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

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 [11C]carfentanil 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 (F2,25=12.2, P<0.001), sadness increasing IL-18 (T27=2.6, P=0.01) and neutral mood reducing IL-18 (T27=−4.1, P<0.001). In depressed volunteers, changes in IL-18 were more pronounced (F2,25=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.

An integrative review of the enjoyment of sadness associated with music

“…Both oxytocin and prolactin inhibit the sympathetic and HPA activity during stress, influence cardiovascular dynamics [72], reduce stress responsiveness on neuronal and behavioural levels [73], and are known to pro- With respect to music-induced sadness, stress and adaptive reactions to 325 sadness are unlikely to lead to increases in enjoyment, since the logic and the evidence is on the contrary [70]. Only the consoling reaction has the potential of generating pleasure in this context, since the complex endocrine response involved in consoling reaction is associated with strong positive emotions (reviewed in [73]).…”

“…Such withdrawal is achieved through decreased serotonic and dopaminergic activity, and HPA 310 dysregulation [68,69]. The stress reaction to sadness is similar in purpose, and refers to changes in the immune response, particularly to the heightened inflammatory responses [70,71], which are all associated with negative mood states.…”

“…The actual experiences induced by music expressing sadness, however, may not 70 always be aligned with the expressed emotional content [21]. These deviations are explained by distinct emotion induction mechanisms and construction of meaning, explained in the third premise.…”

“…Also NK cell activity and immunoglobulins are known to be influenced by negative and positive mood manipulations [84,70]. One can assume that music would be able to generate a similar pattern of distinct reactions since it is at least equally potent manipulator of emotions and moods [85].…”

IL-18 Serum Levels and Variants of the Serotonin Transporter Gene Are Related to Awareness of Emotions in Healthy Subjects: A Preliminary Study

“…In addition, the mood state can regulate IL-18 levels in relation to central opioid neurotransmission [15], and, as previously observed in post-stroke patients, IL-18 may be a pathogenic mediator of emotional awareness disturbance, suggesting that IL-18-mediated mechanisms might underlie specific psychiatric modifications, including alexithymia [16]. Like IL-18, other proinflammatory cytokines, including IL-6, are also able to regulate the neuroendocrine system, affecting neuropsychological behavior and possibly playing a role in depression, anxiety, subjective stress, and alexithymia [5, 17-19].…”