Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery

G. Savulich, R. Riccelli, L. Passamonti, M. Correia, J.F.W. Deakin, R. Elliott, R.S.A. Flechais, A.R. Lingford-Hughes, J. McGonigle, A. Murphy, D.J. Nutt, C. Orban, L.M. Paterson, L.J. Reed, D.G. Smith, J. Suckling, R. Tait, E.M. Taylor, B.J. Sahakian, T.W. Robbins & 1 others K.D. Ersche

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Naltrexone is an opioid receptor antagonist used in the management of alcohol dependence. Although the endogenous opioid system has been implicated in emotion regulation, the effects of mu-opioid receptor blockade on brain systems underlying negative emotional processing are not clear in addiction. Individuals meeting criteria for alcohol dependence alone (n=18, alcohol) and in combination with cocaine and/or opioid dependence (n=21, alcohol/drugs) and healthy individuals without a history of alcohol or drug dependence (n=21) were recruited. Participants were alcohol and drug abstinent before entered into this double-blind, placebo-controlled, randomized, crossover study. Functional magnetic resonance imaging was used to investigate brain response while viewing aversive and neutral images relative to baseline on 50 mg of naltrexone and placebo. We found that naltrexone modulated task-related activation in the medial prefrontal cortex and functional connectivity between the anterior cingulate cortex and the hippocampus as a function of childhood adversity (for aversive versus neutral images) in all groups. Furthermore, there was a group-by-treatment-by-condition interaction in the right amygdala, which was mainly driven by a normalization of response for aversive relative to neutral images under naltrexone in the alcohol/drugs group. We conclude that early childhood adversity is one environmental factor that influences pharmacological response to naltrexone. Pharmacotherapy with naltrexone may also have some ameliorative effects on negative emotional processing in combined alcohol and drug dependence, possibly due to alterations in endogenous opioid transmission or the kappa-opioid receptor antagonist actions of naltrexone.
Original languageEnglish
Article numbere1054
Number of pages9
JournalTranslational Psychiatry
Volume7
DOIs
Publication statusPublished - 7 Mar 2017
Externally publishedYes

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Naltrexone
Alcoholism
Alcohols
Opioid Analgesics
Narcotic Antagonists
Substance-Related Disorders
Placebos
Pharmaceutical Preparations
kappa Opioid Receptor
mu Opioid Receptor
Gyrus Cinguli
Brain
Amygdala
Prefrontal Cortex
Cocaine
Cross-Over Studies
Hippocampus
Emotions
Magnetic Resonance Imaging
Pharmacology

Cite this

Savulich, G., Riccelli, R., Passamonti, L., Correia, M., Deakin, J. F. W., Elliott, R., ... Ersche, K. D. (2017). Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery. Translational Psychiatry, 7, [e1054]. https://doi.org/10.1038/tp.2017.34
Savulich, G. ; Riccelli, R. ; Passamonti, L. ; Correia, M. ; Deakin, J.F.W. ; Elliott, R. ; Flechais, R.S.A. ; Lingford-Hughes, A.R. ; McGonigle, J. ; Murphy, A. ; Nutt, D.J. ; Orban, C. ; Paterson, L.M. ; Reed, L.J. ; Smith, D.G. ; Suckling, J. ; Tait, R. ; Taylor, E.M. ; Sahakian, B.J. ; Robbins, T.W. ; Ersche, K.D. / Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery. In: Translational Psychiatry. 2017 ; Vol. 7.
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abstract = "Naltrexone is an opioid receptor antagonist used in the management of alcohol dependence. Although the endogenous opioid system has been implicated in emotion regulation, the effects of mu-opioid receptor blockade on brain systems underlying negative emotional processing are not clear in addiction. Individuals meeting criteria for alcohol dependence alone (n=18, alcohol) and in combination with cocaine and/or opioid dependence (n=21, alcohol/drugs) and healthy individuals without a history of alcohol or drug dependence (n=21) were recruited. Participants were alcohol and drug abstinent before entered into this double-blind, placebo-controlled, randomized, crossover study. Functional magnetic resonance imaging was used to investigate brain response while viewing aversive and neutral images relative to baseline on 50 mg of naltrexone and placebo. We found that naltrexone modulated task-related activation in the medial prefrontal cortex and functional connectivity between the anterior cingulate cortex and the hippocampus as a function of childhood adversity (for aversive versus neutral images) in all groups. Furthermore, there was a group-by-treatment-by-condition interaction in the right amygdala, which was mainly driven by a normalization of response for aversive relative to neutral images under naltrexone in the alcohol/drugs group. We conclude that early childhood adversity is one environmental factor that influences pharmacological response to naltrexone. Pharmacotherapy with naltrexone may also have some ameliorative effects on negative emotional processing in combined alcohol and drug dependence, possibly due to alterations in endogenous opioid transmission or the kappa-opioid receptor antagonist actions of naltrexone.",
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Savulich, G, Riccelli, R, Passamonti, L, Correia, M, Deakin, JFW, Elliott, R, Flechais, RSA, Lingford-Hughes, AR, McGonigle, J, Murphy, A, Nutt, DJ, Orban, C, Paterson, LM, Reed, LJ, Smith, DG, Suckling, J, Tait, R, Taylor, EM, Sahakian, BJ, Robbins, TW & Ersche, KD 2017, 'Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery', Translational Psychiatry, vol. 7, e1054. https://doi.org/10.1038/tp.2017.34

Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery. / Savulich, G.; Riccelli, R.; Passamonti, L.; Correia, M.; Deakin, J.F.W.; Elliott, R.; Flechais, R.S.A.; Lingford-Hughes, A.R.; McGonigle, J.; Murphy, A.; Nutt, D.J.; Orban, C.; Paterson, L.M.; Reed, L.J.; Smith, D.G.; Suckling, J.; Tait, R.; Taylor, E.M.; Sahakian, B.J.; Robbins, T.W.; Ersche, K.D.

In: Translational Psychiatry, Vol. 7, e1054, 07.03.2017.

Research output: Contribution to journalArticle

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T1 - Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery

AU - Savulich, G.

AU - Riccelli, R.

AU - Passamonti, L.

AU - Correia, M.

AU - Deakin, J.F.W.

AU - Elliott, R.

AU - Flechais, R.S.A.

AU - Lingford-Hughes, A.R.

AU - McGonigle, J.

AU - Murphy, A.

AU - Nutt, D.J.

AU - Orban, C.

AU - Paterson, L.M.

AU - Reed, L.J.

AU - Smith, D.G.

AU - Suckling, J.

AU - Tait, R.

AU - Taylor, E.M.

AU - Sahakian, B.J.

AU - Robbins, T.W.

AU - Ersche, K.D.

PY - 2017/3/7

Y1 - 2017/3/7

N2 - Naltrexone is an opioid receptor antagonist used in the management of alcohol dependence. Although the endogenous opioid system has been implicated in emotion regulation, the effects of mu-opioid receptor blockade on brain systems underlying negative emotional processing are not clear in addiction. Individuals meeting criteria for alcohol dependence alone (n=18, alcohol) and in combination with cocaine and/or opioid dependence (n=21, alcohol/drugs) and healthy individuals without a history of alcohol or drug dependence (n=21) were recruited. Participants were alcohol and drug abstinent before entered into this double-blind, placebo-controlled, randomized, crossover study. Functional magnetic resonance imaging was used to investigate brain response while viewing aversive and neutral images relative to baseline on 50 mg of naltrexone and placebo. We found that naltrexone modulated task-related activation in the medial prefrontal cortex and functional connectivity between the anterior cingulate cortex and the hippocampus as a function of childhood adversity (for aversive versus neutral images) in all groups. Furthermore, there was a group-by-treatment-by-condition interaction in the right amygdala, which was mainly driven by a normalization of response for aversive relative to neutral images under naltrexone in the alcohol/drugs group. We conclude that early childhood adversity is one environmental factor that influences pharmacological response to naltrexone. Pharmacotherapy with naltrexone may also have some ameliorative effects on negative emotional processing in combined alcohol and drug dependence, possibly due to alterations in endogenous opioid transmission or the kappa-opioid receptor antagonist actions of naltrexone.

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