Dataset Information

Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group.

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.

SUBMITTER: Han LKM

PROVIDER: S-EPMC8589647 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group.

Han Laura K M LKM Dinga Richard R Hahn Tim T Ching Christopher R K CRK Eyler Lisa T LT Aftanas Lyubomir L Aghajani Moji M Aleman André A Baune Bernhard T BT Berger Klaus K Brak Ivan I Filho Geraldo Busatto GB Carballedo Angela A Connolly Colm G CG Couvy-Duchesne Baptiste B Cullen Kathryn R KR Dannlowski Udo U Davey Christopher G CG Dima Danai D Duran Fabio L S FLS Enneking Verena V Filimonova Elena E Frenzel Stefan S Frodl Thomas T Fu Cynthia H Y CHY Godlewska Beata R BR Gotlib Ian H IH Grabe Hans J HJ Groenewold Nynke A NA Grotegerd Dominik D Gruber Oliver O Hall Geoffrey B GB Harrison Ben J BJ Hatton Sean N SN Hermesdorf Marco M Hickie Ian B IB Ho Tiffany C TC Hosten Norbert N Jansen Andreas A Kähler Claas C Kircher Tilo T Klimes-Dougan Bonnie B Krämer Bernd B Krug Axel A Lagopoulos Jim J Leenings Ramona R MacMaster Frank P FP MacQueen Glenda G McIntosh Andrew A McLellan Quinn Q McMahon Katie L KL Medland Sarah E SE Mueller Bryon A BA Mwangi Benson B Osipov Evgeny E Portella Maria J MJ Pozzi Elena E Reneman Liesbeth L Repple Jonathan J Rosa Pedro G P PGP Sacchet Matthew D MD Sämann Philipp G PG Schnell Knut K Schrantee Anouk A Simulionyte Egle E Soares Jair C JC Sommer Jens J Stein Dan J DJ Steinsträter Olaf O Strike Lachlan T LT Thomopoulos Sophia I SI van Tol Marie-José MJ Veer Ilya M IM Vermeiren Robert R J M RRJM Walter Henrik H van der Wee Nic J A NJA van der Werff Steven J A SJA Whalley Heather H Winter Nils R NR Wittfeld Katharina K Wright Margaret J MJ Wu Mon-Ju MJ Völzke Henry H Yang Tony T TT Zannias Vasileios V de Zubicaray Greig I GI Zunta-Soares Giovana B GB Abé Christoph C Alda Martin M Andreassen Ole A OA Bøen Erlend E Bonnin Caterina M CM Canales-Rodriguez Erick J EJ Cannon Dara D Caseras Xavier X Chaim-Avancini Tiffany M TM Elvsåshagen Torbjørn T Favre Pauline P Foley Sonya F SF Fullerton Janice M JM Goikolea Jose M JM Haarman Bartholomeus C M BCM Hajek Tomas T Henry Chantal C Houenou Josselin J Howells Fleur M FM Ingvar Martin M Kuplicki Rayus R Lafer Beny B Landén Mikael M Machado-Vieira Rodrigo R Malt Ulrik F UF McDonald Colm C Mitchell Philip B PB Nabulsi Leila L Otaduy Maria Concepcion Garcia MCG Overs Bronwyn J BJ Polosan Mircea M Pomarol-Clotet Edith E Radua Joaquim J Rive Maria M MM Roberts Gloria G Ruhe Henricus G HG Salvador Raymond R Sarró Salvador S Satterthwaite Theodore D TD Savitz Jonathan J Schene Aart H AH Schofield Peter R PR Serpa Mauricio H MH Sim Kang K Soeiro-de-Souza Marcio Gerhardt MG Sutherland Ashley N AN Temmingh Henk S HS Timmons Garrett M GM Uhlmann Anne A Vieta Eduard E Wolf Daniel H DH Zanetti Marcus V MV Jahanshad Neda N Thompson Paul M PM Veltman Dick J DJ Penninx Brenda W J H BWJH Marquand Andre F AF Cole James H JH Schmaal Lianne L

Molecular psychiatry 20200518 9

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 yea ...[more]

PMID: 32424236

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Project description:There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, pFWE = 0.037; right: d = -0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, pFWE < 0.001; right: d = -0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.

Project description:ObjectiveMajor depressive disorder is associated with an increased risk of mortality and aging-related diseases. The authors examined whether major depression is associated with higher epigenetic aging in blood as measured by DNA methylation (DNAm) patterns, whether clinical characteristics of major depression have a further impact on these patterns, and whether the findings replicate in brain tissue.MethodDNAm age was estimated using all methylation sites in blood of 811 depressed patients and 319 control subjects with no lifetime psychiatric disorders and low depressive symptoms from the Netherlands Study of Depression and Anxiety. The residuals of the DNAm age estimates regressed on chronological age were calculated to indicate epigenetic aging. Major depression diagnosis and clinical characteristics were assessed with questionnaires and psychiatric interviews. Analyses were adjusted for sociodemographic characteristics, lifestyle, and health status. Postmortem brain samples of 74 depressed patients and 64 control subjects were used for replication. Pathway enrichment analysis was conducted using ConsensusPathDB to gain insight into the biological processes underlying epigenetic aging in blood and brain.ResultsSignificantly higher epigenetic aging was observed in patients with major depression compared with control subjects (Cohen's d=0.18), with a significant dose effect with increasing symptom severity in the overall sample. In the depression group, epigenetic aging was positively and significantly associated with childhood trauma score. The case-control difference was replicated in an independent data set of postmortem brain samples. The top significantly enriched Gene Ontology terms included neuronal processes.ConclusionsAs compared with control subjects, patients with major depression exhibited higher epigenetic aging in blood and brain tissue, suggesting that they are biologically older than their corresponding chronological age. This effect was even more profound in the presence of childhood trauma.

Project description:ObjectiveNeuroimaging studies show structural differences in both cortical and subcortical brain regions in children and adults with autism spectrum disorder (ASD) compared with healthy subjects. Findings are inconsistent, however, and it is unclear how differences develop across the lifespan. The authors investigated brain morphometry differences between individuals with ASD and healthy subjects, cross-sectionally across the lifespan, in a large multinational sample from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) ASD working group.MethodThe sample comprised 1,571 patients with ASD and 1,651 healthy control subjects (age range, 2-64 years) from 49 participating sites. MRI scans were preprocessed at individual sites with a harmonized protocol based on a validated automated-segmentation software program. Mega-analyses were used to test for case-control differences in subcortical volumes, cortical thickness, and surface area. Development of brain morphometry over the lifespan was modeled using a fractional polynomial approach.ResultsThe case-control mega-analysis demonstrated that ASD was associated with smaller subcortical volumes of the pallidum, putamen, amygdala, and nucleus accumbens (effect sizes [Cohen's d], 0.13 to -0.13), as well as increased cortical thickness in the frontal cortex and decreased thickness in the temporal cortex (effect sizes, -0.21 to 0.20). Analyses of age effects indicate that the development of cortical thickness is altered in ASD, with the largest differences occurring around adolescence. No age-by-ASD interactions were observed in the subcortical partitions.ConclusionsThe ENIGMA ASD working group provides the largest study of brain morphometry differences in ASD to date, using a well-established, validated, publicly available analysis pipeline. ASD patients showed altered morphometry in the cognitive and affective parts of the striatum, frontal cortex, and temporal cortex. Complex developmental trajectories were observed for the different regions, with a developmental peak around adolescence. These findings suggest an interplay in the abnormal development of the striatal, frontal, and temporal regions in ASD across the lifespan.

Dataset Information

Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group.

Publications

Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group.

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