Reduced Orbitofrontal Gray Matter Concentration as a Marker of Premorbid Childhood Trauma in Cocaine Use Disorder

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.

Early Life Stress and Substance Use Disorders: Underlying Neurobiology and Pathways to Adverse Outcomes

“…However, several studies investigating how ELS affects the neurobiology of stress systems in individuals with SUDs are emerging. Bachi, Parvaz, Moeller, Gan, Zilverstand, Goldstein, et al (2018) identified lower OFC gray matter volume (GMV) in individuals with cocaine use disorders and histories of ELS, compared to individuals with cocaine use disorders and no ELS history (Bachi et al, 2018). Another imaging study found that lower GMV in subfields of the hippocampus were uniquely associated with childhood maltreatment and predictive of severity of relapse (Van Dam et al, 2014).…”

Effects of Childhood Maltreatment on Social Cognition and Brain Functional Connectivity in Borderline Personality Disorder Patients

“…This same circuit has been related to morphologic and functional brain changes associated with a history of child abuse (27). For example, studies show a decrease in gray matter volume on the orbitofrontal cortex and temporal regions (28–30), as well as greater functional brain activation in amygdala (31) and basal ganglia in response to paradigms of emotional identification (32). Resting-state fMRI studies have shown both increased (33) and decreased (34) in functional connectivity in the fronto-amygdala circuit in samples of adolescents exposed to trauma.…”

The Effects of Childhood Trauma on Drug Use

“…Childhood trauma could also contribute to neurodevelopmental issues and promote impaired constraint for drug use [4]. These neurological changes can lead to a significant reduction in grey matter concentration of the orbitofrontal cortex (OFC), which is a part of the brain that functions as a mediator for cognitive and impulse control behaviors, as well as reward processing [4,19,20].…”

“…Childhood trauma could also contribute to neurodevelopmental issues and promote impaired constraint for drug use [4]. These neurological changes can lead to a significant reduction in grey matter concentration of the orbitofrontal cortex (OFC), which is a part of the brain that functions as a mediator for cognitive and impulse control behaviors, as well as reward processing [4,19,20]. The changes in the brain may contribute to the tendency for ACE victims to turn to drugs to achieve pleasant sensations, due to their inhibited impulse control and the need to abandon negative emotions.…”

“…Recent research has also demonstrated those who experienced childhood neglect also displayed anxiety or depression, which might suggest a reason for the connection between the negligence and drug use [14]. There is also research that shows that childhood maltreatment could influence one's susceptibility to drugs and the structural remodeling of the brain [4]. Various types of drugs have been used in association with childhood trauma; however, no single drug was reported to have a greater association than the others.…”