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bioRxiv · 10.1101/2025.05.08.652983

Structural Covariance Network Properties Predictive of Early Adolescent Alcohol Initiation

Byrne, H.·Visontay, R.·Devine, E. K.·Wade, N. E.·Jacobus, J.·Squeglia, L. M.·Mewton, L.
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Abstract

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.

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Byrne, H., Visontay, R., Devine, E. K., Wade, N. E., Jacobus, J., Squeglia, L. M., Mewton, L.. 2025-05-11. Structural Covariance Network Properties Predictive of Early Adolescent Alcohol Initiation. https://doi.org/10.1101/2025.05.08.652983

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