Differences in region-of-interest thickness or volume between substance-dependent participants and nondependent control subjects were assessed in each region of interest with two linear mixed-effects models, using SPSS Statistics for Windows, version 21.0 (IBM, Armonk, N.Y.). The linear mixed-effects model effectively accounts for site effects, including sites that did not collect data on nondependent control subjects (31). In model 1, substance-dependent individuals were treated as one group regardless of the substance used; individuals dependent on any of the five substances of interest were coded as “dependent” and control subjects as “nondependent.” Model 1 permitted inclusion of individuals who were dependent on more than one substance. In model 2, dependence on the five substances was coded as individual categories in a single fixed factor: individuals were coded as belonging to one and only one of six categories: “nondependent” or dependent on “alcohol,” “nicotine,” “cocaine,” “methamphetamine,” or “cannabis.” Model 2 did not permit inclusion of individuals who were dependent on more than one substance. In both models, MRI site was entered as a random factor, and sex, age, and total intracranial volume were