Abstract
Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18–75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen’s d = 0.14, 95% CI: 0.08–0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.
Highlights
Major depressive disorder (MDD) is associated with an increased risk of cognitive decline [1], metabolic dysregulation [2], and cellular aging [3, 4], indicating that the burden of MDD goes beyond mental ill-health and functional impairment, and extends to poor somatic health [5], and age-related diseases [6]
Extended author information available on the last page of the article to poor quality of life and increased costs for society and healthcare [9]. This underscores the importance of identifying brain aging patterns in MDD patients to determine whether and how they deviate from healthy patterns of aging
Significant brain-PAD differences in years were observed in patients with a remitted disease status (+2.19 years, p < 0.0001, d = 0.18), with a current depression (+1.5 years, p < 0.0001, d = 0.18), in those that were using antidepressant medication at the time of scanning (+1.4 years, p < 0.0001, d = 0.15), medication-free depressed patients (+0.7 years, p = 0.0225, d = 0.07), Using a new parsimonious multisite brain age algorithm based on FreeSurfer regions of interest (ROIs) from over 2800 males and 4100 females, we found subtle age-associated gray matter differences in adults with MDD
Summary
Major depressive disorder (MDD) is associated with an increased risk of cognitive decline [1], metabolic dysregulation [2], and cellular aging [3, 4], indicating that the burden of MDD goes beyond mental ill-health and functional impairment, and extends to poor somatic health [5], and age-related diseases [6]. Extended author information available on the last page of the article to poor quality of life and increased costs for society and healthcare [9]. This underscores the importance of identifying brain aging patterns in MDD patients to determine whether and how they deviate from healthy patterns of aging. We conducted exploratory analyses to investigate whether higher brain-PAD in MDD patients was associated with demographics (age, sex) and clinical characteristics such as disease recurrence, antidepressant use, remission status, depression severity, and age of onset of depression
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