Mind-Body Interface Laboratory (MBI-Lab) & Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan; Institute of Psychiatry, King's College London, UK; College of Medicine & Brain Disease Research Center (BDRC), China Medical University Hospital, Taichung, Taiwan.
College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan.
Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jan 3;80(Pt C):227-233. doi: 10.1016/j.pnpbp.2017.06.020. Epub 2017 Jun 23.
Omega-3 polyunsaturated fatty acids (PUFAs) have been proven critical in the development and management of major depressive disorder (MDD) by a number of epidemiological, clinical and preclinical studies, but the molecular mechanisms underlying this therapeutic action are yet to be understood. Although eicosapentaenoic acid (EPA) seems to be the active component of omega-3 PUFAs' antidepressant effects, the biological research about the difference of specific genetic regulations between EPA and docosahexaenoic acid (DHA), the two main components of omega-3 PUFAs, is still lacking in human subjects.
We conducted a 12-week randomized-controlled trial comparing the effects of EPA and DHA on gene expressions of phospholipase A2 (cPLA2) and cyclooxygenase-2 (COX2), serotonin transporter (5HTT), and Tryptophan hydroxylase 2 (TPH-2) in 27 MDD patients. In addition, the erythrocyte PUFA compositions and the candidate gene expressions were also compared between these 27 MDD patients and 22 healthy controls.
EPA was associated with a significant decrease in HAM-D scores (CI: -13 to -21, p<0.001) and significant increases in erythrocyte levels of EPA (CI: +1.0% to +2.9%, p=0.001) and DHA (CI: +2.9% to +5.6%, p=0.007). DHA treatment was associated with a significant decrease in HAM-D scores (CI: -6 to -14, p<0.001) and a significant increase in DHA levels (CI: +0.2% to +2.3%, p=0.047), but not of EPA levels. The cPLA2 gene expression levels were significantly increased in patients received EPA (1.9 folds, p=0.038), but not DHA (1.08 folds, p=0.92). There was a tendency for both EPA and DHA groups to decrease COX-2 gene expressions. The gene expressions of COX-2, cPLA2, TPH-2 and 5-HTT did not differ between MDD cases and healthy controls.
EPA differentiates from DHA in clinical antidepressant efficacy and in upregulating cPLA2 gene regulations, which supports the clinical observation showing the superiority of EPA's antidepressant effects.
ClinicalTrials.gov identifier: NCT02615405.
多项流行病学、临床和临床前研究已经证实，ω-3 多不饱和脂肪酸（PUFA）在重度抑郁症（MDD）的发展和治疗中起着关键作用，但这种治疗作用的分子机制仍有待理解。尽管二十碳五烯酸（EPA）似乎是ω-3 PUFAs 抗抑郁作用的活性成分，但关于 EPA 和二十二碳六烯酸（DHA）——ω-3 PUFAs 的两种主要成分——之间特定基因调控差异的生物学研究在人体研究中仍然缺乏。
我们进行了一项为期 12 周的随机对照试验，比较了 EPA 和 DHA 对 27 名 MDD 患者的磷酸脂酶 A2（cPLA2）和环氧化酶-2（COX2）、5-羟色胺转运体（5HTT）和色氨酸羟化酶 2（TPH-2）基因表达的影响。此外，还比较了这 27 名 MDD 患者和 22 名健康对照组之间的红细胞 PUFA 组成和候选基因表达。
EPA 与 HAM-D 评分的显著下降（CI：-13 至-21，p<0.001）和红细胞 EPA（CI：+1.0%至+2.9%，p=0.001）和 DHA（CI：+2.9%至+5.6%，p=0.007）水平的显著增加有关。DHA 治疗与 HAM-D 评分的显著下降（CI：-6 至-14，p<0.001）和 DHA 水平的显著增加（CI：+0.2%至+2.3%，p=0.047）有关，但 EPA 水平没有变化。接受 EPA 治疗的患者 cPLA2 基因表达水平显著升高（1.9 倍，p=0.038），而不是 DHA（1.08 倍，p=0.92）。EPA 和 DHA 组均有降低 COX-2 基因表达的趋势。COX-2、cPLA2、TPH-2 和 5-HTT 的基因表达在 MDD 病例和健康对照组之间没有差异。
EPA 在临床抗抑郁疗效和上调 cPLA2 基因调控方面与 DHA 不同，这支持了 EPA 抗抑郁作用具有优势的临床观察。
ClinicalTrials.gov 标识符：NCT02615405。
