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

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          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 p FWE-corr < 0.001) and CUD-L (cluster-level p FWE-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.

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          Most cited references 71

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          Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications.

          The loss of control over drug intake that occurs in addiction was initially believed to result from disruption of subcortical reward circuits. However, imaging studies in addictive behaviours have identified a key involvement of the prefrontal cortex (PFC) both through its regulation of limbic reward regions and its involvement in higher-order executive function (for example, self-control, salience attribution and awareness). This Review focuses on functional neuroimaging studies conducted in the past decade that have expanded our understanding of the involvement of the PFC in drug addiction. Disruption of the PFC in addiction underlies not only compulsive drug taking but also accounts for the disadvantageous behaviours that are associated with addiction and the erosion of free will.
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            Childhood abuse, neglect, and household dysfunction and the risk of illicit drug use: the adverse childhood experiences study.

             S. Dube,  V. Felitti,  M. Dong (2003)
            Illicit drug use is identified in Healthy People 2010 as a leading health indicator because it is associated with multiple deleterious health outcomes, such as sexually transmitted diseases, human immunodeficiency virus, viral hepatitis, and numerous social problems among adolescents and adults. Improved understanding of the influence of stressful or traumatic childhood experiences on initiation and development of drug abuse is needed. We examined the relationship between illicit drug use and 10 categories of adverse childhood experiences (ACEs) and total number of ACEs (ACE score). A retrospective cohort study of 8613 adults who attended a primary care clinic in California completed a survey about childhood abuse, neglect, and household dysfunction; illicit drug use; and other health-related issues. The main outcomes measured were self-reported use of illicit drugs, including initiation during 3 age categories: or=19 years); lifetime use for each of 4 birth cohorts dating back to 1900; drug use problems; drug addiction; and parenteral drug use. Each ACE increased the likelihood for early initiation 2- to 4-fold. The ACE score had a strong graded relationship to initiation of drug use in all 3 age categories as well as to drug use problems, drug addiction, and parenteral drug use. Compared with people with 0 ACEs, people with >or=5 ACEs were 7- to 10-fold more likely to report illicit drug use problems, addiction to illicit drugs, and parenteral drug use. The attributable risk fractions as a result of ACEs for each of these illicit drug use problems were 56%, 64%, and 67%, respectively. For each of the 4 birth cohorts examined, the ACE score also had a strong graded relationship to lifetime drug use. The ACE score had a strong graded relationship to the risk of drug initiation from early adolescence into adulthood and to problems with drug use, drug addiction, and parenteral use. The persistent graded relationship between the ACE score and initiation of drug use for 4 successive birth cohorts dating back to 1900 suggests that the effects of adverse childhood experiences transcend secular changes such as increased availability of drugs, social attitudes toward drugs, and recent massive expenditures and public information campaigns to prevent drug use. Because ACEs seem to account for one half to two third of serious problems with drug use, progress in meeting the national goals for reducing drug use will necessitate serious attention to these types of common, stressful, and disturbing childhood experiences by pediatric practice.
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              Development and validation of a brief screening version of the Childhood Trauma Questionnaire.

              The goal of this study was to develop and validate a short form of the Childhood Trauma Questionnaire (the CTQ-SF) as a screening measure for maltreatment histories in both clinical and nonreferred groups. Exploratory and confirmatory factor analyses of the 70 original CTQ items were used to create a 28-item version of the scale (25 clinical items and three validity items) and test the measurement invariance of the 25 clinical items across four samples: 378 adult substance abusing patients from New York City, 396 adolescent psychiatric inpatients, 625 substance abusing individuals from southwest Texas, and 579 individuals from a normative community sample (combined N=1978). Results showed that the CTQ-SF's items held essentially the same meaning across all four samples (i.e., measurement invariance). Moreover, the scale demonstrated good criterion-related validity in a subsample of adolescents on whom corroborative data were available. These findings support the viability of the CTQ-SF across diverse clinical and nonreferred populations.

                Author and article information

                Front Hum Neurosci
                Front Hum Neurosci
                Front. Hum. Neurosci.
                Frontiers in Human Neuroscience
                Frontiers Media S.A.
                15 February 2018
                : 12
                1Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai , New York, NY, United States
                2Department of Psychiatry, Stony Brook University School of Medicine , Stony Brook, NY, United States
                3Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University , Mannheim, Germany
                Author notes

                Edited by: Dieter J. Meyerhoff, University of California, San Francisco, United States

                Reviewed by: Joaquim Radua, Fidmag Sisters Hospitallers, Spain; Ryan Patrick Bell, Duke University Medical Center, United States; Colleen A. Hanlon, Medical University of South Carolina, United States

                *Correspondence: Nelly Alia-Klein nelly.alia-klein@ 123456mssm.edu
                Copyright © 2018 Bachi, Parvaz, Moeller, Gan, Zilverstand, Goldstein and Alia-Klein.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 4, Tables: 3, Equations: 0, References: 97, Pages: 12, Words: 9431
                Funded by: National Institute on Drug Abuse 10.13039/100000026
                Award ID: T32-DA007135-31, K01DA037452, R01DA041528, U01DA041174
                Funded by: National Institute of Mental Health 10.13039/100000025
                Award ID: R01MH090134
                Funded by: Icahn School of Medicine at Mount Sinai 10.13039/100007277
                Award ID: KL2TR001435, Department of Environmental Medicine and Public Health support
                Original Research


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