Biology subjects

Devine, E. K.

Publications and source records attributed to Devine, E. K..

4 recordsLinked to original sources

bioRxiv2026

Brain Age Gap Associations with Externalising Behaviours in Youth: A Longitudinal Investigation in the Adolescent Brain Cognitive Development (ABCD) Cohort

Background. Early adolescence is a period of heightened risk for the emergence of externalising psychopathology, making it an important window for identifying neurodevelopmental risk markers. Differences between predicted brain age and chronological age - termed the brain age gap - reflect variation from age-typical patterns of brain structure. While brain age gap has been closely linked with internalising behaviours in adolescence, less is known about its relationship with externalising symptoms. This study examined whether brain age gap in late childhood/early adolescence (9-11 years) is associated with current externalising symptoms and whether it predicts externalising trajectories over seven-year follow-up. Methods. Participants were 10,516 adolescents (aged 9-11 at baseline; up to 18 years at follow-up) from the Adolescent Brain Cognitive Development (ABCD) Study who met inclusion/exclusion criteria. Brain age gap for each participant was derived from an external validated prediction model (Drobinin et al., 2022) applied to baseline measurements of cortical volume, area, and subcortical volume. Linear mixed-effects models were used to test cross-sectional and longitudinal associations between baseline brain age gap and externalising symptoms, as assessed using the Child Behaviour Checklist. Primary models were adjusted for age, sex, pubertal status, and prior to inclusion of sociodemographic covariates (ethnoracial identity and caregiver highest education). Results. A higher/more positive brain age gap was associated with greater externalising symptoms at baseline (B[SE]=0.067[0.033], p=.042), but this association was removed following sociodemographic adjustment (B[SE]=0.056[0.033], p=.088). Longitudinally, a significant brain age gap x age interaction was identified that remained evident after sociodemographic adjustment, with this relationship weakening across adolescence (B[SE]=-0.007[0.003], p=.033). Conclusions. These findings suggest that a more positive brain age gap, indicating more mature-appearing brain structure for age, in late childhood/early adolescence may be associated with externalising psychopathology, but this relationship is likely to be age- and context-dependent rather than a stable marker of persistent behavioural risk.

neuroscience↗

bioRxiv2026

The Brain Age Gap as a Predictor of Alcohol Initiation in Adolescence

BackgroundGrowing evidence suggests regional and network-level brain imaging features in late childhood are predictive of alcohol use in adolescence. However, the directionality of these effects (i.e. whether they reflect accelerated or delayed neuromaturation) are mixed. We applied a Brain Age Gap Estimation (BrainAGE) model to examine whether overall deviations from typical brain aging trajectories are predictive of (1) alcohol initiation and (2) use behaviour (experimentation versus binge drinking) in adolescence. MethodsData from the Adolescent Brain Cognitive Development study release 6.0 were used. Baseline (ages 9-11) structural imaging features (cortical volume, area, and subcortical volume) were used to estimate BrainAGE. Alcohol use was determined using self-report data from the Substance Use Interview and Timeline Follow-Back across follow-ups (waves 1-6; ages 10-17). Logistic generalized mixed effects models examined whether BrainAGE predicted group status between (1) non-initiators (n=3,639) and initiators (n=1,176), and; (2) experimentation (at least one full drink, no binge episodes; n=461) and binge drinking (at least one episode; n=438). ResultsWhen adjusting for age, sex, and pubertal status, a one-standard-deviation decrease in BrainAGE (equivalent to 1.64 years) at baseline was associated with a 9.5% increase in odds of alcohol initiation in adolescence. However, this effect did not survive adjustment for sociodemographic and prior alcohol exposure covariates. Further, BrainAGE did not discriminate between experimentation and binge drinking. ConclusionsFindings suggest BrainAGE in late childhood may reflect potential risk for alcohol initiation, but not behaviours, in adolescence. However, this association likely reflects complex interactions between brain structure and contextual factors, warranting further investigation.

neuroscience↗

bioRxiv2026

Unified Multi-Cohort Harmonisation and Normative Modelling of Neuroimaging Data via Hierarchical GAMLSS

