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Widespread attenuating changes in brain connectivity associated with the general factor of psychopathology in 9- and 10-year olds

ABSTRACT: Convergent research identifies a general factor (“P factor”) that confers transdiagnostic risk for psychopathology. Large-scale networks are key organizational units of the human brain. However, studies of altered network connectivity patterns associated with the P factor are limited, especially in early adolescence when most mental disorders are first emerging. We studied 11,875 9- and 10-year olds from the Adolescent Brain and Cognitive Development (ABCD) study, of whom 6593 had high-quality resting-state scans. Network contingency analysis was used to identify altered interconnections associated with the P factor among 16 large-scale networks. These connectivity changes were then further characterized with quadrant analysis that quantified the directionality of P factor effects in relation to neurotypical patterns of positive versus negative connectivity across connections. The results showed that the P factor was associated with altered connectivity across 28 network cells (i.e., sets of connections linking pairs of networks); pPERMUTATION values < 0.05 FDR-corrected for multiple comparisons. Higher P factor scores were associated with hypoconnectivity within default network and hyperconnectivity between default network and multiple control networks. Among connections within these 28 significant cells, the P factor was predominantly associated with “attenuating” effects (67%; pPERMUTATION < 0.0002), i.e., reduced connectivity at neurotypically positive connections and increased connectivity at neurotypically negative connections. These results demonstrate that the general factor of psychopathology produces attenuating changes across multiple networks including default network, involved in spontaneous responses, and control networks involved in cognitive control. Moreover, they clarify mechanisms of transdiagnostic risk for psychopathology and invite further research into developmental causes of distributed attenuated connectivity.

SUBMITTER: Sripada C

PROVIDER: S-EPMC8578613 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceGeneral and specific factors of psychopathology are associated with future adverse outcomes, indicating that they might be useful for identifying individuals at greatest risk. However, it remains unknown if these associations are attributable to confounders that may influence both the psychopathology factors and later outcomes.ObjectiveTo analyze associations between psychopathology factors and clinically relevant outcomes within family pairs, adjusting for unmeasured confounds by applying co-twin control and sibling comparison designs.Design, setting, and participantsThis longitudinal cohort study with a follow-up range of 9 to 13 years included all Swedish twins born from 1959 to 1985 who participated in the Study of Twin Adults: Genes and Environment (60% response rate) and the oldest pair of all Swedish siblings born from 1959 to 1985 per the Multi-Generation Register. Twins were evaluated based on responses to a hierarchical factor model derived using multivariate statistics. Sibling pairs were evaluated based on psychiatric diagnoses per the Swedish National Patient Register. Information on outcome events and prescriptions were derived from the National Patient Register, Prescribed Drug Register, and Crime Register. Baseline assessment was in August 2005, and data were analyzed from January 2022 to February 2023.ExposuresHierarchical factor model consisting of 1 general and 4 specific factors fit to 48 psychiatric symptoms on which twin participants self-reported in 2005 and 1 general and 3 specific factors fit to 9 register-based psychiatric diagnoses assigned to sibling participants prior to 2005.Main outcomes and measuresOutcomes consisted of 7 register-based events occurring after 2005, including suicidal behavior, substance overdoses, and criminal suspicion or convictions (data available until the end of 2013), and prescription of antidepressants, antialcohol or antiopioid medication, antipsychotics, and stimulants (data available until the end of 2017).ResultsThe study included 32 328 twins (mean [SD] age, 34 [8] years; 16 076 [49.73%] male) and 1 942 106 siblings (mean [SD] age, 34 [7] years; 991 500 [51.05%] male). General psychopathology was significantly associated with all 7 outcomes within sibling pairs (mean within-pair odds ratio [OR], 2.28; 95% CI, 2.19-2.37) and dizygotic twin pairs (within-pairs OR, 1.65; 95% CI, 1.38-1.98) and with 3 outcomes within monozygotic twin pairs (mean within-pairs OR, 1.77; 95% CI, 1.35-2.36). Within sibling pairs, the specific internalizing factor was associated with antidepressant prescriptions (within-pairs OR, 1.65; 95% CI, 1.59-1.71), the specific substance misuse factor was associated prescription of antialcohol and antiopioid medication (within-pairs OR, 2.36; 95% CI, 2.20-2.54), and the specific psychotic factor was associated with antipsychotic medications (within-pairs OR, 1.61; 95% CI, 1.51-1.72). Similar results emerged within twin pairs.Conclusion and relevanceIn this cohort study, general psychopathology was significantly associated with all 7 outcomes within sibling and dizygotic twin pairs and 3 outcomes within monozygotic twin pairs at 10 years. Within twin and sibling pairs, the specific factors were primarily associated with related outcomes. Several of the associations in this cohort study could not be attributed to unmeasured confounds shared by family members, suggesting that interventions toward broad psychopathology dimensions might help reduce the risk of future clinically relevant events.

