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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. The anatomical structure of sex differences in trust propensity: A voxel-based morphometry study.

Author: Safari N, Fang H, Veerareddy A, Xu P, and Krueger F
Subjects: Humans, Male, Female, Young Adult, Adult, Brain diagnostic imaging, Brain anatomy & histology, Brain physiology, Brain Mapping, Gray Matter diagnostic imaging, Gray Matter anatomy & histology, Gray Matter physiology, Trust, Sex Characteristics, Magnetic Resonance Imaging
Abstract: Trust is a key component of human relationships. Sex differences in trust behavior have been elucidated by parental investment theory and social role theory, attributing men's higher trust propensity to their increased engagement in physically and socially risky activities aimed at securing additional resources. Although sex differences in trust behavior exist and the neuropsychological signatures of trust are known, the underlying anatomical structure of sex differences is still unexplored. Our study aimed to investigate the anatomical structure of sex differences in trust behavior toward strangers (i.e., trust propensity, TP) by employing voxel-based morphometry (VBM) in a sample of healthy young adults. We collected behavioral data for TP as measured with participants in the role of trustors completing the one-shot trust game (TG) with anonymous partners as trustees. We conducted primary region of interest (ROI) and exploratory whole-brain (WB) VBM analyses of high-resolution structural images to test for the association between TP and regional gray matter volume (GMV) associated with sex differences. Confirming previous studies, our behavioral results demonstrated that men trusted more than women during the one-shot TG. Our WB analysis showed a greater GMV related to TP in men than women in the precuneus (PreC), whereas our ROI analysis in regions of the default-mode network (dorsomedial prefrontal cortex [dmPFC], PreC, superior temporal gyrus) to simulate the partner's trustworthiness, central-executive network (ventrolateral PFC) to implement a calculus-based trust strategy, and action-perception network (precentral gyrus) to performance cost-benefit calculations, as proposed by a neuropsychoeconomic model of trust. Our findings advance the neuropsychological understanding of sex differences in TP, which has implications for interpersonal partnerships, financial transactions, and societal engagements., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
Published: 2024
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4. Connectome-based prediction of decreased trust propensity in older adults with mild cognitive impairment: A resting-state functional magnetic resonance imaging study.

Author: Chen Y, He H, Ding Y, Tao W, Guan Q, and Krueger F
Subjects: Humans, Male, Aged, Female, Middle Aged, Brain diagnostic imaging, Brain physiopathology, Nerve Net diagnostic imaging, Nerve Net physiopathology, Cognitive Dysfunction physiopathology, Cognitive Dysfunction diagnostic imaging, Connectome methods, Magnetic Resonance Imaging, Trust
Abstract: Trust propensity (TP) relies more on social than economic rationality to transform the perceived probability of betrayal into positive reciprocity expectations in older adults with normal cognition. While deficits in social rationality have been observed in older adults with mild cognitive impairment (MCI), there is limited research on TP and its associated resting-state functional connectivity (RSFC) mechanisms in this population. To measure TP and related psychological functions (affect, motivation, executive cognition, and social cognition), MCI (n = 42) and normal healthy control (NHC, n = 115) groups completed a one-shot trust game and additional assessments of related psychological functions. RSFC associated with TP was analyzed using connectome-based predictive modeling (CPM) and lesion simulations. Our behavioral results showed that the MCI group trusted less (i.e., had lower TP) than the NHC group, with lower TP associated with higher sensitivity to the probability of betrayal in the MCI group. In the MCI group, only negative CPM models (RSFC negatively correlated with TP) significantly predicted TP, with a high salience network (SN) contribution. In contrast, in the NHC group, positive CPM models (RSFC positively correlated with TP) significantly predicted TP, with a high contribution from the default mode network (DMN). In addition, the total network strength of the NHC-specific positive network was lower in the MCI group than in the NHC group. Our findings demonstrated a decrease in TP in the MCI group compared to the NHC group, which is associated with deficits in social rationality (social cognition, associated with DMN) and increased sensitivity to betrayal (affect, associated with SN) in a trust dilemma. In conclusion, our study contributes to understanding MCI-related alterations in trust and their underlying neural mechanisms., Competing Interests: Declaration of competing interest The authors are unaware of any conflicts of interest, financial or otherwise., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2024
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5. 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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6. Neural processing of audiovisual and painful analogue trauma and its relationship with subsequent audiovisual and pain intrusions.

