Abstract
BACKGROUND: Individual studies have analyzed brain age acceleration in schizophrenia, bipolar disorder (BD), and major depressive disorder (MDD), showing that each of these psychiatric conditions is associated with an older brain age compared to chronological age. However, no studies have directly compared brain age across these three major mental illnesses. AIMS & OBJECTIVES: All three disorders involve accelerated brain aging, likely influenced by common factors such as oxidative stress, inflammation, and dysregulated neural connectivity. Comparing their brain age to normal controls can reveal shared pathways of neurodegeneration, and may help identify specific targets for therapeutic interventions. METHOD: We recruited 796 subjects, including 262 BD patients, 256 MDD patients, 82 patients with schizophrenia, and 196 normal controls. The brain age gaps in different brain regions were calculated, and compare the brain age errors of 90 brain regions among diagnostic groups with those of the healthy controls. RESULTS: In the depression group, among 90 gray matter volumes, 43 brain regions showed significant differences in brain-age gap compared to healthy individuals. The three most severely aged brain regions in the depression group were the right lenticular nucleus, pallidum (11.45 ± 9.71), the left lenticular nucleus, pallidum (10.94 ± 9.11), and the right cuneus (4.67 ± 7.99). In the BD group, 54 brain regions showed significant differences in brain-age gap compared to healthy individuals. The three most severely aged brain regions were the left lenticular nucleus, pallidum (11.28 ± 7.77), the right lenticular nucleus, pallidum (11.17 ± 8.20), and the right cuneus (4.97 ± 7.59). In the schizophrenia group, as many as 79 brain regions exhibited significant differences in brain-age gap compared to healthy individuals. Among these, 45 regions showed accelerated aging, including the bilateral insula, bilateral superior frontal gyrus, right inferior frontal gyrus, bilateral Rolandic operculum, bilateral Heschl's gyrus, bilateral cuneus, bilateral supplementary motor cortex, and etc. (figure 1) DISCUSSION & CONCLUSIONS: The schizophrenia group exhibited more accelerated brain structural aging, not only encompassing the regions observed in the MDD and BD groups, but also including key regions such as the left insula, which is associated with the unique clinical symptoms of schizophrenia.