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

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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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Correspondence to D T Hsu.

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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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Hsu, D., Sanford, B., Meyers, K. et al. It still hurts: altered endogenous opioid activity in the brain during social rejection and acceptance in major depressive disorder. Mol Psychiatry 20, 193–200 (2015). https://doi.org/10.1038/mp.2014.185

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