Abstract

Extensive evidence indicates that current and recently abstinent cocaine abusers compared to drug-naïve controls have decreased grey matter in regions such as the anterior cingulate, lateral prefrontal and insular cortex. Relatively little is known, however, about the persistence of these deficits in long-term abstinence despite the implications this has for recovery and relapse. Optimized voxel based morphometry was used to assess how local grey matter volume varies with years of drug use and length of abstinence in a cross-sectional study of cocaine users with various durations of abstinence (1–102 weeks) and years of use (0.3–24 years). Lower grey matter volume associated with years of use was observed for several regions including anterior cingulate, inferior frontal gyrus and insular cortex. Conversely, higher grey matter volumes associated with abstinence duration were seen in non-overlapping regions that included the anterior and posterior cingulate, insular, right ventral and left dorsal prefrontal cortex. Grey matter volumes in cocaine dependent individuals crossed those of drug-naïve controls after 35 weeks of abstinence, with greater than normal volumes in users with longer abstinence. The brains of abstinent users are characterized by regional grey matter volumes, which on average, exceed drug-naïve volumes in those users who have maintained abstinence for more than 35 weeks. The asymmetry between the regions showing alterations with extended years of use and prolonged abstinence suggest that recovery involves distinct neurobiological processes rather than being a reversal of disease-related changes. Specifically, the results suggest that regions critical to behavioral control may be important to prolonged, successful, abstinence.

Highlights

  • Cocaine is a major worldwide public health issue for which current treatments are unsatisfactory [1,2]

  • Understanding the differences between the brains of cocaine users and nonusers is a critical step in identifying neurobiological characteristics of addiction that may guide the development of therapeutic interventions

  • Length of abstinence was verified with the counselor at the addiction treatment centers. Exclusion criteria for both cocaine dependent (CD) and control participants were: (1) Any DSM IV, Axis 1 diagnosis excluding dependence or a past diagnosis of depression caused by CD based on the Structural Clinical Interview for the DSM-IV (SCID); (2) Head trauma resulting in loss of consciousness for longer than 30 minutes; (3) Presence of any past or current brain pathology; (4) A HIV diagnosis; (5) Contraindications for MRI; (6) Under 19 or over 55 year of age; (7) The presence of white matter (WM) hyperintensity

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Summary

Introduction

Cocaine is a major worldwide public health issue for which current treatments are unsatisfactory [1,2]. Voxel based morphometry [5] is a technique that can examine local tissue volume differences Using this method, relative to healthy drug-naıve controls, grey matter changes have been observed in multiple regions of the brain of cocaine addicts. A recent study compared grey and white matter densities in abstinent (1–16 weeks) and current CD individuals and healthy control participants and observed that the current users, compared to controls and abstainers, had lower tissue density in frontal, temporal, cerebellar and subcortical regions. The aim of the present study, using a cross-sectional design, was to examine volume differences in cortical grey matter in a sample of former cocaine addicts who varied in length of abstinence and duration of use. They may be useful biomarkers for possible investigation in future longitudinal studies of abstinence

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