Association of Plasma Interleukin-18 Levels with Emotion Regulation and μ-Opioid Neurotransmitter Function in Major Depression and Healthy Volunteers

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 [11 C] 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.