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1. Unraveling robust brain-behavior links of depressive complaints through granular network models for understanding heterogeneity.

Author

Freichel R, Lenartowicz A, Douw L, Kruschwitz JD, Banaschewski T, Barker GJ, Bokde ALW, Desrivières S, Flor H, Grigis A, Garavan H, Heinz A, Brühl R, Martinot JL, Martinot MP, Artiges E, Nees F, Orfanos DP, Paus T, Poustka L, Holz N, Baeuchl C, Smolka MN, Vaidya N, Whelan R, Frouin V, Schumann G, Walter H, and Blanken TF

Subjects
Humans, Female, Male, Adolescent, Brain diagnostic imaging, Brain physiopathology, Cohort Studies, Hippocampus diagnostic imaging, Hippocampus pathology, Hippocampus physiopathology, Cerebral Cortex diagnostic imaging, Cerebral Cortex physiopathology, Cerebral Cortex pathology, Psychiatric Status Rating Scales, Young Adult, Gyrus Cinguli diagnostic imaging, Gyrus Cinguli physiopathology, Depression physiopathology, Depression psychology, Magnetic Resonance Imaging
Abstract

Background: Depressive symptoms are highly prevalent, present in heterogeneous symptom patterns, and share diverse neurobiological underpinnings. Understanding the links between psychopathological symptoms and biological factors is critical in elucidating its etiology and persistence. We aimed to evaluate the utility of using symptom-brain network models to parse the heterogeneity of depressive complaints in a large adolescent sample., Methods: We used data from the third wave of the IMAGEN study, a multi-center panel cohort study involving 1317 adolescents (52.49 % female, mean ± SD age = 18.5 ± 0.7). Two network models were estimated: one including an overall depressive symptom severity sum score based on the Adolescent Depression Rating Scale (ADRS), and one incorporating individual ADRS item scores. Both networks included measures of cortical thickness in several regions (insula, cingulate, mOFC, fusiform gyrus) and hippocampal volume derived from neuroimaging., Results: The network based on individual item scores revealed associations between cortical thickness measures and specific depressive complaints, obscured when using an aggregate depression severity score. Notably, the insula's cortical thickness showed negative associations with cognitive dysfunction (partial cor. = -0.15); the cingulate's cortical thickness showed negative associations with feelings of worthlessness (partial cor. = -0.10), and mOFC was negatively associated with anhedonia (partial cor. = -0.05)., Limitations: This cross-sectional study relied on the self-reported assessment of depression complaints and used a non-clinical sample with predominantly healthy participants (19 % with depression or sub-threshold depression)., Conclusions: This study showcases the utility of network models in parsing heterogeneity in depressive complaints, linking individual complaints to specific neural substrates. We outline the next steps to integrate neurobiological and cognitive markers to unravel MDD's phenotypic heterogeneity., Competing Interests: Declaration of competing interest Dr. Banaschewski served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire. He received conference support or speaker's fee by Lilly, Medice, Novartis and Shire. He has been involved in clinical trials conducted by Shire & Viforpharma. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. The present work is unrelated to the above grants and relationships. Dr. Barker has received honoraria from General Electric Healthcare for teaching on scanner programming courses. Dr. Poustka served in an advisory or consultancy role for Roche and Viforpharm and received speaker's fee by Shire. She received royalties from Hogrefe, Kohlhammer and Schattauer. The present work is unrelated to the above grants and relationships. The other authors report no biomedical financial interests or conflicts of interest. All authors have approved the final article., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Published
2024
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2. Investigating grey matter volumetric trajectories through the lifespan at the individual level.

Author

Shi R, Xiang S, Jia T, Robbins TW, Kang J, Banaschewski T, Barker GJ, Bokde ALW, Desrivières S, Flor H, Grigis A, Garavan H, Gowland P, Heinz A, Brühl R, Martinot JL, Martinot MP, Artiges E, Nees F, Orfanos DP, Paus T, Poustka L, Hohmann S, Millenet S, Fröhner JH, Smolka MN, Vaidya N, Walter H, Whelan R, Schumann G, Lin X, Sahakian BJ, and Feng J

Subjects
Humans, Adolescent, Female, Male, Young Adult, Brain diagnostic imaging, Brain growth & development, Adult, Longitudinal Studies, Organ Size, Neuroimaging, Cognition physiology, Longevity, Middle Aged, United Kingdom, Gray Matter diagnostic imaging, Magnetic Resonance Imaging
Abstract

Adolescents exhibit remarkable heterogeneity in the structural architecture of brain development. However, due to limited large-scale longitudinal neuroimaging studies, existing research has largely focused on population averages, and the neurobiological basis underlying individual heterogeneity remains poorly understood. Here we identify, using the IMAGEN adolescent cohort followed up over 9 years (14-23 y), three groups of adolescents characterized by distinct developmental patterns of whole-brain gray matter volume (GMV). Group 1 show continuously decreasing GMV associated with higher neurocognitive performances than the other two groups during adolescence. Group 2 exhibit a slower rate of GMV decrease and lower neurocognitive performances compared with Group 1, which was associated with epigenetic differences and greater environmental burden. Group 3 show increasing GMV and lower baseline neurocognitive performances due to a genetic variation. Using the UK Biobank, we show these differences may be attenuated in mid-to-late adulthood. Our study reveals clusters of adolescent neurodevelopment based on GMV and the potential long-term impact., (© 2024. The Author(s).)

Published
2024
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3. Adolescent to young adult longitudinal development of subcortical volumes in two European sites with four waves.

Author

Backhausen LL, Fröhner JH, Lemaître H, Artiges E, Martinot MP, Herting MM, Sticca F, Banaschewski T, Barker GJ, Bokde ALW, Desrivières S, Flor H, Grigis A, Garavan H, Gowland P, Heinz A, Brühl R, Nees F, Papadopoulos-Orfanos D, Poustka L, Hohmann S, Robinson L, Walter H, Winterer J, Whelan R, Schumann G, Martinot JL, Smolka MN, and Vetter NC

Subjects
Humans, Male, Adolescent, Female, Young Adult, Longitudinal Studies, Adolescent Development, Sex Characteristics, Magnetic Resonance Imaging methods, Brain diagnostic imaging
Abstract

Adolescent subcortical structural brain development might underlie psychopathological symptoms, which often emerge in adolescence. At the same time, sex differences exist in psychopathology, which might be mirrored in underlying sex differences in structural development. However, previous studies showed inconsistencies in subcortical trajectories and potential sex differences. Therefore, we aimed to investigate the subcortical structural trajectories and their sex differences across adolescence using for the first time a single cohort design, the same quality control procedure, software, and a general additive mixed modeling approach. We investigated two large European sites from ages 14 to 24 with 503 participants and 1408 total scans from France and Germany as part of the IMAGEN project including four waves of data acquisition. We found significantly larger volumes in males versus females in both sites and across all seven subcortical regions. Sex differences in age-related trajectories were observed across all regions in both sites. Our findings provide further evidence of sex differences in longitudinal adolescent brain development of subcortical regions and thus might eventually support the relationship of underlying brain development and different adolescent psychopathology in boys and girls., (© 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Published
2024
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4. Differential associations of adolescent versus young adult cannabis initiation with longitudinal brain change and behavior.

Author

Albaugh MD, Owens MM, Juliano A, Ottino-Gonzalez J, Cupertino R, Cao Z, Mackey S, Lepage C, Rioux P, Evans A, Banaschewski T, Bokde ALW, Conrod P, Desrivières S, Flor H, Grigis A, Gowland P, Heinz A, Ittermann B, Martinot JL, Martinot MP, Artiges E, Nees F, Orfanos DP, Paus T, Poustka L, Millenet S, Fröhner JH, Smolka MN, Walter H, Whelan R, Schumann G, Potter A, and Garavan H

Subjects
Humans, Adolescent, Male, Young Adult, Female, Longitudinal Studies, Marijuana Use, Adult, Prospective Studies, Marijuana Smoking, Marijuana Abuse, Prefrontal Cortex drug effects, Magnetic Resonance Imaging methods, Brain drug effects, Cannabis adverse effects
Abstract

Leveraging ~10 years of prospective longitudinal data on 704 participants, we examined the effects of adolescent versus young adult cannabis initiation on MRI-assessed cortical thickness development and behavior. Data were obtained from the IMAGEN study conducted across eight European sites. We identified IMAGEN participants who reported being cannabis-naïve at baseline and had data available at baseline, 5-year, and 9-year follow-up visits. Cannabis use was assessed with the European School Survey Project on Alcohol and Drugs. T1-weighted MR images were processed through the CIVET pipeline. Cannabis initiation occurring during adolescence (14-19 years) and young adulthood (19-22 years) was associated with differing patterns of longitudinal cortical thickness change. Associations between adolescent cannabis initiation and cortical thickness change were observed primarily in dorso- and ventrolateral portions of the prefrontal cortex. In contrast, cannabis initiation occurring between 19 and 22 years of age was associated with thickness change in temporal and cortical midline areas. Follow-up analysis revealed that longitudinal brain change related to adolescent initiation persisted into young adulthood and partially mediated the association between adolescent cannabis use and past-month cocaine, ecstasy, and cannabis use at age 22. Extent of cannabis initiation during young adulthood (from 19 to 22 years) had an indirect effect on psychotic symptoms at age 22 through thickness change in temporal areas. Results suggest that developmental timing of cannabis exposure may have a marked effect on neuroanatomical correlates of cannabis use as well as associated behavioral sequelae. Critically, this work provides a foundation for neurodevelopmentally informed models of cannabis exposure in humans., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2023
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5. Conduct problems are associated with accelerated thinning of emotion-related cortical regions in a community-based sample of adolescents.

Author

Albaugh MD, Hudziak JJ, Spechler PA, Chaarani B, Lepage C, Jeon S, Rioux P, Evans AC, Banaschewski T, Bokde ALW, Desrivières S, Flor H, Gowland P, Heinz A, Ittermann B, Martinot JL, Martinot MP, Nees F, Orfanos DP, Poustka L, Millenet S, Fröhner JH, Smolka MN, Walter H, Whelan R, Schumann G, Potter AS, and Garavan H

Subjects
Adult, Female, Adolescent, Humans, Prefrontal Cortex pathology, Emotions, Parietal Lobe, Magnetic Resonance Imaging methods, Cerebral Cortex pathology
Abstract

Few studies have examined the association between conduct problems and cerebral cortical development. Herein, we characterize the association between age-related brain change and conduct problems in a large longitudinal, community-based sample of adolescents. 1,039 participants from the IMAGEN study possessed psychopathology and surface-based morphometric data at study baseline (M = 14.42 years, SD = 0.40; 559 females) and 5-year follow-up. Self-reports of conduct problems were obtained using the Strengths and Difficulties Questionnaire (SDQ). Vertex-level linear mixed effects models were implemented using the Matlab toolbox, SurfStat. To investigate the extent to which cortical thickness maturation was qualified by dimensional measures of conduct problems, we tested for an interaction between age and SDQ Conduct Problems (CP) score. There was no main effect of CP score on cortical thickness; however, a significant "Age by CP" interaction was revealed in bilateral insulae, left inferior frontal gyrus, left rostral anterior cingulate, left posterior cingulate, and bilateral inferior parietal cortices. Across regions, follow-up analysis revealed higher levels of CP were associated with accelerated age-related thinning. Findings were not meaningfully altered when controlling for alcohol use, co-occurring psychopathology, and socioeconomic status. Results may help to further elucidate neurodevelopmental patterns linking adolescent conduct problems with adverse adult outcomes., Competing Interests: Declaration of Competing Interest Dr. Banaschewski has served as an advisor or consultant to Bristol-Myers Squibb, Desitin Arzneimittel, Eli Lilly, Medice, Novartis, Pfizer, Shire, UCB, and Vifor Pharma; he has received conference attendance support, conference support, or speaking fees from Eli Lilly, Janssen McNeil, Medice, Novartis, Shire, and UCB; and he is involved in clinical trials conducted by Eli Lilly, Novartis, and Shire; the present work is unrelated to these relationships. The other authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Published
2023
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6. Federated Analysis in COINSTAC Reveals Functional Network Connectivity and Spectral Links to Smoking and Alcohol Consumption in Nearly 2,000 Adolescent Brains.

Author

Gazula H, Rootes-Murdy K, Holla B, Basodi S, Zhang Z, Verner E, Kelly R, Murthy P, Chakrabarti A, Basu D, Bhagyalakshmi Nanjayya S, Lenin Singh R, Lourembam Singh R, Kalyanram K, Kartik K, Kalyanaraman K, Ghattu K, Kuriyan R, Kurpad SS, Barker GJ, Bharath RD, Desrivieres S, Purushottam M, Orfanos DP, Sharma E, Hickman M, Toledano M, Vaidya N, Banaschewski T, Bokde ALW, Flor H, Grigis A, Garavan H, Gowland P, Heinz A, Brühl R, Martinot JL, Paillére Martinot ML, Artiges E, Nees F, Paus T, Poustka L, Fröhner JH, Robinson L, Smolka MN, Walter H, Winterer J, Whelan R, Turner JA, Sarwate AD, Plis SM, Benegal V, Schumann G, and Calhoun VD

Subjects
Humans, Adolescent, Neural Pathways diagnostic imaging, Alcohol Drinking, Ethanol, Smoking, Brain Mapping, Magnetic Resonance Imaging, Brain diagnostic imaging
Abstract

With the growth of decentralized/federated analysis approaches in neuroimaging, the opportunities to study brain disorders using data from multiple sites has grown multi-fold. One such initiative is the Neuromark, a fully automated spatially constrained independent component analysis (ICA) that is used to link brain network abnormalities among different datasets, studies, and disorders while leveraging subject-specific networks. In this study, we implement the neuromark pipeline in COINSTAC, an open-source neuroimaging framework for collaborative/decentralized analysis. Decentralized exploratory analysis of nearly 2000 resting-state functional magnetic resonance imaging datasets collected at different sites across two cohorts and co-located in different countries was performed to study the resting brain functional network connectivity changes in adolescents who smoke and consume alcohol. Results showed hypoconnectivity across the majority of networks including sensory, default mode, and subcortical domains, more for alcohol than smoking, and decreased low frequency power. These findings suggest that global reduced synchronization is associated with both tobacco and alcohol use. This proof-of-concept work demonstrates the utility and incentives associated with large-scale decentralized collaborations spanning multiple sites., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2023
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7. Linked patterns of biological and environmental covariation with brain structure in adolescence: a population-based longitudinal study.

Author

Modabbernia A, Reichenberg A, Ing A, Moser DA, Doucet GE, Artiges E, Banaschewski T, Barker GJ, Becker A, Bokde ALW, Quinlan EB, Desrivières S, Flor H, Fröhner JH, Garavan H, Gowland P, Grigis A, Grimmer Y, Heinz A, Insensee C, Ittermann B, Martinot JL, Martinot MP, Millenet S, Nees F, Orfanos DP, Paus T, Penttilä J, Poustka L, Smolka MN, Stringaris A, van Noort BM, Walter H, Whelan R, Schumann G, and Frangou S

Subjects
Adolescent, Adult, Brain diagnostic imaging, Cross-Sectional Studies, Humans, Longitudinal Studies, Young Adult, Canonical Correlation Analysis, Magnetic Resonance Imaging
Abstract

Adolescence is a period of major brain reorganization shaped by biologically timed and by environmental factors. We sought to discover linked patterns of covariation between brain structural development and a wide array of these factors by leveraging data from the IMAGEN study, a longitudinal population-based cohort of adolescents. Brain structural measures and a comprehensive array of non-imaging features (relating to demographic, anthropometric, and psychosocial characteristics) were available on 1476 IMAGEN participants aged 14 years and from a subsample reassessed at age 19 years (n = 714). We applied sparse canonical correlation analyses (sCCA) to the cross-sectional and longitudinal data to extract modes with maximum covariation between neuroimaging and non-imaging measures. Separate sCCAs for cortical thickness, cortical surface area and subcortical volumes confirmed that each imaging phenotype was correlated with non-imaging features (sCCA r range: 0.30-0.65, all P FDR  < 0.001). Total intracranial volume and global measures of cortical thickness and surface area had the highest canonical cross-loadings (|ρ| = 0.31-0.61). Age, physical growth and sex had the highest association with adolescent brain structure (|ρ| = 0.24-0.62); at baseline, further significant positive associations were noted for cognitive measures while negative associations were observed at both time points for prenatal parental smoking, life events, and negative affect and substance use in youth (|ρ| = 0.10-0.23). Sex, physical growth and age are the dominant influences on adolescent brain development. We highlight the persistent negative influences of prenatal parental smoking and youth substance use as they are modifiable and of relevance for public health initiatives., (© 2020. The Author(s).)

Published
2021
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8. The Human Brain Is Best Described as Being on a Female/Male Continuum: Evidence from a Neuroimaging Connectivity Study.

