. 2019 Oct;22(10):1617-1623.

doi: 10.1038/s41593-019-0471-7. Epub 2019 Sep 24.

Common brain disorders are associated with heritable patterns of apparent aging of the brain

Tobias Kaufmann¹, Dennis van der Meer^{2

3}, Nhat Trung Doan², Emanuel Schwarz⁴, Martina J Lund², Ingrid Agartz^{2

5

6}, Dag Alnæs², Deanna M Barch^{7

8

9}, Ramona Baur-Streubel¹⁰, Alessandro Bertolino^{11

12}, Francesco Bettella², Mona K Beyer^{13

14}, Erlend Bøen^{5

15}, Stefan Borgwardt^{16

17

18}, Christine L Brandt², Jan Buitelaar^{19

20}, Elisabeth G Celius^{13

21}, Simon Cervenka⁶, Annette Conzelmann²², Aldo Córdova-Palomera², Anders M Dale^{23

24

25

26}, Dominique J F de Quervain^{27

28}, Pasquale Di Carlo¹², Srdjan Djurovic^{29

30}, Erlend S Dørum^{2

31

32}, Sarah Eisenacher⁴, Torbjørn Elvsåshagen^{2

13

21}, Thomas Espeseth³¹, Helena Fatouros-Bergman⁶, Lena Flyckt⁶, Barbara Franke³³, Oleksandr Frei², Beathe Haatveit^{2

31}, Asta K Håberg^{34

35}, Hanne F Harbo^{13

21}, Catharina A Hartman³⁶, Dirk Heslenfeld^{37

38}, Pieter J Hoekstra³⁹, Einar A Høgestøl^{13

21}, Terry L Jernigan^{40

41

42}, Rune Jonassen⁴³, Erik G Jönsson^{2

6}; Karolinska Schizophrenia Project (KaSP); Peter Kirsch^{44

45}, Iwona Kłoszewska⁴⁶, Knut K Kolskår^{2

31

32}, Nils Inge Landrø^{5

31}, Stephanie Le Hellard³⁰, Klaus-Peter Lesch^{47

48

49}, Simon Lovestone⁵⁰, Arvid Lundervold^{51

52}, Astri J Lundervold⁵³, Luigi A Maglanoc^{2

31}, Ulrik F Malt^{13

54}, Patrizia Mecocci⁵⁵, Ingrid Melle², Andreas Meyer-Lindenberg⁴, Torgeir Moberget², Linn B Norbom^{2

31}, Jan Egil Nordvik⁵⁶, Lars Nyberg⁵⁷, Jaap Oosterlaan^{37

58}, Marco Papalino¹², Andreas Papassotiropoulos^{27

59

60}, Paul Pauli¹⁰, Giulio Pergola¹², Karin Persson^{61

62}, Geneviève Richard^{2

31

32}, Jaroslav Rokicki^{2

31}, Anne-Marthe Sanders^{2

31

32}, Geir Selbæk^{13

61

62}, Alexey A Shadrin², Olav B Smeland², Hilkka Soininen^{63

64}, Piotr Sowa¹⁴, Vidar M Steen^{30

65}, Magda Tsolaki⁶⁶, Kristine M Ulrichsen^{2

31

32}, Bruno Vellas⁶⁷, Lei Wang⁶⁸, Eric Westman^{17

69}, Georg C Ziegler⁴⁷, Mathias Zink^{4

70}, Ole A Andreassen², Lars T Westlye^{71

72}

Collaborators, Affiliations

Collaborators

Karolinska Schizophrenia Project (KaSP):
Lars Farde, Lena Flyckt, Göran Engberg, Sophie Erhardt, Helena Fatouros-Bergman, Simon Cervenka, Lilly Schwieler, Fredrik Piehl, Ingrid Agartz, Karin Collste, Pauliina Victorsson, Anna Malmqvist, Mikael Hedberg, Funda Orhan

