Exposome and Trans-syndromal Developmental Trajectories Toward Psychosis

Barzilay, Ran; Pries, Lotta-Katrin; Moore, Tyler M.; Gur, Raquel E.; Os, Jim van; Rutten, Bart P. F.; Gülöksüz, Sinan

doi:10.1016/j.bpsgos.2022.05.001

Cited by 12 publications

(12 citation statements)

References 73 publications

(93 reference statements)

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“…While associations between specific environmental exposures and development have long been studied, there is a need for an integrative approach able to leverage comprehensive environmental data to systematically capture the exposome, examine its relationship with health measures, and facilitate its integration into human development studies. 21 Specifically, there is a gap in large-scale studies of the association between the exposome and child and adolescent development. The availability of rich data spanning multiple levels of environment in youth cohorts provides an opportunity to address this gap.…”

Section: Introductionmentioning

confidence: 99%

Modeling environment through a general exposome factor in two independent adolescent cohorts

et al. 2022

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Exposures to perinatal, familial, social, and physical environmental stimuli can have substantial effects on human development. We aimed to generate a single measure that capture’s the complex network structure of the environment (i.e., exposome) using multi-level data (participant’s report, parent report and geocoded measures) of environmental exposures (primarily from the psychosocial environment) in two independent adolescent cohorts: The Adolescent Brain Cognitive Development Study (ABCD Study, N = 11,235, mean age 10.9 years, 47.7% females) and an age- and sex-matched sample from the Philadelphia Neurodevelopmental Cohort (PNC, N = 4,993). We conducted a series of data-driven iterative factor analyses and bifactor modeling in the ABCD Study, reducing dimensionality from 348 variables tapping to environment to six orthogonal exposome subfactors and a general (adverse) exposome factor. The general exposome factor was associated with overall psychopathology (B = 0.28, 95%CI 0.26-0.3) and key health-related outcomes: obesity (OR = 1.4, 95%CI 1.3-1.5) and advanced pubertal development (OR = 1.3, 95%CI 1.2-1.5). A similar approach in PNC reduced dimensionality of environment from 29 variables to four exposome subfactors and a general exposome factor. PNC analyses yielded consistent associations of the general exposome factor with psychopathology (B = 0.15, 95%CI 0.13-0.17), obesity (OR = 1.4, 95%CI 1.3-1.6) and advanced pubertal development (OR = 1.3, 95%CI 1-1.6). In both cohorts, inclusion of exposome factors greatly increased variance explained in overall psychopathology compared to models relying solely on demographics and parental education (from <4% to > 38% in ABCD; from <4% to > 18.5% in PNC). Findings suggest that a general exposome factor capturing multi-level environmental exposures can be derived and can consistently explain variance in youth’s mental and general health.

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Section: Introductionmentioning

confidence: 99%

Modeling environment through a general exposome factor in two independent adolescent cohorts

et al. 2022

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“…Factor analytic approaches have made it possible to quantify both a general exposome score as well as sub-factors capturing specific aspects of perinatal, familial, social, and physical environments ( Moore et al, 2022 ), all of which are associated with mental functioning. This approach has revealed that a child’s exposome is associated with psychopathology ( Moore et al, 2022 , Barzilay et al, 2022 , Pries et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

A general exposome factor explains individual differences in functional brain network topography and cognition in youth

Keller,

Moore,

Luo

et al. 2024

Developmental Cognitive Neuroscience

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“… 1 , 2 Exposure to multiple childhood adversities involving hostility and threat increases the risk for psychotic spectrum disorders, 1 thought to be the outcome of impact of adversities on brain development, 3 , 4 and emphasize importance of social determinants as etiology. 5 , 6 Most adverse environmental exposures are highly correlated and interactive 7 showing continuity of risks for further adversities and psychopathology along a pathway from childhood to adulthood, with worsening cycles of disadvantage and vulnerability. 1 However, it remains unclear why some exposed individuals later present with psychotic symptoms whereas others present with nonpsychotic psychopathology.…”

Section: Introductionmentioning

confidence: 99%

Childhood Adversity Determines the Syndemic Effects of Violence, Substance Misuse, and Sexual Behavior on Psychotic Spectrum Disorder Among Men

Zhang,

Coid

2023

Schizophrenia Bulletin

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Background and hypothesis Childhood adversity (CA) increases the risk for several adult psychiatric conditions. It is unclear why some exposed individuals experience psychotic symptoms and others do not. We investigated whether a syndemic explained a psychotic outcome determined by CA. Study design We used self-reported cross-sectional data from 7461 British men surveyed in different population subgroups. Latent class analysis (LCA) identified categorical psychopathological outcomes. LCs were tested by interaction analysis between syndemic factors derived from confirmatory factor analysis according to CA experiences. Pathway analysis using partial least squares path modeling. Results A 4-class model with excellent fit identified an LC characterized by both psychotic and anxiety symptoms (class 4). A syndemic model of joint effects, adducing a 3-component latent variable of substance misuse (SM), high-risk sexual behavior (SH), violence and criminality (VC) showed synergy between components and explained the psychotic outcome (class 4). We found significant interactions between factor scores on the multiplicative scale, specific only to class 4 (psychosis), including SM × SH, SH × VC, and SM × VC (OR > 1, P < .05); and on the additive scale SM × SH (relative excess risk due to interaction >0, P < .05), but only for men who experienced CA. Conclusion Multiplicative synergistic interactions between SM, SH, and VC constituted a mechanism determining a psychotic outcome, but not for anxiety disorder, mixed anxiety disorder/depression, or depressive disorder. This was specific to men who had experienced CA along direct and syndemic pathways. Population interventions should target SM and VC in adulthood but prioritize primary prevention strategies for CA.

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Exposome and Trans-syndromal Developmental Trajectories Toward Psychosis

Cited by 12 publications

References 73 publications

Modeling environment through a general exposome factor in two independent adolescent cohorts

Modeling environment through a general exposome factor in two independent adolescent cohorts

A general exposome factor explains individual differences in functional brain network topography and cognition in youth

Childhood Adversity Determines the Syndemic Effects of Violence, Substance Misuse, and Sexual Behavior on Psychotic Spectrum Disorder Among Men

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