Author

Zhang Y, Luo Q, Huang CC, Lo CZ, Langley C, Desrivières S, Quinlan EB, Banaschewski T, Millenet S, Bokde ALW, Flor H, Garavan H, Gowland P, Heinz A, Ittermann B, Martinot JL, Artiges E, Paillère-Martinot ML, Nees F, Orfanos DP, Poustka L, Fröhner JH, Smolka MN, Walter H, Whelan R, Tsai SJ, Lin CP, Bullmore E, Schumann G, Sahakian BJ, and Feng J

Subjects
Adult, Aged, Brain physiology, Databases, Factual trends, Female, Humans, Magnetic Resonance Imaging trends, Male, Middle Aged, Nerve Net physiology, Neuroimaging methods, Young Adult, Brain diagnostic imaging, Magnetic Resonance Imaging methods, Nerve Net diagnostic imaging, Sex Characteristics
Abstract

Psychological androgyny has long been associated with greater cognitive flexibility, adaptive behavior, and better mental health, but whether a similar concept can be defined using neural features remains unknown. Using the neuroimaging data from 9620 participants, we found that global functional connectivity was stronger in the male brain before middle age but became weaker after that, when compared with the female brain, after systematic testing of potentially confounding effects. We defined a brain gender continuum by estimating the likelihood of an observed functional connectivity matrix to represent a male brain. We found that participants mapped at the center of this continuum had fewer internalizing symptoms compared with those at the 2 extreme ends. These findings suggest a novel hypothesis proposing that there exists a neuroimaging concept of androgyny using the brain gender continuum, which may be associated with better mental health in a similar way to psychological androgyny., (© The Author(s) 2021. Published by Oxford University Press.)

Published
2021
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9. Reward Versus Nonreward Sensitivity of the Medial Versus Lateral Orbitofrontal Cortex Relates to the Severity of Depressive Symptoms.

Author

Xie C, Jia T, Rolls ET, Robbins TW, Sahakian BJ, Zhang J, Liu Z, Cheng W, Luo Q, Zac Lo CY, Wang H, Banaschewski T, Barker GJ, Bokde ALW, Büchel C, Quinlan EB, Desrivières S, Flor H, Grigis A, Garavan H, Gowland P, Heinz A, Hohmann S, Ittermann B, Martinot JL, Paillère Martinot ML, Nees F, Orfanos DP, Paus T, Poustka L, Fröhner JH, Smolka MN, Walter H, Whelan R, Schumann G, and Feng J

Subjects
Adolescent, Adult, Frontal Lobe, Humans, Prefrontal Cortex, Reward, Young Adult, Depression, Magnetic Resonance Imaging
Abstract

Background: The orbitofrontal cortex (OFC) is implicated in depression. The hypothesis investigated was whether the OFC sensitivity to reward and nonreward is related to the severity of depressive symptoms., Methods: Activations in the monetary incentive delay task were measured in the IMAGEN cohort at ages 14 years (n = 1877) and 19 years (n = 1140) with a longitudinal design. Clinically relevant subgroups were compared at ages 19 (high-severity group: n = 116; low-severity group: n = 206) and 14., Results: The medial OFC exhibited graded activation increases to reward, and the lateral OFC had graded activation increases to nonreward. In this general population, the medial and lateral OFC activations were associated with concurrent depressive symptoms at both ages 14 and 19 years. In a stratified high-severity depressive symptom group versus control group comparison, the lateral OFC showed greater sensitivity for the magnitudes of activations related to nonreward in the high-severity group at age 19 (p = .027), and the medial OFC showed decreased sensitivity to the reward magnitudes in the high-severity group at both ages 14 (p = .002) and 19 (p = .002). In a longitudinal design, there was greater sensitivity to nonreward of the lateral OFC at age 14 for those who exhibited high depressive symptom severity later at age 19 (p = .003)., Conclusions: Activations in the lateral OFC relate to sensitivity to not winning, were associated with high depressive symptom scores, and at age 14 predicted the depressive symptoms at ages 16 and 19. Activations in the medial OFC were related to sensitivity to winning, and reduced reward sensitivity was associated with concurrent high depressive symptom scores., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Published
2021
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10. Brain-predicted age difference score is related to specific cognitive functions: a multi-site replication analysis.

Author

Boyle R, Jollans L, Rueda-Delgado LM, Rizzo R, Yener GG, McMorrow JP, Knight SP, Carey D, Robertson IH, Emek-Savaş DD, Stern Y, Kenny RA, and Whelan R

Subjects
Cognition, Humans, Longitudinal Studies, Neuroimaging, Neuropsychological Tests, Brain diagnostic imaging, Magnetic Resonance Imaging
Abstract

Brain-predicted age difference scores are calculated by subtracting chronological age from 'brain' age, which is estimated using neuroimaging data. Positive scores reflect accelerated ageing and are associated with increased mortality risk and poorer physical function. To date, however, the relationship between brain-predicted age difference scores and specific cognitive functions has not been systematically examined using appropriate statistical methods. First, applying machine learning to 1359 T1-weighted MRI scans, we predicted the relationship between chronological age and voxel-wise grey matter data. This model was then applied to MRI data from three independent datasets, significantly predicting chronological age in each dataset: Dokuz Eylül University (n = 175), the Cognitive Reserve/Reference Ability Neural Network study (n = 380), and The Irish Longitudinal Study on Ageing (n = 487). Each independent dataset had rich neuropsychological data. Brain-predicted age difference scores were significantly negatively correlated with performance on measures of general cognitive status (two datasets); processing speed, visual attention, and cognitive flexibility (three datasets); visual attention and cognitive flexibility (two datasets); and semantic verbal fluency (two datasets). As such, there is firm evidence of correlations between increased brain-predicted age differences and reduced cognitive function in some domains that are implicated in cognitive ageing.

Published
2021
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11. The empirical replicability of task-based fMRI as a function of sample size.

Author

Bossier H, Roels SP, Seurinck R, Banaschewski T, Barker GJ, Bokde ALW, Quinlan EB, Desrivières S, Flor H, Grigis A, Garavan H, Gowland P, Heinz A, Ittermann B, Martinot JL, Artiges E, Nees F, Orfanos DP, Poustka L, Fröhner Dipl-Psych JH, Smolka MN, Walter H, Whelan R, Schumann G, and Moerkerke B

Subjects
Brain Mapping methods, Humans, Reproducibility of Results, Brain Mapping standards, Magnetic Resonance Imaging methods, Magnetic Resonance Imaging standards, Sample Size
Abstract

Replicating results (i.e. obtaining consistent results using a new independent dataset) is an essential part of good science. As replicability has consequences for theories derived from empirical studies, it is of utmost importance to better understand the underlying mechanisms influencing it. A popular tool for non-invasive neuroimaging studies is functional magnetic resonance imaging (fMRI). While the effect of underpowered studies is well documented, the empirical assessment of the interplay between sample size and replicability of results for task-based fMRI studies remains limited. In this work, we extend existing work on this assessment in two ways. Firstly, we use a large database of 1400 subjects performing four types of tasks from the IMAGEN project to subsample a series of independent samples of increasing size. Secondly, replicability is evaluated using a multi-dimensional framework consisting of 3 different measures: (un)conditional test-retest reliability, coherence and stability. We demonstrate not only a positive effect of sample size, but also a trade-off between spatial resolution and replicability. When replicability is assessed voxelwise or when observing small areas of activation, a larger sample size than typically used in fMRI is required to replicate results. On the other hand, when focussing on clusters of voxels, we observe a higher replicability. In addition, we observe variability in the size of clusters of activation between experimental paradigms or contrasts of parameter estimates within these., Competing Interests: Declaration of competing interest Dr. Banaschewski has served as an advisor or consultant to Bristol-Myers Squibb, Desitin Arzneimittel, Eli Lilly, Medice, Novartis, Pfizer, Shire, UCB, and Vifor Pharma; he has received conference attendance support, conference support, or speaking fees from Eli Lilly, Janssen McNeil, Medice, Novartis, Shire, and UCB; and he is involved in clinical trials conducted by Eli Lilly, Novartis, and Shire; the present work is unrelated to these relationships. Dr. Barker has received honoraria from General Electric Healthcare for teaching on scanner programming courses and acts as a consultant for IXICO. The other authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2020
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12. Predicting change trajectories of neuroticism from baseline brain structure using whole brain analyses and latent growth curve models in adolescents.

Author

Kühn S, Mascherek A, Banaschewski T, Bokde ALW, Büchel C, Quinlan EB, Desrivières S, Flor H, Grigis A, Garavan H, Gowland P, Heinz A, Ittermann B, Martinot JL, Martinot MP, Nees F, Orfanos DP, Paus T, Poustka L, Millenet S, Fröhner JH, Smolka MN, Walter H, Whelan R, Schumann G, Lindenberger U, and Gallinat J

Subjects
Adolescent, Female, Follow-Up Studies, Healthy Volunteers, Humans, Male, Patient Dropouts, Prognosis, Self Report, Young Adult, Magnetic Resonance Imaging, Models, Neurological, Neuroticism, Pituitary Gland diagnostic imaging
Abstract

Adolescence is a vulnerable time for personality development. Especially neuroticism with its link to the development of psychopathology is of interest concerning influential factors. The present study exploratorily investigates neuroanatomical signatures for developmental trajectories of neuroticism based on a voxel-wise whole-brain structural equation modelling framework. In 1,814 healthy adolescents of the IMAGEN sample, the NEO-FFI was acquired at three measurement occasions across five years. Based on a partial measurement invariance second-order latent growth curve model we conducted whole-brain analyses on structural MRI data at age 14 years, predicting change in neuroticism over time. We observed that a reduced volume in the pituitary gland was associated with the slope of neuroticism over time. However, no relations with prefrontal areas emerged. Both findings are discussed against the background of possible genetic and social influences that may account for this result.

Published
2020
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13. Psychosocial Stress and Brain Function in Adolescent Psychopathology.

Author

Quinlan EB, Cattrell A, Jia T, Artiges E, Banaschewski T, Barker G, Bokde ALW, Bromberg U, Büchel C, Brühl R, Conrod PJ, Desrivieres S, Flor H, Frouin V, Gallinat J, Garavan H, Gowland P, Heinz A, Martinot JL, Paillère Martinot ML, Nees F, Papadopoulos-Orfanos D, Paus T, Poustka L, Smolka MN, Vetter NC, Walter H, Whelan R, Glennon JC, Buitelaar JK, Happé F, Loth E, Barker ED, and Schumann G

Subjects
Adolescent, Amygdala physiopathology, Attention Deficit Disorder with Hyperactivity diagnosis, Attention Deficit Disorder with Hyperactivity psychology, Conduct Disorder diagnosis, Conduct Disorder psychology, Female, Humans, Male, Neural Pathways physiopathology, Parietal Lobe physiopathology, Stress, Psychological complications, Stress, Psychological psychology, Attention Deficit Disorder with Hyperactivity physiopathology, Brain physiopathology, Conduct Disorder physiopathology, Emotions physiology, Facial Expression, Magnetic Resonance Imaging, Pattern Recognition, Visual physiology, Social Environment, Stress, Psychological physiopathology
Abstract

Objective: The authors sought to explore how conduct, hyperactivity/inattention, and emotional symptoms are associated with neural reactivity to social-emotional stimuli, and the extent to which psychosocial stress modulates these relationships., Method: Participants were community adolescents recruited as part of the European IMAGEN study. Bilateral amygdala regions of interest were used to assess the relationship between the three symptom domains and functional MRI neural reactivity during passive viewing of dynamic angry and neutral facial expressions. Exploratory functional connectivity and whole brain multiple regression approaches were used to analyze how the symptoms and psychosocial stress relate to other brain regions., Results: In response to the social-emotional stimuli, adolescents with high levels of conduct or hyperactivity/inattention symptoms who had also experienced a greater number of stressful life events showed hyperactivity of the amygdala and several regions across the brain. This effect was not observed with emotional symptoms. A cluster in the midcingulate was found to be common to both conduct problems and hyperactivity symptoms. Exploratory functional connectivity analyses suggested that amygdala-precuneus connectivity is associated with hyperactivity/inattention symptoms., Conclusions: The results link hyperactive amygdala responses and regions critical for top-down emotional processing with high levels of psychosocial stress in individuals with greater conduct and hyperactivity/inattention symptoms. This work highlights the importance of studying how psychosocial stress affects functional brain responses to social-emotional stimuli, particularly in adolescents with externalizing symptoms.

Published
2017
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14. Functional Neuroimaging Predictors of Self-Reported Psychotic Symptoms in Adolescents.

Author

Bourque J, Spechler PA, Potvin S, Whelan R, Banaschewski T, Bokde ALW, Bromberg U, Büchel C, Quinlan EB, Desrivières S, Flor H, Frouin V, Gowland P, Heinz A, Ittermann B, Martinot JL, Paillère-Martinot ML, McEwen SC, Nees F, Orfanos DP, Paus T, Poustka L, Smolka MN, Vetter NC, Walter H, Schumann G, Garavan H, and Conrod PJ

Subjects
Adolescent, Affect physiology, Amygdala physiopathology, Case-Control Studies, Europe, Female, Follow-Up Studies, Hippocampus physiopathology, Humans, Male, Nerve Net physiopathology, Predictive Value of Tests, Prefrontal Cortex physiopathology, Psychotic Disorders psychology, Reference Values, Reward, Risk Assessment, Statistics as Topic, Anticipation, Psychological physiology, Brain physiopathology, Inhibition, Psychological, Magnetic Resonance Imaging, Psychotic Disorders diagnosis, Psychotic Disorders physiopathology, Self Report
Abstract

Objective: This study investigated the neural correlates of psychotic-like experiences in youths during tasks involving inhibitory control, reward anticipation, and emotion processing. A secondary aim was to test whether these neurofunctional correlates of risk were predictive of psychotic symptoms 2 years later., Method: Functional imaging responses to three paradigms-the stop-signal, monetary incentive delay, and faces tasks-were collected in youths at age 14, as part of the IMAGEN study. At baseline, youths from London and Dublin sites were assessed on psychotic-like experiences, and those reporting significant experiences were compared with matched control subjects. Significant brain activity differences between the groups were used to predict, with cross-validation, the presence of psychotic symptoms in the context of mood fluctuation at age 16, assessed in the full sample. These prediction analyses were conducted with the London-Dublin subsample (N=246) and the full sample (N=1,196)., Results: Relative to control subjects, youths reporting psychotic-like experiences showed increased hippocampus/amygdala activity during processing of neutral faces and reduced dorsolateral prefrontal activity during failed inhibition. The most prominent regional difference for classifying 16-year-olds with mood fluctuation and psychotic symptoms relative to the control groups (those with mood fluctuations but no psychotic symptoms and those with no mood symptoms) was hyperactivation of the hippocampus/amygdala, when controlling for baseline psychotic-like experiences and cannabis use., Conclusions: The results stress the importance of the limbic network's increased response to neutral facial stimuli as a marker of the extended psychosis phenotype. These findings might help to guide early intervention strategies for at-risk youths.

Published
2017
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15. Ventral Striatum Connectivity During Reward Anticipation in Adolescent Smokers.

Author

Jollans L, Zhipeng C, Icke I, Greene C, Kelly C, Banaschewski T, Bokde AL, Bromberg U, Büchel C, Cattrell A, Conrod PJ, Desrivières S, Flor H, Frouin V, Gallinat J, Garavan H, Gowland P, Heinz A, Ittermann B, Martinot JL, Artiges E, Nees F, Papadopoulos Orfanos D, Paus T, Smolka MN, Walter H, Schumann G, and Whelan R

Subjects
Adolescent, Brain Mapping, Female, Humans, Inhibition, Psychological, Machine Learning, Male, Risk Reduction Behavior, Anticipation, Psychological physiology, Magnetic Resonance Imaging, Motivation physiology, Nerve Net physiopathology, Prefrontal Cortex physiopathology, Reward, Smoking physiopathology, Smoking psychology, Ventral Striatum physiopathology
Abstract

Substance misusers, including adolescent smokers, often have reduced reward system activity during processing of non-drug rewards. Using a psychophysiological interaction approach, we examined functional connectivity with the ventral striatum during reward anticipation in a large (N = 206) sample of adolescent smokers. Increased smoking frequency was associated with (1) increased connectivity with regions involved in saliency and valuation, including the orbitofrontal cortex and (2) reduced connectivity between the ventral striatum and regions associated with inhibition and risk aversion, including the right inferior frontal gyrus. These results demonstrate that functional connectivity during reward processing is relevant to adolescent addiction.

Published
2016
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16. Multi-feature computational framework for combined signatures of dementia in underrepresented settings.

Author

Moguilner, Sebastian, Birba, Agustina, Fittipaldi, Sol, Gonzalez-Campo, Cecilia, Tagliazucchi, Enzo, Reyes, Pablo, Matallana, Diana, Parra, Mario, Slachevsky, Andrea, Farías, Gonzalo, Cruzat, Josefina, García, Adolfo, Eyre, Harris, La Joie, Renaud, Rabinovici, Gil, Whelan, Robert, and Ibáñez, Agustín

Subjects
feature selection, harmonization, machine learning, multimodal neuroimaging, neurodegeneration, Alzheimer Disease, Bayes Theorem, Biomarkers, Brain, Frontotemporal Dementia, Humans, Magnetic Resonance Imaging, Neuropsychological Tests
Abstract

Objective.The differential diagnosis of behavioral variant frontotemporal dementia (bvFTD) and Alzheimers disease (AD) remains challenging in underrepresented, underdiagnosed groups, including Latinos, as advanced biomarkers are rarely available. Recent guidelines for the study of dementia highlight the critical role of biomarkers. Thus, novel cost-effective complementary approaches are required in clinical settings.Approach. We developed a novel framework based on a gradient boosting machine learning classifier, tuned by Bayesian optimization, on a multi-feature multimodal approach (combining demographic, neuropsychological, magnetic resonance imaging (MRI), and electroencephalography/functional MRI connectivity data) to characterize neurodegeneration using site harmonization and sequential feature selection. We assessed 54 bvFTD and 76 AD patients and 152 healthy controls (HCs) from a Latin American consortium (ReDLat).Main results. The multimodal model yielded high area under the curve classification values (bvFTD patients vs HCs: 0.93 (±0.01); AD patients vs HCs: 0.95 (±0.01); bvFTD vs AD patients: 0.92 (±0.01)). The feature selection approach successfully filtered non-informative multimodal markers (from thousands to dozens).Results. Proved robust against multimodal heterogeneity, sociodemographic variability, and missing data.Significance. The model accurately identified dementia subtypes using measures readily available in underrepresented settings, with a similar performance than advanced biomarkers. This approach, if confirmed and replicated, may potentially complement clinical assessments in developing countries.