Affiliations

¹ NORMENT, Division of Mental Health and Addiction Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway. bias.kaufmann@medisin.uio.no.
² NORMENT, Division of Mental Health and Addiction Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
³ School of Mental Health and Neuroscience Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
⁴ Department of Psychiatry and Psychotherapy Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁵ Department of Psychiatry Diakonhjemmet Hospital, Oslo, Norway.
⁶ Centre for Psychiatry Research, Department of Clinical Neuroscience Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
⁷ Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, USA.
⁸ Department of Psychiatry Washington, University in St. Louis, St. Louis, USA.
⁹ Department of Radiology Washington, University in St. Louis, St. Louis, USA.
¹⁰ Department of Psychology I, University of Würzburg, Würzburg, Germany.
¹¹ Institute of Psychiatry Bari University Hospital, Bari, Italy.
¹² Department of Basic Medical Science, Neuroscience and Sense Organs University of Bari, Bari, Italy.
¹³ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
¹⁴ Division of Radiology and Nuclear Medicine, Section of Neuroradiology Oslo University Hospital, Oslo, Norway.
¹⁵ Psychosomatic and CL Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
¹⁶ Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
¹⁷ Department of Psychiatry, Psychosomatics and Psychotherapy University of Lübeck, Lübeck, Germany.
¹⁸ Institute of Psychiatry King's College, London, UK.
¹⁹ Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center, Nijmegen, The Netherlands.
²⁰ Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.
²¹ Department of Neurology, Oslo University Hospital, Oslo, Norway.
²² Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy University of Tübingen, Tübingen, Germany.
²³ Center for Multimodal Imaging and Genetics, University of California at San Diego, La Jolla, CA, USA.
²⁴ Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
²⁵ Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
²⁶ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
²⁷ Division of Cognitive Neuroscience, University of Basel, Basel, Switzerland.
²⁸ Transfaculty Research Platform Molecular and Cognitive Neurosciences University of Basel, Basel, Switzerland.
²⁹ Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
³⁰ NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway.
³¹ Department of Psychology, University of Oslo, Oslo, Norway.
³² Sunnaas Rehabilitation Hospital HT, Nesodden, Norway.
³³ Departments of Human Genetics and Psychiatry, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center, Nijmegen, The Netherlands.
³⁴ Department of Neuromedicine and Movement Science Norwegian, University of Science and Technology, Trondheim, Norway.
³⁵ Department of Radiology and Nuclear Medicine St. Olavs Hospital, Trondheim, Norway.
³⁶ Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
³⁷ Clinical Neuropsychology section Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
³⁸ Department of Cognitive Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
³⁹ Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁴⁰ Center for Human Development, University of California, San Diego, USA.
⁴¹ Department of Cognitive Science, University of California, San Diego, USA.
⁴² Departments of Psychiatry and Radiology, University of California, San Diego, USA.
⁴³ Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway.
⁴⁴ Department of Clinical Psychology Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁴⁵ Bernstein Center for Computational Neuroscience Heidelberg/Mannheim, Mannheim, Germany.
⁴⁶ Department of Old Age Psychiatry and Psychotic Disorders Medical University of Lodz, Lodz, Poland.
⁴⁷ Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany.
⁴⁸ Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine Sechenov First Moscow State Medical University, Moscow, Russia.
⁴⁹ Department of Neuroscience, School for Mental Health and Neuroscience (MHeNS) Maastricht University, Maastricht, The Netherlands.
⁵⁰ Department of Psychiatry, Warneford Hospital University of Oxford, Oxford, UK.
⁵¹ Department of Biomedicine, University of Bergen, Bergen, Norway.
⁵² Mohn Medical Imaging and Visualization Centre, Department of Radiology, Haukeland University Hospital, Bergen, Norway.
⁵³ Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
⁵⁴ Department of Research and Education, Oslo University Hospital, Oslo, Norway.
⁵⁵ Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.
⁵⁶ CatoSenteret Rehabilitation Center Son, Oslo, Norway.
⁵⁷ Departments of Radiation Sciences and Integrative Medical Biology, Umeå Center for Functional Brain Imaging Umeå University, Umeå, Sweden.
⁵⁸ Emma Children's Hospital, Amsterdam UMC University of Amsterdam and Vrije Universiteit Amsterdam, Emma Neuroscience Group, Department of Pediatrics, Amsterdam Reproduction & Development, Amsterdam, The Netherlands.
⁵⁹ Division of Molecular Neuroscience University of Basel, Basel, Switzerland.
⁶⁰ Life Sciences Training Facility, Department Biozentrum University of Basel, Basel, Switzerland.
⁶¹ Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.
⁶² Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway.
⁶³ Department of Neurology, Institute of Clinical Medicine University of Eastern Finland, Kuopio, Finland.
⁶⁴ Neurocenter, Neurology Kuopio University Hospital, Kuopio, Finland.
⁶⁵ Dr. E. Martens Research Group for Biological Psychiatry, Department of Medical Genetics Haukeland University Hospital, Bergen, Norway.
⁶⁶ 1st Department of Neurology Aristotle University of Thessaloniki, Thessaloniki, Greece.
⁶⁷ UMR Inserm 1027, CHU Toulouse, UPS, Toulouse, France.
⁶⁸ Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁶⁹ Department of Neurobiology Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
⁷⁰ District hospital Ansbach, Ansbach, Germany.
⁷¹ NORMENT, Division of Mental Health and Addiction Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway. l.t.westlye@psykologi.uio.no.
⁷² Department of Psychology, University of Oslo, Oslo, Norway. l.t.westlye@psykologi.uio.no.

