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That substance abuse is associated with differences in brain structure and function, and related neurocognitive impairment is undisputed. Causally informative study designs, such as the prospective, longitudinal study leveraged by Kim-Spoon et al. (202, as well as twin and family studies, are necessary for answering vexing but critical questions about substance use and the developing brain. Investigations that seek to differentiate cause from consequence and identify the factors that initiate the cycle of addiction have the potential

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