Increasingly, it has been recognized that analysis at the symptom, rather than diagnostic, level will drive progress in the field of immunopsychiatry. Network analysis offers a useful tool in this pursuit with the ability to identify associations between immune markers and individual symptoms, independent of all other variables modeled. However, investigation into how methodological decisions (i.e., including vs. excluding participants with C-reactive protein (CRP) >10 mg/L, regularized vs. nonregularized networks) influence results is necessary to establish best practices for the use of network analysis in immunopsychiatry. In a sample of 3,464 adult participants from the 2015-2016 National Health and Nutrition Examination Survey dataset, this study found consistent support for associations between CRP and fatigue and changes in appetite and some support for additional CRP-criterion associations. Methodologically, results consistently demonstrated that including individuals with CRP >10 mg/L and estimating nonregularized networks provided better estimates of these associations. Thus, we recommend considering the use of nonregularized networks in immunopsychiatry and inclusion of cases with CRP values >10 mg/L when testing the association between CRP and depression criteria, unless contraindicated by the research question being tested. Additionally, results most consistently suggest that CRP is uniquely related to fatigue and changes in appetite, supporting their inclusion in an immunometabolic phenotype of depression. Finally, these associations suggest that fatigue and changes in appetite might be particularly receptive to anti-inflammatory treatments. However, future research with more nuanced measures is necessary to parse out whether appetite increases or decreases drive this association. Further, longitudinal research is an important next step to test how these relationships manifest over time.

中文翻译：

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处理极端 C 反应蛋白 (CRP) 值和正则化如何影响网络分析中的 CRP 和抑郁标准关联

人们越来越认识到，在症状而非诊断层面进行分析将推动免疫精神病学领域的进步。网络分析提供了一种有用的工具，能够识别免疫标志物和个体症状之间的关联，独立于所有其他建模变量。然而，有必要调查方法学决策（即，包括与排除 C 反应蛋白 (CRP) > 10 mg/L、规范化与非规范化网络的参与者）如何影响结果，以建立使用网络分析的最佳实践免疫精神病学。在来自 2015-2016 年国家健康和营养检查调查数据集的 3,464 名成年参与者的样本中，这项研究发现一致支持 CRP 与疲劳和食欲变化之间的关联，并且对其他 CRP 标准关联提供了一些支持。在方法论上，结果一致表明，包括 CRP >10 mg/L 的个体并估计非正则化网络可以更好地估计这些关联。因此，我们建议考虑在免疫精神病学中使用非正则化网络，并在测试 CRP 与抑郁标准之间的关联时纳入 CRP 值 >10 mg/L 的病例，除非被测试的研究问题有禁忌。此外，结果一致表明，CRP 与疲劳和食欲变化具有独特的相关性，支持它们包含在抑郁症的免疫代谢表型中。最后，这些关联表明疲劳和食欲变化可能特别容易接受抗炎治疗。然而，未来有必要进行更细致的研究，以解析食欲是增加还是减少推动了这种关联。此外，纵向研究是测试这些关系如何随着时间的推移而表现出来的重要下一步。