Contributing Factors to Advanced Brain Aging in Depression and Anxiety Disorders

ABSTRACT Brain aging has shown to be more advanced in patients with Major Depressive Disorder (MDD). This study examines which factors underlie this older brain age. Adults aged 18-57 years from the Netherlands Study of Depression and Anxiety underwent structural MRI. A pre-trained brain age prediction model based on >2,000 samples from the ENIGMA consortium was applied to predict age in 65 controls and 220 patients with current MDD and/or anxiety disorder. Brain-predicted age differences (brain-PAD) were calculated (predicted brain age minus chronological age) and associated with clinical, psychological, and biological factors. After correcting for antidepressant use, brain-PAD was significantly higher in MDD (+2.78 years) and anxiety patients (+2.91 years) compared to controls. Findings further indicate unique contributions of higher severity of somatic depression symptoms to advanced brain aging and a potential protective effect of antidepressant medication (-2.53 years).