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

D T Hsu; B J Sanford; K K Meyers; T M Love; K E Hazlett; S J Walker; B J Mickey; R A Koeppe; S A Langenecker; J-K Zubieta

doi:10.1038/mp.2014.185

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

Mol Psychiatry. 2015 Feb;20(2):193-200. doi: 10.1038/mp.2014.185. Epub 2015 Jan 20.

Authors

D T Hsu¹, B J Sanford², K K Meyers³, T M Love², K E Hazlett⁴, S J Walker⁵, B J Mickey², R A Koeppe⁶, S A Langenecker⁷, J-K Zubieta⁸

Affiliations

¹ 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.
² Department of Psychiatry, The Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
³ Department of Psychology, Wayne State University, Detroit, MI, USA.
⁴ Department of Psychology, Marquette University, Milwaukee, WI, USA.
⁵ Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA.
⁶ Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
⁷ Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.
⁸ 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.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Analgesics, Opioid / pharmacokinetics
Brain / diagnostic imaging
Brain / drug effects
Brain / metabolism*
Carbon Radioisotopes / pharmacokinetics
Depressive Disorder, Major / pathology*
Depressive Disorder, Major / psychology*
Emotions
Feedback
Female
Fentanyl / analogs & derivatives
Fentanyl / pharmacokinetics
Humans
Hydrocortisone / blood
Image Processing, Computer-Assisted
Magnetic Resonance Imaging
Male
Positron-Emission Tomography
Protein Binding / drug effects
Psychiatric Status Rating Scales
Psychological Distance*
Radiography
Receptors, Opioid, mu / metabolism*
Social Facilitation*
Young Adult

Substances

Analgesics, Opioid
Carbon Radioisotopes
Receptors, Opioid, mu
carfentanil
Fentanyl
Hydrocortisone

Abstract

Publication types

MeSH terms

Substances

Grants and funding