Childhood maltreatment, altered limbic neurobiology, and substance use relapse severity via trauma-specific reductions in limbic gray matter volume.

IMPORTANCE: Substance use disorders (SUDs) are among the most common sequelae of childhood maltreatment, yet the independent contributions of SUDs and childhood maltreatment to neurobiological changes and the effect of the latter on relapse risk (a critical variable in addiction treatment) are relatively unknown.

OBJECTIVES: To identify structural neural characteristics independently associated with childhood maltreatment (CM; a common type of childhood adversity), comparing a sample with SUD with a demographically comparable control sample, and to examine the relationship between CM-related structural brain changes and subsequent relapse.

DESIGN, SETTING, AND PARTICIPANTS: Structural magnetic resonance imaging study comparing 79 treatment-engaged participants with SUD in acute remission in inpatient treatment at a community mental health center vs 98 healthy control participants at an outpatient research center at an academic medical center. Both groups included individuals with a range of CM experiences. Participants with SUD were followed up prospectively for 90 days to assess relapse and relapse severity.

INTERVENTION: Standard 12-step, recovery-based, inpatient addiction treatment for all participants with SUD.

MAIN OUTCOMES AND MEASURES: Gray matter volume (GMV), subsequent substance use relapse, days to relapse, and severity of relapse.

RESULTS: Controlling for SUD and psychiatric comorbidity, CM (dichotomously classified) was uniquely associated with lower GMV across all participants in the left hippocampus (cornu ammonis 1-3, dentate gyrus), parahippocampus (presubiculum, parasubiculum, prosubiculum, subiculum, and entorhinal cortex), and anterior fusiform gyrus (corrected P < .05; uncorrected P = .001). Among the sample with SUD, CM prospectively predicted a shorter relapse to use of any drug (P = .048), while CM-related GMV reductions predicted severity of substance use relapse (P = .04).

CONCLUSIONS AND RELEVANCE: Findings indicate that CM was related to decreased GMV in limbic regions, which in turn predicted increased risk of relapse in SUD. These results suggest that CM may significantly affect the course of SUD treatment outcomes and that SUD treatment planning may benefit from identifying and addressing CM.