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

Molecular Psychiatry volume 20, pages 193200 (2015) | Download Citation

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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 [11C]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.

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Acknowledgements

This research was supported by National Institute of Health grants K01 MH085035 (DTH), K23 MH074459 (SAL), R01 DA022520 and R01 DA027494 (JKZ), a Brain & Behavior Research Foundation Young Investigator Award (DTH), Rachel Upjohn Clinical Scholars Award (DTH), pilot grants from the Michigan Institute for Clinical & Health Research (DTH), and the Phil F Jenkins Foundation (JKZ). We thank the Nuclear Medicine technologists for performing the PET scans, Ramin Ranjbar for performing the cortisol assays, and Dr Audrey Seasholtz for analysis support of cortisol assays (University of Michigan).

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Affiliations

  1. Department of Psychiatry, Stony Brook University, Stony Brook, NY, USA

    • D T Hsu
  2. Department of Psychiatry, The Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA

    • D T Hsu
    • , B J Sanford
    • , T M Love
    • , B J Mickey
    •  & J-K Zubieta
  3. Department of Psychology, Wayne State University, Detroit, MI, USA

    • K K Meyers
  4. Department of Psychology, Marquette University, Milwaukee, WI, USA

    • K E Hazlett
  5. Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA

    • S J Walker
  6. Department of Radiology, University of Michigan, Ann Arbor, MI, USA

    • R A Koeppe
    •  & J-K Zubieta
  7. Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA

    • S A Langenecker

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Competing interests

Dr RAK is a consultant for Avid Corp., Merck and Johnson & Johnson; Dr BJM received salary support from St. Jude Medical for research unrelated to this manuscript. The remaining authors declare no conflict of interest.

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Correspondence to D T Hsu.

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https://doi.org/10.1038/mp.2014.185

Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)