Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Department of Psychiatry, Yamanashi University Graduate School of Medicine, Yamanashi, Japan.
Transl Psychiatry. 2019 Aug 27;9(1):208. doi: 10.1038/s41398-019-0536-0.
Inflammation and altered polyunsaturated fatty acid (PUFA) levels have been implicated in bipolar disorder (BD). A recent genome-wide association study identified a locus in the fatty acid desaturase (FADS) gene cluster conferring susceptibility to BD. In this study, we examined PUFA levels in patients with BD in relation to proinflammatory cytokines, FADS genotype, and dietary habits. We enrolled 83 patients with BD and 217 healthy controls who underwent plasma PUFA measurement. A subsample of 65 patients and 90 controls underwent plasma interleukin (IL)-6 and tumor necrosis factor alpha (TNFα) measurement, and three FADS single nucleotide polymorphisms (SNPs) were genotyped. Information on fish consumption was obtained by a self-reported diet history questionnaire. In comparing PUFA levels between patients and controls, significant differences were found for all 7 PUFAs tested. Specifically, n-3 eicosapentaenoic acid (EPA) level was decreased, and n-6 arachidonic acid level was increased in the patients (p < 0.0001 for both). Plasma IL-6 and TNFα levels were both significantly increased in the patients. Plasma EPA level was negatively correlated with IL-6 and TNFα levels. The FADS genotype, which was associated with increased n-6 PUFA levels, was also associated with marked elevation in TNFα levels. Less frequent fish intake was associated with low EPA and high IL-6 level. Taken together, our results provide strong evidence for altered plasma PUFA and proinflammatory cytokine levels in patients with BD. Furthermore, FADS genotype and fish consumption may contribute not only to altered PUFA levels but also to inflammation in BD.
炎症和多不饱和脂肪酸 (PUFA) 水平的改变与双相情感障碍 (BD) 有关。最近的全基因组关联研究确定了脂肪酸去饱和酶 (FADS) 基因簇中的一个位点，该位点与 BD 的易感性有关。在这项研究中，我们研究了 BD 患者的 PUFA 水平与促炎细胞因子、FADS 基因型和饮食习惯的关系。我们招募了 83 名 BD 患者和 217 名健康对照者进行血浆 PUFA 测量。一个亚组的 65 名患者和 90 名对照者进行了血浆白细胞介素 (IL)-6 和肿瘤坏死因子-α (TNFα) 测量，并对三个 FADS 单核苷酸多态性 (SNP) 进行了基因分型。通过自我报告的饮食史问卷获得了鱼类消费信息。在比较患者和对照组的 PUFA 水平时，发现所有 7 种测试的 PUFA 水平均存在显著差异。具体来说，n-3 二十碳五烯酸 (EPA) 水平降低，n-6 花生四烯酸水平升高（两者均 p<0.0001）。患者的血浆 IL-6 和 TNFα 水平均显著升高。血浆 EPA 水平与 IL-6 和 TNFα 水平呈负相关。与 n-6 PUFA 水平升高相关的 FADS 基因型也与 TNFα 水平的显著升高相关。较少食用鱼类与 EPA 水平降低和 IL-6 水平升高有关。综上所述，我们的研究结果为 BD 患者血浆 PUFA 和促炎细胞因子水平改变提供了有力证据。此外，FADS 基因型和鱼类摄入不仅可能导致 PUFA 水平改变，还可能导致 BD 中的炎症。
