title: It still hurts: altered endogenous opioid activity in the brain during social rejection and acceptance in major depressive disorder.
abstract: The μ-opioid receptor (MOR) system, well known for dampening physical pain, is also hypothesized to dampen 'social pain.' We used positron emission tomography scanning with the selective MOR radioligand [(11)C]carfentanil to test the hypothesis that MOR system activation (reflecting endogenous opioid release) in response to social rejection and acceptance is altered in medication-free patients diagnosed with current major depressive disorder (MDD, n=17) compared with healthy controls (HCs, n=18). During rejection, MDD patients showed reduced endogenous opioid release in brain regions regulating stress, mood and motivation, and slower emotional recovery compared with HCs. During acceptance, only HCs showed increased social motivation, which was positively correlated with endogenous opioid release in the nucleus accumbens, a reward structure. Altered endogenous opioid activity in MDD may hinder emotional recovery from negative social interactions and decrease pleasure derived from positive interactions. Both effects may reinforce depression, trigger relapse and contribute to poor treatment outcomes.
authors.affiliation: 1] Department of Psychiatry, Stony Brook University, Stony Brook, NY, USA [2] Department of Psychiatry, The Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
authors.forename: D T
authors.initials: DT
authors.lastname: Hsu
authors.affiliation: Department of Psychiatry, The Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Sanford
authors.affiliation: Department of Psychology, Wayne State University, Detroit, MI, USA.
authors.forename: K K
authors.initials: KK
authors.lastname: Meyers
authors.affiliation: Department of Psychiatry, The Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Love
authors.affiliation: Department of Psychology, Marquette University, Milwaukee, WI, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Hazlett
authors.affiliation: Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Walker
authors.affiliation: Department of Psychiatry, The Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Mickey
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Koeppe
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Langenecker
authors.affiliation: 1] Department of Psychiatry, The Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA [2] Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: J-K
authors.initials: JK
authors.lastname: Zubieta
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003865:Major Depressive Disorder / Q000473:pathology* / Q000523:psychology*; D004644:Emotions; D005246:Feedback; D005260:Female; D005283:Fentanyl / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D011569:Psychiatric Status Rating Scales; D012929:Psychological Distance; D011859:Radiography; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D012932:Social Facilitation; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D002250:Carbon Radioisotopes; D017450:Receptors, Opioid, mu; C017114:carfentanil; D005283:Fentanyl; D006854:Hydrocortisone