It still hurts: altered endogenous opioid activity in the brain during social rejection and acceptance in major depressive disorder

• Published in: Molecular psychiatry Vol. 20; no. 2; pp. 193 - 200
• Main Authors: Hsu, D T, Sanford, B J, Meyers, K K, Love, T M, Hazlett, K E, Walker, S J, Mickey, B J, Koeppe, R A, Langenecker, S A, Zubieta, J-K
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2015; Nature Publishing Group
• Subjects: 59; 59/78; 692/699/476/1414; Adult; Analgesics, Opioid - pharmacokinetics; Behavioral Sciences; Biological Psychology; Brain - diagnostic imaging; Brain - drug effects; Brain - metabolism; Carbon Radioisotopes - pharmacokinetics; Depressive Disorder, Major - pathology; Depressive Disorder, Major - psychology; Diagnosis; Drug therapy; Emission analysis; Emotions; Feedback; Female; Fentanyl - analogs & derivatives; Fentanyl - pharmacokinetics; Health aspects; Humans; Hydrocortisone - blood; Hypotheses; Image Processing, Computer-Assisted; immediate-communication; Magnetic Resonance Imaging; Major depressive disorder; Male; Medicine; Medicine & Public Health; Menstruation; Mental depression; Mood; Motivation; Narcotics; Neurosciences; Nucleus accumbens; Opioid receptors; Opioids; Pain; PET imaging; Pharmacotherapy; Positron emission tomography; Protein Binding - drug effects; Psychiatric Status Rating Scales; Psychiatry; Radiography; Ratings & rankings; Receptors, Opioid, mu - metabolism; Reinforcement; Risk factors; Self esteem; Social Distance; Social Facilitation; Social interaction; Social interactions; Tomography; Young Adult; United States; Ann Arbor Michigan; United States > US
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2014.185

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.