Dataset Information

Effect of schizophrenia common variants on infant brain volumes: cross-sectional study in 207 term neonates in developing Human Connectome Project.

ABSTRACT: Increasing lines of evidence suggest deviations from the normal early developmental trajectory could give rise to the onset of schizophrenia during adolescence and young adulthood, but few studies have investigated brain imaging changes associated with schizophrenia common variants in neonates. This study compared the brain volumes of both grey and white matter regions with schizophrenia polygenic risk scores (PRS) for 207 healthy term-born infants of European ancestry. Linear regression was used to estimate the relationship between PRS and brain volumes, with gestational age at birth, postmenstrual age at scan, ancestral principal components, sex and intracranial volumes as covariates. The schizophrenia PRS were negatively associated with the grey (β = -0.08, p = 4.2 × 10^-3) and white (β = -0.13, p = 9.4 × 10^-3) matter superior temporal gyrus volumes, white frontal lobe volume (β = -0.09, p = 1.5 × 10^-3) and the total white matter volume (β = -0.062, p = 1.66 × 10^-2). This result also remained robust when incorporating individuals of Asian ancestry. Explorative functional analysis of the schizophrenia risk variants associated with the right frontal lobe white matter volume found enrichment in neurodevelopmental pathways. This preliminary result suggests possible involvement of schizophrenia risk genes in early brain growth, and potential early life structural alterations long before the average age of onset of the disease.

SUBMITTER: Le H

PROVIDER: S-EPMC10085987 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Effect of schizophrenia common variants on infant brain volumes: cross-sectional study in 207 term neonates in developing Human Connectome Project.

Le Hai H Dimitrakopoulou Konstantina K Patel Hamel H Curtis Charles C Cordero-Grande Lucilio L Edwards A David AD Hajnal Joseph J Tournier Jacques-Donald JD Deprez Maria M Cullen Harriet H

Translational psychiatry 20230410 1

Increasing lines of evidence suggest deviations from the normal early developmental trajectory could give rise to the onset of schizophrenia during adolescence and young adulthood, but few studies have investigated brain imaging changes associated with schizophrenia common variants in neonates. This study compared the brain volumes of both grey and white matter regions with schizophrenia polygenic risk scores (PRS) for 207 healthy term-born infants of European ancestry. Linear regression was use ...[more]

PMID: 37037832

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Project description:The Developing Human Connectome Project is an Open Science project that provides the first large sample of neonatal functional MRI data with high temporal and spatial resolution. These data enable mapping of intrinsic functional connectivity between spatially distributed brain regions under normal and adverse perinatal circumstances, offering a framework to study the ontogeny of large-scale brain organization in humans. Here, we characterize in unprecedented detail the maturation and integrity of resting state networks (RSNs) at term-equivalent age in 337 infants (including 65 born preterm). First, we applied group independent component analysis to define 11 RSNs in term-born infants scanned at 43.5-44.5 weeks postmenstrual age (PMA). Adult-like topography was observed in RSNs encompassing primary sensorimotor, visual and auditory cortices. Among six higher-order, association RSNs, analogues of the adult networks for language and ocular control were identified, but a complete default mode network precursor was not. Next, we regressed the subject-level datasets from an independent cohort of infants scanned at 37-43.5 weeks PMA against the group-level RSNs to test for the effects of age, sex and preterm birth. Brain mapping in term-born infants revealed areas of positive association with age across four of six association RSNs, indicating active maturation in functional connectivity from 37 to 43.5 weeks PMA. Female infants showed increased connectivity in inferotemporal regions of the visual association network. Preterm birth was associated with striking impairments of functional connectivity across all RSNs in a dose-dependent manner; conversely, connectivity of the superior parietal lobules within the lateral motor network was abnormally increased in preterm infants, suggesting a possible mechanism for specific difficulties such as developmental coordination disorder, which occur frequently in preterm children. Overall, we found a robust, modular, symmetrical functional brain organization at normal term age. A complete set of adult-equivalent primary RSNs is already instated, alongside emerging connectivity in immature association RSNs, consistent with a primary-to-higher order ontogenetic sequence of brain development. The early developmental disruption imposed by preterm birth is associated with extensive alterations in functional connectivity.

Dataset Information

Effect of schizophrenia common variants on infant brain volumes: cross-sectional study in 207 term neonates in developing Human Connectome Project.

Publications

Effect of schizophrenia common variants on infant brain volumes: cross-sectional study in 207 term neonates in developing Human Connectome Project.

Similar Datasets

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