Published
2022

17. Reward Processing in Novelty Seekers: A Transdiagnostic Psychiatric Imaging Biomarker.

Author

Qi, Shile, Schumann, Gunter, Bustillo, Juan, Turner, Jessica A, Jiang, Rongtao, Zhi, Dongmei, Fu, Zening, Mayer, Andrew R, Vergara, Victor M, Silva, Rogers F, Iraji, Armin, Chen, Jiayu, Damaraju, Eswar, Ma, Xiaohong, Yang, Xiao, Stevens, Michael, Mathalon, Daniel H, Ford, Judith M, Voyvodic, James, Mueller, Bryon A, Belger, Aysenil, Potkin, Steven G, Preda, Adrian, Zhuo, Chuanjun, Xu, Yong, Chu, Congying, Banaschewski, Tobias, Barker, Gareth J, Bokde, Arun LW, Quinlan, Erin Burke, Desrivières, Sylvane, Flor, Herta, Grigis, Antoine, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Martinot, Jean-Luc, Paillère Martinot, Marie-Laure, Artiges, Eric, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomáš, Poustka, Luise, Hohmann, Sarah, Fröhner, Juliane H, Smolka, Michael N, Walter, Henrik, Whelan, Robert, Calhoun, Vince D, Sui, Jing, and IMAGEN Consortium

Subjects
IMAGEN Consortium, Humans, Magnetic Resonance Imaging, Reward, Attention Deficit Disorder with Hyperactivity, Depressive Disorder, Major, Adolescent, Adult, Young Adult, Biomarkers, ADHD, Attention-deficit/hyperactivity disorder, MDD, Major depressive disorders, Novelty seeking, Reward processing, Schizophrenia, Substance use, Prevention, Serious Mental Illness, Pediatric, Mental Health, Neurosciences, Brain Disorders, Substance Misuse, Behavioral and Social Science, Depression, Alcoholism, Alcohol Use and Health, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Mental health, Good Health and Well Being, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundDysfunctional reward processing is implicated in multiple mental disorders. Novelty seeking (NS) assesses preference for seeking novel experiences, which is linked to sensitivity to reward environmental cues.MethodsA subset of 14-year-old adolescents (IMAGEN) with the top 20% ranked high-NS scores was used to identify high-NS-associated multimodal components by supervised fusion. These features were then used to longitudinally predict five different risk scales for the same and unseen subjects (an independent dataset of subjects at 19 years of age that was not used in predictive modeling training at 14 years of age) (within IMAGEN, n ≈1100) and even for the corresponding symptom scores of five types of patient cohorts (non-IMAGEN), including drinking (n = 313), smoking (n = 104), attention-deficit/hyperactivity disorder (n = 320), major depressive disorder (n = 81), and schizophrenia (n = 147), as well as to classify different patient groups with diagnostic labels.ResultsMultimodal biomarkers, including the prefrontal cortex, striatum, amygdala, and hippocampus, associated with high NS in 14-year-old adolescents were identified. The prediction models built on these features are able to longitudinally predict five different risk scales, including alcohol drinking, smoking, hyperactivity, depression, and psychosis for the same and unseen 19-year-old adolescents and even predict the corresponding symptom scores of five types of patient cohorts. Furthermore, the identified reward-related multimodal features can classify among attention-deficit/hyperactivity disorder, major depressive disorder, and schizophrenia with an accuracy of 87.2%.ConclusionsAdolescents with higher NS scores can be used to reveal brain alterations in the reward-related system, implicating potential higher risk for subsequent development of multiple disorders. The identified high-NS-associated multimodal reward-related signatures may serve as a transdiagnostic neuroimaging biomarker to predict disease risks or severity.

Published
2021

18. Trajectories of cortical structures associated with stress across adolescence: a bivariate latent change score approach

Author

Nweze, Tochukwu, Banaschewski, Tobias, Ajaelu, Cyracius, Okoye, Chukwuemeka, Ezenwa, Michael, Whelan, Robert, Papadopoulos Orfanos, Dimitri, Bokde, Arun LW, Desrivières, Sylvane, Grigis, Antoine, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Brühl, Rüdiger, Martinot, Jean-Luc, Martinot, Marie-Laure Paillère, Artiges, Eric, Nees, Frauke, Paus, Tomáš, Poustka, Luise, Hohmann, Sarah, Millenet, Sabina, Fröhner, Juliane H, Smolka, Michael N, Walter, Henrik, Schumann, Gunter, Hanson, Jamie L, IMAGEN Consortium, and Apollo - University of Cambridge Repository

Subjects
Adult, Cerebral Cortex, Adolescent, Sexually Transmitted Diseases, bivariate latent change score model, longitudinal models, Stress, Magnetic Resonance Imaging, cognitive functioning, Young Adult, longitudinal mediation analysis, Cross-Sectional Studies, Humans, cortical development, Longitudinal Studies
Abstract

Funder: Cambridge Trust (University of Cambridge); Id: http://dx.doi.org/10.13039/501100000735, Funder: National Institute for Health Research (NIHR) Biomedical Research Centre at South London, Funder: Maudsley NHS Foundation Trust and King's College London, Funder: Medical Research Foundation; Id: http://dx.doi.org/10.13039/501100009187, Funder: Mission Interministérielle de Lutte‐contre‐les‐Drogues‐et‐les‐Conduites‐Addictives (MILDECA), Funder: Assistance‐Publique‐Hôpitaux‐de‐Paris and INSERM, Funder: Paris Sud University IDEX 2012, Funder: Fédération pour la Recherche sur le Cerveau; Id: http://dx.doi.org/10.13039/501100006424, BACKGROUND: Stress exposure in childhood and adolescence has been linked to reductions in cortical structures and cognitive functioning. However, to date, most of these studies have been cross-sectional, limiting the ability to make long-term inferences, given that most cortical structures continue to develop through adolescence. METHODS: Here, we used a subset of the IMAGEN population cohort sample (N = 502; assessment ages: 14, 19, and 22 years; mean age: 21.945 years; SD = 0.610) to understand longitudinally the long-term interrelations between stress, cortical development, and cognitive functioning. To these ends, we first used a latent change score model to examine four bivariate relations - assessing individual differences in change in the relations between adolescent stress exposure and volume, surface area, and cortical thickness of cortical structures, as well as cognitive outcomes. Second, we probed for indirect neurocognitive effects linking stress to cortical brain structures and cognitive functions using rich longitudinal mediation modeling. RESULTS: Latent change score modeling showed that greater baseline adolescence stress at age 14 predicted a small reduction in the right anterior cingulate volume (Std. β = -.327, p = .042, 95% CI [-0.643, -0.012]) and right anterior cingulate surface area (Std. β = -.274, p = .038, 95% CI [-0.533, -0.015]) across ages 14-22. These effects were very modest in nature and became nonsignificant after correcting for multiple comparisons. Our longitudinal analyses found no evidence of indirect effects in the two neurocognitive pathways linking adolescent stress to brain and cognitive outcomes. CONCLUSION: Findings shed light on the impact of stress on brain reductions, particularly in the prefrontal cortex that have consistently been implicated in the previous cross-sectional studies. However, the magnitude of effects observed in our study is smaller than that has been reported in past cross-sectional work. This suggests that the potential impact of stress during adolescence on brain structures may likely be more modest than previously noted.

Published
2023

19. Genetic variants associated with longitudinal changes in brain structure across the lifespan

Author

Brouwer, Rachel M, Klein, Marieke, Kremen, William S, Guimaraes, Joao P O F T, Homuth, Georg, Hottenga, Jouke-Jan, Knol, Maria J, Kwok, John B J, Le Hellard, Stephanie, Mather, Karen A, Milaneschi, Yuri, Morris, Derek W, Nöthen, Markus M., Panizzon, Matthew S, Papiol, Sergi, Rietschel, Marcella, Santoro, Marcos L, Steen, Vidar M, Stein, Jason L, Streit, Fabian, Tankard, Rick M, Teumer, Alexander, van 't Ent, Dennis, van der Meer, Dennis, Olde Loohuis, Loes M, van Eijk, Kristel R, Vassos, Evangelos, Vázquez-Bourgon, Javier, Witt, Stephanie H, Consortium, IMAGEN, Adams, Hieab H H, Agartz, Ingrid, Ames, David, Amunts, Katrin, Andreassen, Ole A, Whelan, Christopher D, Arango, Celso, Banaschewski, Tobias, Baune, Bernhard T, Belangero, Sintia I, Bokde, Arun L W, Boomsma, Dorret I, Bressan, Rodrigo A, Brodaty, Henry, Buitelaar, Jan K, Cahn, Wiepke, Aghajani, Moji, Caspers, Svenja, Cichon, Sven, Crespo-Facorro, Benedicto, Cox, Simon R, Dannlowski, Udo, Elvsåshagen, Torbjørn, Espeseth, Thomas, Falkai, Peter, Fisher, Simon E, Flor, Herta, Alloza, Clara, Fullerton, Janice M, Garavan, Hugh, Gowland, Penny A, Grabe, Hans, Hahn, Tim, Heinz, Andreas, Hillegers, Manon, Hoare, Jacqueline, Hoekstra, Pieter J, Ikram, Mohammad A, Alnæs, Dag, Jackowski, Andrea P, Jansen, Andreas, Jönsson, Erik G, Kahn, Rene S, Kircher, Tilo, Korgaonkar, Mayuresh S, Krug, Axel, Lemaitre, Herve, Malt, Ulrik F, Martinot, Jean-Luc, Artiges, Eric, McDonald, Colm, Mitchell, Philip B, Muetzel, Ryan L, Murray, Robin M, Nees, Frauke, Nenadić, Igor, Oosterlaan, Jaap, Ophoff, Roel A, Pan, Pedro M, Penninx, Brenda W J H, Ayesa-Arriola, Rosa, Poustka, Luise, Sachdev, Perminder S, Salum, Giovanni A, Schofield, Peter R, Schumann, Gunter, Shaw, Philip, Sim, Kang, Smolka, Michael N, Stein, Dan J, Trollor, Julian N, Barker, Gareth J, van den Berg, Leonard H, Veldink, Jan H, Walter, Henrik, Westlye, Lars T, Whelan, Robert, White, Tonya, Wright, Margaret J, Medland, Sarah E, Franke, Barbara, Thompson, Paul M, Grasby, Katrina L, Bastin, Mark E, Hulshoff Pol, Hilleke E, Brühl, Rüdiger, Papadopoulos Orfanos, Dimitri, Paus, Tomáš, Millenet, Sabina, Blok, Elisabet, Bøen, Erlend, Breukelaar, Isabella A, Bright, Joanna K, Buimer, Elizabeth E L, Bülow, Robin, Cannon, Dara M, Ciufolini, Simone, Crossley, Nicolas A, Schnack, Hugo G, Damatac, Christienne G, Dazzan, Paola, de Mol, Casper L, de Zwarte, Sonja M C, Desrivières, Sylvane, Díaz-Caneja, Covadonga M, Doan, Nhat Trung, Dohm, Katharina, Fröhner, Juliane H, Goltermann, Janik, Jahanshad, Neda, Grigis, Antoine, Grotegerd, Dominik, Han, Laura K M, Harris, Mathew, Hartman, Catharina A, Heany, Sarah J, Heindel, Walter, Heslenfeld, Dirk J., Hohmann, Sarah, Ittermann, Bernd, Teeuw, Jalmar, Jansen, Philip R, Janssen, Joost, Jia, Tianye, Jiang, Jiyang, Jockwitz, Christiane, Karali, Temmuz, Keeser, Daniel, Koevoets, Martijn G J C, Lenroot, Rhoshel K, Malchow, Berend, Thomopoulos, Sophia I, Mandl, René C W, Medel, Vicente, Meinert, Susanne, Morgan, Catherine A, Mühleisen, Thomas W, Nabulsi, Leila, Opel, Nils, de la Foz, Víctor Ortiz-García, Overs, Bronwyn J, Paillère Martinot, Marie-Laure, Sprooten, Emma, Redlich, Ronny, Marques, Tiago Reis, Repple, Jonathan, Roberts, Gloria, Roshchupkin, Gennady V, Setiaman, Nikita, Shumskaya, Elena, Stein, Frederike, Sudre, Gustavo, Takahashi, Shun, Franz, Carol E, Thalamuthu, Anbupalam, Tordesillas-Gutiérrez, Diana, van der Lugt, Aad, van Haren, Neeltje E M, Wardlaw, Joanna M, Wen, Wei, Westeneng, Henk-Jan, Wittfeld, Katharina, Zhu, Alyssa H, Zugman, Andre, Gogtay, Nitin, Armstrong, Nicola J, Bonfiglio, Gaia, Bralten, Janita, Dalvie, Shareefa, Davies, Gail, Di Forti, Marta, Ding, Linda, Donohoe, Gary, Forstner, Andreas J, Gonzalez-Peñas, Javier, Child and Adolescent Psychiatry / Psychology, Erasmus MC other, Anesthesiology, Epidemiology, Radiology & Nuclear Medicine, Clinical Genetics, Psychiatry, the IMAGEN Consortium, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Pediatric surgery, APH - Aging & Later Life, APH - Mental Health, APH - Digital Health, European Commission, European Research Council, Comunidad de Madrid, Instituto de Salud Carlos III, Fundación Mutua Madrileña, Fundación Alicia Koplowitz, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Psychiatry 2, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Complex Trait Genetics, Cognitive Psychology, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Methodology, Clinical Neuropsychology, IBBA, General Paediatrics, ARD - Amsterdam Reproduction and Development, and Paediatrics

Subjects
Neuroinformatics, EXPRESSION, Aging, SUSCEPTIBILITY LOCI, Longevity, SURFACE-AREA, INDIVIDUAL-DIFFERENCES, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, Aging/genetics, Humans, ddc:610, GENOME-WIDE ASSOCIATION, METAANALYSIS, RISK, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], General Neuroscience, 220 Statistical Imaging Neuroscience, Longevity/genetics, Brain, Magnetic Resonance Imaging, genetics [Aging], VOLUME, RELIABILITY, sense organs, CORTICAL THICKNESS, genetics [Longevity], Genome-Wide Association Study
Abstract

et al., Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging., The ENIGMA-Plasticity Working Group is part of the ENIGMA World Aging Center, funded by NIA grants R56 AG058854 and R01 AG058854. The ENIGMA Consortium core funding was supported by NIH Consortium Grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centers of Excellence. 1000BRAINS: 1000BRAINS is a population-based cohort based on the Heinz-Nixdorf Recall Study and is supported, in part, by the German National Cohort. We thank the Heinz Nixdorf Foundation (Germany) for their generous support in terms of the Heinz Nixdorf Study. The authors are supported by the Initiative and Networking Fund of the Helmholtz Association (Svenja Caspers) and the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements 785907 (Human Brain Project SGA2; Svenja Caspers, Sven Cichon and Katrin Amunts). This work was further supported by the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders) under the auspices of the e:Med Program (grant 01ZX1314A; Sven Cichon) and by the Swiss National Science Foundation (SNSF, grant 156791; Sven Cichon). The authors acknowledge grants supporting their work from the European Union’s Horizon 2020 Research and Innovation Programme (H2020/2014–2020) under grant agreements 667302 (CoCA), 728018 (Eat2beNICE), 785907 (HBP SGA2) and 772376 (EScORIAL) and the Netherlands ALS Foundation.Additional support is received from the European Community’s Seventh Framework Programme (FP7/2007—2013) under grant agreements n° 602805 (Aggressotype), n° 603016 (MATRICS), n° 602450 (IMAGEMEND) and n° 278948 (TACTICS) and from the European Community’s Horizon 2020 Programme (H2020/2014—2020) under grant agreements n° 643051 (MiND) and n° 667302 (CoCA). FP7 Ideas: the European Research Council (ERC-230374 to D.B.). This work was supported by Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012 and PI19/024), co-financed by ERDF Funds from the European Commission, ‘A way of making Europe’, CIBERSAM; Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds; European Union Seventh Framework Program under grant agreements FP7- HEALTH-2013-2.2.1-2-603196 (Project PSYSCAN) and European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement 115916, Project PRISM and grant agreement 777394, Project AIMS-2-TRIALS), Fundación Familia Alonso, Fundación Alicia Koplowitz and Fundación Mutua Madrileña. The Horizon 2020 funded ERC Advanced Grant ‘STRATIFY’ (Brain network based stratification of reinforcement-related disorders) (695313). The FP7 project MATRICS (603016). The research leading to these results also received support from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement 278948 (TACTICS), 602805 (Aggressotype), 603016 (MATRICS) and 602450 (Imagemend) and the Innovation Medicine Initiative grants 115300 (EU-AIMS) and 777394 (AIMS-2-TRIALS).PAFIP: PAFIP was supported by the Instituto de Salud Carlos III (PI14/00639, PI14/00918 and PI17/01056) and Fundación Instituto de Investigación Marqués de Valdecilla (NCT0235832 and NCT025KG Jebsen Stiftelsen and H2020 CoMorMent (847776).34363). European Union Marie Curie Research Training Network (MRTN-CT-2006-035987).

