TY - JOUR
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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?eid=2-s2.0-85014863531&doi=10.1038%2ftp.2017.34&partnerID=40&md5=6ea31a96e3f618b1f9b69e486f6dc8f6
U2 - 10.1038/tp.2017.34
DO - 10.1038/tp.2017.34
M3 - Article
VL - 7
JO - Translational Psychiatry
JF - Translational Psychiatry
SN - 2158-3188
M1 - e1054
ER -