PMID: 31551603
PMCID: PMC6823048
DOI: 10.1038/s41593-019-0471-7

Common brain disorders are associated with heritable patterns of apparent aging of the brain

Tobias Kaufmann et al. Nat Neurosci. 2019 Oct.

. 2019 Oct;22(10):1617-1623.

doi: 10.1038/s41593-019-0471-7. Epub 2019 Sep 24.

Authors

Collaborators

Karolinska Schizophrenia Project (KaSP):
Lars Farde, Lena Flyckt, Göran Engberg, Sophie Erhardt, Helena Fatouros-Bergman, Simon Cervenka, Lilly Schwieler, Fredrik Piehl, Ingrid Agartz, Karin Collste, Pauliina Victorsson, Anna Malmqvist, Mikael Hedberg, Funda Orhan

Affiliations

¹ NORMENT, Division of Mental Health and Addiction Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway. bias.kaufmann@medisin.uio.no.
² NORMENT, Division of Mental Health and Addiction Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
³ School of Mental Health and Neuroscience Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
⁴ Department of Psychiatry and Psychotherapy Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁵ Department of Psychiatry Diakonhjemmet Hospital, Oslo, Norway.
⁶ Centre for Psychiatry Research, Department of Clinical Neuroscience Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
⁷ Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, USA.
⁸ Department of Psychiatry Washington, University in St. Louis, St. Louis, USA.
⁹ Department of Radiology Washington, University in St. Louis, St. Louis, USA.
¹⁰ Department of Psychology I, University of Würzburg, Würzburg, Germany.
¹¹ Institute of Psychiatry Bari University Hospital, Bari, Italy.
¹² Department of Basic Medical Science, Neuroscience and Sense Organs University of Bari, Bari, Italy.
¹³ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
¹⁴ Division of Radiology and Nuclear Medicine, Section of Neuroradiology Oslo University Hospital, Oslo, Norway.
¹⁵ Psychosomatic and CL Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
¹⁶ Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
¹⁷ Department of Psychiatry, Psychosomatics and Psychotherapy University of Lübeck, Lübeck, Germany.
¹⁸ Institute of Psychiatry King's College, London, UK.
¹⁹ Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center, Nijmegen, The Netherlands.
²⁰ Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.
²¹ Department of Neurology, Oslo University Hospital, Oslo, Norway.
²² Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy University of Tübingen, Tübingen, Germany.
²³ Center for Multimodal Imaging and Genetics, University of California at San Diego, La Jolla, CA, USA.
²⁴ Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
²⁵ Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
²⁶ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
²⁷ Division of Cognitive Neuroscience, University of Basel, Basel, Switzerland.
²⁸ Transfaculty Research Platform Molecular and Cognitive Neurosciences University of Basel, Basel, Switzerland.
²⁹ Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
³⁰ NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway.
³¹ Department of Psychology, University of Oslo, Oslo, Norway.
³² Sunnaas Rehabilitation Hospital HT, Nesodden, Norway.
³³ Departments of Human Genetics and Psychiatry, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center, Nijmegen, The Netherlands.
³⁴ Department of Neuromedicine and Movement Science Norwegian, University of Science and Technology, Trondheim, Norway.
³⁵ Department of Radiology and Nuclear Medicine St. Olavs Hospital, Trondheim, Norway.
³⁶ Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
³⁷ Clinical Neuropsychology section Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
³⁸ Department of Cognitive Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
³⁹ Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁴⁰ Center for Human Development, University of California, San Diego, USA.
⁴¹ Department of Cognitive Science, University of California, San Diego, USA.
⁴² Departments of Psychiatry and Radiology, University of California, San Diego, USA.
⁴³ Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway.
⁴⁴ Department of Clinical Psychology Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁴⁵ Bernstein Center for Computational Neuroscience Heidelberg/Mannheim, Mannheim, Germany.
⁴⁶ Department of Old Age Psychiatry and Psychotic Disorders Medical University of Lodz, Lodz, Poland.
⁴⁷ Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany.
⁴⁸ Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine Sechenov First Moscow State Medical University, Moscow, Russia.
⁴⁹ Department of Neuroscience, School for Mental Health and Neuroscience (MHeNS) Maastricht University, Maastricht, The Netherlands.
⁵⁰ Department of Psychiatry, Warneford Hospital University of Oxford, Oxford, UK.
⁵¹ Department of Biomedicine, University of Bergen, Bergen, Norway.
⁵² Mohn Medical Imaging and Visualization Centre, Department of Radiology, Haukeland University Hospital, Bergen, Norway.
⁵³ Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
⁵⁴ Department of Research and Education, Oslo University Hospital, Oslo, Norway.
⁵⁵ Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.
⁵⁶ CatoSenteret Rehabilitation Center Son, Oslo, Norway.
⁵⁷ Departments of Radiation Sciences and Integrative Medical Biology, Umeå Center for Functional Brain Imaging Umeå University, Umeå, Sweden.
⁵⁸ Emma Children's Hospital, Amsterdam UMC University of Amsterdam and Vrije Universiteit Amsterdam, Emma Neuroscience Group, Department of Pediatrics, Amsterdam Reproduction & Development, Amsterdam, The Netherlands.
⁵⁹ Division of Molecular Neuroscience University of Basel, Basel, Switzerland.
⁶⁰ Life Sciences Training Facility, Department Biozentrum University of Basel, Basel, Switzerland.
⁶¹ Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.
⁶² Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway.
⁶³ Department of Neurology, Institute of Clinical Medicine University of Eastern Finland, Kuopio, Finland.
⁶⁴ Neurocenter, Neurology Kuopio University Hospital, Kuopio, Finland.
⁶⁵ Dr. E. Martens Research Group for Biological Psychiatry, Department of Medical Genetics Haukeland University Hospital, Bergen, Norway.
⁶⁶ 1st Department of Neurology Aristotle University of Thessaloniki, Thessaloniki, Greece.
⁶⁷ UMR Inserm 1027, CHU Toulouse, UPS, Toulouse, France.
⁶⁸ Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁶⁹ Department of Neurobiology Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
⁷⁰ District hospital Ansbach, Ansbach, Germany.
⁷¹ NORMENT, Division of Mental Health and Addiction Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway. l.t.westlye@psykologi.uio.no.
⁷² Department of Psychology, University of Oslo, Oslo, Norway. l.t.westlye@psykologi.uio.no.

