Acute experimental changes in mood state regulate immune function in relation to central opioid neurotransmission: a model of human CNS-peripheral inflammatory interaction.
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)C]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.
Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA.
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Prossin
Division of Rheumatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.|Medical Service, Veteran's Administration Ann Arbor, Ann Arbor, MI, USA.
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Koch
Division of Rheumatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
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Campbell
Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA.|Laboratório de Microbiologia Experimental, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
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Barichello
Department of Psychiatry, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA.
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Zalcman
Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI, USA.|Molecular and Behavioral Neuroscience Institute, Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI, USA.|Department of Radiology, University of Michigan Medical School, Ann Arbor, MI, USA.
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Zubieta
D000328:Adult; D000339:Affect / Q000502:physiology; D000679:Amygdala / Q000378:metabolism; D001921:Brain / Q000503:physiopathology; D003865:Major Depressive Disorder / Q000378:metabolism; D004644:Emotions; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors; D020382:Interleukin-18 / Q000378:metabolism*; D010146:Pain / Q000503:physiopathology; D010147:Pain Measurement; D049268:Positron-Emission Tomography / Q000379:methods*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
D007155:Immunologic Factors; D020382:Interleukin-18; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu