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Multilayer network associations between the exposome and childhood brain development.

ABSTRACT: Growing up in a high poverty neighborhood is associated with elevated risk for academic challenges and health problems. Here, we take a data-driven approach to exploring how measures of children's environments relate to the development of their brain structure and function in a community sample of children between the ages of 4 and 10 years. We constructed exposomes including measures of family socioeconomic status, children's exposure to adversity, and geocoded measures of neighborhood socioeconomic status, crime, and environmental toxins. We connected the exposome to two structural measures (cortical thickness and surface area, n = 170) and two functional measures (participation coefficient and clustering coefficient, n = 130). We found dense connections within exposome and brain layers and sparse connections between exposome and brain layers. Lower family income was associated with thinner visual cortex, consistent with the theory that accelerated development is detectable in early-developing regions. Greater neighborhood incidence of high blood lead levels was associated with greater segregation of the default mode network, consistent with evidence that toxins are deposited into the brain along the midline. Our study demonstrates the utility of multilayer network analysis to bridge environmental and neural explanatory levels to better understand the complexity of child development.

SUBMITTER: Simpson-Kent IL

PROVIDER: S-EPMC10634748 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Multilayer network associations between the exposome and childhood brain development.

Simpson-Kent Ivan L IL Gataviņš Mārtiņš M MM Tooley Ursula A UA Boroshok Austin L AL McDermott Cassidy L CL Park Anne T AT Delgado Reyes Lourdes L Bathelt Joe J Tisdall M Dylan MD Mackey Allyson P AP

bioRxiv : the preprint server for biology 20231025

Growing up in a high poverty neighborhood is associated with elevated risk for academic challenges and health problems. Here, we take a data-driven approach to exploring how measures of children's environments relate to the development of their brain structure and function in a community sample of children between the ages of 4 and 10 years. We constructed exposomes including measures of family socioeconomic status, children's exposure to adversity, and geocoded measures of neighborhood socioeco ...[more]

PMID: 37961103

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Project description:BackgroundMaternal exposure to environmental chemicals during pregnancy can influence various maternal and offspring health parameters. Modification of maternal metabolism by environmental exposure may be an important pathway for these impacts. However, there is limited evidence regarding exposure to a wide array of chemicals and the metabolome during pregnancy.ObjectivesWe investigated the relationship between the urinary exposome and metabolome during pregnancy.MethodsUrine samples were collected in the first and third trimesters from 1,024 pregnant women recruited in prenatal clinics in Jiangsu Province, China. The exposome was analyzed using the first trimester sample with ultra-high performance liquid chromatography-high resolution accurate mass spectrometry (UHPLC-HRMS) and inductively coupled plasma mass spectrometry. The metabolome was analyzed using the third trimester sample with UHPLC-HRMS. We evaluated associations between each of 106 exposures in the first trimester with 139 metabolites in the third trimester.ResultsWe identified 1,245 significant associations (p<3.39×10-6, Bonferroni correction) between chemical exposures and maternal metabolism during pregnancy. Among elements, the largest number of the significant metabolic associations were observed for magnesium, and among organic compounds, for 4-tert-octylphenol. We used exposome-metabolome associations to explore mechanisms underlying published associations between prenatal chemical exposures and offspring health outcomes. This integration of the literature with our results suggests that reported associations between 10 analytes and birth weight, gestational age, fat deposition, neurobehavioral development, immunological disorders, and hypertension may be partially mediated by metabolites associated with these exposures.DiscussionThis high-dimensional analysis of the urinary exposome and metabolome identified many associations between chemical exposures and maternal metabolism during pregnancy. Integration of these associations with the literature on health outcomes of exposure suggests that environmental modulation of the maternal metabolome may play a role in the association between prenatal exposure on pregnancy and child health outcomes. https://doi.org/10.1289/EHP9745.

Project description:ImportanceCognitive impairment occurs across the psychosis spectrum and is associated with functional outcome. However, it is unknown whether these shared manifestations of cognitive dysfunction across diagnostic categories also reflect shared neurobiological mechanisms or whether the source of impairment differs.ObjectiveTo examine whether the general cognitive deficit observed across psychotic disorders is similarly associated with functional integrity of 2 brain networks widely implicated in supporting many cognitive domains.Design, setting, and participantsA total of 201 healthy control participants and 375 patients with psychotic disorders from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium were studied from September 29, 2007, to May 31, 2011. The B-SNIP recruited healthy controls and stable outpatients from 6 sites: Baltimore, Maryland; Boston, Massachusetts; Chicago, Illinois; Dallas, Texas; Detroit, Michigan; and Hartford, Connecticut. All participants underwent cognitive testing and resting-state functional magnetic resonance imaging. Data analysis was performed from April 28, 2015, to February 21, 2017.Main outcomes and measuresThe Brief Assessment of Cognition in Schizophrenia was used to measure cognitive ability. A principal axis factor analysis on the Brief Assessment of Cognition in Schizophrenia battery yielded a single factor (54% variance explained) that served as the measure of general cognitive ability. Functional network integrity measures included global and local efficiency of the whole brain, cingulo-opercular network (CON), frontoparietal network, and auditory network and exploratory analyses of all networks from the Power atlas. Group differences in network measures, associations between cognition and network measures, and mediation models were tested.ResultsThe final sample for the current study included 201 healthy controls, 143 patients with schizophrenia, 103 patients with schizoaffective disorder, and 129 patients with psychotic bipolar disorder (mean [SD] age, 35.1 [12.0] years; 281 male [48.8%] and 295 female [51.2%]; 181 white [31.4%], 348 black [60.4%], and 47 other [8.2%]). Patients with schizophrenia (Cohen d = 0.36, P < .001) and psychotic bipolar disorder (Cohen d = 0.33, P = .002) had significantly reduced CON global efficiency compared with healthy controls. All patients with psychotic disorders had significantly reduced CON local efficiency, but the clinical groups did not differ from one another. The CON global efficiency was significantly associated with general cognitive ability across all groups (β = 0.099, P = .009) and significantly mediated the association between psychotic disorder status and general cognition (β = -0.037; 95% CI, -0.076 to -0.014). Subcortical network global efficiency was also significantly reduced in psychotic disorders (F3,587 = 4.01, P = .008) and positively predicted cognitive ability (β = 0.094, P = .009).Conclusions and relevanceThese findings provide evidence that reduced CON and subcortical network efficiency play a role in the general cognitive deficit observed across the psychosis spectrum. They provide new support for the dimensional hypothesis that a shared neurobiological mechanism underlies cognitive impairment in psychotic disorders.

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Multilayer network associations between the exposome and childhood brain development.

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Multilayer network associations between the exposome and childhood brain development.

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