TY - JOUR
T1 - Association of plasma interleukin-18 levels with emotion regulation and μ-opioid neurotransmitter function in major depression and healthy volunteers
AU - Prossin, Alan R.
AU - Koch, Alisa E.
AU - Campbell, Phillip L.
AU - McInnis, Melvin G.
AU - Zalcman, Steven S.
AU - Zubieta, Jon Kar
N1 - Funding Information:
This study was supported by grants from the Rachel Upjohn Clinical Scholars Program at the University of Michigan Depression Center (ARP), the Pritzker Foundation , and the Phil F. Jenkins Foundation (JKZ). Investigator support was contributed from the following funds: the Prechter Bipolar Research Fund (ARP and MGM), the Veterans Administration Research Service , National Institutes of Health Grant ( AR48267 ), and the Frederick G.L. Huetwell and William D. Robinson Professorship (AEK). We acknowledge the contributions of Virginia Murphy-Weinberg, RN, MS; Tiffany Love, Ph.D.; Heng Wang, B.Sc.; and the Nuclear Medicine technologists (Jill M. Rothley, Certified Nuclear Medicine Technologist [CNMT]; Edward J. McKenna, CNMT; Andrew R. Weeden, CNMT; Paul Kison, CNMT; and Shayna Huber, CNMT) of the Positron Emission Tomography Center at the University of Michigan to the performance of the studies.
PY - 2011/4/15
Y1 - 2011/4/15
N2 - Background Alterations in central neurotransmission and immune function have been documented in major depression (MDD). Central and peripheral endogenous opioids are linked to immune functioning in animal models, stress-activated, and dysregulated in MDD. We examined the relationship between μ-opioid receptor (OR)-mediated neurotransmission and a proinflammatory cytokine (interleukin [IL]-18). Methods We studied 28 female subjects (14 MDDs, 14 control subjects) with positron emission tomography and [11C] carfentanil (μ-OR selective) during neutral and sadness states. With a simple regression model in SPM2 (Wellcome Trust, London, England) we identified brain regions where baseline μ-OR availability (nondisplaceable binding potential [BPND]) and sadness-induced changes in μ-OR BPND were associated with baseline IL-18. Results Baseline IL-18 was greater in MDDs than control subjects [t(25) = 2.13, p = .04]. In control subjects IL-18 was correlated with negative emotional ratings at baseline and during sadness induction. In MDDs, IL-18 was positively correlated with baseline regional μ-OR BPND and with sadness-induced μ-opioid system activation in the subgenual anterior cingulate, ventral basal ganglia, and amygdala. Conclusions This study links plasma IL-18 with sadness-induced emotional responses in healthy subjects, the diagnosis of MDD, and μ-opioid functioning, itself involved in stress adaptation, emotion regulation, and reward. This suggests that IL-18 represents a marker associated with emotion regulation/dysregulation at least in part through central opioid mechanisms.
AB - Background Alterations in central neurotransmission and immune function have been documented in major depression (MDD). Central and peripheral endogenous opioids are linked to immune functioning in animal models, stress-activated, and dysregulated in MDD. We examined the relationship between μ-opioid receptor (OR)-mediated neurotransmission and a proinflammatory cytokine (interleukin [IL]-18). Methods We studied 28 female subjects (14 MDDs, 14 control subjects) with positron emission tomography and [11C] carfentanil (μ-OR selective) during neutral and sadness states. With a simple regression model in SPM2 (Wellcome Trust, London, England) we identified brain regions where baseline μ-OR availability (nondisplaceable binding potential [BPND]) and sadness-induced changes in μ-OR BPND were associated with baseline IL-18. Results Baseline IL-18 was greater in MDDs than control subjects [t(25) = 2.13, p = .04]. In control subjects IL-18 was correlated with negative emotional ratings at baseline and during sadness induction. In MDDs, IL-18 was positively correlated with baseline regional μ-OR BPND and with sadness-induced μ-opioid system activation in the subgenual anterior cingulate, ventral basal ganglia, and amygdala. Conclusions This study links plasma IL-18 with sadness-induced emotional responses in healthy subjects, the diagnosis of MDD, and μ-opioid functioning, itself involved in stress adaptation, emotion regulation, and reward. This suggests that IL-18 represents a marker associated with emotion regulation/dysregulation at least in part through central opioid mechanisms.
KW - Cytokines
KW - depression
KW - inflammation
KW - neuroimaging
KW - opioid
KW - positron emission tomography
KW - psychoneuroimmunology
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U2 - 10.1016/j.biopsych.2010.10.014
DO - 10.1016/j.biopsych.2010.10.014
M3 - Article
C2 - 21145535
AN - SCOPUS:79953182281
SN - 0006-3223
VL - 69
SP - 808
EP - 812
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 8
ER -