Dysregulation of Serum Magnesium and Glycine N-methyltransferase in Psychiatric Disorders: A Network and Mediation Analysis of Cross-sectional Data

Abstract

Objective: Magnesium and glycine N-methyltransferase (GNMT) are physiologically interconnected cofactors implicated in neuropsychiatric disorders through effects on N-methyl-D-aspartate receptor function, one-carbon metabolism, and neuronal bioenergetics.However, their simultaneous role across multiple psychiatric diagnoses remains underexplored.Hence, this study was conducted to investigate alterations in serum magnesium and GNMT across major psychiatric disorders and evaluate their diagnostic and mechanistic relevance.Methods: In this cross-sectional study, 270 participants (schizophrenia, depression, bipolar affective disorder, somatoform disorder, and healthy controls) were evaluated.Serum magnesium and GNMT were measured using standard assays.Group differences were analyzed using Kruskal-Wallis and Bonferroni-corrected Mann-Whitney tests with ranked analysis of covariance employed for simultaneous adjustment of age, sex, and body mass index.Diagnostic performance was assessed using receiver operating characteristic analysis.Network, bivariate ellipse, and mediation analyses were conducted to examine biomarker interactions and indirect effects.Results: Magnesium deficiency was observed in schizophrenia (r = 0.33) and depression (r = 0.37) compared with controls.The schizophrenia finding remained robust after full covariate adjustment (p = 0.001) and in an age-restricted sensitivity analysis (p ＜ 0.002).The depression finding was significant in the full adjusted model (p = 0.022) but attenuated in the age-restricted subsample, warranting cautious interpretation.GNMT elevation in depression (r = 0.28) did not survive simultaneous covariate adjustment.Combined biomarkers yielded exploratory area under the curve values up to 0.85, pending external validation.Mediation analysis showed no significant indirect effects.Conclusion: Robust magnesium dysregulation in schizophrenia, and preliminary biomarker alterations in depression requiring age-balanced replication, represent candidate diagnostic markers with potential therapeutic implications.These findings support further prospective validation and investigation of magnesium-based adjunctive strategies in psychiatric care.

The authors' abstract, as published at the source. Clinical Psychopharmacology and Neuroscience, 2026 · DOI ↗