Published
2022

20. Neural network involving medial orbitofrontal cortex and dorsal periaqueductal gray regulation in human alcohol abuse

Author

Jia, Tianye, Xie, Chao, Banaschewski, Tobias, Barker, Gareth J, Bokde, Arun LW, Büchel, Christian, Quinlan, Erin Burke, Desrivières, Sylvane, Flor, Herta, Grigis, Antoine, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean-Luc, Martinot, Marie-Laure Paillère, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Poustka, Luise, Fröhner, Juliane H, Smolka, Michael N, Walter, Henrik, Whelan, Robert, Schumann, Gunter, Robbins, Trevor W, Feng, Jianfeng, IMAGEN Consortium, Jia, Tianye [0000-0001-5399-2953], Xie, Chao [0000-0002-9137-3835], Banaschewski, Tobias [0000-0003-4595-1144], Barker, Gareth J [0000-0002-5214-7421], Bokde, Arun LW [0000-0003-0114-4914], Büchel, Christian [0000-0003-1965-906X], Quinlan, Erin Burke [0000-0003-2927-1632], Desrivières, Sylvane [0000-0002-9120-7060], Flor, Herta [0000-0003-4809-5398], Gowland, Penny [0000-0002-4900-4817], Ittermann, Bernd [0000-0002-4087-471X], Martinot, Marie-Laure Paillère [0000-0002-0452-2450], Nees, Frauke [0000-0002-7796-8234], Orfanos, Dimitri Papadopoulos [0000-0002-1242-8990], Poustka, Luise [0000-0002-7738-4394], Fröhner, Juliane H [0000-0002-8493-6396], Smolka, Michael N [0000-0001-5398-5569], Walter, Henrik [0000-0002-9403-6121], Whelan, Robert [0000-0002-2790-7281], Schumann, Gunter [0000-0002-7740-6469], Robbins, Trevor W [0000-0003-0642-5977], Feng, Jianfeng [0000-0002-9328-5732], and Apollo - University of Cambridge Repository

Subjects
Cerebral Cortex, Alcoholism, Adolescent, Humans, Periaqueductal Gray, Prefrontal Cortex, Neural Networks, Computer, Magnetic Resonance Imaging
Abstract

Prompted by recent evidence of neural circuitry in rodent models, functional magnetic resonance imaging and functional connectivity analyses were conducted for a large adolescent population at two ages, together with alcohol abuse measures, to characterize a neural network that may underlie the onset of alcoholism. A network centered on the medial orbitofrontal cortex (mOFC), as well as including the dorsal periaqueductal gray (dPAG), central nucleus of the amygdala, and nucleus accumbens, was identified, consistent with the rodent models, with evidence of both inhibitory and excitatory coregulation by the mOFC over the dPAG. Furthermore, significant relationships were detected between raised baseline excitatory coregulation in this network and impulsivity measures, supporting a role for negative urgency in alcohol dependence.

Published
2021

21. The interaction of child abuse and rs1360780 of the FKBP5 gene is associated with amygdala resting-state functional connectivity in young adults

Author

Wesarg, Christiane, Veer, Ilya M., Oei, Nicole Y. L., Daedelow, Laura S., Lett, Tristram A., Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L.W., Quinlan, Erin Burke, Desrivières, Sylvane, Flor, Herta, Grigis, Antoine, Garavan, Hugh, Brühl, Rüdiger, Martinot, Jean‐Luc, Artiges, Eric, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Poustka, Luise, Hohmann, Sarah, Fröhner, Juliane H., Smolka, Michael N., Whelan, Robert, Schumann, Gunter, Heinz, Andreas, Walter, Henrik, IMAGEN Consortium, Preventive Youth Care (RICDE, FMG), and Ontwikkelingspsychologie (Psychologie, FMG)

Subjects
Adult, Male, Adolescent, child abuse, resting-state functional connectivity, Adult Survivors of Child Abuse, resting‐state functional connectivity, amygdala, Magnetic Resonance Imaging, Polymorphism, Single Nucleotide, Tacrolimus Binding Proteins, Young Adult, FKBP5, Adverse Childhood Experiences, rs1360780, Connectome, Humans, Female, Gene-Environment Interaction, salience network, gene–environment interaction, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, Research Articles, Research Article
Abstract

Extensive research has demonstrated that rs1360780, a common single nucleotide polymorphism within the FKBP5 gene, interacts with early‐life stress in predicting psychopathology. Previous results suggest that carriers of the TT genotype of rs1360780 who were exposed to child abuse show differences in structure and functional activation of emotion‐processing brain areas belonging to the salience network. Extending these findings on intermediate phenotypes of psychopathology, we examined if the interaction between rs1360780 and child abuse predicts resting‐state functional connectivity (rsFC) between the amygdala and other areas of the salience network. We analyzed data of young European adults from the general population (N = 774; mean age = 18.76 years) who took part in the IMAGEN study. In the absence of main effects of genotype and abuse, a significant interaction effect was observed for rsFC between the right centromedial amygdala and right posterior insula (p, In 774 young European adults, we examined if child abuse and rs1360780 of the FKBP5 gene interact in predicting resting‐state functional connectivity (rsFC) between the amygdala and other areas of the salience network. An interaction was found in rsFC with the right posterior insula, driven by stronger rsFC in TT allele carriers with a history of abuse. After exposure to childhood abuse, individuals with the rs1360780 TT genotype may become more vulnerable to develop psychopathology due to altered amygdala functional connectivity.

Published
2021

22. Longitudinal Trajectory of the Link Between Ventral Striatum and Depression in Adolescence.

Author

Pan, Pedro Mario, Sato, João R., Paillère Martinot, Marie-Laure, Martinot, Jean-Luc, Artiges, Eric, Penttilä, Jani, Grimmer, Yvonne, van Noort, Betteke M., Becker, Andreas, Banaschewski, Tobias, Bokde, Arun L. W., Desrivières, Sylvane, Flor, Herta, Garavan, Hugh, Ittermann, Bernd, Nees, Frauke, Papadopoulos Orfanos, Dimitri, Poustka, Luise, Fröhner, Juliane H., and Whelan, Robert

Subjects
ANHEDONIA, MAGNETIC resonance imaging, TELENCEPHALON, REWARD (Psychology), MENTAL depression, RESEARCH funding
Abstract

Objective: Research in adolescent depression has found aberrant intrinsic functional connectivity (iFC) among the ventral striatum (VS) and several brain regions implicated in reward processing. The present study probes this question by taking advantage of the availability of data from a large youth cohort, the IMAGEN Consortium.Methods: iFC data from 303 adolescents (48% of them female) were used to examine associations of VS connectivity at baseline (at age 14) with depressive disorders at baseline and at 2-year (N=250) and 4-year (N=219) follow-ups. Eleven regions of interest, key nodes of the reward system, were used to probe the reward network and calculate the connectivity strength of the VS within this network (VS connectivityrw). The main analyses assessed associations of VS connectivityrw with depressive disorders, anhedonia, and low mood using logistic regression. Autoregressive models accounting for carryover effects over time were conducted to further evaluate these brain-behavior associations.Results: Higher right VS connectivityrw was associated with higher probability of depressive disorders at baseline (odds ratio=2.65, 95% CI=1.40, 5.05). This finding was confirmed in the autoregressive model, adjusting for carryover effects of the depressive disorders across the three time points. VS connectivityrw was not predictive of depressive disorders at follow-up assessments. Longitudinal associations between VS connectivityrw and anhedonia emerged in the structural equation model: left VS connectivityrw was associated with anhedonia at 2 years (odds ratio=2.20, 95% CI=1.54, 3.14), and right VS connectivityrw was linked to anhedonia at 4 years (odds ratio=1.87, 95% CI=1.09, 3.21). VS connectivityrw did not predict low mood at any time point in the structural equation model.Conclusions: The connectivity strength of the VS within the reward network showed distinct patterns of association with depressive disorders and anhedonia from mid to late adolescence, suggesting that the role of this circuitry in depression changes with age. This study replicates, in an independent sample, the association between the VS and depression previously reported in younger adolescents. The findings suggest a role of VS connectivityrw in anhedonia but not in low mood. [ABSTRACT FROM AUTHOR]

Published
2022
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23. The genetic architecture of the human cerebral cortex

Author

Grasby, Katrina L, Jahanshad, Neda, Shatokhina, Natalia, Mirza-Schreiber, Nazanin, Moreira, Jose C V, Mühleisen, Thomas W, Müller-Myhsok, Bertram, Najt, Pablo, Nakahara, Soichiro, Nho, Kwangsik, Olde Loohuis, Loes M, Orfanos, Dimitri Papadopoulos, Pearson, John F, Zsembik, Leo C P, Pitcher, Toni L, Pütz, Benno, Quidé, Yann, Ragothaman, Anjanibhargavi, Rashid, Faisal M, Reay, William R, Redlich, Ronny, Reinbold, Céline S, Repple, Jonathan, Richard, Geneviève, Thomopoulos, Sophia I, Riedel, Brandalyn C, Risacher, Shannon L, Rocha, Cristiane S, Mota, Nina Roth, Salminen, Lauren, Saremi, Arvin, Saykin, Andrew J, Schlag, Fenja, Schmaal, Lianne, Schofield, Peter R, Zhu, Alyssa H, Secolin, Rodrigo, Shapland, Chin Yang, Shen, Li, Shin, Jean, Shumskaya, Elena, Sønderby, Ida E, Sprooten, Emma, Tansey, Katherine E, Teumer, Alexander, Thalamuthu, Anbupalam, Strike, Lachlan T, Tordesillas-Gutiérrez, Diana, Turner, Jessica A, Uhlmann, Anne, Vallerga, Costanza Ludovica, van der Meer, Dennis, van Donkelaar, Marjolein M J, van Eijk, Liza, van Erp, Theo G M, van Haren, Neeltje E M, van Rooij, Daan, Agartz, Ingrid, van Tol, Marie-José, Veldink, Jan H, Verhoef, Ellen, Walton, Esther, Wang, Mingyuan, Wang, Yunpeng, Wardlaw, Joanna M, Wen, Wei, Westlye, Lars T, Whelan, Christopher D, Alhusaini, Saud, Witt, Stephanie H, Wittfeld, Katharina, Wolf, Christiane, Wolfers, Thomas, Wu, Jing Qin, Yasuda, Clarissa L, Zaremba, Dario, Zhang, Zuo, Zwiers, Marcel P, Artiges, Eric, Almeida, Marcio A A, Assareh, Amelia A, Ayesa-Arriola, Rosa, Belger, Aysenil, Brandt, Christine L, Brown, Gregory G, Cichon, Sven, Curran, Joanne E, Davies, Gareth E, Degenhardt, Franziska, Dennis, Michelle F, Alnæs, Dag, Dietsche, Bruno, Djurovic, Srdjan, Doherty, Colin P, Espiritu, Ryan, Garijo, Daniel, Gil, Yolanda, Gowland, Penny A, Green, Robert C, Häusler, Alexander N, Heindel, Walter, Amlien, Inge K, Ho, Beng-Choon, Hoffmann, Wolfgang U, Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Jack, Clifford R, Jang, MiHyun, Jansen, Andreas, Kimbrel, Nathan A, Kolskår, Knut, Painter, Jodie N, Andersson, Micael, Koops, Sanne, Krug, Axel, Lim, Kelvin O, Luykx, Jurjen J, Mathalon, Daniel H, Mather, Karen A, Mattay, Venkata S, Matthews, Sarah, Mayoral Van Son, Jaqueline, McEwen, Sarah C, Ard, Tyler, Melle, Ingrid, Morris, Derek W, Mueller, Bryon A, Nauck, Matthias, Nordvik, Jan E, Nöthen, Markus M, O'Leary, Daniel S, Opel, Nils, Martinot, Marie-Laure Paillère, Pike, G Bruce, Armstrong, Nicola J, Preda, Adrian, Quinlan, Erin B, Rasser, Paul E, Ratnakar, Varun, Reppermund, Simone, Steen, Vidar M, Tooney, Paul A, Torres, Fábio R, Veltman, Dick J, Voyvodic, James T, Ashley-Koch, Allison, Whelan, Robert, White, Tonya, Yamamori, Hidenaga, Adams, Hieab H H, Bis, Joshua C, Debette, Stephanie, Decarli, Charles, Fornage, Myriam, Gudnason, Vilmundur, Hofer, Edith, Atkins, Joshua R, Ikram, M Arfan, Launer, Lenore, Longstreth, W. T., Lopez, Oscar L, Mazoyer, Bernard, Mosley, Thomas H, Roshchupkin, Gennady V, Satizabal, Claudia L, Schmidt, Reinhold, Seshadri, Sudha, Bernard, Manon, Yang, Qiong, Initiative, Alzheimer’s Disease Neuroimaging, Consortium, CHARGE, Consortium, EPIGEN, Consortium, IMAGEN, Consortium, SYS, Initiative, Parkinson’s Progression Markers, Alvim, Marina K M, Ames, David, Anderson, Tim J, Brouwer, Rachel M, Andreassen, Ole A, Arias-Vasquez, Alejandro, Bastin, Mark E, Baune, Bernhard T, Beckham, Jean C, Blangero, John, Boomsma, Dorret I, Brodaty, Henry, Brunner, Han G, Buckner, Randy L, Buimer, Elizabeth E L, Buitelaar, Jan K, Bustillo, Juan R, Cahn, Wiepke, Cairns, Murray J, Calhoun, Vince, Carr, Vaughan J, Caseras, Xavier, Caspers, Svenja, Cavalleri, Gianpiero L, Cendes, Fernando, Bülow, Robin, Corvin, Aiden, Crespo-Facorro, Benedicto, Dalrymple-Alford, John C, Dannlowski, Udo, de Geus, Eco J C, Deary, Ian J, Delanty, Norman, Depondt, Chantal, Desrivières, Sylvane, Donohoe, Gary, Bürger, Christian, Espeseth, Thomas, Fernández, Guillén, Fisher, Simon E, Flor, Herta, Forstner, Andreas J, Francks, Clyde, Franke, Barbara, Glahn, David C, Gollub, Randy L, Grabe, Hans J, Colodro-Conde, Lucía, Cannon, Dara M, Gruber, Oliver, Håberg, Asta K, Hariri, Ahmad R, Hartman, Catharina A, Hashimoto, Ryota, Heinz, Andreas, Henskens, Frans A, Hillegers, Manon H J, Hoekstra, Pieter J, Holmes, Avram J, Chakravarty, Mallar, Hong, L Elliot, Hopkins, William D, Hulshoff Pol, Hilleke E, Jernigan, Terry L, Jönsson, Erik G, Kahn, René S, Kennedy, Martin A, Kircher, Tilo T J, Kochunov, Peter, Kwok, John B J, Chen, Qiang, Le Hellard, Stephanie, Loughland, Carmel M, Martin, Nicholas G, Martinot, Jean-Luc, McDonald, Colm, McMahon, Katie L, Meyer-Lindenberg, Andreas, Michie, Patricia T, Morey, Rajendra A, Mowry, Bryan, Cheung, Joshua W, Nyberg, Lars, Oosterlaan, Jaap, Ophoff, Roel A, Pantelis, Christos, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W J H, Polderman, Tinca J C, Posthuma, Danielle, Rietschel, Marcella, Couvy-Duchesne, Baptiste, Roffman, Joshua L, Rowland, Laura M, Sachdev, Perminder S, Sämann, Philipp G, Schall, Ulrich, Schumann, Gunter, Scott, Rodney J, Sim, Kang, Sisodiya, Sanjay M, Smoller, Jordan W, Dale, Anders M, Sommer, Iris E, St Pourcain, Beate, Stein, Dan J, Toga, Arthur W, Trollor, Julian N, Van der Wee, Nic J A, van 't Ent, Dennis, Völzke, Henry, Walter, Henrik, Weber, Bernd, Dalvie, Shareefa, Weinberger, Daniel R, Wright, Margaret J, Zhou, Juan, Stein, Jason L, Thompson, Paul M, Medland, Sarah E, Consortium, Enhancing NeuroImaging Genetics through Meta-Analysis, Witte, A Veronica, Darin, Abigail, Fleisher, Adam, de Araujo, Tânia K, Pierce, Aimee, Mintz, Akiva, Lerner, Alan, Reith, Alastair D, Hofman, Albert, Espay, Alberto, Ihlenfeld, Albrecht, Ing, Alex, Iranzo, Alex, Beiser, Alexa S, de Zubicaray, Greig I, Norbash, Alexander, Barbot, Alexis, Rudolph, Alice, Portillo, Alicia, Chalker, Alison, Levey, Allan I, Rosen, Allyson, Smith, Amanda, Catafau, Ana, de Zwarte, Sonja M C, Ulysse, Anaztasia, Uitterlinden, André G, Becker, Andreas, Budson, Andrew E, Kertesz, Andrew, Siderowf, Andrew, Bralten, Janita, den Braber, Anouk, Singleton, Andrew, James, Angela, Oliver, Angela, Mishra, Aniket, Hake, Ann Marie, Burke, Anna, Sarrael, Antero, Porsteinsson, Anton P, Stringaris, Argyris, McCoy, Arita, Doan, Nhat Trung, Villringer, Arno, Lenahan, Art, Toga, Arthur, Bokde, Arun, Rawlins, Ashlee, Lamb, Ashley, Lee, Athena, Raj, Balebail Ashok, Tran, Baochan, Dohm, Katharina, Ruggeri, Barbara, Saba, Barbara, Lane, Barton, Yanez, Beatriz, Ances, Beau, Dunlop, Becky, Mudge, Benita, Ravina, Bernard, Ittermann, Bernd, Ehrlich, Stefan, van Noort, Betteke, Lind, Betty, Shah, Bina, Stefanovic, Bojana, Goldstein, Bonnie S, Bonakdarpour, Borna, Matthews, Brandy R, Borowski, Bret, Ott, Brian R, Reynolds, Brigid, Engelbrecht, Hannah-Ruth, Mollenhauer, Brit, Miller, Bruce L, Psaty, Bruce M, Spann, Bryan M, Sadowsky, Carl, Linder, Carly, Franz, Carol E, Tanner, Caroline, Kopil, Catherine, Thomas, Cathi-Ann, Erk, Susanne, Ward, Chad, Bernick, Charles, Smith, Charles D, DeCarli, Charles, Caspell, Chelsea, Deeley, Cheryl, Riordan, Cheryl, Mathis, Chet, Onyike, Chiadi, Heyn, Chris Chinthaka, Fan, Chun Chieh, Hosein, Chris, Leach, Christi, Bÿchel, Christian, Gigliotti, Christina, Hunter, Christine, Belden, Christine M, Tzourio, Christophe, Coffey, Christopher, van Dyck, Christopher H, Clark, Christopher M, Fedko, Iryna O, Wu, Chuang-Kuo, Albers, Colleen S, Chu, Congying, Brand, Connie, Isensee, Corinna, van Duijn, Cornelia M, Bishop, Courtney, Bodge, Courtney, Foley, Sonya F, Tatsuoka, Curtis, Casaceli, Cynthia, Carlsson, Cynthia M, Mathews, Dana, D'Agostino, Daniel, Silverman, Daniel H S, Marson, Daniel, Berg, Daniela, Harvey, Danielle, Jennings, Danna, Ford, Judith M, Wolk, David A, Goldstein, David B, Bachman, David, Brooks, David, Clark, David, Geldmacher, David, Hart, David, Holtzman, David, Jones, David, Hibar, Derrek P, Fukunaga, Masaki, Knopman, David, Hewitt, David L, Perry, David, Russell, David, Standaert, David, Winkfield, David, Green, Davis Robert C, Fontaine, Deborah, Miller, Delwyn D, Gessert, Devon, Garrett, Melanie E, Kerwin, Diana, Willeke, Diana, Drost, Dick, Papadopoulos, Dimitri, Rowe, Dominic, Simpson, Donna M, Muni, Donna, Galasko, Douglas, Scharre, Douglas W, Fillmer, Ariane, Ge, Tian, Bartha, Rob, Celmins, Dzintra, Zimmerman, Earl A, Teng, Edmond, Tolosa, Eduardo, Coleman, Edward, Zamrini, Edward, Mitsis, Effie, Finger, Elizabeth, Giddaluru, Sudheer, Oates, Elizabeth, Sosa, Elizabeth, Woo, Ellen, Rogalski, Emily, Lethbridge, Emma, Dooley, Eoin, Foster, Eric, Reiman, Eric M, Quinlan, Erin Burke, Goldman, Aaron L, Franklin, Erin, Heinzen, Erin L, Fletcher, Evan, Sprenger, Fabienne, Crivello, Fabrice, Biondo, Francesca, Parfitt, Francine, Hefti, Franz, Beyer, Frauke, Nees, Frauke, Green, Melissa J, Leonard, Gabriel, Robert, Gabriel, Thai, Gaby, Marshall, Gad A, Barker, Gareth, Conrad, Gary, Tremont, Geoffrey, Bartzokis, George, Groenewold, Nynke A, Hsiung, Ging-Yuek Robin, Malferrari, Giulia, Chiang, Gloria, Pearlson, Godfrey D, Liang, Grace, Jicha, Greg, Sorensen, Greg, Todd, Gretchen, Jimenez, Gustavo, Grotegerd, Dominik, Zare, Habil, Grabe, Hans Jörgen, Vanderswag, Helen, Schmidt, Helena, Venkov, Heli, Lemaitre, Hervé, Gurholt, Tiril P, Grossman, Hillel, Shill, Holly, Soares, Holly, Lin, Honghuang, Capote, Horacio, Bergman, Howard, Chertkow, Howard, Feldman, Howard, Fillit, Howard, Rosen, Howard J, Gutman, Boris A, Koleva, Hristina, Fernandez, Hubert, Garavan, Hugh, Shim, Hyungsub, Grachev, Igor D, Richard, Irene, Filippi, Irina, Rachinsky, Irina, Wurster, Isabel, Lind, Penelope A, Hansell, Narelle K, Mintzer, Jacobo, Ziolkowski, Jaimie, Brewer, James, Lah, James J, Leverenz, James, Becker, James T, Tetrud, James, Singleton-Garvin, Jamika, Egebjerg, Jan, Cellar, Janet S, Harris, Mathew A, Pentilla, Jani, Brosch, Jared R, Tinklenberg, Jared, Karlawish, Jason H, Meyer, Javier Villanueva, Himali, Jayandra J, Poline, Jean-Baptiste, Gunter, Jeff, Kaye, Jeffrey A, Harrison, Marc B, Dalley, Jeffrey, Burns, Jeffrey M, Petrella, Jeffrey R, Mule, Jennifer, Salazar, Jennifer, Rotter, Jerome I, Yesavage, Jerome, Cedarbaum, Jesse, Jiang, Jiyang, Haswell, Courtney C, Allard, Joanne, Lord, Joanne L, Hetelle, Joel, Kwok, John B, Brockington, John, Morris, John C, Hsiao, John, Morris, John, Olichney, John, Trojanowki, John Q, Hauser, Michael, Rogers, John, Seibyl, John, Yankey, Jon, Dubow, Jordan S, Jankovic, Joseph, Quinn, Joseph, Kass, Joseph S, Taylor, Joy L, Heidebrink, Judith L, Herms, Stefan, Trollor, Julian, Fröhner, Juliane, Anderson, Karen, Blank, Karen, Crawford, Karen, Smith, Karen Ekstam, Bell, Karen L, Williams, Karen, Kieburtz, Karl, Heslenfeld, Dirk J, Gauss, Katharina, Gloer, Katherine, Johnson, Kathleen, Tingus, Kathleen, DeMarco, Kathryn, Sink, Kaycee M, Hawkins, Keith A, Johnson, Keith A, Kantarci, Kejal, Ho, New Fei, Faber, Kelley, Harless, Kelly, Makino, Kelly M, Marek, Kenneth, Spicer, Kenneth, Shianna, Kevin, Chen, Kewei, Nam, Ki Won, Martin, Kim, Poki-Walker, Kim, Hoehn, David, Seppi, Klaus, Johnson, Kris, Fargher, Kristin, Lipowski, Kristine, Espay, Kristy, Womack, Kyle, Chahine, Lama, Flashman, Laura A, Daedelow, Laura, Hoffmann, Per, Leary, Laura, Beckett, Laurel, Honig, Lawrence S, Thal, Leon, Shaw, Leslie M, Kuller, Lew, Apostolova, Liana, Teodoro, Liberty, Rees, Linda, Pizzagalli, Fabrizio, Holleran, Laurena, Lewis, Lindsay, Hergesheimer, Lindsey, Silbert, Lisa C, Ravdin, Lisa, Taylor-Reinwald, Lisa, Uribe, Liz, Schneider, Lon S, Daiello, Lori A, Richer, Louis, Poustka, Luise, Hoogman, Martine, Pirpamer, Lukas, Mesulam, M Marcel, Ismail, M Saleem, Ranola, Madelaine, Korecka, Magdalena, Raichle, Marc, Seltzer, Marc, van der Brug, Marcel, Hottenga, Jouke-Jan, Mesulam, Marek-Marsel, Carrillo, Maria, Carroll, Maria, Knol, Maria J, Kataki, Maria, Greig-Custo, Maria T, Paillere, Marie-Laure, Albert, Marilyn, Love, Marissa Natelson, Ikeda, Masashi, Mintun, Mark A, Frasier, Mark, Logue, Mark, Minton, Mark, Loeffler, Markus, Scholz, Markus, Baca, Marne, Farlow, Martin R, Sadowski, Martin, Janowitz, Deborah, Creech, Mary L, Hynes, Mary L, Quiceno, Mary, Oakley, MaryAnn, Harris, Mat, Senjem, Matt, Bernstein, Matthew, Panizzon, Matthew S, Stern, Matthew, Becerra, Mauricio, Jansen, Iris E, Witbracht, Megan, Vernooij, Meike W, Brandabur, Melanie, Keltz, Melanie, Lamar, Melissa, Yang, Mia, Ahlijanian, Michael, Borrie, Michael, Neale, Michael C, Donohue, Michael, Jia, Tianye, Lyons, Michael J, Lin, Michael, Rapp, Michael, Smolka, Michael, Weiner, Michael W, Weiner, Michael, Figurski, Michal, Perron, Michel, Assaly, Michele, Luciano, Michelle, Jockwitz, Christiane, Rainka, Michelle, Dang, Mimi, Sheikh, Mohammed O, Ghanbari, Mohsen, Gaikwad, Mrunalini, Chowdhury, Munir, Trncic, Nadira, Amin, Najaf, Johnson, Nancy, Kanai, Ryota, Kowalksi, Nancy, Monahan, Nancy, Gillespie, Nathan A, Pacini, Nathaniel, Buckholtz, Neil, Kowall, Neil, Graff-Radford, Neill R, Fox, Nick, Pavese, Nicola, Karama, Sherif, Cairns, Nigel J, Schuff, Norbert, Foster, Norm, Relkin, Norman, Oyonumo, Ntekim E, Pomara, Nunzio, James, Olga, Ogunlana, Olu, Ching, Christopher R K, Kasperaviciute, Dalia, Carmichael, Owen, Doraiswamy, P Murali, Casalin, Paola, Barone, Paolo, Fatica, Parianne, Conrod, Patricia, Johnson, Patricia Lynn, Samuels, Patricia, Aisen, Paul, Malloy, Paul, Kaufmann, Tobias, Thompson, Paul, Ogrocki, Paula, Bezivin-Frere, Pauline, Maillard, Pauline, Fontoura, Paulo, Taylor, Peggy, Hogarth, Penelope, Gowland, Penny, Davies, Peter, Kelly, Sinead, Hardy, Peter, Snyder, Peter J, Snyder, Peter, Amouyel, Philippe, Muglia, Pierandrea, Tariot, Pierre, Lu, Po H, Varma, Pradeep, Vemuri, Prashanthi, Kikuchi, Masataka, Doody, Rachelle S, Carter, Raina, Shah, Raj C, Griffith, Randall, Yeh, Randy, Duara, Ranjan, Tarawneh, Rawan, James, Raymond, Turner, Raymond Scott, Klein, Marieke, Hernando, Raymundo, Silverstein, Rebecca, Sperling, Reisa A, Wilson, Renee, Carson, Richard E, Frank, Richard, El Khouli, Riham, Koeppe, Robert A, Santulli, Robert B, Knapp, Michael, Hauser, Robert, Umek, Robert, Radtke, Rodney, Killiany, Ronald, Petersen, Ronald, Rodriguez, Rosemarie, Miranda, Ruben, Knodt, Annchen R, Bruehl, Ruediger, Xia, Rui, Swerdlow, Russell H, Ottmann, Ruth, Millenet, Sabina, Borges-Neto, Salvador, Frank, Samuel, Black, Sandra, Weintraub, Sandra, Obradov, Sanja, Krämer, Bernd, Asthana, Sanjay, Vaishnavi, Sanjeev, Dolen, Sara, Mason, Sara S, Hohmann, Sarah, Kremen, Sarah, Miller, Sarah, Walter, Sarah, Herring, Scott, Neu, Scott, Lam, Max, Aydin, Semiha, Ahmad, Shahzad, Harlan, Sherry, Sirrel, Sherye A, Lasch, Shirley, Hu, Shu-Ching, Li, Shuo, Kittur, Smita, Chowdhury, Sohini, Lancaster, Thomas M, Pawluczyk, Sonia, Maingault, Sophie, Schneider, Stacy, Seiler, Stephan, Guthrie, Stephanie, Kielb, Stephanie, Reeder, Stephanie, Correia, Stephen, Pasternak, Stephen, McMahon, Mary Agnes B, Lee, Phil H, Salloway, Stephen, Johnson, Sterling, Williams, Steve, Chao, Steven, Arnold, Steven E, Paul, Steven, Potkin, Steven, Factor, Stewart, Isaacson, Stuart, Lett, Tristram A, Kim, Sungeun, Ainscough, Susan, Schultz, Susan K, Landau, Susan, Mendick, Susan, Rountree, Susan, Ostrowizki, Suzanne, Veillette, Suzanne, van der Lee, Sven J, Desrivieres, Sylvane, Lewis, Lindsay B, Lee, T-Y, Simuni, Tanya, Foroud, Tatiana, Foroud, Tatiana M, Wong, Terence Z, Villena, Teresa, Comery, Thomas, Obisesan, Thomas O, Lopes-Cendes, Iscia, Banaschewski, Tobias, Sherer, Todd, Montine, Tom, Paus, Tomáš, Robbins, Trevor, Bromberg, Uli, Völker, Uwe, Pavlik, Valory, Arnedo, Vanessa, Kiyasova, Vera, Bates, Vernice, Logovinsky, Veronika, Sossi, Vesna, Shibley, Victoria, Frouin, Vincent, Lee, Virginia, Poewe, Werner, Jagust, William, Brooks, William M, Macciardi, Fabio, Pavlosky, William, Potter, William, Kremen, William S, Longstreth, William T, Niessen, Wiro J, Jian, Xueqiu, Stern, Yaakov, Saba, Yasaman, Cabrera, Yuliana, Grimmer, Yvonne, Marquand, Andre F, Khachaturian, Zaven, Mari, Zoltan, Mathias, Samuel R, Melzer, Tracy R, Milaneschi, Yuri, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Movement Disorder (MD), Alzheimer’s Disease Neuroimaging Initiative, CHARGE Consortium, EPIGEN Consortium, IMAGEN Consortium, SYS Consortium, Parkinson’s Progression Markers Initiative, Stochastics, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, Science and Society, Cognitive Psychology, IBBA, APH - Personalized Medicine, Complex Trait Genetics, APH - Methodology, Clinical Neuropsychology, Sociology and Social Gerontology, Amsterdam Neuroscience - Complex Trait Genetics, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA Klinische Genetica (5), Neurology, Psychiatry, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), Human genetics, APH - Digital Health, Psychology, Precision Medicine Institute of Psychiatry, Child and Adolescent Psychiatry / Psychology, Radiology & Nuclear Medicine, Clinical Genetics, Epidemiology, Medical Informatics, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Neurodegeneratives Diseases Institute (IMN-UMR CNRS 5293), Centre National de la Recherche Scientifique (CNRS), General Paediatrics, ARD - Amsterdam Reproduction and Development, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), [SDV]Life Sciences [q-bio], LOCI, Genome-wide association study, Brain mapping, 0302 clinical medicine, Cognition, Cortex (anatomy), ComputingMilieux_MISCELLANEOUS, Cerebral Cortex, 0303 health sciences, Brain Mapping, Multidisciplinary, COMMON VARIANTS, Parkinson Disease, Organ Size, Central sulcus, Magnetic Resonance Imaging, medicine.anatomical_structure, Cerebral cortex, Neuroinformatics, EXPRESSION, endocrine system, central sulcus, SURFACE-AREA, Biology, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetic variation, medicine, Attention deficit hyperactivity disorder, Humans, General, Gene, METAANALYSIS, 030304 developmental biology, Progenitor, CORTICAL SULCI, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Genetic variants, Genetic Variation, Attention Deficit Disorder with Hyperactivity, Genetic Loci, Genome-Wide Association Study, functional annotation, medicine.disease, Genetic architecture, 030104 developmental biology, Evolutionary biology, OBSERVER-INDEPENDENT CHARACTERIZATION, Multiple comparisons problem, ddc:320, genome-wide association, Neuroscience, 030217 neurology & neurosurgery
Abstract

Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group., The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

Published
2020

24. A Voxelwise and Genome-Wide Association Study

Author

Luo, Qiang, Chen, Qiang, Wang, Wenjia, Desrivières, Sylvane, Quinlan, Erin Burke, Jia, Tianye, Macare, Christine, Robert, Gabriel H., Cui, Jing, Guedj, Mickaël, Palaniyappan, Lena, Kherif, Ferath, Banaschewski, Tobias, Bokde, Arun L. W., Büchel, Christian, Flor, Herta, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean-Luc, Artiges, Eric, Paillère-Martinot, Marie-Laure, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Poustka, Luise, Fröhner, Juliane H., Smolka, Michael N., Walter, Henrik, Whelan, Robert, Callicott, Joseph H., Mattay, Venkata S., Pausova, Zdenka, Dartigues, Jean-François, Tzourio, Christophe, Crivello, Fabrice, Berman, Karen F., Li, Fei, Paus, Tomáš, Weinberger, Daniel R., Murray, Robin M., Schumann, Gunter, and Feng, Jianfeng

Subjects
Adult, Male, Adolescent, Research, Siblings, Mutation, Missense, Putamen, Schizophrenia, Neuroimaging, Hypertrophy, Magnetic Resonance Imaging, Case-Control Studies, mental disorders, RC0321, Online First, Humans, Female, Genetic Predisposition to Disease, Gray Matter, Cation Transport Proteins, Original Investigation, Genome-Wide Association Study
Abstract

Key Points Question Is there any genetic variant associated with adolescent brain development that can inform psychopathology of schizophrenia? Findings In this imaging genetics study of brain structure, a significant association between a missense mutation in SLC39A8 (a gene previously associated with schizophrenia) and gray matter volume in putamen was discovered and replicated using 10 411 healthy participants from 5 independent studies. Compared with healthy control individuals, such association was significantly weakened in both patients with schizophrenia and unaffected siblings. Meaning Common genetic variant indicates an involvement of neuronal ion transport in both pathophysiology of schizophrenia and structural development of putamen., Importance Deviation from normal adolescent brain development precedes manifestations of many major psychiatric symptoms. Such altered developmental trajectories in adolescents may be linked to genetic risk for psychopathology. Objective To identify genetic variants associated with adolescent brain structure and explore psychopathologic relevance of such associations. Design, Setting, and Participants Voxelwise genome-wide association study in a cohort of healthy adolescents aged 14 years and validation of the findings using 4 independent samples across the life span with allele-specific expression analysis of top hits. Group comparison of the identified gene-brain association among patients with schizophrenia, unaffected siblings, and healthy control individuals. This was a population-based, multicenter study combined with a clinical sample that included participants from the IMAGEN cohort, Saguenay Youth Study, Three-City Study, and Lieber Institute for Brain Development sample cohorts and UK biobank who were assessed for both brain imaging and genetic sequencing. Clinical samples included patients with schizophrenia and unaffected siblings of patients from the Lieber Institute for Brain Development study. Data were analyzed between October 2015 and April 2018. Main Outcomes and Measures Gray matter volume was assessed by neuroimaging and genetic variants were genotyped by Illumina BeadChip. Results The discovery sample included 1721 adolescents (873 girls [50.7%]), with a mean (SD) age of 14.44 (0.41) years. The replication samples consisted of 8690 healthy adults (4497 women [51.8%]) from 4 independent studies across the life span. A nonsynonymous genetic variant (minor T allele of rs13107325 in SLC39A8, a gene implicated in schizophrenia) was associated with greater gray matter volume of the putamen (variance explained of 4.21% in the left hemisphere; 8.66; 95% CI, 6.59-10.81; P = 5.35 × 10−18; and 4.44% in the right hemisphere; t = 8.90; 95% CI, 6.75-11.19; P = 6.80 × 10−19) and also with a lower gene expression of SLC39A8 specifically in the putamen (t127 = −3.87; P = 1.70 × 10−4). The identified association was validated in samples across the life span but was significantly weakened in both patients with schizophrenia (z = −3.05; P = .002; n = 157) and unaffected siblings (z = −2.08; P = .04; n = 149). Conclusions and Relevance Our results show that a missense mutation in gene SLC39A8 is associated with larger gray matter volume in the putamen and that this association is significantly weakened in schizophrenia. These results may suggest a role for aberrant ion transport in the etiology of psychosis and provide a target for preemptive developmental interventions aimed at restoring the functional effect of this mutation., This imaging genetics study examines genetic variants associated with adolescent brain structure and explores the psychopathologic relevance of such associations in the development of schizophrenia.

