Department of Psychology, Temple University, Philadelphia, PA, USA.
Mol Psychiatry. 2021 Jul;26(7):3302-3314. doi: 10.1038/s41380-020-00867-4. Epub 2020 Aug 17.
The innate immune system is dysregulated in depression; however, less is known about the longitudinal associations of depression and inflammatory biomarkers. We investigated the prospective associations of depression and inflammatory biomarkers [interleukin-6 (IL-6), Tumor Necrosis Factor-Alpha (TNF-α), and C-reactive protein (CRP)] in community samples, both unadjusted and adjusted for covariates. The review, registered with PROSPERO, searched for published and unpublished studies via MEDLINE/PsycINFO/PsycARTICLES/EMBASE/Proquest Dissertation. Standardized Fisher transformations of the correlation/beta coefficients, both unadjusted and adjusted for covariates, were extracted from studies examining the prospective associations of depression and inflammatory biomarkers. Systematic review conducted in January, 2019 included 38 studies representing 58,256 participants, with up to 27 studies included in random-effects meta-analysis. Higher CRP/IL-6 were associated with future depressive symptoms, and higher depressive symptoms were associated with higher future CRP/IL-6 in both unadjusted and adjusted analyses - this is the first meta-analysis reporting an adjusted association of IL-6 with future depression. The adjusted prospective associations of depression with CRP/CRP with depression were substantially attenuated and small in magnitude. No significant associations were observed for TNF-α. No conclusive results were observed in studies of clinical depression. Meta-regression indicated that the association of CRP and future depression was larger in older samples and in studies not controlling for possible infection. Small, prospective associations of depression and inflammatory biomarkers are observed in both directions, particularly for IL-6; however, the strength and importance of this relationship is likely obscured by the heterogeneity in depression and profound study/methodological differences. Implications for future studies are discussed.
固有免疫系统在抑郁症中失调；然而，对于抑郁症和炎症生物标志物的纵向关联知之甚少。我们研究了社区样本中抑郁症和炎症生物标志物[白细胞介素 6 (IL-6)、肿瘤坏死因子-α (TNF-α)和 C 反应蛋白 (CRP)]的前瞻性关联，包括未调整和调整协变量的关联。该综述在 PROSPERO 上注册，通过 MEDLINE/PsycINFO/PsycARTICLES/EMBASE/Proquest Dissertation 搜索已发表和未发表的研究。从研究中提取了未调整和调整协变量的抑郁症和炎症生物标志物前瞻性关联的相关性/β系数的标准化 Fisher 变换。系统评价于 2019 年 1 月进行，纳入了 38 项研究，代表了 58256 名参与者，多达 27 项研究纳入了随机效应荟萃分析。在未调整和调整分析中，较高的 CRP/IL-6 与未来的抑郁症状相关，较高的抑郁症状与未来较高的 CRP/IL-6 相关——这是首次报告 IL-6 与未来抑郁有调整关联的荟萃分析。调整后的抑郁症与 CRP/CRP 与抑郁症的前瞻性关联明显减弱，且关联程度较小。TNF-α 未观察到显著关联。在临床抑郁症的研究中未观察到明确的结果。元回归表明，在年龄较大的样本和未控制可能感染的研究中，CRP 与未来抑郁的关联更大。在两个方向上都观察到了抑郁症和炎症生物标志物的小、前瞻性关联，特别是对于 IL-6；然而，这种关系的强度和重要性可能因抑郁症的异质性和深刻的研究/方法学差异而被掩盖。讨论了对未来研究的影响。
