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 via PubMed
Summary
AI-generated from the abstractA meta-analysis of 135 fMRI studies involving 6,391 participants found that youth and adults with major depressive disorder (MDD) show different patterns of brain activation during tasks. Compared to adults with MDD, youth with MDD had distinct activation differences in the subgenual anterior cingulate cortex (sgACC) and dorsolateral prefrontal cortex (dlPFC). After controlling for illness duration, youth showed less activation than adults with shorter-duration MDD in regions like the sgACC. Among adults, those with longer-duration MDD showed less activation in the dlPFC compared to those with shorter-duration MDD. These results suggest that both age and length of illness matter for understanding brain changes in depression.
Study at a glance
| 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) |
| Keywords | Adults Quantitative whole-brain meta-analysis Youth |
| Key finding | 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.