TY - JOUR
T1 - A stable and replicable neural signature of lifespan adversity in the adult brain
AU - Holz, Nathalie E.
AU - Zabihi, Mariam
AU - Kia, Seyed Mostafa
AU - Monninger, Maximillian
AU - Aggensteiner, Pascal M.
AU - Siehl, Sebastian
AU - Floris, Dorothea L.
AU - Bokde, Arun L.W.
AU - Desrivières, Sylvane
AU - Flor, Herta
AU - Grigis, Antoine
AU - Garavan, Hugh
AU - Gowland, Penny
AU - Heinz, Andreas
AU - Brühl, Rüdiger
AU - Martinot, Jean Luc
AU - Paillère Martinot, Marie Laure
AU - Orfanos, Dimitri Papadopoulos
AU - Paus, Tomáš
AU - Poustka, Luise
AU - Fröhner, Juliane H.
AU - Smolka, Michael N.
AU - Vaidya, Nilakshi
AU - Walter, Henrik
AU - Whelan, Robert
AU - Schumann, Gunter
AU - Meyer-Lindenberg, Andreas
AU - Brandeis, Daniel
AU - Buitelaar, Jan K.
AU - Nees, Frauke
AU - Beckmann, Christian
AU - Martinot, Jean Luc
AU - Paillère Martinot, Marie Laure
AU - Fröhner, Juliane H.
AU - Smolka, Michael N.
AU - Walter, Henrik
AU - Banaschewski, Tobias
AU - Marquand, Andre F.
N1 - Funding Information:
N.E.H. and T.B. gratefully acknowledge grant support from the German Research Foundation (grants DFG HO 5674/2-1 and GRK2350/1). N.E.H. further acknowledges funding from the Olympia Morata Program of the University of Heidelberg, the Ministry of Science, Research and the Arts of the State of Baden-Württemberg, Germany (Special support program SARS CoV-2 pandemic) and the Radboud Excellence Fellowship. A.F.M. gratefully acknowledges support by grants from the European Research Council (ERC; grants ‘MENTALPRECISION’ 10100118), the Wellcome Trust under an Innovator award (‘BRAINCHART’, 215698/Z/19/Z) and the Dutch Organization for Scientific Research (VIDI grant 016.156.415). C.F.B. gratefully acknowledges funding from the Wellcome Trust Collaborative Award in Science (215573/Z/19/Z), a Strategic Award (098369/Z/12/Z) and the Netherlands Organization for Scientific Research Vici (grants 17854) and NWO-CAS (grant 012-200-013). D.L.F. is supported by funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement 101025785. T.B. gratefully acknowledges grant support by the German Federal Ministry of Education and Research (01EE1408E ESCAlife, FKZ 01GL1741[X] ADOPT, 01EE1406C Verbund AERIAL, 01EE1409C Verbund ASD-Net, 01GL1747C STAR and 01GL1745B IMAC-Mind), German Research Foundation (TRR 265/1), Innovative Medicines Initiative Joint Undertaking (IMI JU FP7 115300 EU-AIMS; grant 777394 EU-AIMS-2-TRIALS) and the European Union—H2020 (Eat2beNICE, grant 728018; PRIME, grant 847879). A.M.L. acknowledges grant support by the German Research Foundation (DFG) (Research Training Group, GRK2350/1 project B02; Collaborative Research Center, SFB 1158 project B09; Collaborative Research Center, TRR 265 project S02; grant ME 1591/4-1), German Federal Ministry of Education and Research (BMBF; grants 01EF1803A, 01ZX1314G and 01GQ1003B), European Union’s Seventh Framework Program (FP7; grants 602450, 602805, 115300, HEALTH-F2-2010-241909, Horizon 2020 CANDY grant 847818 and Eat2beNICE grant 728018), Innovative Medicines Initiative (IMI) Joint Undertaking (grant 115008, PRISM grant 115916, EU-AIMS grant 115300 and AIMS-2-TRIALS grant 777394) and Ministry of Science, Research and the Arts of the State of Baden-Wuerttemberg, Germany (MWK; grant 42-04HV.MED(16)/16/1). Furthermore, this work received support from the following sources: the European Union-funded FP6 Integrated Project IMAGEN (reinforcement-related behavior in normal brain function and psychopathology; LSHM-CT-2007-037286), the Horizon 2020 funded ERC Advanced Grant ‘STRATIFY’ (brain network-based stratification of reinforcement-related disorders; 695313), Human Brain Project (HBP SGA 2, 785907, and HBP SGA 3, 945539), the Medical Research Council grant Consortium on Vulnerability to Externalizing Disorders and Addictions (c-VEDA; MR/N000390/1), the National Institute of Health (NIH; R01DA049238, a decentralized macro and micro gene-by-environment interaction analysis of substance use behavior and its brain biomarkers), the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, BMBF (grants 01GS08152; 01EV0711; Forschungsnetz AERIAL 01EE1406A, 01EE1406B