Major Depressive Disorder in Youth and Adults: A Quantitative Whole-Brain Meta-Analysis of Functional Magnetic Resonance Imaging Studies.
Caitlin Baten, Gladys Zamora, Amanda M. Klassen, Justin Rackley, Akua F Nimarko, Ellen Woo, Arielle S Keller, J Paul Hamilton, Dawson W Hedges, Matthew D. Sacchet, Ian H Gotlib, Chris H. Miller
Biological psychiatry. Cognitive neuroscience and neuroimaging January 13, 2026 DOI: 10.1016/j.bpsc.2026.01.001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Peer reviewed |
|---|---|
| Sample size | 6,391 |
| Population | Participants diagnosed with major depressive disorder (MDD) and age-matched healthy controls (HCs) |
| Topics | Depression |
| Keywords | Adults Quantitative whole-brain meta-analysis Youth |
| Key findings | Youth and adults with MDD show differential brain activation patterns in regions such as the sgACC and dlPFC, with illness duration also affecting activation differences among adults. |
Abstract
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. Following PRISMA guidelines, we searched PubMed through November 2023 and selected 135 primary studies (N = 6,391) based on the following inclusion criteria: (1)task-based fMRI activation, (2) voxel-wise whole-brain analyses, and (3) compared participants diagnosed with MDD to age-matched healthy controls (HCs). We used multilevel kernel density analysis with ensemble thresholding (P < .05 - .0001; FDR-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. 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). 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.