Evidence of alterations of Beta-endorphin levels and Mu-opioid receptor gene expression in bipolar disorder

Andrea Escelsior, Bruno Sterlini, Samuele Tardito, Tiziana Altosole, Paola Magioncalda, Matteo Martino, Gianluca Serafini, Martino Belveri Murri, Andrea Aguglia, Andrea Amerio, Beatriz Pereira da Silva, Alice Trabucco, Daniela Fenoglio, Gilberto Filaci, Mario Amore

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5 Citations (Scopus)


Despite the well-recognized effects of endogenous opioids on mood and behavior, research on its role in bipolar disorder (BD) is still limited to small or anecdotal reports. Considering that Beta-endorphins (β-END) and Mu-opioid receptors (MOR), in particular, have a crucial activity in affective modulation, we hypothesized their alteration in BD. A cross-sectional study was conducted. We compared: (1) BD type I (BD-I) patients (n = 50) vs healthy controls (n = 27), (2) two BD-I subject subgroups: manic (MAN; n = 25) vs depressed (DEP; n = 25) subjects. Plasma levels of β-END and MOR gene expression in peripheral blood mononuclear cells were analyzed using ELISA Immunoassay qRT-PCR. We found that subjects with BD exhibited a significant upregulation of MOR gene expression and a decrease of β-END (p<0.0001 for both). MAN display higher MOR levels than DEP (p<0.001) and HC (p<0.0001). Plasma levels of β-END were lower in DEP compared to MAN (p<0.05) and HC (p<0.0001). The main limitations are the cross-sectional design and the lack of a group of euthymic subjects. Although preliminary, our results suggest a dysregulation of the endogenous opioid systems in BD. In particular, both MAN and DEP showed a reduction of β-END levels, whereas MAN was associated with MOR gene overexpression.

Original languageEnglish
Article number114787
JournalPsychiatry Research
Publication statusPublished - Oct 2022


  • Beta-endorphin
  • Bipolar affective disorder
  • Endogenous opioid system
  • Mu-opioid receptor
  • Psychiatric disorders

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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