Project description:AimTo examine individual variability between perceived physical features and hormones of pubertal maturation in 9-10-year-old children as a function of sociodemographic characteristics.MethodsCross-sectional metrics of puberty were utilized from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study-a multi-site sample of 9-10 year-olds (n = 11,875)-and included perceived physical features via the pubertal development scale (PDS) and child salivary hormone levels (dehydroepiandrosterone and testosterone in all, and estradiol in females). Multi-level models examined the relationships among sociodemographic measures, physical features, and hormone levels. A group factor analysis (GFA) was implemented to extract latent variables of pubertal maturation that integrated both measures of perceived physical features and hormone levels.ResultsPDS summary scores indicated more males (70%) than females (31%) were prepubertal. Perceived physical features and hormone levels were significantly associated with child's weight status and income, such that more mature scores were observed among children that were overweight/obese or from households with low-income. Results from the GFA identified two latent factors that described individual differences in pubertal maturation among both females and males, with factor 1 driven by higher hormone levels, and factor 2 driven by perceived physical maturation. The correspondence between latent factor 1 scores (hormones) and latent factor 2 scores (perceived physical maturation) revealed synchronous and asynchronous relationships between hormones and concomitant physical features in this large young adolescent sample.ConclusionsSociodemographic measures were associated with both objective hormone and self-report physical measures of pubertal maturation in a large, diverse sample of 9-10 year-olds. The latent variables of pubertal maturation described a complex interplay between perceived physical changes and hormone levels that hallmark sexual maturation, which future studies can examine in relation to trajectories of brain maturation, risk/resilience to substance use, and other mental health outcomes.

Project description:BACKGROUND:Sugar-sweetened drinks (SSDs) are known to be cariogenic, but this association has not been well investigated in population-based repeated cross-sectional studies in recent years. Therefore, this study examined whether SSD intake is associated with higher caries experience in 10- and 15-year-olds. METHODS:The study sample included participants from the Munich study centre of two birth cohorts with data on non-cavitated caries lesions (NCCL/S), caries experience (DMF/S index), overall caries burden (DMF?+?NCCL/S) and SSD intake. In total, 915 and 996 children were included from the 10- and 15-year follow-ups, respectively. Intake (g/day) of SSDs, comprising cola, lemonade, ice-tea, sport/energy drinks, fruit squashes and nectars, was calculated from food frequency questionnaires. For analyses, the SSD intake was converted into portions (250?ml/day). Multiple logistic regression and prospective analysis models were performed to test associations between SSD intake and various definitions of caries, adjusting for sex, parental education, body mass index (BMI) categories, study cohort, plaque-affected sextants, mode of SSD consumption, energy content of SSDs, and total energy intake. RESULTS:The mean overall caries burden at 10 and 15?years of age was 1.81 (SD: 2.71) and 6.04 (SD: 8.13), respectively. The average consumption of SSDs at the 10- and 15-year follow-ups was 0.48 (SD: 0.85) and 0.83 (SD 1.40) portions/day, respectively. After adjusting for confounders, in 10-year-olds, SSD intake was significantly associated with higher caries experience based on the indices DMF/S (adjusted odds ratio: 1.29; 95% CI: 1.06-1.57), NCCL/S (1.24; 1.03-1.49) and DMF?+?NCCL/S (1.27; 1.05-1.55). At the 15-year follow-up, SSD consumption was significantly associated with increased DMF/S index (1.12; 1.01-1.25) only. Prospective model associating 10-year SSD intake with 15-year caries experience was not significant. CONCLUSIONS:SSD intake significantly increases the caries burden in 10-year-olds, with attenuated effects in 15-year-olds. To prevent caries, SSD consumption should be reduced, especially in children and adolescents.

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Widespread attenuating changes in brain connectivity associated with the general factor of psychopathology in 9- and 10-year olds

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