Published
2019

25. Common genetic variants influence human subcortical brain structures

Author

Hibar, Derrek P, Stein, Jason L, Aribisala, Benjamin S, de Zubicaray, Greig I, Dillman, Allissa, Duggirala, Ravi, Dyer, Thomas D, Erk, Susanne, Fedko, Iryna O, Ferrucci, Luigi, Foroud, Tatiana M, Fox, Peter T, Fukunaga, Masaki, Armstrong, Nicola J, Gibbs, J Raphael, Göring, Harald H H, Green, Robert C, Guelfi, Sebastian, Hansell, Narelle K, Hartman, Catharina A, Hegenscheid, Katrin, Heinz, Andreas, Hernandez, Dena G, Heslenfeld, Dirk J, Bernard, Manon, Hoekstra, Pieter J, Holsboer, Florian, Homuth, Georg, Hottenga, Jouke-Jan, Ikeda, Masashi, Jack, Clifford R, Jenkinson, Mark, Johnson, Robert, Kanai, Ryota, Keil, Maria, Bohlken, Marc M, Kent, Jack W, Kochunov, Peter, Kwok, John B, Lawrie, Stephen M, Liu, Xinmin, Longo, Dan L, McMahon, Katie L, Meisenzahl, Eva, Melle, Ingrid, Mohnke, Sebastian, Boks, Marco P, Montgomery, Grant W, Mostert, Jeanette C, Mühleisen, Thomas W, Nalls, Michael A, Nichols, Thomas E, Nilsson, Lars G, Nöthen, Markus M, Ohi, Kazutaka, Olvera, Rene L, Perez-Iglesias, Rocio, Bralten, Janita, Pike, G Bruce, Potkin, Steven G, Reinvang, Ivar, Reppermund, Simone, Rietschel, Marcella, Romanczuk-Seiferth, Nina, Rosen, Glenn D, Rujescu, Dan, Schnell, Knut, Schofield, Peter R, Brown, Andrew A, Smith, Colin, Steen, Vidar M, Sussmann, Jessika E, Thalamuthu, Anbupalam, Toga, Arthur W, Traynor, Bryan J, Troncoso, Juan, Turner, Jessica A, Valdés Hernández, Maria C, van 't Ent, Dennis, Chakravarty, M Mallar, van der Brug, Marcel, van der Wee, Nic J A, van Tol, Marie-Jose, Veltman, Dick J, Wassink, Thomas H, Westman, Eric, Zielke, Ronald H, Zonderman, Alan B, Ashbrook, David G, Hager, Reinmar, Chen, Qiang, Lu, Lu, McMahon, Francis J, Morris, Derek W, Williams, Robert W, Brunner, Han G, Buckner, Randy L, Buitelaar, Jan K, Cahn, Wiepke, Calhoun, Vince D, Cavalleri, Gianpiero L, Ching, Christopher R K, Crespo-Facorro, Benedicto, Dale, Anders M, Davies, Gareth E, Delanty, Norman, Depondt, Chantal, Djurovic, Srdjan, Drevets, Wayne C, Espeseth, Thomas, Gollub, Randy L, Ho, Beng-Choon, Renteria, Miguel E, Cuellar-Partida, Gabriel, Hoffmann, Wolfgang, Hosten, Norbert, Kahn, René S, Le Hellard, Stephanie, Meyer-Lindenberg, Andreas, Müller-Myhsok, Bertram, Nauck, Matthias, Nyberg, Lars, Pandolfo, Massimo, Penninx, Brenda W J H, den Braber, Anouk, Roffman, Joshua L, Sisodiya, Sanjay M, Smoller, Jordan W, van Bokhoven, Hans, van Haren, Neeltje E M, Völzke, Henry, Walter, Henrik, Weiner, Michael W, Wen, Wei, White, Tonya, Giddaluru, Sudheer, Agartz, Ingrid, Andreassen, Ole A, Blangero, John, Boomsma, Dorret I, Brouwer, Rachel M, Cannon, Dara M, Cookson, Mark R, de Geus, Eco J C, Deary, Ian J, Donohoe, Gary, Goldman, Aaron L, Fernández, Guillén, Fisher, Simon E, Francks, Clyde, Glahn, David C, Grabe, Hans J, Gruber, Oliver, Hardy, John, Hashimoto, Ryota, Hulshoff Pol, Hilleke E, Jönsson, Erik G, Grimm, Oliver, Kloszewska, Iwona, Lovestone, Simon, Mattay, Venkata S, Mecocci, Patrizia, McDonald, Colm, McIntosh, Andrew M, Ophoff, Roel A, Paus, Tomas, Pausova, Zdenka, Ryten, Mina, Guadalupe, Tulio, Sachdev, Perminder S, Saykin, Andrew J, Simmons, Andy, Singleton, Andrew, Soininen, Hilkka, Wardlaw, Joanna M, Weale, Michael E, Weinberger, Daniel R, Adams, Hieab H H, Launer, Lenore J, Hass, Johanna, Seiler, Stephan, Schmidt, Reinhold, Chauhan, Ganesh, Satizabal, Claudia L, Becker, James T, Yanek, Lisa, van der Lee, Sven J, Ebling, Maritza, Fischl, Bruce, Longstreth, W. T., Woldehawariat, Girma, Greve, Douglas, Schmidt, Helena, Nyquist, Paul, Vinke, Louis N, van Duijn, Cornelia M, Xue, Luting, Mazoyer, Bernard, Bis, Joshua C, Gudnason, Vilmundur, Seshadri, Sudha, Holmes, Avram J, Ikram, M Arfan, Initiative, Alzheimer’s Disease Neuroimaging, Consortium, CHARGE, EPIGEN, IMAGEN, SYS, Martin, Nicholas G, Wright, Margaret J, Schumann, Gunter, Franke, Barbara, Hoogman, Martine, Thompson, Paul M, Medland, Sarah E, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Jagust, William, Trojanowki, John Q, Beckett, Laurel, Arias-Vasquez, Alejandro, Janowitz, Deborah, Morris, John, Shaw, Leslie M, Khachaturian, Zaven, Sorensen, Greg, Carrillo, Maria, Kuller, Lew, Raichle, Marc, Paul, Steven, Jia, Tianye, Davies, Peter, Fillit, Howard, Hefti, Franz, Holtzman, Davie, Mesulman, M Marcel, Potter, William, Snyder, Peter, Schwartz, Adam, Montine, Tom, Kim, Sungeun, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Jiminez, Gus, Harvey, Danielle, Klein, Marieke, Bernstein, Matthew, Fox, Nick, Thompson, Paul, Schuff, Norbert, DeCarli, Charles, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Kraemer, Bernd, Vemuri, Prashanthi, Jones, David, Kantarci, Kejal, Ward, Chad, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Lee, Phil H, Landau, Susan, Cairns, Nigel J, Householder, Erin, Taylor-Reinwald, Lisa, Trojanowki, J. Q., Shaw, Les, Lee, Virginia M Y, Korecka, Magdalena, Figurski, Michal, Olde Loohuis, Loes M, Crawford, Karen, Neu, Scott, Potkin, Steven, Shen, Li, Faber, Kelley, Nho, Kwangsik, Luciano, Michelle, Thal, Leon, Frank, Richard, Snyder, Peter J, Buckholtz, Neil, Macare, Christine, Albert, Marilyn, Hsiao, John, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Carter, Raina, Dolen, Sara, Gutman, Boris A, Schneider, Lon S, Mather, Karen A, Pawluczyk, Sonia, Beccera, Mauricio, Teodoro, Liberty, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Fleisher, Adam, Heidebrink, Judith L, Lord, Joanne L, Desrivières, Sylvane, Mattheisen, Manuel, Mason, Sara S, Albers, Colleen S, Knopman, David, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Milaneschi, Yuri, Honig, Lawrence S, Bell, Karen L, Ances, Beau, Morris, John C, Carroll, Maria, Leon, Sue, Mintun, Mark A, Schneider, Stacy, Oliver, Angela, Marson, Daniel, Griffith, Randall, Clark, David, Geldmacher, David, Brockington, John, Roberson, Erik, Grossman, Hillel, Mitsis, Effie, deToledo-Morrell, Leyla, Shah, Raj C, Papmeyer, Martina, Duara, Ranjan, Varon, Daniel, Greig, Maria T, Roberts, Peggy, Onyike, Chiadi, D'Agostino, Daniel, Kielb, Stephanie, Galvin, James E, Pogorelec, Dana M, Ramasamy, Adaikalavan, Cerbone, Brittany, Michel, Christina A, Rusinek, Henry, de Leon, Mony J, Glodzik, Lidia, De Santi, Susan, Doraiswamy, P Murali, Petrella, Jeffrey R, Wong, Terence Z, Arnold, Steven E, Risacher, Shannon L, Karlawish, Jason H, Wolk, David, Smith, Charles D, Jicha, Greg, Hardy, Peter, Sinha, Partha, Oates, Elizabeth, Conrad, Gary, Lopez, Oscar L, Oakley, MaryAnn, Roiz-Santiañez, Roberto, Simpson, Donna M, Porsteinsson, Anton P, Goldstein, Bonnie S, Martin, Kim, Makino, Kelly M, Ismail, M Saleem, Brand, Connie, Mulnard, Ruth A, Thai, Gaby, Mc-Adams-Ortiz, Catherine, Rose, Emma J, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Diaz-Arrastia, Ramon, King, Richard, Weiner, Myron, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I, Lah, James J, Salami, Alireza, Cellar, Janet S, Burns, Jeffrey M, Anderson, Heather S, Swerdlow, Russell H, Apostolova, Liana, Tingus, Kathleen, Woo, Ellen, Silverman, Daniel H S, Lu, Po H, Bartzokis, George, Sämann, Philipp G, Graff-Radford, Neill R, Parfitt, Francine, Kendall, Tracy, Johnson, Heather, Farlow, Martin R, Hake, Ann Marie, Matthews, Brandy R, Herring, Scott, Hunt, Cynthia, van Dyck, Christopher H, Jahanshad, Neda, Schmaal, Lianne, Carson, Richard E, MacAvoy, Martha G, Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Hsiung, Yuek Robin, Feldman, Howard, Schork, Andrew J, Mudge, Benita, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Kerwin, Diana, Mesulam, Marek-Marsel, Lipowski, Kristine, Shin, Jean, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A, Johnson, Keith A, Strike, Lachlan T, Marshall, Gad, Frey, Meghan, Yesavage, Jerome, Taylor, Joy L, Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan N, Belden, Christine M, Jacobson, Sandra A, Teumer, Alexander, Sirrel, Sherye A, Kowall, Neil, Killiany, Ronald, Budson, Andrew E, Norbash, Alexander, Johnson, Patricia Lynn, Obisesan, Thomas O, Wolday, Saba, Allard, Joanne, Lerner, Alan, van Donkelaar, Marjolein M J, Ogrocki, Paula, Hudson, Leon, Fletcher, Evan, Carmichael, Owen, Olichney, John, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Rob, van Eijk, Kristel R, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M, Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Reeder, Stephanie, Bates, Vernice, Walters, Raymond K, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W, Kataki, Maria, Adeli, Anahita, Zimmerman, Earl A, Celmins, Dzintra, Brown, Alice D, Pearlson, Godfrey D, Blank, Karen, Westlye, Lars T, Anderson, Karen, Santulli, Robert B, Kitzmiller, Tamar J, Schwartz, Eben S, Sink, Kaycee M, Williamson, Jeff D, Garg, Pradeep, Watkins, Franklin, Ott, Brian R, Querfurth, Henry, Whelan, Christopher D, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J, Miller, Bruce L, Mintzer, Jacobo, Spicer, Kenneth, Bachman, David, Finger, Elizabether, Toro, Roberto, Winkler, Anderson M, Pasternak, Stephen, Rachinsky, Irina, Drost, Dick, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K, Ponto, Laura L Boles, Zwiers, Marcel P, Shim, Hyungsub, Smith, Karen Elizabeth, Relkin, Norman, Chaing, Gloria, Raudin, Lisa, Smith, Amanda, Fargher, Kristin, Raj, Balebail Ashok, Amin, Najaf, Becker, Diane, Alhusaini, Saud, Beiser, Alexa, Debette, Stéphanie, DeStefano, Anita, Hofer, Edith, Hofman, Albert, Niessen, Wiro J, Smith, Albert, Tzourio, Christophe, Vaidya, Dhananjay, Athanasiu, Lavinia, Vernooij, Meike W, Goldstein, David B, Heinzen, Erin L, Shianna, Kevin, Radtke, Rodney, Ottmann, Ruth, Albrecht, Lisa, Andrew, Chris, Arroyo, Mercedes, Artiges, Eric, Ehrlich, Stefan, Aydin, Semiha, Bach, Christine, Banaschewski, Tobias, Barbot, Alexis, Barker, Gareth, Boddaert, Nathalie, Bokde, Arun, Bricaud, Zuleima, Bromberg, Uli, Bruehl, Ruediger, Hakobjan, Marina M H, Büchel, Christian, Cachia, Arnaud, Cattrell, Anna, Conrod, Patricia, Constant, Patrick, Crombag, Hans, Czech, Katharina, Dalley, Jeffrey, Decideur, Benjamin, Desrivieres, Sylvane, Hartberg, Cecilie B, Fadai, Tahmine, Flor, Herta, Frouin, Vincent, Fuchs, Birgit, Gallinat, Jürgen, Garavan, Hugh, Briand, Fanny Gollier, Gowland, Penny, Head, Kay, Heinrichs, Bert, Haukvik, Unn K, Heym, Nadja, Hübner, Thomas, Ihlenfeld, Albrecht, Ireland, James, Ittermann, Bernd, Ivanov, Nikolay, Jones, Jennifer, Klaassen, Arno, Heister, Angelien J G A M, Lalanne, Christophe, Lathrop, Mark, Lanzerath, Dirk, Lemaitre, Hervé, Lüdemann, Katharina, Mallik, Catherine, Mangin, Jean-François, Mann, Karl, Mar, Adam, Hoehn, David, Martinot, Jean-Luc, Massicotte, Jessica, Mennigen, Eva, Mesquita de Carvahlo, Fabiana, Mignon, Xavier, Miranda, Ruben, Müller, Kathrin, Nees, Frauke, Nymberg, Charlotte, Paillere, Marie-Laure, Wittfeld, Katharina, Kasperaviciute, Dalia, Pena-Oliver, Yolanda, Poline, Jean-Baptiste, Poustka, Luise, Rapp, Michael, Reed, Laurence, Robert, Gabriel, Reuter, Jan, Liewald, David C M, Ripke, Stephan, Ripley, Tamzin, Robbins, Trevor, Rodehacke, Sarah, Romanowski, Alexander, Ruggeri, Barbara, Schilling, Christina, Schmäl, Christine, Schmidt, Dirk, Lopez, Lorna M, Schneider, Sophia, Schroeder, Markus, Schubert, Florian, Schwartz, Yannick, Smolka, Michael, Sommer, Wolfgang, Spanagel, Rainer, Speiser, Claudia, Spranger, Tade, Stedman, Alicia, Makkinje, Remco R R, Steiner, Sabina, Stephens, Dai, Strache, Nicole, Ströhle, Andreas, Struve, Maren, Subramaniam, Naresh, Theobald, David, Topper, Lauren, Vollstaedt-Klein, Sabine, Walaszek, Bernadeta, Matarin, Mar, Weiß, Katharina, Werts, Helen, Whelan, Robert, Williams, Steve, Yacubian, Juliana, Ziesch, Veronika, Zilbovicius, Monica, Wong, C Peng, Lubbe, Steven, Naber, Marlies A M, Martinez-Medina, Lourdes, Kepa, Agnes, Fernandes, Alinda, Tahmasebi, Amir, Abrahamowicz, Michal, Gaudet, Daniel, Leonard, Gabriel, Perron, Michel, Richer, Louis, Seguin, Jean, McKay, D Reese, Veillette, Suzanne, Needham, Margaret, Nugent, Allison C, Pütz, Benno, Abramovic, Lucija, Royle, Natalie A, Sprooten, Emma, Trabzuni, Daniah, van der Marel, Saskia S L, van Hulzen, Kimm J E, Walton, Esther, Wolf, Christiane, Almasy, Laura, Ames, David, Andersson, Micael, Arepalli, Sampath, Assareh, Amelia A, Bastin, Mark E, Brodaty, Henry, Bulayeva, Kazima B, Carless, Melanie A, Cichon, Sven, Corvin, Aiden, Curran, Joanne E, Czisch, Michael, MUMC+: DA Klinische Genetica (5), RS: GROW - Developmental Biology, RS: GROW - R4 - Reproductive and Perinatal Medicine, Université de Montréal. Faculté de médecine. Département de psychiatrie et d'addictologie, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), QIMR Berghofer Medical Research Institute, Department of Psychiatry, Donders Centre for Neuroscience, Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen], Department of Human Genetics, Radboud University Medical Center [Nijmegen], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, PRES Sorbonne Paris Cité, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Gènes, Synapses et Cognition (CNRS - UMR3571 ), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Greifswald University Hospital, University Medical Center [Utrecht], European Commission, University of Edinburgh, Lagos State University (LASU), Heriot-Watt University [Edinburgh] (HWU), Unité d'expérimentation sur les Ruminants de Theix, Institut National de la Recherche Agronomique (INRA), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], University of Oslo (UiO), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], School of Technical Physics, Xidian University, Dept. of Mechanical Engineering, McMaster University [Hamilton, Ontario], Biological Psychology, Neuroscience Campus Amsterdam & EMGO Institute for Health and Care Research, VU University & VU Medical Center, Amsterdam 1081 BT, The Netherlands, Haukeland University Hospital, University of Bergen (UiB), Physicochimie des Processus de Combustion et de l’Atmosphère - UMR 8522 (PC2A), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Universität Heidelberg [Heidelberg] = Heidelberg University, Language and Genetics Department [Nijmegen], Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, International Max Planck Research School for Language Sciences (IMPRS ), Georgia Institute of Technology [Atlanta], National Institutes of Health [Bethesda] (NIH), Yale University [New Haven], Massachusetts General Hospital [Boston], Mental Health Sciences Unit, University College of London [London] (UCL), Beijing Normal University (BNU), Indiana University School of Medicine, Indiana University System, Indiana Alzheimer Disease Center, Indiana University System-Indiana University System, Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany, Scottish Fish Immunology Research Centre, School of Biological Sciences, University of Aberdeen, University of California (UC), Medstar Research Institute, Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia, Department of Genomics, Life and Brain Center, Universität Bonn = University of Bonn, Institute of Human Genetics, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], VU University Medical Center [Amsterdam], Respiratory Epidemiology and Public Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-MRC-HPA Centre for Environment and Health, Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Umeå Centre for Functional Brain Imaging (UFBI), Umeå University, Umeå 901 87, Sweden, Aging Research Center [Karolinska Institutet] (ARC ), Stockholm University-Karolinska Institutet [Stockholm], Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Department of Neurosciences [Univ California San Diego] (Neuro - UC San Diego), School of Medicine [Univ California San Diego] (UC San Diego), University of California [San Diego] (UC San Diego), University of California (UC)-University of California (UC)-University of California [San Diego] (UC San Diego), Department of Cognitive Sciences [Univ California San Diego] (CogSci - UC San Diego), The Hospital for sick children [Toronto] (SickKids), Queensland Institute of Medical Research, School of Psychology, University of Queensland, Brisbane 4072, Australia, University of Queensland [Brisbane], Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia, Department of Genomics of Common Disease, Imperial College London, Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Deutsche Bundesbank, Department of Neurology and Neurosurgery [Montreal], McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), MetaGenoPolis, Department of Psychiatric Research and Development, Diakonhjemmet Hospital, Oslo 0319, Norway, UCL Institute of Neurology and Epilepsy Society, Department of Medicine, Clinical And Experimental Epilepsy, Dpt of Psychiatry [New Haven], Yale School of Medicine [New Haven, Connecticut] (YSM), Hartford Hospital, Neuropsychiatric Genetics Research Group and Department of Psychiatry, Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 2, Ireland, Institute of Food & Health, University College Dublin, University College Dublin [Dublin] (UCD), Statistical Genetics Group, State Key Laboratory of Lead Compound Research, WuXi AppTec, Co., Ltd, Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL, Institute of Neurology [London], Department of Genetics, King Faisal Specialist Hospital and Research Centre (KFSH & RC), Centre épigénétique et destin cellulaire (EDC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Dundee Technopole, CXR Biosciences Ltd, Ninewells Hospital and Medical School, Biomedical Research Centre, University of Dundee, Southwest Foundation for Biomedical Research, Department of Psychiatry and National Ageing Research Institute, University of Melbourne, Department of Clinical Genetics, Department of Medical Parasitology and Mycology, School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-Tehran University of Medical Siences, Centre for Healthy Brain Ageing, University of New South Wales [Sydney] (UNSW), Dementia Collaborative Research Centre, N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia, Texas Biomedical Research Institute [San Antonio, TX], Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Division of Medical Genetics, University of Basel (Unibas), Trinity College Dublin-St. James's Hospital, Neuropsychiatric Genetics Research Group, Trinity College Dublin, Department of Materials Science & Metallurgy, University of Cambridge [UK] (CAM), Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], School of Psychology, University of Queensland, Laboratory of Neurogenetics, The University of Texas Health Science Center at Houston (UTHealth), Department of Genomics, Department of Medical and Molecular Genetics, South Texas Veterans Health Care System, San Antonio, Texas 78229, USA, Biofunctional Imaging, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan, Public Health Genomics Unit, Department of Biomolecular Engineering, Rheinische Friedrich-Wilhelms-Universität Bonn, Estación Experimental de Pastos y Forrajes 'Indio Hatuey', University Medical Center Groningen [Groningen] (UMCG), Neuronal Plasticity / Mouse Behaviour, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Department of Psychiatry, Fujita Health University School of Medicine, Toyoake 470-1192, Japan, Department of Radiology, Mayo Clinic, Department of Clinical Neurology [Oxford], University of Oxford-FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital], University of Maryland School of Medicine, University of Maryland System, University of Sussex, Institute of Cognitive Neuroscience, United Kingdom Met Office [Exeter], University of Maryland [Baltimore County] (UMBC), University of Maryland System-University of Maryland System-University of Maryland School of Medicine, Department of Civil and Structural Engineering, The Hong Kong Polytechnic University [Hong Kong] (POLYU)-The Hong Kong Polytechnic University [Hong Kong] (POLYU), Columbia University Irving Medical Center (CUIMC), Lymphocyte Cell Biology Unit, Laboratory of