Author: Miedl SF, Franke LK, Danböck SK, Martini M, Hettegger S, Kronbichler M, Flor H, and Wilhelm FH
Subjects: Humans, Female, Adult, Gyrus Cinguli physiopathology, Gyrus Cinguli diagnostic imaging, Young Adult, Prefrontal Cortex physiopathology, Prefrontal Cortex diagnostic imaging, Bayes Theorem, Magnetic Resonance Imaging, Pain psychology, Pain physiopathology, Stress Disorders, Post-Traumatic physiopathology, Stress Disorders, Post-Traumatic psychology
Abstract: Background: Posttraumatic stress disorder and medically unexplained pain frequently co-occur. While pain is common during traumatic events, the processing of pain during trauma and its relation to audiovisual and pain intrusions is poorly understood. Objective: Here we investigate neural activations during painful analogue trauma, focusing on areas that have been related to threat and pain processing, and how they predict intrusion formation. We also examine the moderating role of cumulative lifetime adversity. Methods: Sixty-five healthy women were assessed using functional magnetic resonance imaging. An analogue trauma was induced by an adaptation of the trauma-film paradigm extended by painful electrical stimulation in a 2 (film: aversive, neutral) x 2 (pain: pain, no-pain) design, followed by 7-day audiovisual and pain intrusion assessment using event-based ecological momentary assessment. Intrusions were fitted with Bayesian multilevel regression and a hurdle lognormal distribution. Results: Conjunction analysis confirmed a wide network including anterior insula (AI) and dorsal anterior cingulate cortex (dACC) being active both, during aversive films and pain. Pain resulted in activation in areas amongst posterior insula and deactivation in a network around ventromedial prefrontal cortex (VMPFC). Higher AI and dACC activity during aversive>neutral film predicted greater audiovisual intrusion probability over time and predicted greater audiovisual intrusion frequency particularly for participants with high lifetime adversity. Lower AI, dACC, hippocampus, and VMPFC activity during pain>no-pain predicted greater pain intrusion probability particularly for participants with high lifetime adversity. Weak regulatory VMPFC activation was associated with both increased audiovisual and pain intrusion frequency. Conclusions: Enhanced AI and dACC processing during aversive films, poor pain vs. no-pain discrimination in AI and dACC, as well as weak regulatory VMPFC processing may be driving factors for intrusion formation, particularly in combination with high lifetime adversity. Results shed light on a potential path for the etiology of PTSD and medically unexplained pain.
Published: 2024
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7. 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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8. 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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9. 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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10. An fMRI investigation of the intention-outcome interactions in second- and third-party punishment.

Author: Feng C, Yang Q, Azem L, Atanasova KM, Gu R, Luo W, Hoffman M, Lis S, and Krueger F
Subjects: Brain Mapping, Humans, Intention, Neuroimaging, Magnetic Resonance Imaging, Punishment psychology
Abstract: Second-party punishment (SPP) and third-party punishment (TPP) are two basic forms of costly punishment that play an essential role in maintaining social orders. Despite scientific breakthroughs in understanding that costly punishment is driven by an integration of the wrongdoers' intention and the outcome of their actions, so far, few studies have compared the neurocognitive processes associated with the intention-outcome integration between SPP and TPP. Here, we combined economic exchange games measuring SPP and TPP with functional magnetic resonance imaging (fMRI) to compare the neuropsychological architectures underlying the intention-outcome integration during one-shot interactions with anonymous partners across four types of norm violations (no norm, accidental, attempted, and intentional violations). Our behavioral findings showed that third-parties punished only attempted norm violations less frequently than second-parties. Our neuroimaging findings revealed higher activities in the right temporoparietal junction (TPJ) and dorsolateral prefrontal cortex (dlPFC) for attempted norm violations during TPP relative to SPP; more activities in these regions with less punishment frequency; and enhancement of functional connectivity of the right TPJ with the right dlPFC and dorsomedial PFC. Our findings demonstrated specific psychological and neural mechanisms of intention-outcome interactions between SPP and TPP -helping to unravel the complex neurocognitive processes of costly punishment., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Published: 2022
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11. 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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12. 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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13. 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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14. 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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15. 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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16. 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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17. 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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18. No Signal Intensity Increase in the Dentate Nucleus on Unenhanced T1-weighted MR Images after More than 20 Serial Injections of Macrocyclic Gadolinium-based Contrast Agents.

