Subcortical volume or cortical thickness was significantly lower on average in substance-dependent individuals compared with nondependent control subjects across widespread parts of the brain (i.e., 22 distinct regions of interest out of a total of 82) (see Table 2; see also Table S2 in the online supplement). Some of these differences were substance specific, and others appear to constitute a shared neural substrate associated with dependence regardless of the substance used (see Table 3 and Figure 1). A majority of the identified regions of interest were smaller or thinner specifically in the brains of alcohol-dependent individuals (e.g., the left and right posterior cingulate and superior frontal cortex). A more limited set of seven regions with lower cortical thickness across substance dependence groups included the left and right insula, the left inferior parietal cortex, the right medial orbitofrontal cortex, the left and right middle temporal gyrus, and the left supramarginal gyrus. No region of interest was significantly larger or thicker in substance-dependent individuals relative to control subjects. An unexpected finding of the study was the absence of substance-specific linear effects on