Department of Medicine, University of Illinois at Chicago, Chicago, IL, 60608, USA.
Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, 60612, USA.
J Psychiatr Res. 2023 Apr;160:9-18. doi: 10.1016/j.jpsychires.2023.01.044. Epub 2023 Feb 3.
Although we have effective treatments for depression and anxiety, we lack mechanistic understanding or evidence-based strategies to tailor these treatments in the context of major comorbidities such as obesity. The current feasibility study uses functional neuroimaging and biospecimen data to determine if changes in inflammatory markers, fecal short-chain fatty acids, and neural circuit-based targets can predict depression and anxiety outcomes among participants with comorbid obesity. Blood and stool samples and functional magnetic resonance imaging data were obtained at baseline and 2 months, during the parent ENGAGE-2 trial. From 30 participants with both biospecimen and fMRI data, this subsample study explored the relationship among changes in inflammatory markers and fecal short-chain fatty acids and changes in neural targets, and their joint relationship with depression and anxiety symptoms. Bivariate and partial correlation, canonical correlation, and partial least squares analyses were conducted, with adjustments for age, sex, and treatment group. Initial correlation analyses revealed three inflammatory markers (IL-1RA, IL-6, and TNF-α) and five neural targets (in Negative Affect, Positive Affect, and Default Mode Circuits) with significantly associated changes at 2 months. Partial least squares analyses then showed that changes in IL-1RA and TNF-α and changes in three neural targets (in Negative Affect and Positive Affect Circuits) at 2 months were associated with changes in depression and anxiety symptoms at 6 months. This study sheds light on the plausibility of incorporation of inflammatory and gastrointestinal biomarkers with neural targets as predictors of depression and comorbid anxiety outcomes among patients with obesity.
尽管我们有有效的抑郁症和焦虑症治疗方法，但在肥胖等主要合并症的背景下，我们缺乏对这些治疗方法的机制理解或基于证据的策略。本可行性研究使用功能神经影像学和生物样本数据来确定炎症标志物、粪便短链脂肪酸和基于神经回路的靶标变化是否可以预测肥胖合并症参与者的抑郁和焦虑结果。在 ENGAGE-2 试验的基线和 2 个月时采集血液和粪便样本以及功能磁共振成像数据。从具有生物样本和 fMRI 数据的 30 名参与者中，这项子样本研究探讨了炎症标志物和粪便短链脂肪酸变化与神经靶标变化之间的关系，以及它们与抑郁和焦虑症状的联合关系。进行了双变量和偏相关、典型相关和偏最小二乘分析，并进行了年龄、性别和治疗组的调整。初始相关分析显示，有三个炎症标志物（IL-1RA、IL-6 和 TNF-α）和五个神经靶标（在负性情绪、正性情绪和默认模式回路中）在 2 个月时有显著相关的变化。偏最小二乘分析随后表明，2 个月时 IL-1RA 和 TNF-α 的变化以及三个神经靶标（在负性情绪和正性情绪回路中）的变化与 6 个月时抑郁和焦虑症状的变化相关。这项研究揭示了将炎症和胃肠道生物标志物与神经靶标结合作为肥胖患者抑郁和合并性焦虑结果预测因子的可能性。
