Blood concentrations of neopterin and biopterin in subjects with depression: A systematic review and meta-analysis

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 120; p. 110633
• Main Authors: Cavaleri, Daniele, Bartoli, Francesco, Capogrosso, Chiara A., Guzzi, Pierluca, Moretti, Federico, Riboldi, Ilaria, Misiak, Błażej, Kishi, Taro, Rubin, Robert T., Fuchs, Dietmar, Crocamo, Cristina, Carrà, Giuseppe
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 10.01.2023
• Subjects: Biopterin; Biopterins; Depression; Depressive Disorder, Major; Humans; Meta-analysis; Neopterin; Pteridines; Systematic review; Depression; Systematic review; Biopterin; Neopterin; Meta-analysis
• ISSN: 0278-5846; 1878-4216; 1878-4216
• DOI: 10.1016/j.pnpbp.2022.110633

Pteridines, such as neopterin, biopterin, and tetrahydrobiopterin (BH4), 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 I2 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 (I2 = 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 (I2 = 77.9%) and quality of studies. Finally, no sufficient data were available for a meta-analysis on BH4. As a whole, our work partly supports the hypothesis of an imbalance of pteridine metabolism in depression. •We conducted a meta-analysis on blood pteridine concentrations in depression.•Blood neopterin concentrations were higher in depression.•Drug-free participants with depression showed a greater increase.•No differences in blood biopterin concentrations were estimated.•Our meta-analysis partly supports imbalances of pteridine metabolism in depression.