Magnetic resonance spectroscopy studies in children and adolescents with depression: A systematic review and meta-analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational case-control studies
PubMed 40555350 · doi:10.1016/j.jad.2025.119747
What was done
The authors conducted a systematic review and meta-analysis of proton magnetic resonance spectroscopy (1H-MRS) studies comparing brain metabolite levels in adolescents with depression versus healthy controls. Searches were performed across PubMed, Cochrane Library, Scopus, Embase, and Web of Science from January 1965 to December 2023. Random-effects models pooled standardized mean differences (SMD), and heterogeneity was evaluated using Q and I² statistics alongside regional subgroup analyses.
What was found
Across 26 included studies (465 adolescent patients and 409 healthy controls): - Overall brain NAA levels were significantly reduced in depressed adolescents (SMD: -0.20, 95% CI: -0.34 to -0.05). - In the dorsolateral prefrontal cortex white matter, right-sided NAA (SMD: -0.76, 95% CI: -1.36 to -0.15) and left-sided choline (SMD: -0.54, 95% CI: -0.96 to -0.12) were decreased. - In the anterior cingulate cortex (ACC), NAA (SMD: -0.35, 95% CI: -0.65 to -0.05), choline (SMD: -0.34, 95% CI: -0.67 to -0.00), and creatine (SMD: -0.50, 95% CI: -0.96 to -0.03) were decreased. - In the left prefrontal cortex, NAA/Cr ratios were reduced (SMD: -1.67, 95% CI: -3.29 to -0.05).
Why it matters
This meta-analysis provides consolidated neurochemical evidence of prefrontal and anterior cingulate alterations in adolescent depression. Notably, the finding of reduced creatine in the ACC indicates that using creatine as an internal reference standard may distort metabolite ratio interpretations in this population.
Limits
The total sample size across 26 studies is relatively modest (averaging fewer than 20 patients per study), resulting in wide confidence intervals for several regional analyses. All included primary studies were observational case-control designs. The abstract does not report data on medication status, illness duration, comorbid psychiatric conditions, or specific MRS technical parameters.