PMID: 31551603
PMCID: PMC6823048
DOI: 10.1038/s41593-019-0471-7

Erratum in

Publisher Correction: Common brain disorders are associated with heritable patterns of apparent aging of the brain.
Kaufmann T, van der Meer D, Doan NT, Schwarz E, Lund MJ, Agartz I, Alnæs D, Barch DM, Baur-Streubel R, Bertolino A, Bettella F, Beyer MK, Bøen E, Borgwardt S, Brandt CL, Buitelaar J, Celius EG, Cervenka S, Conzelmann A, Córdova-Palomera A, Dale AM, de Quervain DJF, Di Carlo P, Djurovic S, Dørum ES, Eisenacher S, Elvsåshagen T, Espeseth T, Fatouros-Bergman H, Flyckt L, Franke B, Frei O, Haatveit B, Håberg AK, Harbo HF, Hartman CA, Heslenfeld D, Hoekstra PJ, Høgestøl EA, Jernigan TL, Jonassen R, Jönsson EG; Karolinska Schizophrenia Project (KaSP); Kirsch P, Kłoszewska I, Kolskår KK, Landrø NI, Le Hellard S, Lesch KP, Lovestone S, Lundervold A, Lundervold AJ, Maglanoc LA, Malt UF, Mecocci P, Melle I, Meyer-Lindenberg A, Moberget T, Norbom LB, Nordvik JE, Nyberg L, Oosterlaan J, Papalino M, Papassotiropoulos A, Pauli P, Pergola G, Persson K, Richard G, Rokicki J, Sanders AM, Selbæk G, Shadrin AA, Smeland OB, Soininen H, Sowa P, Steen VM, Tsolaki M, Ulrichsen KM, Vellas B, Wang L, Westman E, Ziegler GC, Zink M, Andreassen OA, Westlye LT. Kaufmann T, et al. Nat Neurosci. 2020 Feb;23(2):295. doi: 10.1038/s41593-019-0553-6. Nat Neurosci. 2020. PMID: 31848485

Abstract

Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.

