Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Department of Biostatistics, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
J Affect Disord. 2019 Mar 1;246:42-51. doi: 10.1016/j.jad.2018.12.037. Epub 2018 Dec 17.
Treatment-resistant depression (TRD) contributes substantially to the burden of mood disorders and is undoubtedly an important subpopulation in whom there are clear unmet treatment needs. Despite a paucity of research focusing specifically on TRD, recent studies indicate that inflammatory activity may be particularly elevated in these patients.
36 patients with TRD were investigated longitudinally before and after undertaking a specialist inpatient treatment program. 27 inflammatory proteins were compared between patients and a matched sample of non-depressed controls, as well as between treatment responders and non-responders. Treatment outcomes were calculated from depression severity scores before and after admission, and at a long-term follow-up 3-12 months after discharge.
TRD patients had higher levels of numerous inflammatory proteins than controls, and elevated interleukins 6 and 8, tumour necrosis factor, c-reactive protein and macrophage inflammatory protein-1 were associated with poorer treatment outcomes. A separate set of proteins (either anti-inflammatory in nature or attenuated at baseline) showed increases during treatment, regardless of clinical response. Participants with the greatest elevations in inflammation tended to be older, more cognitively impaired and more treatment-resistant at baseline.
The small sample and large number of comparisons examined in this study must be taken into account when interpreting these results.
However, this study provides empirical support for theories that more severe, chronic or treatment-resistant depressive disorders are associated with dysregulated inflammatory activity. If a predictor or predictors of response in TRD are established, improved and targeted care might be more reliably provided to this vulnerable population.
治疗抵抗性抑郁症（TRD）对情绪障碍的负担有很大贡献，无疑是一个重要的亚人群，他们有明显的未满足的治疗需求。尽管针对 TRD 的研究很少，但最近的研究表明，这些患者的炎症活性可能特别升高。
36 例 TRD 患者在接受专科住院治疗前后进行了纵向研究。将 27 种炎症蛋白与患者和非抑郁对照组进行了比较，也与治疗反应者和非反应者进行了比较。治疗结果是根据入院前后的抑郁严重程度评分以及出院后 3-12 个月的长期随访来计算的。
TRD 患者的许多炎症蛋白水平高于对照组，白细胞介素 6 和 8、肿瘤坏死因子、C 反应蛋白和巨噬细胞炎症蛋白-1 升高与治疗结果较差相关。一组单独的蛋白质（要么具有抗炎作用，要么在基线时减弱）在治疗过程中无论临床反应如何都会增加。炎症水平升高最大的参与者在基线时年龄较大，认知障碍较严重，治疗抵抗性较强。
在解释这些结果时，必须考虑到本研究中样本量小和检查的比较数量多。
然而，这项研究为更严重、慢性或治疗抵抗性抑郁障碍与失调的炎症活动相关的理论提供了经验支持。如果能够确定和预测 TRD 的反应，那么对这个脆弱人群的治疗就可以更可靠地提供。
