Magnetic resonance spectroscopy studies in children and adolescents with depression: A systematic review and meta-analysis

Background: Numerous studies have focused on the levels of brain metabolites in patients with depression. However, there are relatively few studies on magnetic resonance spectroscopy (MRS) of adolescent depression and the related neurobiological mechanisms lack consistent conclusions. To summarize the nature of brain metabolite changes in adolescents with depression, we conducted meta-analyses of metabolite levels in proton magnetic resonance spectroscopy (1H-MRS) studies. Methods: We searched the PubMed, Cochrane Library, Scopus, Embase, and Web of Science databases from January 1965 to December 2023. Heterogeneity across studies was evaluated using the Q and I2 tests, and the random-effects model was used for analysis. Subgroup analyses were also conducted to explore potential sources of inconsistency. Results: A total of 26 studies involving 465 adolescent patients with depression and 409 healthy controls (HC) were included in this systematic review. N-acetyl aspartate (NAA) levels (SMD: -0.20, 95%CI: -0.34 to -0.05) were decreased in adolescents with depression when all brain areas were combined. In the dorsolateral prefrontal cortex white matter region, right-sided NAA (SMD: -0.76, 95 % CI: -1.36 to -0.15) and left-sided choline (Cho) levels (SMD: - 0.54, 95 % CI: -0.96 to -0.12) were decreased. The levels of NAA (SMD: -0.35, 95 % CI: -0.65 to -0.05), Cho (SMD: -0.34, 95 % CI: -0.67 to -0.00) and creatine (Cr) (SMD: -0.50, 95 % CI: -0.96 to -0.03) in the anterior cingulate cortex (ACC) are reduced. The NAA/Cr levels (SMD: -1.67, 95 % CI: -3.29 to -0.05) in the left prefrontal cortex (PFC) are decreased. Conclusions: Our results suggest that the reduction in NAA levels throughout the brain regions, especially in the prefrontal cortex, among adolescent patients with depression may be due to neuronal loss. The decrease in Cr concentration indicates that using relative creatine concentration may affect the study results. The PFC and ACC may play an important role in adolescent depression.