Our study has limitations: the substance dependent cohort was treatment-seeking and abstinent at time of study, and it included only a few female participants. Our findings may therefore not generalize to female or treatment-naïve substance dependent individuals. The variance of the subcortical volume measures obtained with our automated segmentation method (expectation maximization segmentation) is larger than that shown in manually outlined structures of cocaine dependent individuals (Jacobsen et al., 2001), which might have made it impossible to detect small group differences. The measured tissue volumes comprise of several sub-regions that subserve specific cognitive functions. Thus, our lobar outcome measures lack functional specificity, which likely contributed to the few correlations with neurocognitive measures. Finally, we did not screen participants for DSM-IV Axis II disorders, such as antisocial personality disorders (Fein et al., 2007; Grant et al., 2004; Pridmore et al., 2005), nor did we measure potential group differences in nutrition, exercise and genetic predispositions. All these conditions may also influence brain morphometry and should ideally be considered in future studies of both treatment-naïve and treatment-seeking individuals with well-defined dependence on alcohol
