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Brain networks underlying vulnerability and resilience to drug addiction.

Published version
Peer-reviewed

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Authors

Meng, Chun 
Ziauddeen, Hisham 
Stochl, Jan 
Williams, Guy B 

Abstract

Regular drug use can lead to addiction, but not everyone who takes drugs makes this transition. How exactly drugs of abuse interact with individual vulnerability is not fully understood, nor is it clear how individuals defy the risks associated with drugs or addiction vulnerability. We used resting-state functional MRI (fMRI) in 162 participants to characterize risk- and resilience-related changes in corticostriatal functional circuits in individuals exposed to stimulant drugs both with and without clinically diagnosed drug addiction, siblings of addicted individuals, and control volunteers. The likelihood of developing addiction, whether due to familial vulnerability or drug use, was associated with significant hypoconnectivity in orbitofrontal and ventromedial prefrontal cortical-striatal circuits-pathways critically implicated in goal-directed decision-making. By contrast, resilience against a diagnosis of substance use disorder was associated with hyperconnectivity in two networks involving 1) the lateral prefrontal cortex and medial caudate nucleus and 2) the supplementary motor area, superior medial frontal cortex, and putamen-brain circuits respectively implicated in top-down inhibitory control and the regulation of habits. These findings point toward a predisposing vulnerability in the causation of addiction, related to impaired goal-directed actions, as well as countervailing resilience systems implicated in behavioral regulation, and may inform novel strategies for therapeutic and preventative interventions.

Description

Keywords

cocaine, fMRI, functional connectivity, resilience, vulnerability, Adult, Brain, Case-Control Studies, Central Nervous System Stimulants, Female, Genetic Predisposition to Disease, Humans, Male, Nerve Net, Psychology, Substance-Related Disorders

Journal Title

Proc Natl Acad Sci U S A

Conference Name

Journal ISSN

0027-8424
1091-6490

Volume Title

117

Publisher

Proceedings of the National Academy of Sciences
Sponsorship
Medical Research Council (G0701497)
Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) (unknown)
Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) (unknown)
Wellcome Trust (105602/Z/14/Z)
Wellcome Trust (104631/Z/14/Z)
Medical Research Council (G1000183)
Medical Research Council (MC_G0802534)
Medical Research Council (G0001354)
This research was funded by a Medical Research Council (MRC) grant (G0701497), financially supported by the NIHR Cambridge Biomedical Research Centre, and conducted within the Behavioural and Clinical Neuroscience Institute (BCNI). CM was supported by the Wellcome Trust grant to KDE (105602/Z/14/Z) and the NIHR Cambridge Biomedical Research Centre. JS was partly supported by the NIHR CLAHRC East of England and by the Charles University PRVOUK programme P38. TWR is a recipient of a Wellcome Trust Senior Investigator Award (104631/z/14/z). TWR discloses consultancy with Cambridge Cognition, Greenfield Bioventures and Unilever; he receives royalties for CANTAB from Cambridge Cognition, research grants from Shionogi and GlaxoSmithKline and editorial honoraria from Springer Verlag and Elsevier. ETB is a National Institute for Health Research Senior Investigator.
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