Author: Radbruch A, Haase R, Kieslich PJ, Weberling LD, Kickingereder P, Wick W, Schlemmer HP, and Bendszus M
Subjects: Adult, Contrast Media administration & dosage, Female, Humans, Image Enhancement, Injections, Macrocyclic Compounds administration & dosage, Male, Meglumine administration & dosage, Organometallic Compounds administration & dosage, Retrospective Studies, Cerebellar Nuclei diagnostic imaging, Cerebellar Nuclei drug effects, Contrast Media pharmacology, Magnetic Resonance Imaging methods, Meglumine pharmacology, Organometallic Compounds pharmacology
Abstract: Purpose To determine the effect of more than 20 serial injections of macrocyclic gadolinium-based contrast agents (GBCAs) on the signal intensity (SI) of the dentate nucleus (DN) on unenhanced T1-weighted magnetic resonance (MR) images. Materials and Methods In this retrospective, institutional review board-approved study, 33 patients who underwent at least 20 consecutive MR imaging examinations (plus an additional MR imaging for reference) with the exclusive use of macrocyclic GBCAs gadoterate meglumine and gadobutrol were analyzed. SI ratio differences were calculated for DN-to-pons and DN-to-middle cerebellar peduncle (MCP) ratios by subtracting the SI ratio at the first MR imaging examination from the SI ratio at the last MR imaging examination. One-sample t tests were used to examine if the SI ratio differences differed from 0, and Bayes factors were calculated to quantify the strength of evidence for each test. Results Patients underwent a mean of 23.03 ± (standard deviation) 4.20 GBCA administrations (mean accumulated dose, 491.21 mL ± 87.04 of a 0.5 M GBCA solution) with an average of 12.09 weeks ± 2.16 between every administration. Both ratio differences did not differ significantly from 0 (DN-to-pons ratio: -0.0032 ± 0.0154, P = .248; DN-to-MCP ratio: -0.0011 ± 0.0093, P = .521), and one-sided Bayes factors provided substantial to strong evidence against an SI ratio increase (Bayes factor for DN-to-pons ratio = 0.09 and that for DN-to-MCP ratio = 0.12). Conclusion The study indicates that 20 or more serial injections of macrocyclic GBCAs administered with on average 3 months between each injection are not associated with an SI increase in the DN. © RSNA, 2016.
Published: 2017
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19. Intraindividual Analysis of Signal Intensity Changes in the Dentate Nucleus After Consecutive Serial Applications of Linear and Macrocyclic Gadolinium-Based Contrast Agents.

