Acute experimental changes in mood state regulate immune function in relation to central opioid neurotransmission: A model of human CNS-peripheral inflammatory interaction

A. R. Prossin, A. E. Koch, P. L. Campbell, T. Barichello, S. S. Zalcman, J. K. Zubieta

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Although evidence shows depressed moods enhance risk for somatic diseases, molecular mechanisms underlying enhanced somatic susceptibility are ill-defined. Knowledge of these molecular mechanisms will inform development of treatment and prevention strategies across comorbid depressive and somatic illnesses. Existing evidence suggests that interleukin-18 (IL-18; an IL-1 family cytokine) is elevated in depression and implicated in pathophysiology underlying comorbid medical illnesses. We previously identified strong associations between baseline IL-18 and μ-opioid receptor availability in major depressive disorder (MDD) volunteers. Combined with the evidence in animal models, we hypothesized that experimental mood induction would change IL-18, the extent proportional to opioid neurotransmitter release. Using the Velten technique in a 11 Ccarfentanil positron emission tomography neuroimaging study, we examined the impact of experimentally induced mood (sad, neutral) on plasma IL-18 and relationships with concurrent changes in the central opioid neurotransmission in 28 volunteers (healthy, MDD). Results showed mood induction impacted IL-18 (F 2,25 =12.2, P<0.001), sadness increasing IL-18 (T 27 =2.6, P=0.01) and neutral mood reducing IL-18 (T 27 =-4.1, P<0.001). In depressed volunteers, changes in IL-18 were more pronounced (F 2,25 =3.6, P=0.03) and linearly proportional to sadness-induced μ-opioid activation (left ventral pallidum, bilateral anterior cingulate cortices, right hypothalamus and bilateral amygdala). These data demonstrate that dynamic changes of a pro-inflammatory IL-1 superfamily cytokine, IL-18, and its relationship to μ-opioid neurotransmission in response to experimentally induced sadness. Further testing is warranted to delineate the role of neuroimmune interactions involving IL-18 in enhancing susceptibility to medical illness (that is, diabetes, heart disease and persistent pain states) in depressed individuals.

Original languageEnglish (US)
Pages (from-to)243-251
Number of pages9
JournalMolecular Psychiatry
Volume21
Issue number2
DOIs
StatePublished - Feb 1 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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