Mac Giollabhui Naoise, Mischoulon David, Dunlop Boadie W, Kinkead Becky, Schettler Pamela J, Liu Richard T, Okereke Olivia I, Lamon-Fava Stefania, Fava Maurizio, Rapaport Mark Hyman
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.
Brain Behav Immun Health. 2023 Jul 7;32:100666. doi: 10.1016/j.bbih.2023.100666. eCollection 2023 Oct.
Cognitive impairment related to major depressive disorder (MDD) is highly prevalent, debilitating and is lacking in effective treatments; dysregulated inflammatory physiology is a putative mechanism and may represent a therapeutic target. In depressed individuals exhibiting a pro-inflammatory phenotype who were enrolled in a 12-week randomized placebo-controlled trial of 3 doses of omega-3 polyunsaturated fatty acids (ω-3-FA), we examined: (i) the relationship between dysregulated inflammatory physiology and baseline cognitive impairment; (ii) improvement in cognitive impairment following treatment; and (iii) the association between baseline inflammatory biomarkers and change in cognitive impairment for those receiving treatment. We randomized 61 unmedicated adults aged 45.50 years (75% female) with DSM-5 MDD, body mass index >25 kg/m, and C-reactive protein (CRP) ≥3.0 mg/L to three doses of ω-3-FA (1, 2, or 4 g daily) or matching placebo. Analyses focused on 45 study completers who had inflammatory biomarkers assessed [circulating CRP, interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) as well as lipopolysaccharide (LPS)-stimulated concentrations of IL-6 and TNFα in peripheral blood mononuclear cells (PBMC)] and on the highest dose ω-3-FA (4 g daily; n = 11) compared to placebo (n = 10). Impairment in motivational symptoms (e.g., alertness, energy, enthusiasm) and higher-order cognitive functions (e.g., word-finding, memory) were assessed by a validated self-report measure. Among all 45 participants at baseline, lower concentrations of IL-6 in LPS-stimulated PBMC were associated with greater impairment in higher-order cognitive functions (r = -0.35, = .02). Based on hierarchical linear modeling, individuals receiving 4 g/day of ω-3-FA reported significant improvement in motivational symptoms compared to placebo (B = -0.07, = .03); in the 4 g/day group, lower baseline concentrations of TNFα in LPS-stimulated PBMC were associated with significant improvement in motivational symptoms ( = .71, = .02) following treatment. In this exploratory clinical trial, daily supplementation with 4 g of ω-3-FA improves motivational symptoms in depressed individuals exhibiting an inflammatory phenotype.
与重度抑郁症（MDD）相关的认知障碍非常普遍，使人衰弱且缺乏有效的治疗方法；炎症生理失调是一种可能的机制，可能代表一个治疗靶点。在一项针对表现出促炎表型的抑郁症患者的12周随机安慰剂对照试验中，该试验使用了3种剂量的ω-3多不饱和脂肪酸（ω-3-FA），我们研究了：（i）炎症生理失调与基线认知障碍之间的关系；（ii）治疗后认知障碍的改善情况；以及（iii）接受治疗者的基线炎症生物标志物与认知障碍变化之间的关联。我们将61名年龄在45至50岁之间（75%为女性）、患有DSM-5重度抑郁症、体重指数>25kg/m²且C反应蛋白（CRP）≥3.0mg/L的未服药成年人随机分为三组，分别给予三种剂量的ω-3-FA（每日1g、2g或4g）或匹配的安慰剂。分析集中在45名完成研究的参与者身上，他们评估了炎症生物标志物[循环CRP、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNFα）以及外周血单核细胞（PBMC）中脂多糖（LPS）刺激后的IL-6和TNFα浓度]；并将ω-3-FA最高剂量组（每日4g；n = 11）与安慰剂组（n = 10）进行比较。通过一项经过验证的自我报告测量方法评估动机症状（如警觉性、精力、热情）和高阶认知功能（如找词、记忆）的损害情况。在所有45名参与者的基线水平上，LPS刺激的PBMC中IL-6浓度较低与高阶认知功能的更大损害相关（r = -0.35，P = 0.02）。基于分层线性模型，与安慰剂相比，接受每日4g ω-3-FA的个体报告动机症状有显著改善（B = -0.07，P = 0. 03）；在每日4g组中，LPS刺激的PBMC中TNFα的较低基线浓度与治疗后动机症状的显著改善相关（β = 0.71，P = 0.02）。在这项探索性临床试验中，每日补充4g ω-3-FA可改善表现出炎症表型的抑郁症患者的动机症状。