PubMed Disclaimer

Conflict of interest statement

Competing financial interests

Some authors received educational speaker’s honorarium from Lundbeck (O.A. Andreassen, A. Bertolino, T. Elvsåshagen, M. Zink, N. I. Landrø), Sunovion (O.A. Andreassen), Shire (B. Franke), Medice (B. Franke), Otsuka (A. Bertolino, M. Zink) and Jannsen (A. Bertolino), Roche (M. Zink), Ferrer (M. Zink), Trommsdorff (M. Zink), Servier (M. Zink), all of these unrelated to this work. A. Bertolino is a stockholder of Hoffmann-La Roche Ltd and has received consultant fees from Biogen Idec. E. G. Celius and H. F. Harbo have received travel support, honoraria for advice and lecturing from Almirall (Celius), Biogen Idec (both), Genzyme (both), Merck (both), Novartis(both), Roche (both), Sanofi-Aventis (both) and Teva (both). They have received unrestricted research grants from Novartis (Celius, Harbo), Biogen Idec (Celius) and Genzyme (Celius). G. Pergola has been the academic supervisor of a Roche collaboration grant (years 2015-16) that funds his salary. None of the mentioned external parties had any role in the analysis, writing or decision to publish this work. Other authors declare no competing financial interests.

Figures

**Figure 1. Sample distributions and imaging features used for brain age prediction.**
a, Age distributions of the training (left) and the ten test samples (right) per sex and diagnosis. The grey shades behind each clinical group reflect its age-, sex- and site-matched control group. b, Cortical features from the Human Connectome Project (HCP) atlas as well as cerebellar/subcortical features used for brain age prediction. Colours were assigned randomly to each feature. All features were used in the full brain feature set (left), whereas only those from specific regions (occipital, frontal, temporal, parietal, cingulate, insula, cerebellar/subcortical) were included in the regional feature set (right). For illustration purpose, the left hemisphere is shown.

**Figure 2. Apparent brain aging is common in several brain disorders and sensitive to clinical and cognitive measures.**
a, The gap between chronological age and brain age was increased in several disorders. The grey shades behind each clinical group reflect its age-, sex- and site-matched controls. The test samples comprised n=925 ASD / n=925 HC, n=725 ADHD / n=725 HC, n=94 SZRISK / n=94 HC, n=1110 SZ / n=1110 HC, n=300 PSYMIX / n=300 HC, n=459 BD / n=459 HC, n=254 MS / n=254 HC, n=208 MDD / n=208 HC, n=974 MCI / n=974 HC, n=739 DEM / n=739 HC; in total n=10,141 independent subjects. Cohen’s d effect sizes (pooled standard deviation units) and two-sided P-values are provided. b, Several disorders showed specific patterns in regional brain age gaps. Colours indicate Cohen’s d effect sizes for group comparisons. Sample size as specified in panel a. Corresponding correlation matrix of the effect sizes is depicted in Suppl. Fig. 9. c, Effect sizes of significant region by group interactions from repeated measures ANOVAs run for each combination of regions and groups (1260 tests in total). Sample size as specified in panel a yet excluding HC; n=5788 independent subjects. Only significant (p<FDR; Benjamini-Hochberg) effects are shown. Suppl. Fig. 10 depicts effect sizes for all 1260 tests. d, Correlation coefficients for linear associations between brain age gaps and cognitive and clinical scores. Sample size comprised n=389 SZ for GAF_symptom, n=269 SZ for GAF_function, n=646 SZ for PANSS_positive, n=626 SZ for PANSS_negative, n=195 MS for EDSS, n=907 MCI and n=686 DEM for MMSE. Associations were computed using linear models accounting for age, age², sex, scanning site and Euler number, and the resulting t-statistics were transformed to r. Significant (P<FDR; Benjamini-Hochberg; two-sided) associations are marked with a black box. Corresponding scatter plots are depicted in Suppl. Fig 11.

**Figure 3. The brain age gaps are heritable, and the genetic underpinnings overlap with those observed for several disorders.**
Genetic analyses were performed using data from n=20,170 healthy adult individuals with European ancestry a, Heritability (h2) estimated using LD Score regression. Error bars reflect standard error. b, Significantly (P<FDR) overlapping loci between brain age gaps and disorders, identified using *conjunctional FDR*. c, Corresponding to panel b, the overlapping genes across all disorders, coloured by significance and sized by frequency of detection.

See this image and copyright information in PMC

References

1. WHO. World Health Statistics 2016. 2016.
1. Insel TR, Cuthbert BN. Brain disorders? Precisely. Science. 2015;348:499–500. doi: 10.1126/science.aab2358. - DOI - PubMed
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Common brain disorders are associated with heritable patterns of apparent aging of the brain

Collaborators

Affiliations

Common brain disorders are associated with heritable patterns of apparent aging of the brain

Authors

Collaborators

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical