Major Depressive Disorder in Youth and Adults: A Quantitative Whole-Brain Meta-Analysis of Functional Magnetic Resonance Imaging Studies

BACKGROUND: Major depressive disorder (MDD) is a highly prevalent psychiatric disorder with limited treatment success in both youth and adults. Functional magnetic resonance imaging (fMRI) studies have reported partially differential patterns of activation in youth and adults diagnosed with MDD that may be attributable to age or length of illness. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched PubMed through November 2023 and selected 135 primary studies (N = 6391) based on the following inclusion criteria: 1) task-based fMRI activation, 2) voxelwise whole-brain analyses, and 3) comparison between participants diagnosed with MDD and age-matched healthy control participants (HCs). We used multilevel kernel density analysis with ensemble thresholding (p < .05-.0001, false discovery rate corrected) to find activation differences between 1) youth with MDD and HCs, 2) youth and adults with MDD, 3) youth and adults with shorter-duration MDD, and 4) adults with longer- and shorter-duration MDD. RESULTS: Relative to adults with MDD, youth with MDD demonstrated significant patterns of differential activation in regions such as the subgenual anterior cingulate cortex (sgACC) and dorsolateral prefrontal cortex (dlPFC) (p < .0025). Second, after controlling for length of illness, relative to adults with shorter-duration MDD, youth demonstrated hypoactivation in regions such as the sgACC (p < .01). Lastly, when controlling for age, relative to adults with shorter-duration MDD, adults with longer-duration MDD demonstrated hypoactivation in regions such as the dlPFC (p < .05). CONCLUSIONS: These findings underscore the importance of considering age and length of illness in developmental models of MDD and inform neural models and clinical interventions for depression.