Author: Radbruch A, Weberling LD, Kieslich PJ, Hepp J, Kickingereder P, Wick W, Schlemmer HP, and Bendszus M
Subjects: Adult, Animals, Cerebellar Nuclei diagnostic imaging, Female, Gadolinium DTPA pharmacology, Humans, Male, Meglumine pharmacology, Middle Aged, Organometallic Compounds pharmacology, Retrospective Studies, Cerebellar Nuclei drug effects, Contrast Media pharmacology, Gadolinium pharmacology, Magnetic Resonance Imaging methods, Signal Processing, Computer-Assisted
Abstract: Purpose: Recent studies reported an increase in the dentate nucleus (DN)-to-pons signal intensity (SI) ratio (DN-pons SI ratio) on unenhanced T1-weighted images in patients who received consecutive serial injections of linear gadolinium-based contrast agents (GBCAs). In contrast, most studies found no increase in the DN-pons SI ratio when patients were treated with consecutive serial injections of macrocyclic GBCAs. However, the potential difference between macrocyclic and linear GBCAs has never been assessed in individuals who received subsequent applications of both contrast agents. In this retrospective study, we assessed the evolution of the DN-pons SI ratio change in patients that were treated with a comparable number of serial consecutive injections of the linear GBCA gadopentetate dimeglumine and subsequent serial injections of the macrocyclic GBCAs gadobutrol and gadoterate meglumine., Materials and Methods: Data of 36 patients was analyzed. All patients underwent at least 5 consecutive administrations of the linear GBCA gadopentetate dimeglumine followed by an equal number of consecutive administrations of the macrocyclic GBCA gadobutrol. In 12 of the 36 patients, 5 or more final consecutive injections of the macrocyclic GBCA gadoterate meglumine were analyzed additionally. The difference of DN-pons SI ratios on unenhanced T1-weighted images was calculated by subtracting the ratio at the first examination from the ratio at the last examination in each of the 3 periods., Results: The mean DN-pons SI ratio difference in the gadopentetate dimeglumine period was significantly greater than 0 (mean ± SD, 0.0448 ± 0.0345; P < 0.001), whereas the mean DN-pons SI ratio difference in the subsequent gadobutrol and gadoterate meglumine period was significantly smaller than 0 (gadobutrol: -0.0178 ± 0.0459, P = 0.026; gadoterate meglumine: -0.0250 ± 0.0284, P = 0.011)., Conclusions: In this observational study, the application of the linear GBCA gadopentetate dimeglumine was associated with a DN-pons SI ratio increase, whereas subsequent applications of the macrocyclic GBCAs gadobutrol or gadoterate meglumine in the same patients were not. Rather, the current data tentatively suggest a decrease in preexisting hyperintensities over time when linear GBCAs are changed to macrocyclic GBCAs, potentially indicating a washout effect or precipitation of gadolinium. Future patient studies need to include control groups to replicate the present results, and additional animal studies should be conducted to clarify the underlying mechanism of the proposed SI decrease.
Published: 2016
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20. High-Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-Weighted Images: Evaluation of the Macrocyclic Gadolinium-Based Contrast Agent Gadobutrol.

Author: Radbruch A, Weberling LD, Kieslich PJ, Hepp J, Kickingereder P, Wick W, Schlemmer HP, and Bendszus M
Subjects: Cerebrospinal Fluid, Female, Gadolinium, Humans, Male, Middle Aged, Reproducibility of Results, Retrospective Studies, Thalamus pathology, Cerebellar Nuclei pathology, Contrast Media, Globus Pallidus pathology, Magnetic Resonance Imaging methods, Organometallic Compounds
Abstract: Objective: The aim of this study was to compare changes in the signal intensity (SI) ratio of the dentate nucleus (DN) to the pons, DN to cerebrospinal fluid (CSF), and globus pallidus (GP) to thalamus on unenhanced T1-weighted magnetic resonance imaging (MRI) scans after serial injections of the macrocyclic gadolinium-based contrast agent gadobutrol., Materials and Methods: Thirty patients who had received at least 5 MRI examinations (plus an additional last MRI for reference) with the exclusive use of gadobutrol, resulting in a total cumulative dose of 54.1 ± 30.4 mL gadobutrol, were analyzed retrospectively. Signal intensity ratio differences were calculated for DN-to-pons, DN-to-CSF, and GP-to-thalamus ratios by subtracting the SI ratio at the first MRI from the SI ratio at the last MRI scan. One-sample t tests were employed to examine if they differed from 0. Regression and correlational analyses were performed to examine whether the SI ratio differences were predicted by a number of control variables., Results: Signal intensity ratio differences did not differ significantly from 0, neither for the DN-to-pons ratio (-0.0035 ± 0.0476, P = 0.69), the DN-to-CSF ratio (-0.0539 ± 0.3217, P = 0.37), nor the GP-to-thalamus ratio (-0.0020 ± 0.0211, P = 0.60). None of the control variables predicted changes in SI ratios., Conclusions: In contrast to a recently published study, we did not find signal increases in the DN or in the GP after serial injections of gadobutrol, even though the total dose applied here was considerably larger than in the respective study. This finding adds further support to the hypothesis that the molecular structure of a gadolinium-based contrast agent as either macrocyclic or linear is a crucial factor for its potential to cause gadolinium deposition in the brain. Future studies should further assess this hypothesis by additional animal investigations as well as histopathological and clinical correlation studies.
