Abstract
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We identified a reproducible cortical and subcortical brain structural covariation pattern.
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A novel pattern discovery method Joint and Individual Variance Explained (JIVE) was used.
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The cortical and subcortical structural covariation pattern is related to alcohol use initiation.
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The identified pattern is dominated by covariation among brainstem, thalamus and PFC.
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A thalamic-PFC-brainstem circuitry might be related to alcohol use initiation.
Binge drinking and age at first full drink (AFD) of alcohol prior to 21 years (AFD < 21) have been linked to neuroanatomical differences in cortical and subcortical grey matter (GM) volume, cortical thickness, and surface area. Despite the importance of understanding network-level relationships, structural covariation patterns among these morphological measures have yet to be examined in relation to binge drinking and AFD < 21. Here, we used the Joint and Individual Variance Explained (JIVE) method to characterize structural covariation patterns common across and specific to morphological measures in 293 participants (149 individuals with past-12-month binge drinking and 144 healthy controls) from the Human Connectome Project (HCP). An independent dataset (Nathan Kline Institute Rockland Sample; NKI-RS) was used to examine reproducibility/generalizability. We identified a reproducible joint component dominated by structural covariation between GM volume in the brainstem and thalamus proper, and GM volume and surface area in prefrontal cortical regions. Using linear mixed regression models, we found that participants with AFD < 21 showed lower joint component scores in both the HCP (beta = 0.059, p-value = 0.016; Cohen’s d = 0.441) and NKI-RS (beta = 0.023, p-value = 0.040, Cohen’s d = 0.216) datasets, whereas the individual thickness component associated with binge drinking (p-value = 0.02) and AFD < 21 (p-value < 0.001) in the HCP dataset was not statistically significant in the NKI-RS sample. Our findings were also generalizable to the HCP full sample (n = 880 participants). Taken together, our results show that use of JIVE analysis in high-dimensional, large-scale, psychiatry-related datasets led to discovery of a reproducible cortical and subcortical structural covariation pattern involving brain regions relevant to thalamic-PFC-brainstem neural circuitry which is related to AFD < 21 and suggests a possible extension of existing addiction neurocircuitry in humans.