TY - JOUR
T1 - Acute experimental changes in mood state regulate immune function in relation to central opioid neurotransmission
T2 - A model of human CNS-peripheral inflammatory interaction
AU - Prossin, A. R.
AU - Koch, A. E.
AU - Campbell, P. L.
AU - Barichello, T.
AU - Zalcman, S. S.
AU - Zubieta, J. K.
N1 - Funding Information:
Robert Dantzer, Melvin McInnis, Virginia Murphy-Weinberg, Tiffany Love, Heng Wang, Susan Kennedy, Jill Rothley, Edward McKenna, Andrew Weeden, Paul Kison and Shayna Huber provided assistance with a component of this work. This work was funded by K99/R00 DA 033454, Brain and Behavior Research Foundation NARSAD Young Investigators Award, and the University of Michigan Comprehensive Depression Center Rachel Upjohn Clinical Scholars Award (ARP); R01 DA 022520, R01 DA 027492 and the Phil F Jenkins Foundation (JKZ). Presented in part at the annual meeting of the American College of Neuropsychopharmacology (Hawaii, USA; ARP).
Publisher Copyright:
© 2016 Macmillan Publishers Limited All rights reserved.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
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U2 - 10.1038/mp.2015.110
DO - 10.1038/mp.2015.110
M3 - Article
C2 - 26283642
AN - SCOPUS:84955210171
SN - 1359-4184
VL - 21
SP - 243
EP - 251
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 2
ER -