Naltrexone ameliorates functional network abnormalities in alcohol-dependent individuals

Laurel S. Morris, Kwangyeol Baek, Roger Tait, Rebecca Elliott, Karen D. Ersche, Remy Flechais, John McGonigle, Anna Murphy, Liam J. Nestor, Csaba Orban, Filippo Passetti, Louise Paterson, Ilan Rabiner, Laurence Reed, Dana Smith, John Suckling, Eleanor Taylor, Edward T. Bullmore, Anne Lingford-Hughes, Bill Deakin & 4 others David J. Nutt, Barbara Sahakian, Trevor W. Robbins, Valerie Voon

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiate addiction, but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterized. In the current study, we examined the effects of 50-mg naltrexone compared with placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly-drug-dependent individuals compared with 36 healthy volunteers. Graph theoretic and network-based statistical analysis of resting-state functional magnetic resonance imaging (MRI) data revealed that alcohol-dependent subjects had reduced functional connectivity of a dispersed network compared with both poly-drug-dependent and healthy subjects. Higher local efficiency was observed in both patient groups, indicating clustered and segregated network topology and information processing. Naltrexone normalized heightened local efficiency of the neural network in alcohol-dependent individuals, to the same levels as healthy volunteers. Naltrexone failed to have an effect on the local efficiency in abstinent poly-substance-dependent individuals. Across groups, local efficiency was associated with substance, but no alcohol exposure implicating local efficiency as a potential premorbid risk factor in alcohol use disorders that can be ameliorated by naltrexone. These findings suggest one possible mechanism for the clinical effects of naltrexone, namely, the amelioration of disrupted network topology.
LanguageEnglish
Pages425-436
Number of pages12
JournalAddiction Biology
Volume23
Issue number1
Early online date28 Feb 2017
DOIs
Publication statusPublished - Jan 2018
Externally publishedYes

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Naltrexone
Alcohols
Healthy Volunteers
Opioid-Related Disorders
Narcotic Antagonists
Secondary Prevention
Automatic Data Processing
Pharmaceutical Preparations
Alcoholism
Substance-Related Disorders
Placebos
Magnetic Resonance Imaging

Cite this

Morris, L. S., Baek, K., Tait, R., Elliott, R., Ersche, K. D., Flechais, R., ... Voon, V. (2018). Naltrexone ameliorates functional network abnormalities in alcohol-dependent individuals. Addiction Biology, 23(1), 425-436. https://doi.org/10.1111/adb.12503
Morris, Laurel S. ; Baek, Kwangyeol ; Tait, Roger ; Elliott, Rebecca ; Ersche, Karen D. ; Flechais, Remy ; McGonigle, John ; Murphy, Anna ; Nestor, Liam J. ; Orban, Csaba ; Passetti, Filippo ; Paterson, Louise ; Rabiner, Ilan ; Reed, Laurence ; Smith, Dana ; Suckling, John ; Taylor, Eleanor ; Bullmore, Edward T. ; Lingford-Hughes, Anne ; Deakin, Bill ; Nutt, David J. ; Sahakian, Barbara ; Robbins, Trevor W. ; Voon, Valerie. / Naltrexone ameliorates functional network abnormalities in alcohol-dependent individuals. In: Addiction Biology. 2018 ; Vol. 23, No. 1. pp. 425-436.
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Morris, LS, Baek, K, Tait, R, Elliott, R, Ersche, KD, Flechais, R, McGonigle, J, Murphy, A, Nestor, LJ, Orban, C, Passetti, F, Paterson, L, Rabiner, I, Reed, L, Smith, D, Suckling, J, Taylor, E, Bullmore, ET, Lingford-Hughes, A, Deakin, B, Nutt, DJ, Sahakian, B, Robbins, TW & Voon, V 2018, 'Naltrexone ameliorates functional network abnormalities in alcohol-dependent individuals', Addiction Biology, vol. 23, no. 1, pp. 425-436. https://doi.org/10.1111/adb.12503

Naltrexone ameliorates functional network abnormalities in alcohol-dependent individuals. / Morris, Laurel S.; Baek, Kwangyeol; Tait, Roger; Elliott, Rebecca; Ersche, Karen D.; Flechais, Remy; McGonigle, John; Murphy, Anna; Nestor, Liam J.; Orban, Csaba; Passetti, Filippo; Paterson, Louise; Rabiner, Ilan; Reed, Laurence; Smith, Dana; Suckling, John; Taylor, Eleanor; Bullmore, Edward T.; Lingford-Hughes, Anne; Deakin, Bill; Nutt, David J.; Sahakian, Barbara; Robbins, Trevor W.; Voon, Valerie.

In: Addiction Biology, Vol. 23, No. 1, 01.2018, p. 425-436.

Research output: Contribution to journalArticle

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AU - Flechais, Remy

AU - McGonigle, John

AU - Murphy, Anna

AU - Nestor, Liam J.

AU - Orban, Csaba

AU - Passetti, Filippo

AU - Paterson, Louise

AU - Rabiner, Ilan

AU - Reed, Laurence

AU - Smith, Dana

AU - Suckling, John

AU - Taylor, Eleanor

AU - Bullmore, Edward T.

AU - Lingford-Hughes, Anne

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AU - Nutt, David J.

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AU - Robbins, Trevor W.

AU - Voon, Valerie

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N2 - Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiate addiction, but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterized. In the current study, we examined the effects of 50-mg naltrexone compared with placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly-drug-dependent individuals compared with 36 healthy volunteers. Graph theoretic and network-based statistical analysis of resting-state functional magnetic resonance imaging (MRI) data revealed that alcohol-dependent subjects had reduced functional connectivity of a dispersed network compared with both poly-drug-dependent and healthy subjects. Higher local efficiency was observed in both patient groups, indicating clustered and segregated network topology and information processing. Naltrexone normalized heightened local efficiency of the neural network in alcohol-dependent individuals, to the same levels as healthy volunteers. Naltrexone failed to have an effect on the local efficiency in abstinent poly-substance-dependent individuals. Across groups, local efficiency was associated with substance, but no alcohol exposure implicating local efficiency as a potential premorbid risk factor in alcohol use disorders that can be ameliorated by naltrexone. These findings suggest one possible mechanism for the clinical effects of naltrexone, namely, the amelioration of disrupted network topology.

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Morris LS, Baek K, Tait R, Elliott R, Ersche KD, Flechais R et al. Naltrexone ameliorates functional network abnormalities in alcohol-dependent individuals. Addiction Biology. 2018 Jan;23(1):425-436. https://doi.org/10.1111/adb.12503