Published: 2015
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21. Increased Signal Intensity in the Dentate Nucleus on Unenhanced T1-Weighted Images After Gadobenate Dimeglumine Administration.

Author: Weberling LD, Kieslich PJ, Kickingereder P, Wick W, Bendszus M, Schlemmer HP, and Radbruch A
Subjects: Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Male, Meglumine administration & dosage, Middle Aged, Reproducibility of Results, Sensitivity and Specificity, Cerebellar Nuclei anatomy & histology, Cerebellar Nuclei drug effects, Contrast Media administration & dosage, Magnetic Resonance Imaging methods, Meglumine analogs & derivatives, Organometallic Compounds administration & dosage
Abstract: Objectives: The aim of this study was to compare changes in signal intensity (SI) ratios of the dentate nucleus (DN) to pons and cerebrospinal fluid (CSF) on unenhanced T1-weighted magnetic resonance imaging (MRI) scans between the first and last MRI using the linear gadolinium-based contrast agent gadobenate dimeglumine., Materials and Methods: The study was approved by the ethical committee of the University of Heidelberg (S-324/2014), and written informed consent was waived due to the retrospective character of the study. Fifty patients who underwent at least 5 consecutive MRI examinations (plus an additional last MRI for reference) with the exclusive use of gadobenate dimeglumine were analyzed retrospectively. The difference of DN-to-pons and DN-to-CSF mean SI ratios was calculated on unenhanced T1-weighted images between the first and last examination. Results were compared with previously published data on gadopentetate dimeglumine and gadoterate meglumine., Results: Signal intensity ratio differences for DN-to-pons and DN-to-CSF were significantly greater than 0 (pons: 0.0399 ± 0.0307, P < 0.001; CSF: 0.1439 ± 0.1524, P < 0.001). No control variable consistently predicted the SI ratio difference for the DN-to-pons and the DN-to-CSF ratio. Compared with previously published data, the difference in SI increase between gadopentetate dimeglumine and gadobenate dimeglumine was not significant for the DN-to-pons ratio (P = 0.906). In contrast, the DN-to-CSF ratio difference was significantly lower (P < 0.001) for gadobenate dimeglumine. Dentate nucleus-to-pons (P < 0.001) and DN-to-CSF (P = 0.017) ratio differences were both significantly higher for gadobenate dimeglumine than for gadoterate meglumine., Conclusions: The present study found an increase in SI in the DN after serial injections of gadobenate dimeglumine. Further studies are needed to clarify the potential of different linear gadolinium-based contrast agents to cause SI increase in the DN.
Published: 2015
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22. Gadolinium retention in the dentate nucleus and globus pallidus is dependent on the class of contrast agent.

Author: Radbruch A, Weberling LD, Kieslich PJ, Eidel O, Burth S, Kickingereder P, Heiland S, Wick W, Schlemmer HP, and Bendszus M
Subjects: Female, Humans, Male, Middle Aged, Retrospective Studies, Cerebellar Nuclei metabolism, Contrast Media pharmacokinetics, Gadolinium DTPA pharmacokinetics, Globus Pallidus metabolism, Magnetic Resonance Imaging, Meglumine pharmacokinetics, Organometallic Compounds pharmacokinetics
Abstract: Purpose: To compare changes in signal intensity (SI) ratios of the dentate nucleus (DN) and the globus pallidus (GP) to those of other structures on unenhanced T1-weighted magnetic resonance (MR) images between linear and macrocyclic gadolinium-based contrast agents (GBCAs)., Materials and Methods: The study was approved by the ethical committee of the University of Heidelberg (reference no. S-324/2014). Owing to the retrospective character of the study, the ethical committee did not require any written informed consent. Two groups of 50 patients who underwent at least six consecutive MR imaging examinations with the exclusive use of either a linear GBCA (gadopentetate dimeglumine) or a macrocyclic GBCA (gadoterate meglumine) were analyzed retrospectively. The difference in mean SI ratios of DN to pons and GP to thalamus on unenhanced T1-weighted images from the last and first examinations was calculated. One-sample and independent-sample t tests were used to assess the difference in SI ratios for both groups, and regression analysis was performed to account for potential confounders., Results: The SI ratio difference in the linear group was greater than 0 (mean DN difference ± standard deviation, 0.0407 ± 0.0398 [P < .001]; GP, 0.0287 ± 0.0275 [P < .001]) and significantly larger (DN, P < .001 and standardized difference of 1.16; GP, P < .001 and standardized difference of 0.81) than that in the macrocyclic group, which did not differ from 0 (DN, 0.0016 ± 0.0266 [P = .680]; GP, 0.0031 ± 0.0354 [P = .538]). The SI ratio difference between the last and first examinations for the DN remained significantly different between the two groups in the regression analysis (P < .001)., Conclusion: This study indicates that an SI increase in the DN and GP on T1-weighted images is caused by serial application of the linear GBCA gadopentetate dimeglumine but not by the macrocyclic GBCA gadoterate meglumine. Clinical implications of this observation remain unclear., (RSNA, 2015)
Published: 2015
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23. Asymmetry of deep medullary veins on susceptibility weighted MRI in patients with acute MCA stroke is associated with poor outcome.

Author: Mucke J, Möhlenbruch M, Kickingereder P, Kieslich PJ, Bäumer P, Gumbinger C, Purrucker J, Mundiyanapurath S, Schlemmer HP, Bendszus M, and Radbruch A
Subjects: Acute Disease, Aged, Cerebral Veins abnormalities, Disease Susceptibility, Female, Humans, Male, Prognosis, Retrospective Studies, Risk Factors, Survival Rate, Cerebral Veins pathology, Image Processing, Computer-Assisted methods, Infarction, Middle Cerebral Artery diagnosis, Infarction, Middle Cerebral Artery mortality, Magnetic Resonance Imaging methods, Severity of Illness Index
Abstract: Background and Purpose: Due to its sensitivity to deoxyhemoglobin, susceptibility weighted imaging (SWI) enables the visualization of deep medullary veins (DMV) in patients with acute stroke, which are difficult to depict under physiological circumstances. This study assesses the asymmetric appearance of prominent DMV as an independent predictor for stroke severity and outcome., Materials and Methods: SWI of 86 patients with acute middle cerebral artery (MCA) stroke were included. A scoring system from 0 (no visible DMV) to 3 (very prominent DMV) was applied for both hemispheres separately. A difference of scores between ipsi- and contralateral side was defined as asymmetric (AMV+). Occurrence of AMV+ was correlated with the National Institute of Health Stroke Scale (NIHSS) Score on admission and discharge, as well as the modified Rankin Scale (mRS) at discharge. Ordinal regression analysis was used to evaluate NIHSS and mRS as predictors of stroke severity, clinical course of disease and outcome., Results: 55 patients displayed AMV+ while 31 did not show an asymmetry (AMV-). Median NIHSS on admission was 17 (11-21) in the AMV+ group and 9 (5-15) in the AMV- group (p = 0.001). On discharge median NIHSS was 11 (5-20) for AMV+ and 5 (2-14) for AMV- (p = 0.005). The median mRS at discharge was 4 (3-5) in the AMV+ group and 3 (1-4) in AMV- (p = 0.001). Odds ratio was 3.19 (95% CI: 1.24-8.21) for AMV+ to achieve a higher mRS than AMV- (p = 0.016)., Conclusion: The asymmetric appearance of DMV on SWI is a fast and easily evaluable parameter for the prediction of stroke severity and can be used as an additional imaging parameter in patients with acute MCA stroke.
