Prossin A R, Koch A E, Campbell P L, Barichello T, Zalcman S S, Zubieta J-K
Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA.
Division of Rheumatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Mol Psychiatry. 2016 Feb;21(2):243-51. doi: 10.1038/mp.2015.110. Epub 2015 Aug 18.
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.
尽管有证据表明情绪低落会增加躯体疾病的风险，但躯体易感性增强背后的分子机制仍不明确。了解这些分子机制将为共病抑郁和躯体疾病的治疗和预防策略的制定提供依据。现有证据表明，白细胞介素-18（IL-18；一种IL-1家族细胞因子）在抑郁症中升高，并与共病内科疾病的病理生理学有关。我们之前在重度抑郁症（MDD）志愿者中发现基线IL-18与μ-阿片受体可用性之间存在强关联。结合动物模型中的证据，我们假设实验性情绪诱导会改变IL-18，其程度与阿片类神经递质释放成正比。在一项[(11)C]卡芬太尼正电子发射断层扫描神经影像学研究中，我们使用韦尔滕技术，研究了实验性诱导情绪（悲伤、中性）对28名志愿者（健康者、MDD患者）血浆IL-18的影响以及与中枢阿片类神经传递同时发生变化的关系。结果显示情绪诱导会影响IL-18（F2,25 = 12.2，P < 0.001），悲伤会增加IL-18（T27 = 2.6，P = 0.01），中性情绪会降低IL-18（T27 = -4.1，P < 0.001）。在抑郁志愿者中，IL-18的变化更明显（F2,25 = 3.6，P = 0.03），并且与悲伤诱导的μ-阿片激活呈线性比例关系（左侧腹侧苍白球、双侧前扣带回皮质、右侧下丘脑和双侧杏仁核）。这些数据表明，促炎IL-1超家族细胞因子IL-18的动态变化及其与μ-阿片神经传递在实验性诱导悲伤时的关系。有必要进行进一步测试，以阐明涉及IL-18的神经免疫相互作用在增强抑郁个体对内科疾病（即糖尿病、心脏病和持续性疼痛状态）易感性中的作用。
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