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Background and Aims: Recently, we demonstrated that a distinct pattern of structural covariance networks (SCN) from magnetic resonance imaging (MRI)‐derived measurements of brain cortical thickness characterized young adults with alcohol use disorder (AUD) and predicted current and future problematic drinking in adolescents relative to controls. Here, we establish the robustness and value of SCN for identifying heavy alcohol users in three additional independent studies. Design and Setting: Cross‐sectional and longitudinal studies using data from the Pediatric Imaging, Neurocognition and Genetics (PING) study (n = 400, age range = 14–22 years), the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) (n = 272, age range = 17–22 years) and the Human Connectome Project (HCP) (n = 375, age range = 22–37 years). Cases: Cases were defined based on heavy alcohol use patterns or former alcohol use disorder (AUD) diagnoses: 50, 68 and 61 cases were identified. Controls had none or low alcohol use or absence of AUD: 350, 204 and 314 controls were selected. Measurements Graph theory metrics of segregation and integration were used to summarize SCN. Findings Mirroring our prior findings, and across the three data sets, cases had a lower clustering coefficient [area under the curve (AUC) = −0.029, P = 0.002], lower modularity (AUC = −0.14, P = 0.004), lower average shortest path length (AUC = −0.078, P = 0.017) and higher global efficiency (AUC = 0.007, P = 0.010). Local efficiency differences were marginal (AUC = −0.017, P = 0.052). That is, cases exhibited lower network segregation and higher integration, suggesting that adjacent nodes (i.e. brain regions) were less similar in thickness whereas spatially distant nodes were more similar. Conclusion: Structural covariance network (SCN) differences in the brain appear to constitute an early marker of heavy alcohol use in three new data sets and, more generally, demonstrate the utility of SCN‐derived metrics to detect brain‐related psychopathology. [ABSTRACT FROM AUTHOR]

Background and aims: Graph theoretic analysis of structural covariance networks (SCN) provides an assessment of brain organization that has not yet been applied to alcohol dependence (AD). We estimated whether SCN differences are present in adults with AD and heavy‐drinking adolescents at age 19 and age 14, prior to substantial exposure to alcohol. Design Cross‐sectional sample of adults and a cohort of adolescents. Correlation matrices for cortical thicknesses across 68 regions were summarized with graph theoretic metrics. Setting and participants: A total of 745 adults with AD and 979 non‐dependent controls from 24 sites curated by the Enhancing NeuroImaging Genetics through Meta Analysis (ENIGMA)–Addiction consortium, and 297 hazardous drinking adolescents and 594 controls at ages 19 and 14 from the IMAGEN study, all from Europe. Measurements Metrics of network segregation (modularity, clustering coefficient and local efficiency) and integration (average shortest path length and global efficiency). Findings The younger AD adults had lower network segregation and higher integration relative to non‐dependent controls. Compared with controls, the hazardous drinkers at age 19 showed lower modularity [area‐under‐the‐curve (AUC) difference = −0.0142, 95% confidence interval (CI) = −0.1333, 0.0092; P‐value = 0.017], clustering coefficient (AUC difference = −0.0164, 95% CI = −0.1456, 0.0043; P‐value = 0.008) and local efficiency (AUC difference = −0.0141, 95% CI = −0.0097, 0.0034; P‐value = 0.010), as well as lower average shortest path length (AUC difference = −0.0405, 95% CI = −0.0392, 0.0096; P‐value = 0.021) and higher global efficiency (AUC difference = 0.0044, 95% CI = −0.0011, 0.0043; P‐value = 0.023). The same pattern was present at age 14 with lower clustering coefficient (AUC difference = −0.0131, 95% CI = −0.1304, 0.0033; P‐value = 0.024), lower average shortest path length (AUC difference = −0.0362, 95% CI = −0.0334, 0.0118; P‐value = 0.019) and higher global efficiency (AUC difference = 0.0035, 95% CI = −0.0011, 0.0038; P‐value = 0.048). Conclusions: Cross‐sectional analyses indicate that a specific structural covariance network profile is an early marker of alcohol dependence in adults. Similar effects in a cohort of heavy‐drinking adolescents, observed at age 19 and prior to substantial alcohol exposure at age 14, suggest that this pattern may be a pre‐existing risk factor for problematic drinking. [ABSTRACT FROM AUTHOR]