and Forschungsnetz IMAC-Mind 01GL1745B), DFG (grants SM 80/7-2, SFB 940, TRR 265 and NE 1383/14-1), the Medical Research Foundation and Medical Research Council (grants MR/R00465X/1 and MR/S020306/1), NIH funded ENIGMA (grants 5U54EB020403-05 and 1R56AG058854-01), NSFC (grant 82150710554) and European Union-funded project ‘environMENTAL’ (grant 101057429). Further support was provided by grants from the ANR (ANR-12-SAMA-0004, AAPG2019—GeBra), the Eranet Neuron (AF12-NEUR0008-01—WM2NA; and ANR-18-NEUR00002-01—ADORe), the Fondation de France (00081242), the Fondation pour la Recherche Médicale (DPA20140629802), the Mission Interministérielle de Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA), the Assistance-Publique-Hôpitaux-de-Paris and INSERM (interface grant), Paris Sud University IDEX 2012, the Fondation de l’Avenir (grant AP-RM-17-013), the Fédération pour la Recherche sur le Cerveau; NIH, Science Foundation Ireland (16/ERCD/3797), Science Foundation, USA (Axon, Testosterone and Mental Health during Adolescence; RO1 MH085772-01A1) and NIH Consortium (grant U54 EB020403), supported by a cross-NIH alliance that funds Big Data to Knowledge Centers of Excellence. The authors thank S. Heinzel and R. Schmidt for their support in data collection and management and the MARS and IMAGEN participants for their continued participation. In addition, the authors gratefully thank M. Laucht (1946–2020), who was one of the founders of the MARS and who continuously acted as an inspiring and supporting mentor giving impulses for innovative research projects.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/9
Y1 - 2023/9
N2 - Environmental adversities constitute potent risk factors for psychiatric disorders. Evidence suggests the brain adapts to adversity, possibly in an adversity-type and region-specific manner. However, the long-term effects of adversity on brain structure and the association of individual neurobiological heterogeneity with behavior have yet to be elucidated. Here we estimated normative models of structural brain development based on a lifespan adversity profile in a longitudinal at-risk cohort aged 25 years (n = 169). This revealed widespread morphometric changes in the brain, with partially adversity-specific features. This pattern was replicated at the age of 33 years (n = 114) and in an independent sample at 22 years (n = 115). At the individual level, greater volume contractions relative to the model were predictive of future anxiety. We show a stable neurobiological signature of adversity that persists into adulthood and emphasize the importance of considering individual-level rather than group-level predictions to explain emerging psychopathology.
AB - Environmental adversities constitute potent risk factors for psychiatric disorders. Evidence suggests the brain adapts to adversity, possibly in an adversity-type and region-specific manner. However, the long-term effects of adversity on brain structure and the association of individual neurobiological heterogeneity with behavior have yet to be elucidated. Here we estimated normative models of structural brain development based on a lifespan adversity profile in a longitudinal at-risk cohort aged 25 years (n = 169). This revealed widespread morphometric changes in the brain, with partially adversity-specific features. This pattern was replicated at the age of 33 years (n = 114) and in an independent sample at 22 years (n = 115). At the individual level, greater volume contractions relative to the model were predictive of future anxiety. We show a stable neurobiological signature of adversity that persists into adulthood and emphasize the importance of considering individual-level rather than group-level predictions to explain emerging psychopathology.
KW - environmental adversities
KW - psychiatric disorders
KW - adult brain
KW - lifetime adversity
UR - https://www.scopus.com/pages/publications/85168538029
U2 - 10.1038/s41593-023-01410-8
DO - 10.1038/s41593-023-01410-8
M3 - Article
C2 - 37604888
AN - SCOPUS:85168538029
SN - 1097-6256
VL - 26
SP - 1603
EP - 1612
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 9
ER -