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Cumulative Risk on Oxytocin-Pathway Genes Impairs Default Mode Network Connectivity in Trauma-Exposed Youth.

ABSTRACT: Background: Although the default mode network (DMN) is a core network essential for brain functioning, little is known about its developmental trajectory, particularly on factors associated with its coherence into a functional network. In light of adult studies indicating DMN's susceptibility to stress-related conditions, we examined links between variability on oxytocin-pathway genes and DMN connectivity in youth exposed to chronic war-related trauma Methods: Following a cohort of war-exposed children from early childhood, we imaged the brains of 74 preadolescents (age 11-13 years; 39 war-exposed) during rest using magnetoencephalography (MEG). A cumulative risk index on oxytocin-pathway genes was constructed by combining single nucleotide polymorphisms on five genes previously linked with social deficits and psychopathology; OXTR rs1042778, OXTR rs2254298, OXTRrs53576, CD38 rs3796863, and AVPR1A RS3. Avoidant response to trauma reminders in early childhood and anxiety disorders in late childhood were assessed as predictors of disruptions to DMN theta connectivity. Results: Higher vulnerability on oxytocin-pathway genes predicted greater disruptions to DMN theta connectivity. Avoidant symptoms in early childhood and generalized anxiety disorder in later childhood were related to impaired DMN connectivity. In combination, stress exposure, oxytocin-pathway genes, and stress-related symptoms explained 24.6% of the variance in DMN connectivity, highlighting the significant effect of stress on the maturing brain. Conclusions: Findings are the first to link the oxytocin system and maturation of the DMN, a core system sustaining autobiographical memories, alteration of intrinsic and extrinsic attention, mentalization, and sense of self. Results suggest that oxytocin may buffer the effects of chronic early stress on the DMN, particularly theta rhythms that typify the developing brain.

SUBMITTER: Zeev-Wolf M

PROVIDER: S-EPMC7256187 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Cumulative Risk on Oxytocin-Pathway Genes Impairs Default Mode Network Connectivity in Trauma-Exposed Youth.

Zeev-Wolf Maor M Levy Jonathan J Ebstein Richard P RP Feldman Ruth R

Frontiers in endocrinology 20200522

<b>Background:</b> Although the default mode network (DMN) is a core network essential for brain functioning, little is known about its developmental trajectory, particularly on factors associated with its coherence into a functional network. In light of adult studies indicating DMN's susceptibility to stress-related conditions, we examined links between variability on oxytocin-pathway genes and DMN connectivity in youth exposed to chronic war-related trauma <b>Methods:</b> Following a cohort of ...[more]

PMID: 32528417

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Project description:IntroductionAspects of the built environment relate to health factors and equity in living conditions, and may contribute to racial, ethnic, or economic health disparities. For example, urbanicity is linked with negative factors including exposure to gray space (e.g., impervious surfaces such as concrete, streets, or rooftops). While there is existing research on access to green space and urbanicity on some mental health and cognitive outcomes, there is limited research on the presence of gray space linked with cognitive functioning in youth. The goal of this study was to investigate the link between gray space and amygdala-default mode network (DMN) connectivity.MethodsThis study used data from the ABCD Study. Participants (n = 10,144; age M = 119.11 months, female = 47.62%) underwent resting-state fMRI acquisition at baseline. Impervious surfaces (gray space) were measured via the Child Opportunity Index (COI). To examine the relationship between presence of gray space and -amygdala-DMN (left/right) connectivity, we employed linear mixed effects models. Correlations were run between amygdala-DMN connectivity and internalizing and externalizing symptoms. Finally, post hoc sensitivity analyses were run to assess the impact of race.ResultsMore gray space, adjusting for age, sex, and neighborhood-level variables, was significantly associated with increased left amygdala-DMN connectivity (p = 0.0001). This association remained significant after sensitivity analyses for race were completed (p = 0.01). No significant correlations were observed between amygdala-DMN and internalizing or externalizing symptoms.DiscussionFindings suggest gray space was linked with increased left amygdala-DMN connectivity, circuits that have been implicated in affective processing, emotion regulation, and psychopathology. Thus gray space may be related to alterations in connectivity that may enhance risk for emotion dysregulation. Future investigation of these relationships is needed, as neuroimaging findings may represent early dysregulation not yet observed in the behavioral analyses at this age (i.e., the present study did not find significant relationships with parent-reported behavioral outcomes). These findings can help to inform future public policy on improving lived and built environments.

Dataset Information

Cumulative Risk on Oxytocin-Pathway Genes Impairs Default Mode Network Connectivity in Trauma-Exposed Youth.

Publications

Cumulative Risk on Oxytocin-Pathway Genes Impairs Default Mode Network Connectivity in Trauma-Exposed Youth.

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