Background Given the insula’s role in the representation of bodily states associated with hedonic (i. of treatment) and on alcohol and cannabis involvement (e.g. binge drinking alcohol abuse/dependence symptom count) at baseline and over 1-year follow-up. Insula white matter (WM) and gray matter (GM) volumes were determined using FreeSurfer. Results Enhancement motives for drinking served as a link between left insula WM volume and frequency of binge drinking at baseline and 1-year follow-up. This novel finding is consistent with the insula’s role in representing bodily states (e.g. “high” associated with binge drinking) that can motivate drinking behavior. Although right insula WM volume was positively correlated with obsession/craving for alcohol and obsession/craving was positively correlated with alcohol outcomes the indirect effect was not significant. Insula WM volume was not associated with cannabis-related variables. Insula GM volume was not associated with enhancement motives obsession/craving or alcohol involvement. Conclusions Enhancement motives for Npy alcohol use but not obsession/craving for alcohol provided an important link between left insula WM volume and frequency of binge drinking in treated adolescents. Results are consistent with the insula’s role in the processing of hedonic bodily states available to conscious awareness particularly in the form of enhancement motives for alcohol use. in the Figure) used a bootstrapping procedure (5 0 resamples) programmed as an SPSS macro (Preacher and Hayes 2004 A significant indirect effect was indicated when the 95% bias-corrected and accelerated (BCa) confidence interval around the unstandardized coefficient did not include zero (Preacher and Hayes 2004 Importantly an indirect effect can be detected in the absence of a significant direct effect (e.g. Hayes 2009 MacKinnon 2008 that is there does not need to be a significant association between independent and dependent variables. The analysis sample size meets the minimum to test for indirect effects and uses bootstrapping a preferred method for testing indirect effects with small sample size (Preacher and Hayes 2004 Analyses of indirect effects controlled for gender (cf. Thatcher et al. 2010 coded: 0=female 1 and age (due to WM maturation through adolescence; Giorgio et al. 2008 for Dinaciclib (SCH 727965) analyses of baseline variables. For 1-year outcome analyses in addition to gender and age other covariates were: presence of a current alcohol diagnosis at baseline (included as a proxy for baseline alcohol use severity coded: 0=no 1 and residence in a controlled environment in the 6-months prior to 1-year follow-up (included to account for possible limited access to alcohol coded: 0=no 1 Results Descriptive statistics and bivariate correlations Table 2 presents descriptive statistics for white and gray matter insula volumes enhancement motives and obsessive thinking/craving at baseline and alcohol and cannabis involvement at baseline and 1-year follow-up. Alcohol involvement at Dinaciclib (SCH 727965) baseline and 1-year follow-up did not differ (binge drinking frequency: t= ?.31 df=29 p=.8; alcohol abuse/dependence symptom count: t= 1.05 df=29 p=.3). Frequency of cannabis use declined over 1-year follow-up (t= 2.86 df=29 p<.01). Table 2 Descriptive statistics for insula volume enhancement motives and substance use Table 3 presents relevant correlations. Consistent with prediction left insula WM volume was positively Dinaciclib (SCH 727965) correlated (r=.55 p<.01) with alcohol enhancement motives. However left insula WM volume was not correlated with alcohol Obsession/craving although right insula WM volume was (r=.36 p<.05). Left insula WM volume also was correlated with current alcohol abuse/dependence symptom count at 1-year (r=.39 p<.05) but right insula WM volume was not associated Dinaciclib (SCH 727965) with either alcohol or cannabis use. Insula GM volumes were not associated with enhancement motives or Obsession/craving for alcohol or cannabis (Table 3). Table 3 Correlations among insula volume enhancement motives and substance use Post-hoc analyses comparing those with (n=14) and without (n=16) a DSM-IV alcohol diagnosis at baseline indicated that those with an alcohol diagnosis had greater left insula WM volume compared to those with no alcohol diagnosis (.57±.04 vs .55±.03 t= ?2.12 p<.05 respectively Cohen’s d= .78: medium to large effect). Alcohol diagnosis groups did not differ on.