral hippocampal volume (F(2,78) = 0.215,p = .0807) was found. Follow-up regression analyses demonstrated that both high maternal ACEs and smaller left amygdala volume were associated with higher infant negative emotionality at six months of age (ß = .232, p = .040, R2 = 0.094, and ß = -0.337, p = .022, R2 = 0.16, respectively) although statistically significant mediation of this effect was not observed (Indirect effect = 0.0187, 95% CI [-0.0016-0.0557]). Conclusions: Maternal ACEs are associated with both newborn amygdala volume and subsequent infant negative emotionality. These findings linking maternal adverse childhood experiences and infant brain development and temperament provide evidence to support the intergenerational transmission of adversity from mother to child.
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BACKGROUND: The rapid maturation of the fetal brain renders the fetus susceptible to prenatal environmental signals. Prenatal maternal sleep quality is known to have important health implications for newborns including risk for preterm birth, however, the effect on the fetal brain is poorly understood. METHOD: Participants included 94 pregnant participants and their newborns (53% female). Pregnant participants (Mage = 30; SDage= 5.29) reported on sleep quality three times throughout pregnancy. Newborn hippocampal and amygdala volumes were assessed using structural magnetic resonance imaging. Multilevel modeling was used to test the associations between trajectories of prenatal maternal sleep quality and newborn hippocampal and amygdala volume. RESULTS: The overall trajectory of prenatal maternal sleep quality was associated with hippocampal volume (left: b = 0.00003, p = 0.013; right: b = 0.00003, p = .008). Follow up analyses assessing timing of exposure indicate that poor sleep quality early in pregnancy was associated with larger hippocampal volume bilaterally (e.g., late gestation left: b = 0.002, p = 0.24; right: b = 0.004, p = .11). Prenatal sleep quality was not associated with amygdala volume. CONCLUSION: These findings highlight the implications of poor prenatal maternal sleep quality and its role in contributing to newborn hippocampal development.
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Nacimiento Prematuro , Efectos Tardíos de la Exposición Prenatal , Recién Nacido , Embarazo , Humanos , Femenino , Adulto , Masculino , Estudios Prospectivos , Efectos Tardíos de la Exposición Prenatal/patología , Nacimiento Prematuro/patología , Amígdala del Cerebelo/patología , Imagen por Resonancia Magnética/métodos , Hipocampo/patología , SueñoRESUMEN
We develop a computationally efficient alternative, TwinEQTL, to a linear mixed-effects model for twin genome-wide association study data. Instead of analyzing all twin samples together with linear mixed-effects model, TwinEQTL first splits twin samples into 2 independent groups on which multiple linear regression analysis can be validly performed separately, followed by an appropriate meta-analysis-like approach to combine the 2 nonindependent test results. Through mathematical derivations, we prove the validity of TwinEQTL algorithm and show that the correlation between 2 dependent test statistics at each single-nucleotide polymorphism is independent of its minor allele frequency. Thus, the correlation is constant across all single-nucleotide polymorphisms. Through simulations, we show empirically that TwinEQTL has well controlled type I error with negligible power loss compared with the gold-standard linear mixed-effects models. To accommodate expression quantitative loci analysis with twin subjects, we further implement TwinEQTL into an R package with much improved computational efficiency. Our approaches provide a significant leap in terms of computing speed for genome-wide association study and expression quantitative loci analysis with twin samples.