Abstract
Background: Childhood trauma affects neurodevelopment and promotes vulnerability to impaired constraint, depression, and addiction. Reduced gray matter concentration (GMC) in the mesocorticolimbic regions implicated in reward processing and cognitive control may be an underlying substrate, as documented separately in addiction and for childhood trauma. The purpose of this study was to understand the contribution of childhood maltreatment to GMC effects in individuals with cocaine use disorder.Methods: Individuals with cocaine use disorder were partitioned into groups of low vs. high childhood trauma based on median split of the total score of the Childhood Trauma Questionnaire (CTQ; CUD-L, N = 23; CUD-H, N = 24) and compared with age, race, and gender matched healthy controls with low trauma (N = 29). GMC was obtained using voxel-based morphometry applied to T1-weighted MRI scans. Drug use, depression and constraint were assessed with standardized instruments.Results: Whole-brain group comparisons showed reduced GMC in the right lateral orbitofrontal cortex (OFC) in CUD-H as compared with controls (cluster-level pFWE-corr < 0.001) and CUD-L (cluster-level pFWE-corr = 0.035); there were no significant differences between CUD-L and controls. A hierarchical regression analysis across both CUD groups revealed that childhood trauma, but not demographics and drug use, and beyond constraint and depression, accounted for 37.7% of the variance in the GMC in the right lateral OFC (p < 0.001).Conclusions: Beyond other contributing factors, childhood trauma predicted GMC reductions in the OFC in individuals with cocaine use disorder. These findings underscore a link between premorbid environmental stress and morphological integrity of a brain region central for behaviors underlying drug addiction. These results further highlight the importance of accounting for childhood trauma, potentially as a factor predisposing to addiction, when examining and interpreting neural alterations in cocaine addicted individuals.
Highlights
The child maltreatment-morbidity connection makes up for a large fraction of the global burden of all disease and premature mortality (Shalev et al, 2013, 2016; Chen et al, 2016)
The purpose of this study is to examine the potential association between childhood maltreatment and gray matter concentration (GMC) effects in individuals with cocaine use disorder
Reduced GMC in the bilateral middle temporal gyri were observed in CUD-H as compared to CON
Summary
The child maltreatment-morbidity connection makes up for a large fraction of the global burden of all disease and premature mortality (Shalev et al, 2013, 2016; Chen et al, 2016). Previous reports suggest that this accelerated brain development in humans parallels that in rodents (McEwen, 2008; Callaghan and Richardson, 2011) and that it is interpreted to reflect an ontogenetic adaptation to adversity before adulthood (Anisman et al, 1998; de Kloet and Oitzl, 2003; Callaghan and Richardson, 2011) Such neurodevelopmental structural remodeling in mesocorticostriatal regions and in the OFC, may be key in development of substance use disorders since these regions mediate behaviors of cognitive and impulse control and reward processing (e.g., enhanced drug over natural reward salience concomitant with a decrease in inhibitory control), as highlighted by the Impaired Response Inhibition and Salience Attribution (iRISA) model (Goldstein and Volkow, 2002, 2011). The purpose of this study was to understand the contribution of childhood maltreatment to GMC effects in individuals with cocaine use disorder
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