Genetics, Centre for Advanced Imaging, Psychiatry and Psychotherapy, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Division of Mental Health and Addiction, Oslo University Hospital [Oslo], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Genetic Epidemiology Unit, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Statistics [Warwick], University of Warwick [Coventry], Osaka University [Osaka], Institute of Psychiatry, King’s College London, London SE5 8AF, UK, University of Calgary, Psychiatry and Human Behavior, University of California, Irvine, California 92617, USA, University of California [Irvine] (UC Irvine), Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], University Hospital Mannheim | Universitätsmedizin Mannheim-University Hospital Mannheim | Universitätsmedizin Mannheim, Space and Naval Warfare Systems Center, Klinik für Psychiatrie, Martin-Luther-University Halle-Wittenberg, Department of Psychiatry, Division of Medical Psychology, Genetics of Mental Illness and Brain Function, Neuroscience Research Australia, Développement et amélioration des plantes (UMR DAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia, Laboratory of Neuro Imaging [Los Angeles] (LONI), Departamento de Física Aplicada, Universidade de Vigo, Georgia State University, University System of Georgia (USG), Genentech, Inc. [San Francisco], Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Universiteit Leiden, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Department of Neurobiology, Care Sciences and Society, Karolinska Institutet [Stockholm], University of Manchester [Manchester], The University of Tennessee Health Science Center [Memphis] (UTHSC), iangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong 226001, China, Centre for Ultrahigh Bandwidth Devices for Optical Systems (CUDOS), Macquarie University, Cognitive Neuroscience Laboratory (CNL), Harvard University, Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud University [Nijmegen]-Radboud University [Nijmegen], Icahn School of Medicine at Mount Sinai [New York] (MSSM), The Mind Research Network, Department of Electrical and Computer Engineering [Albuquerque] (ECE Department), The University of New Mexico [Albuquerque], Division of Molecular and Cellular Therapeutics, Scottish Association for Marine Science (SAMS), Structural Biology Laboratory, Department of Chemistry, University of York, Neurology Division, Beaumont Hospital, Dublin 9, Ireland, Beaumont Hospital, Department of Neurology, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Deparment of Medical Genetics, Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Department of Psychiatry, University of Iowa, University of Iowa [Iowa City], Institute for Community Medicine, Department Epidemiology of Health Care and Community Health, Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig-Universität Leipzig, Institute of Clinical Chemistry and Laboratory Medicine, Department of Health Science, Division of Health and Rehabilitation, Luleå University of Technology (LUT), Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Psychiatric and Neurodevelopmental Genetics Unit, 849 Department of Human Genetics, Institute for Community Medicine, Institute for Energy Systems and Thermodynamics, Renyi Institute, Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW, Department of Child and Adolescent Psychiatry, Erasmus University Medical Centre, Rotterdam 3000 CB, The Netherlands, Department of Radiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands, Vrije Universiteit Amsterdam [Amsterdam] (VU), Cell Biology and Gene Expression Section, National Institute of Health, Bethesda, Dept of Psychology, Laboratoire de Recherche Magellan, Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Institut d'Administration des Entreprises (IAE) - Lyon, Institut de Socio-économie des Entreprises et des ORganisations (ISEOR), Institut de socio-économie des entreprises et des organisations, Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Laboratoire d'Informatique de Grenoble (LIG), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Centre for Allergy Research, Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital [Stockholm], Medical University of Łódź (MUL), Psychiatry Institute, Department of Health and Human Services, Institute of Gerontology and Geriatrics, Università degli Studi di Perugia = University of Perugia (UNIPG), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Australian Centre for Research into Injury in Sport and its Prevention, Monash University [Clayton], University Medical Center [Utrecht]-Brain Center Rudolf Magnus, School of Psychology [Nottingham], University of Nottingham, UK (UON), McConnell Brain Imaging Centre (MNI), SickKids - The Hospital for sick children, European Centre for Medium-Range Weather Forecasts (ECMWF), University of Eastern Finland, Centre for Population Health Sciences, Lieber Institute for Brain Development [Baltimore] (LIBD), Johns Hopkins University (JHU), Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz 8010, Austria, Austrian Institute of Technology [Vienna] (AIT), INSERM Research Center for Epidemiology and Biostatistics (U897) Team Neuroepidemiology, Bordeaux, France College of Health Sciences, University of Bordeaux, Bordeaux, France, INSERM, Neuroepidemiology U708, Bordeaux, France, Karlsruhe Institute of Technology (KIT), General Internal Medicine, Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine [Baltimore], Harvard Medical School [Boston] (HMS), Computer Science and Artificial Intelligence Laboratory [Cambridge] (CSAIL), Massachusetts Institute of Technology (MIT), University of Washington [Seattle], Department of Physics [Stockholm], Stockholm University, Center for Medical Systems Biology, Netherlands Genomics Initiative, Leiden University Medical Center, Leiden, The Netherlands, Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Boston University [Boston] (BU), Groupe d'Imagerie Neurofonctionnelle (GIN - UMR 5296), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Faculty of Medicine, University of Iceland [Reykjavik], Icelandic Heart Association, Kopavogur, Iceland., Boston University School of Medicine (BUSM), Laboratoire d'Ingénierie des Matériaux de Bretagne (LIMATB), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université de Brest (UBO), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of California-University of California, Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen], Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Gènes, Synapses et Cognition, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), UE 1354 Unité d'expérimentation sur les Ruminants de Theix, Institut National de la Recherche Agronomique (INRA)-Physiologie Animale et Systèmes d'Elevage (PHASE), Institut National de la Recherche Agronomique (INRA)-Unité d'expérimentation sur les Ruminants de Theix (UE RT), Radboud university [Nijmegen], McGill University, University of Bergen (UIB), Universität Heidelberg [Heidelberg], Beijing Normal University, University of California, University of Bonn, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Neurosciences [San Diego], Department of Cognitive Sciences [San Diego], The Hospital for Sick Children, University of Toronto, Toronto M5G 1X8, Canada, McGill University-McGill University, US 1367 MetaGénoPolis, Institut National de la Recherche Agronomique (INRA)-Département Microbiologie et Chaîne Alimentaire (MICA), Institut National de la Recherche Agronomique (INRA)-MetaGénoPolis (MGP), Yale University School of Medicine, King Faisal Specialist Hospital and Research Centre, Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Texas Biomedical Research Institute [San Antonio, Texas], Bijvoet Center of Biomolecular Research, Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne 3101, Australia, Department of Genomics, Life & Brain Center, University of Bonn, Bonn D-53127, Germany, University of Oxford [Oxford]-FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital], School of Psychology, University of Sussex, Brighton BN1 9QH, UK, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Department of Neurology [University of Calgary], Department of Clinical Neuroscience [University of Calgary], University of California [Irvine] (UCI), Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Universidate de Vigo, Harvard University [Cambridge], Radboud university [Nijmegen]-Radboud university [Nijmegen], Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Centre de Recherche Magellan, Institut d'Administration des Entreprises (IAE) - Lyon-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon, Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Università degli Studi di Perugia (UNIPG), Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Bretagne Sud (UBS)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), The Alzheimer’s Disease Neuroimaging Initiative, The CHARGE Consortium, EPIGEN, IMAGEN, SYS, Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen], Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital]-University of Oxford [Oxford], Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), University of Oxford [Oxford]- John Radcliffe Hospital [Oxford University Hospital]-FMRIB Centre, Neurology, Psychiatry, Anatomy and neurosciences, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology, Biological Psychology, Cognitive Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Neuroscience Campus Amsterdam - Brain Imaging Technology, EMGO+ - Mental Health, Child and Adolescent Psychiatry / Psychology, Epidemiology, Radiology & Nuclear Medicine, Laboratory of Neuro Imaging, David Geffen School of Medicine, University of California, Los Angeles, California, USA, Donders Centre for Neuroscience, Radboud University Nijmegen Medical Centre, MRC- SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK, Génétique humaine et Fonctions cognitives - Human Genetics and Cognitive Functions, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald 17487, Germany, Department of Psychiatry, University Medicine Greifswald, Greifswald 17489, Germany, Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands, Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK, Department of Computer Science, Lagos State University, Lagos, Nigeria, Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK, Heriot-Watt University [Edinburgh] ( HWU ), Institut National de la Recherche Agronomique ( INRA ) -Physiologie Animale et Systèmes d'Elevage ( PHASE ) -Unité d'expérimentation sur les Ruminants de Theix ( UE RT ), Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands, Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen 6500 HB, The Netherlands, NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway, NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0424, Norway, Montreal Neurological Institute [Montréal], NORMENT - KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen 5021, Norway, Physicochimie des Processus de Combustion et de l’Atmosphère - UMR 8522 ( PC2A ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen 6525 XD, The Netherlands, International Max Planck Research School for Language Sciences, Nijmegen 6525 XD, The Netherlands, Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland 20892, USA, Department of Psychology, Yale University, New Haven, Connecticut 06511, USA, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA, University College of London [London] ( UCL ), Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Center for Neurobehavioral Genetics, University of California, Los Angeles, California 90095, USA, Université de Bonn, Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam 1081 HL, The Netherlands, Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh EH10 5HF, UK, Imperial College London-School of public health-MRC-HPA Centre for Environment and Health, Cibersam (Centro Investigación Biomédica en Red Salud Mental), Madrid 28029, Spain, Institut Parisien de Chimie Moléculaire ( IPCM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Aging Research Center [Karolinska Institutet] ( ARC ), Max Planck Institute of Psychiatry, Munich 80804, Germany, Multimodal Imaging Laboratory, Department of Neurosciences, University of California, San Diego, California 92093, USA, Department of Cognitive Sciences, University of California, San Diego, California 92161, USA, Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia, Department of Psychology, University of Oslo, Oslo 0373, Norway, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal H3A 2B4, Canada, Molecular and Cellular Therapeutics, The Royal College of Surgeons, Dublin 2, Ireland, Institut National de la Recherche Agronomique ( INRA ) -MetaGénoPolis ( MGP ) -Microbiologie et Chaîne Alimentaire ( MICA ), UCL Institute of Neurology, London, United Kingdom and Epilepsy Society, London WC1N 3BG, UK, Department of Medicine, Imperial College London, London W12 0NN, UK, Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK, Yale School of Medicine, Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut 06106, USA, University College Dublin [Dublin] ( UCD ), Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK, Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia, Centre épigénétique et destin cellulaire ( EDC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), School of public health-Tehran University of Medical Siences, University of New South Wales [Sydney] ( UNSW ), Texas Biomedical Research Institute, San Antonio, Texas 78245, USA, Institute of Neuroscience and Medicine ( INM-1 ), University of Basel ( Unibas ), Cambridge University, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA, University of Texas Health Science Center, San Antonio, Texas 78229, USA, Clinical Research Branch, National Institute on Aging, Baltimore, Maryland 20892, USA, Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald 17475, Germany, University Medical Center Groningen, University of Groningen, University of Greifswald, Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA, NICHD Brain and Tissue Bank for Developmental Disorders, University of Maryland Medical School, Baltimore, Maryland 21201, USA, nstitute of Cognitive Neuroscience, University College London, London WC1N 3AR, UK, Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland, Baltimore, Maryland 21201, USA, Department of Pathology and Cell Biology, Columbia University Medical Center, New York 10032, USA, Lymphocyte Cell Biology Unit, Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA, University of Oslo ( UiO ) -Institute of Clinical Medicine-Oslo University Hospital, Oslo University Hospital, Institute of Clinical Medicine, University of Oslo ( UiO ) -European Network of Bipolar Research Expert Centers (ENBREC) Group, Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, CCM, Berlin 10117, Germany, Erasmus MC, Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIH), Bethesda, Maryland, USA, Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Central Institute of Mental Health, UMR 1098 Développement et Amélioration des Plantes, Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -MontpellierSupAgro ( MontpellierSupAgro ) -Génétique et amélioration des plantes ( G.A.P. ) -Développement et Amélioration des Plantes ( DAP ), Laboratory of Neuro Imaging [Los Angeles] ( LONI ), University of California at Los Angeles [Los Angeles] ( UCLA ), Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK, Genentech, South San Francisco, California 94080, USA, Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands, LUMC, Carver College of Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm SE-141 83, Sweden, Behavioral Epidemiology Section, National Institute on Aging Intramural Research Program, Baltimore, Maryland 20892, USA, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK, Center for Integrative and Translational Genomics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA, Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA, Centre Interlangues - Texte, Image, Langage ( TIL ), Université de Bourgogne ( UB ), Centre for Ultrahigh Bandwidth Devices for Optical Systems ( CUDOS ), Icahn School of Medicine at Mount Sinai [New York], The Mind Research Network & LBERI, Albuquerque, New Mexico 87106, USA, Department of ECE, University of New Mexico, Albuquerque, New Mexico 87131, USA, Scottish Association for Marine Science ( SAMS ), Department of Neurology, Hopital Erasme, Universite Libre de Bruxelles, Brussels 1070, Belgium, National Institutes of Health ( NIH ) -National Institute of Mental Health (NIMH), Harvard Medical School [Boston] ( HMS ) -Massachusetts General Hospital [Boston], Department of Psychiatry, University of Iowa, Iowa City, Iowa 52242, USA, Luleå University of Technology ( LUT ), Broad Institute of MIT and Harvard, Massachusetts General Hospital, Vrije Universiteit Amsterdam [Amsterdam] ( VU ), Université Jean Moulin - Lyon III-Institut d'Administration des Entreprises (IAE) - Lyon, Institut de Socio-économie des Entreprises et des ORganisations ( ISEOR ), University Medicine Greifswald,-HELIOS Hospital Stralsund, Laboratoire d'Informatique de Grenoble ( LIG ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National Polytechnique de Grenoble ( INPG ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University, Osaka 565-0871, Japan, Karolinska University Hospital (Solna), Medical University of Łódź ( MUL ), National Institutes of Health ( NIH ), University of Perugia, Commonwealth Scientific and Industrial Research Organisation, University Medical Center Utrecht-Brain Center Rudolf Magnus, University of Nottingham, UK ( UON ), McConnell Brain Imaging Centre ( MNI ), The Hospital for sick children [Toronto] ( SickKids ), Department of Medical and Molecular Genetics, King’s College London, London SE1 9RT, UK, European Centre for Medium-Range Weather Forecasts ( ECMWF ), Lieber Institute for Brain Development, Baltimore, Maryland 21205, USA, Departments of Psychiatry, Neurology, Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, Austrian Institute of Technology [Vienna] ( AIT ), Karlsruhe Institute of Technology ( KIT ), General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA, Department of Radiology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA, Computer Science and Artificial Intelligence Laboratory [Cambridge] ( CSAIL ), Massachusetts Institute of Technology ( MIT ), Department of Epidemiology, University of Washington, Seattle, Washington, USA, Department of Neurology, University of Washington, Seattle, Washington, USA, Department of Physics, Stockholm University ( Department of Physics, Stockholm University ), Université de Lille, Sciences Humaines et Sociales, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA, Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands, Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA, Groupe d'Imagerie Neurofonctionnelle ( GIN - UMR 5296 ), Service NEUROSPIN ( NEUROSPIN ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université de Bordeaux ( UB ), Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA, Faculty of Medicine, University of Iceland, Reykjavik, Iceland, Department of Neurology, Boston University School of Medicine, Framingham Heart Study, Boston, MA, Department of Neurology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands, Laboratoire d'Ingénierie des Matériaux de Bretagne ( LIMATB ), Université de Bretagne Sud ( UBS ) -Institut Brestois du Numérique et des Mathématiques ( IBNM ), Université de Brest ( UBO ) -Université de Brest ( UBO ) -Université de Brest ( UBO ), King's College, Department of Psychiatry, Radboud university medical center, Nijmegen 6500 HB, The Netherlands, and Broad Institute of © 2012 Nature America, Inc. All rights reserved. Nature Ge N etics aDV a NCE ONLINE PUBLIC a TION 7 l e t t e r s Harvard and MIT, Cambridge, Massachusetts, US

