Department of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900 Monza, Italy.
Department of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900 Monza, Italy.
Prog Neuropsychopharmacol Biol Psychiatry. 2023 Jan 10;120:110633. doi: 10.1016/j.pnpbp.2022.110633. Epub 2022 Sep 9.
Pteridines, such as neopterin, biopterin, and tetrahydrobiopterin (BH), may be involved in depression pathophysiology owing to their links to immune-inflammatory response, oxidative and nitrosative stress, and monoaminergic transmission. Nonetheless, studies assessing pteridines in depression are inconsistent. We conducted a systematic review and meta-analysis of observational studies comparing blood pteridine concentrations between subjects with depression and healthy controls (HCs).
We searched Embase, MEDLINE, and PsycInfo for articles indexed through November 2021. Study quality was appraised, evaluating age and gender comparability between groups, sample representativeness, and methods to assess depression. Random-effects meta-analyses were carried out, generating pooled standardized mean differences (SMDs). Heterogeneity across studies was estimated using the I statistic.
Twenty-four studies, involving 3075 subjects, were included. Individuals with depression showed blood neopterin concentrations higher than HCs (k = 19; SMD = 0.36; p < 0.001) with moderate heterogeneity across studies (I = 58.2%). No moderating role of age, gender, or type of blood sample was found. Sensitivity analyses showed no impact of inconsistency and quality of studies on findings. Neopterin concentrations were higher among individuals with major depressive disorder compared to HCs (SMD = 0.44; p < 0.001). This held true also when considering only drug-free subjects (SMD = 0.68; p = 0.003). No differences in biopterin concentrations were found between subjects with depression and HCs (k = 5; SMD = -0.35; p = 0.086), though this result was limited by inconsistency of findings (I = 77.9%) and quality of studies. Finally, no sufficient data were available for a meta-analysis on BH.
As a whole, our work partly supports the hypothesis of an imbalance of pteridine metabolism in depression.
蝶呤类物质，如新蝶呤、生物蝶呤和四氢生物蝶呤（BH），可能与免疫炎症反应、氧化和硝化应激以及单胺能传递有关，从而参与抑郁的病理生理学。尽管如此，评估抑郁患者蝶呤类物质的研究结果并不一致。我们对比较抑郁患者和健康对照（HC）血液蝶呤浓度的观察性研究进行了系统回顾和荟萃分析。
我们检索了 Embase、MEDLINE 和 PsycInfo 数据库，检索截至 2021 年 11 月的文献。评估了研究质量，评价了组间年龄和性别可比性、样本代表性以及评估抑郁的方法。采用随机效应荟萃分析，生成合并后的标准化均数差（SMD）。采用 I 统计量评估研究间的异质性。
共纳入 24 项研究，涉及 3075 名受试者。与 HCs 相比，抑郁患者的血液新蝶呤浓度更高（k=19；SMD=0.36；p<0.001），研究间存在中度异质性（I=58.2%）。未发现年龄、性别或血液样本类型有调节作用。敏感性分析表明，研究的不一致性和质量对结果没有影响。与 HCs 相比，重度抑郁症患者的新蝶呤浓度更高（SMD=0.44；p<0.001）。仅考虑未用药的受试者时也是如此（SMD=0.68；p=0.003）。抑郁患者和 HCs 之间的生物蝶呤浓度无差异（k=5；SMD=-0.35；p=0.086），但该结果受到研究结果不一致性（I=77.9%）和研究质量的限制。最后，没有足够的数据进行 BH 的荟萃分析。
总的来说，我们的工作部分支持了蝶呤代谢失衡与抑郁有关的假说。
