title: Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity.
abstract: Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroin-dependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treatment. Furthermore, this study suggests that the assessment of amygdala-related connectivity during fear processing may provide a prognostic tool to assess stress levels in heroin-dependent patients and to quantify the efficacy of maintenance treatments in drug addiction.
authors.affiliation: 1 Department of Psychiatry (UPK), University of Basel, Wilhelm Klein-Strasse 27, 4012 Basel, Switzerland 2 Medical Image Analysis Center, University Hospital Basel, Schanzenstrasse 55, 4031 Basel, Switzerland 3 Department of Clinical Research (DFK), University of Basel, Basel, Switzerland andre.schmidt@unibas.ch.
authors.forename: André
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: 1 Department of Psychiatry (UPK), University of Basel, Wilhelm Klein-Strasse 27, 4012 Basel, Switzerland 3 Department of Clinical Research (DFK), University of Basel, Basel, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Walter
authors.affiliation: 1 Department of Psychiatry (UPK), University of Basel, Wilhelm Klein-Strasse 27, 4012 Basel, Switzerland 3 Department of Clinical Research (DFK), University of Basel, Basel, Switzerland.
authors.forename: Hana
authors.initials: H
authors.lastname: Gerber
authors.affiliation: 4 Department of Psychiatry, Psychotherapy and Psychosomatics, Hospital of Psychiatry, University of Zurich, 8032 Zurich, Switzerland.
authors.forename: Erich
authors.initials: E
authors.lastname: Seifritz
authors.affiliation: 5 Department of Clinical Research (DCR), University of Bern, 3010 Bern, Switzerland.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Brenneisen
authors.affiliation: 1 Department of Psychiatry (UPK), University of Basel, Wilhelm Klein-Strasse 27, 4012 Basel, Switzerland 3 Department of Clinical Research (DFK), University of Basel, Basel, Switzerland.
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Wiesbeck
authors.affiliation: 1 Department of Psychiatry (UPK), University of Basel, Wilhelm Klein-Strasse 27, 4012 Basel, Switzerland 3 Department of Clinical Research (DFK), University of Basel, Basel, Switzerland.
authors.forename: Anita
authors.initials: A
authors.lastname: Riecher-Rössler
authors.affiliation: 1 Department of Psychiatry (UPK), University of Basel, Wilhelm Klein-Strasse 27, 4012 Basel, Switzerland 3 Department of Clinical Research (DFK), University of Basel, Basel, Switzerland.
authors.forename: Undine E
authors.initials: UE
authors.lastname: Lang
authors.affiliation: 1 Department of Psychiatry (UPK), University of Basel, Wilhelm Klein-Strasse 27, 4012 Basel, Switzerland 2 Medical Image Analysis Center, University Hospital Basel, Schanzenstrasse 55, 4031 Basel, Switzerland 3 Department of Clinical Research (DFK), University of Basel, Basel, Switzerland 6 Department of Psychosis Studies, Institute of Psychiatry, King's College London, De Crespigny Park 16, SE58AF London, UK.
authors.forename: Stefan
authors.initials: S
authors.lastname: Borgwardt
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000679:Amygdala / Q000473:pathology; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D001499:Bayes Theorem; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004311:Double-Blind Method; D005239:Fear / Q000187:drug effects / Q000523:psychology; D005260:Female; D003932:Heroin / Q000627:therapeutic use*; D006556:Heroin Dependence / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D013315:Stress, Psychological / Q000097:blood / Q000209:etiology / Q000473:pathology*; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D003932:Heroin; D000324:Adrenocorticotropic Hormone
keywords: acute heroin treatment; amygdala connectivity; functional MRI; heroin maintenance; stress