Subjects
CHROMATIN, Male, Netherlands Twin Register (NTR), Aging, Identification, nervous-system, human geography, SEGMENTATION, Caudate nucleus, Apoptosis, Expression, Genome-wide association study, Striatum, Hippocampal formation, Hippocampus, BASAL GANGLIA, 130 000 Cognitive Neurology & Memory, Basal ganglia, genetics [Gene Expression Regulation, Developmental], Hippocampal, Child, anatomy & histology [Skull], Aged, 80 and over, Genetics, Sex Characteristics, KINECTIN, Genome-wide association, Multidisciplinary, Putamen, Brain, Gene Expression Regulation, Developmental, blood, brain, disease incidence, genetic variation, neurology, Organ Size, Human brain, Middle Aged, organization, Magnetic Resonance Imaging, genetics [Genetic Variation], Chromatin, Dynamics, genetics [Membrane Proteins], medicine.anatomical_structure, genetics [Aging], Anatomy & histology, [ SCCO.NEUR ] Cognitive science/Neuroscience, Female, ddc:500, anatomy & histology [Caudate Nucleus], Neuroinformatics, EXPRESSION, Adult, Adolescent, Evolution, anatomy & histology [Hippocampus], ORGANIZATION, genetics [Genetic Loci], Biology, Article, Young Adult, SDG 3 - Good Health and Well-being, Journal Article, medicine, Humans, GENOME-WIDE ASSOCIATION, General, genetics [Apoptosis], Kinectin, Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], HIPPOCAMPAL, IDENTIFICATION, genetics [Organ Size], [SCCO.NEUR]Cognitive science/Neuroscience, Skull, segmentation, Genetic Variation, Membrane Proteins, NERVOUS-SYSTEM, anatomy & histology [Putamen], Genetic Loci, KTN1 protein, human, Caudate Nucleus, anatomy & histology [Brain], Neuroscience, Genome-Wide Association Study
Abstract

Contains fulltext : 144426.pdf (Publisher’s version ) (Closed access) Contains fulltext : 144426pre.pdf (Author’s version preprint ) (Open Access) The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 x 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. 6 p.

Published
2015

26. Structural brain correlates of adolescent resilience.

Author

Burt, Keith B., Whelan, Robert, Conrod, Patricia J., Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L.W., Bromberg, Uli, Büchel, Christian, Fauth‐Bühler, Mira, Flor, Herta, Galinowski, André, Gallinat, Juergen, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Mann, Karl, Nees, Frauke, Papadopoulos‐Orfanos, Dimitri, Paus, Tomas, and Pausova, Zdenka

Subjects
*BRAIN physiology, *ACADEMIC achievement, *ADAPTABILITY (Personality), *ALCOHOL drinking, *MAGNETIC resonance imaging, *PERSONALITY, *QUESTIONNAIRES, *PSYCHOLOGICAL resilience, *SOCIAL skills, *PHENOTYPES, *CROSS-sectional method, *ADOLESCENCE
Abstract

Background: Despite calls for integration of neurobiological methods into research on youth resilience (high competence despite high adversity), we know little about structural brain correlates of resilient functioning. The aim of the current study was to test for brain regions uniquely associated with positive functioning in the context of adversity, using detailed phenotypic classification. Methods: 1,870 European adolescents (Mage = 14.56 years, SDage = 0.44 years, 51.5% female) underwent MRI scanning and completed behavioral and psychological measures of stressful life events, academic competence, social competence, rule-abiding conduct, personality, and alcohol use. Results: The interaction of competence and adversity identified two regions centered on the right middle and superior frontal gyri; grey matter volumes in these regions were larger in adolescents experiencing adversity who showed positive adaptation. Differences in these regions among competence/adversity subgroups were maintained after controlling for several covariates and were robust to alternative operationalization decisions for key constructs. Conclusions: We demonstrate structural brain correlates of adolescent resilience, and suggest that right prefrontal structures are implicated in adaptive functioning for youth who have experienced adversity. [ABSTRACT FROM AUTHOR]

Published
2016
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27. Striatal morphology correlates with sensory abnormalities in unaffected relatives of cervical dystonia patients.

Author

Walsh, Richard A., Whelan, Robert, O'Dwyer, John, O'Riordan, Sean, Hutchinson, Siobhan, O'Laoide, Risteard, Malone, Kevin, Reilly, Richard, and Hutchinson, Michael

Subjects
*DYSTONIA musculorum deformans, *MAGNETIC resonance imaging, *EXTRAPYRAMIDAL disorders, *CAUDATE nucleus, *BASAL ganglia, *EXTRAPYRAMIDAL tracts, *NEUROLOGICAL research
Abstract

Structural grey matter abnormalities have been described in adult-onset primary torsion dystonia (AOPTD). Altered spatial discrimination thresholds are found in familial and sporadic AOPTD and in some unaffected relatives who may be non-manifesting gene carriers. Our hypothesis was that a subset of unaffected relatives with abnormal spatial acuity would have associated structural abnormalities. Twenty-eight unaffected relatives of patients with familial cervical dystonia, 24 relatives of patients with sporadic cervical dystonia and 27 control subjects were recruited. Spatial discrimination thresholds (SDTs) were determined using a grating orientation task. High-resolution magnetic resonance imaging (MRI) images (1.5 T) were analysed using voxel-based morphometry. Unaffected familial relatives with abnormal SDTs had reduced caudate grey matter volume (GMV) bilaterally relative to those with normal SDTs (right Z = 3.45, left Z = 3.81), where there was a negative correlation between SDTs and GMV ( r = −0.76, r2 = 0.58, p < 0.0001). Familial relatives also had bilateral sensory cortical expansion relative to unrelated controls (right Z = 4.02, left Z = 3.79). Unaffected relatives of patients with sporadic cervical dystonia who had abnormal SDTs had reduced putaminal GMV bilaterally compared with those with normal SDTs (right Z = 3.96, left Z = 3.45). Sensory abnormalities in some unaffected relatives correlate with a striatal substrate and may be a marker of genetic susceptibility in these individuals. Further investigation of grey matter changes as a candidate endophenotype may assist future genetic studies of dystonia. [ABSTRACT FROM AUTHOR]

Published
2009
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28. Brain connectivity in frailty: Insights from The Irish Longitudinal Study on Ageing (TILDA).

Author

Zúñiga, Raquel Gutiérrez, Davis, James R.C., Boyle, Rory, De Looze, Céline, Meaney, James F., Whelan, Robert, Kenny, Rose Anne, Knight, Silvin P., and Ortuño, Román Romero

Subjects
*DEFAULT mode network, *FRAILTY, *LARGE-scale brain networks, *LONGITUDINAL method, *FUNCTIONAL magnetic resonance imaging
Abstract

• Connectome-based predictive modeling was used with a Frailty Index. • The frailty network had its main connectivity in the visual network. • The robustness network had its main connectivity in the basal ganglia. • Connectivity patterns were different based on the degree of frailty. Frailty in older adults is associated with greater risk of cognitive decline. Brain connectivity insights could help understand the association, but studies are lacking. We applied connectome-based predictive modeling to a 32-item self-reported Frailty Index (FI) using resting state functional MRI data from The Irish Longitudinal Study on Ageing. A total of 347 participants were included (48.9% male, mean age 68.2 years). From connectome-based predictive modeling, we obtained 204 edges that positively correlated with the FI and composed the "frailty network" characterised by connectivity of the visual network (right); and 188 edges that negatively correlated with the FI and formed the "robustness network" characterized by connectivity in the basal ganglia. Both networks' highest degree node was the caudate but with different patterns: from caudate to visual network in the frailty network; and to default mode network in the robustness network. The FI was correlated with walking speed but not with metrics of global cognition, reinforcing the matching between the FI and the brain connectivity pattern found (main predicted connectivity in basal ganglia). [ABSTRACT FROM AUTHOR]

Published
2023
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29. Brain-predicted age difference score is related to specific cognitive functions: A multi-site replication analysis

Author

Rory Boyle, Silvin P. Knight, Görsev Yener, Ian H. Robertson, Jason P. McMorrow, Daniel Carey, Rossella Rizzo, Laura M. Rueda-Delgado, Robert Whelan, Derya Durusu Emek-Savaş, Yaakov Stern, Lee Jollans, Rose Anne Kenny, Boyle, Rory, Jollans, Lee, Rueda-Delgado, Laura M, Rizzo, Rossella, Yener, Görsev G, McMorrow, Jason P, Knight, Silvin P, Carey, Daniel, Robertson, Ian H, Emek-Savaş, Derya D, Stern, Yaakov, Kenny, Rose Anne, and Whelan, Robert

Subjects
Longitudinal study, medicine.medical_specialty, Cognitive Neuroscience, Neuroimaging, Brain--Aging, Audiology, Neuropsychological Tests, 050105 experimental psychology, Article, 03 medical and health sciences, Behavioral Neuroscience, Cellular and Molecular Neuroscience, 0302 clinical medicine, Cognition, Machine learning, medicine, Verbal fluency test, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Longitudinal Studies, Settore MAT/07 - Fisica Matematica, Episodic memory, Cognitive reserve, Working memory, Biochemical markers, 05 social sciences, Cognitive flexibility, Neuropsychology, Brain, Biomarkers, Brain ageing, Cognitive ageing, Cognitive function, MRI, Machine learning, Magnetic Resonance Imaging, Psychiatry and Mental health, Neurology, Ageing, Neurology (clinical), Psychology, 030217 neurology & neurosurgery
Abstract

Brain-predicted age difference scores are calculated by subtracting chronological age from ‘brain’ age. Positive scores reflect accelerated ageing and are associated with increased mortality risk and poorer physical function. To date, however, the relationship between brain-predicted age difference scores and specific cognitive functions has not been systematically examined. First, applying machine learning to 1,359 T1-weighted MRI scans, we predicted the relationship between chronological age and voxel-wise grey matter data. This model was then applied to MRI data from three independent datasets, significantly predicting chronological age: Dokuz Eylul University (n=175), the Cognitive Reserve/Reference Ability Neural Network study (n=380), and The Irish Longitudinal Study on Ageing (n=487). Each independent dataset had rich neuropsychological data. Brain-predicted age difference scores were significantly negatively correlated with general cognitive status (two datasets); processing speed, visual attention, cognitive flexibility (three datasets); visual attention and cognitive flexibility (two datasets); and semantic verbal fluency (two datasets). They were not significantly correlated with processing speed, cognitive flexibility, response inhibition and selective attention, sustained attention, verbal episodic memory or working memory in any dataset. As such, there is firm evidence of correlations between increased brain-predicted age differences and reduced cognitive function only in some domains that are implicated in cognitive ageing.

Published
2021

30. Very large fMRI study using the IMAGEN database: Sensitivity–specificity and population effect modeling in relation to the underlying anatomy

Author

Thyreau, Benjamin, Schwartz, Yannick, Thirion, Bertrand, Frouin, Vincent, Loth, Eva, Vollstädt-Klein, Sabine, Paus, Tomas, Artiges, Eric, Conrod, Patricia J., Schumann, Gunter, Whelan, Robert, and Poline, Jean-Baptiste

Subjects
*MAGNETIC resonance imaging of the brain, *DATABASES, *SENSITIVITY analysis, *FACE perception, *GAUSSIAN processes, *HUMAN information processing
Abstract

Abstract: In this paper we investigate the use of classical fMRI Random Effect (RFX) group statistics when analyzing a very large cohort and the possible improvement brought from anatomical information. Using 1326 subjects from the IMAGEN study, we first give a global picture of the evolution of the group effect t-value from a simple face-watching contrast with increasing cohort size. We obtain a wide activated pattern, far from being limited to the reasonably expected brain areas, illustrating the difference between statistical significance and practical significance. This motivates us to inject tissue-probability information into the group estimation, we model the BOLD contrast using a matter-weighted mixture of Gaussians and compare it to the common, single-Gaussian model. In both cases, the model parameters are estimated per-voxel for one subgroup, and the likelihood of both models is computed on a second, separate subgroup to reflect model generalization capacity. Various group sizes are tested, and significance is asserted using a 10-fold cross-validation scheme. We conclude that adding matter information consistently improves the quantitative analysis of BOLD responses in some areas of the brain, particularly those where accurate inter-subject registration remains challenging. [Copyright &y& Elsevier]

Published
2012
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