Department of Psychiatry, University of Occupational and Environmental Health, 807-8555 Kitakyushu, Japan.
Medical Center for Dementia, Hospital of University of Occupational and Environmental Health, 807-8555 Kitakyushu, Japan.
J Integr Neurosci. 2023 Jan 11;22(1):13. doi: 10.31083/j.jin2201013.
A close relationship exists between major depressive disorder (MDD) and diabetes mellitus. The metabolomic difference and similarity between patients with and without diabetes mellitus have not been well studied in the context of MDD. We aimed to examine these differences and common serum metabolomics patterns, pathways and biomarkers that can comprehensively reflect the pathogenetic difference and similarity between these MDD groups.
We performed a metabolomics analysis of serum samples of healthy controls (n = 6), patients with MDD and type 2 diabetes mellitus (n = 13), and patients with MDD without type 2 diabetes mellitus (n = 27). Metabolomics analysis was conducted using capillary electrophoresis Fourier transform mass spectrometry and a candidate compound was assigned to the 496 (290 cation, 206 anion) peaks. Moreover, we evaluated the sensitivity and specificity of the candidate biomarkers for distinguishing between MDD patients with or without type 2 diabetes mellitus.
Principal component analysis revealed no clear distinction among the three groups, while naive partial least squares discriminant analysis yielded three relatively good and distinct populations based on the first principal component. Energy conversion by the tricarboxylic acid cycle represented the highest percentage among the top 30 positive factors of the first principal component, and glutamate metabolism and urea cycle represented the highest percentage among the top 30 negative factors of the first principal component. Synthesis and degradation of ketone bodies had high impact in MDD with type 2 diabetes mellitus group and taurine and hypotaurine metabolism had high impact in MDD without type 2 diabetes mellitus group for the pathway.
Patterns of serum metabolites may be different among MDD with type 2 diabetes mellitus, MDD without type 2 diabetes mellitus, and healthy controls groups. Specifically, comorbid type 2 diabetes mellitus could affect metabolomics pathway and alter the distribution of serum metabolites in patients with MDD. These findings may shed light on the influence of the type 2 diabetes on the pathophysiology of MDD.
重度抑郁症（MDD）与糖尿病之间存在密切关系。在 MDD 背景下，患有和不患有糖尿病的患者之间的代谢组学差异和相似性尚未得到很好的研究。我们旨在研究这些差异以及可以全面反映这些 MDD 组之间发病机制差异和相似性的常见血清代谢组学模式、途径和生物标志物。
我们对健康对照组（n=6）、患有 MDD 和 2 型糖尿病的患者（n=13）以及患有 MDD 而无 2 型糖尿病的患者（n=27）的血清样本进行了代谢组学分析。使用毛细管电泳傅里叶变换质谱进行代谢组学分析，并将候选化合物分配给 496（290 阳离子，206 阴离子）峰。此外，我们评估了候选生物标志物用于区分 MDD 患者伴或不伴 2 型糖尿病的敏感性和特异性。
主成分分析显示三组之间没有明显区别，而朴素偏最小二乘判别分析基于第一主成分产生了三个相对较好和明显的群体。三羧酸循环的能量转换在第一主成分的前 30 个正因素中占比最高，而谷氨酸代谢和尿素循环在第一主成分的前 30 个负因素中占比最高。酮体的合成和降解在 MDD 伴 2 型糖尿病组中具有高影响，牛磺酸和次牛磺酸代谢在 MDD 不伴 2 型糖尿病组中对途径具有高影响。
MDD 伴 2 型糖尿病、MDD 不伴 2 型糖尿病和健康对照组之间的血清代谢物模式可能不同。具体而言，合并 2 型糖尿病可能会影响代谢组学途径，并改变 MDD 患者血清代谢物的分布。这些发现可能揭示了 2 型糖尿病对 MDD 病理生理学的影响。
