Risk, reversibility and resilience of brain circuitries linked to opioid dependence: A diffusion tensor imaging study of actively opioid-using subjects and three comparison groups.

Abstract

Drug addiction is linked with micro-structural changes in the fronto-striatal white matter (WM) tracts. However, little is known regarding causality (risk factor for subsequent drug use vs. effect of chronic drug use) and reversibility of such changes. In this study, 30-direction diffusion tensor imaging (DTI) was used to examine WM integrity of selected fronto-striatal circuitries: the orbito-frontal circuit (OFC), anterior cingulate (AC), inferior frontal circuit (IFC), and genu of corpus callosum (CC-G). Fractional anisotropy (FA) as a measure of WM integrity was compared between actively opioid dependent subjects [OD, N = 30], their non-substance-dependent siblings [SG, N = 30], opioid dependent subjects currently abstinent [AG, N = 15] and non-substance-dependent controls [CG, N = 15] who were gender and handedness-matched. Trait impulsivity and executive functions were also compared. Compared to CG, OD group had significantly lower FA in the bilateral IFC and right OFC. Reduced FA in left IFC was also present in SG, when compared to CG, whereas SG had higher FA in the left anterior cingulum than OD. AG had significantly low FA in left IFC and CCG than CG. Trait impulsivity was highest in OD, followed by SG and CG. Non-planning impulsiveness score was significantly correlated with FA of left IFC. OD had impairment in executive functions compared to CG. WM changes in opioid dependence involve fronto-striatal circuits implicated in poor decisional balance and impulsivity. Changes in Left IFC appear to predate the onset of addiction, conferring vulnerability, and persist during abstinence. Behavioral and neuro-psychological assessments concur with the imaging results.