Brain Aging in Major Depressive Disorder: Results from the ENIGMA Major Depressive Disorder working group

Han LKM, Dinga R, Hahn T, Ching CRK, Eyler LT, Aftanas L, Aghajani M, Aleman A, Baune BT, Berger K, Brak I, Filho GB, Carballedo A, Connolly CG, Couvy-Duchesne B, Cullen KR, Dannlowski U, Davey CG, Dima D, Duran FLS, Enneking V, Filimonova E, Frenzel S, Frodl T, Fu CHY, Godlewska BR, Gotlib IH, Grabe HJ, Groenewold NA, Grotegerd D, Gruber O, Hall GB, Harrison BJ, Hatton SN, Hermesdorf M, Hickie IB, Ho TC, Hosten N, Jansen A, Kähler C, Kircher T, Klimes-Dougan B, Krämer B, Krug A, Lagopoulos J, Leenings R, MacMaster FP, MacQueen G, McIntosh A, McLellan Q, McMahon KL, Medland SE, Mueller BA, Mwangi B, Osipov E, Portella MJ, Pozzi E, Reneman L, Repple J, Rosa PGP, Sacchet MD, Sämann PG, Schnell K, Schrantee A, Simulionyte E, Soares JC, Sommer J, Stein DJ, Steinsträter O, Strike LT, Thomopoulos SI, van Tol MJ, Veer IM, Vermeiren RRJM, Walter H, van der Wee NJA, van der Werff SJA, Whalley H, Winter NR, Wittfeld K, Wright MJ, Wu MJ, Völzke H, Yang TT, Zannias V, de Zubicaray GI, Zunta-Soares GB, Abé C, Alda M, Andreassen OA, Bøen E, Bonnin CM, Canales-Rodriguez EJ, Cannon D, Caseras X, Chaim-Avancini TM, Elvsåshagen T, Favre P, Foley SF, Fullerton JM, Goikolea JM, Haarman BCM, Hajek T, Henry C, Houenou J, Howells FM, Ingvar M, Kuplicki R, Lafer B, Landén M, Machado-Vieira R, Malt UF, McDonald C, Mitchell PB, Nabulsi L, Otaduy MCG, Overs BJ, Polosan M, Pomarol-Clotet E, Radua J, Rive MM, Roberts G, Ruhe HG, Salvador R, Sarró S, Satterthwaite TD, Savitz J, Schene AH, Schofield PR, Serpa MH, Sim K, Soeiro-de-Souza MG, Sutherland AN, Temmingh HS, Timmons GM, Uhlmann A, Vieta E, Wolf DH, Zanetti MV, Jahanshad N, Thompson PM, Veltman DJ, Penninx BWJH, Marquand AF, Cole JH, Schmaal L

Zusammenfassung

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.