Large-scale neuroimaging studies increasingly pool data across multiple cohorts, scanners, and acquisition protocols, introducing technical between-cohort variation that must be addressed before meaningful biological inference can be drawn. Existing harmonisation methods, particularly ComBat-based approaches, have been widely adopted for this purpose. However, they remain limited by Gaussian assumptions and by their focus on location or location-scale correction. In this study, we propose a unified hierarchical Generalised Additive Models for Location, Scale and Shape (GAMLSS) framework for multi-cohort harmonisation and normative modelling of structural neuroimaging data. The framework models cohort effects directly within all fitted distributional parameters, accommodates any parametric family for which exact inverse mapping is available, and returns harmonised values on the original measurement scale through centile-based quantile mapping. Normative deviation scores are obtained as a direct by-product of the same fitted model, enabling harmonisation and normative inference to be conducted jointly. The method was evaluated in a pooled longitudinal dataset comprising 88,126 observations across 237 structural neuroimaging features from six cohorts spanning childhood to late life: ABCD, IMAGEN, NCANDA, LIFE, UK Biobank, and MAS. Harmonisation performance was compared with ComBat, ComBat-GAM, and ComBat-LS using complementary criteria assessing data retention, residual batch effects, preservation of age-related and sex-related biological signal, and coherence of post-harmonisation lifespan trajectories. GAMLSS achieved near-complete removal of residual cohort effects, retained almost all valid observations post-harmonisation, and showed the strongest overall preservation of biological signal across validation metrics. In particular, it better preserved biologically plausible age trajectories for distributionally complex features such as white matter hypointensity volume, while simultaneously providing harmonised native-scale values and normative deviation scores within a single framework. These findings suggest that hierarchical GAMLSS offers a flexible and practical alternative to existing ComBat-based methods for large-scale neuroimaging harmonisation, particularly for features with non-Gaussian residual distributions and settings where cohort effects extend beyond differences in mean and variance.

neuroscience↗

bioRxiv2025

Structural Covariance Network Properties Predictive of Early Adolescent Alcohol Initiation

ImportanceEarly alcohol initiation (before age 15) is associated with adverse outcomes. Understanding mechanisms behind early alcohol initiation is essential for informing prevention efforts. ObjectiveTo examine whether structural covariance network properties at ages 9-10 years predict early alcohol initiation. DesignCase-control, population-based study design. SettingData from the Adolescent Brain Cognitive Development study were used. Baseline structural brain imaging data (ages 9-10) were used for generation and comparison of structural covariance networks. Data from baseline to 4-year follow-up ([≤]age 15) assessments were used to determine alcohol initiation. ParticipantsParticipants were excluded if they reported consuming a full drink of alcohol at baseline, or did not meet imaging inclusion criteria. Controls were excluded if they had not yet been assessed or were missing substance use data at 4-year follow-up. In total, 3,878 participants met study criteria, of which 182 participants initiated alcohol. Structural covariance network properties were compared between the full sample and a 1:1 propensity-matched sample based on age, sex, race, ethnicity, religion, parental education, prenatal alcohol exposure, and baseline alcohol sipping. Main Outcomes and MeasuresStructural covariance networks were estimated using regional cortical thickness and volume measurements. Measures of network segregation (modularity, clustering coefficient), integration (characteristic path length, global efficiency), and resilience (degree assortativity) were compared between groups. Early alcohol initiation was defined as consuming a full drink between baseline and 4-year follow-up ResultsAlcohol initiators (n=182, median[IQR] age, 10.3[9.9-10.8]; 101 female[55.5%]) demonstrated lower network segregation (modularity: area-under-the-curve[AUC] difference[95%CI]=-0.017[-0.017,-0.007], p=0.030; clustering coefficient: AUC[95%CI]=-0.026[-0.027,-0.012], p=0.0495) and higher network integration (characteristic path length: AUC[95%CI]=-0.106[-0.099,-0.046], p=0.020; global efficiency: AUC[95%CI]=0.011[0.005,0.011], p=0.010), compared to non-initiators (n=3,696, median[IQR] age, 9.9[9.4-10.4]; 1750 female[47.4%]) when controlling for age, sex, and mean cortical thickness. Within the matched sample, only differences in network integration were preserved (characteristic path length: AUC[95%CI]=-0.044[-0.032,0.035], p=0.010; global efficiency: AUC[95%CI]=0.003[-0.003,0.003], p=0.040). There were no differences between full or matched samples when comparing cortical volume structural covariance networks. Conclusions and RelevanceDifferences in cortical thickness structural covariance network properties at ages 9-10 predicted alcohol initiation before age 15. These findings suggest cortical thickness network topology may reflect a neuroanatomical risk marker for early alcohol initiation. Key pointsO_ST_ABSQuestionC_ST_ABSDo structural covariance network properties at age 9-10 years predict alcohol initiation prior to age 15? FindingsIn this case-control study of 3,878 participants, early adolescent alcohol initiators demonstrated differences in cortical thickness network integration and segregation compared to their non-initiating peers. MeaningAlcohol-naive adolescents who initiate alcohol use early in life demonstrate differences in structural brain network organization compared to their abstinent peers, which may reflect a neuroanatomical risk marker for early alcohol use.

neuroscience↗