Published: 2015
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24. Real-time direct volume rendering in functional magnetic resonance imaging.

Author: Hesser J, Männer R, Braus DF, Ende G, and Henn FA
Subjects: Brain anatomy & histology, Brain physiology, Computer Systems, Heart anatomy & histology, Humans, Image Processing, Computer-Assisted methods, Magnetic Resonance Imaging methods, Neurosciences methods
Abstract: Direct volume rendering is a visualization method that allows display of all information hidden in three-dimensional data sets of, for example, computed tomography or magnetic resonance imaging (MRI). In contrast to commonly used surface rendering methods, these algorithms need no preprocessing but suffer from a high computational complexity. A real-time rendering system, VIRIM (Vitec: Visualization Technology GmbH, Mannheim, Germany), cuts down rendering times of minutes on normal workstations to an interactive rate of 1 second or less. The immediate visual feedback allows interactive steering of the visualization process to achieve insight into the internal three-dimensional structure of objects. Additional information is obtained by using an interactive gray-value segmentation tool that both allows segmentation of the data set according to bone, tissue, and liquor and display of multifunctional data sets (e.g., functional MRI [fMRI] data sets). Thus, real-time direct volume rendering allows segmentation and volume data processing of functional and anatomical MR data sets simultaneously. As this method can be integrated in the clinical routine, it is of great importance for real-time motion artifact detection and the interpretation of fMRI data acquired during cognitive experiments with normal subjects and psychiatric patients. Because of the free programmability of VIRIM, more complex matching procedures are currently being investigated for future implementation.
Published: 1997
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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. Neurobiological Correlates of Change in Adaptive Behavior in Autism

Author: Pretzsch, Charlotte, Schäfer, Tim, Lombardo, Michael, Warrier, Varun, Mann, Caroline, Bletsch, Anke, Chatham, Chris, Floris, Dorothea, Tillmann, Julian, Yousaf, Afsheen, Jones, Emily, Charman, Tony, Ambrosino, Sara, Bourgeron, Thomas, Dumas, Guillaume, Loth, Eva, Oakley, Bethany, Buitelaar, Jan, Cliquet, Freddy, Leblond, Claire, Baron-Cohen, Simon, Beckmann, Christian, Banaschewski, Tobias, Durston, Sarah, Freitag, Christine, LEAP Group, Eu-Aims, Murphy, Declan G.M., Ecker, Christine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Frankfurt University Hospital, Goethe-University Frankfurt am Main, University of Trento [Trento], University of Cambridge [UK] (CAM), F. Hoffmann-La Roche [Basel], Universität Zürich [Zürich] = University of Zurich (UZH), University of Vienna [Vienna], Centre for Brain and Cognitive Development [Birkbeck College], Birkbeck College [University of London], Utrecht University [Utrecht], Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], Radboud University Medical Center [Nijmegen], University Hospital Mannheim | Universitätsmedizin Mannheim, Heidelberg University, University Medical Center [Utrecht], European Project: 115300,EC:FP7:SP1-JTI,IMI-JU-03-2010,EU-AIMS(2012), and European Project: 777394,H2020-JTI-IMI2-2016-10-two-stage,AIMS-2-TRIALS(2018)
Subjects: Psychiatry and Mental health, All institutes and research themes of the Radboud University Medical Center, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Autism Spectrum Disorder, 130 000 Cognitive Neurology & Memory, [SCCO.NEUR]Cognitive science/Neuroscience, Adaptation, Psychological, 220 Statistical Imaging Neuroscience, Humans, Autistic Disorder, Magnetic Resonance Imaging, Follow-Up Studies
Abstract: Objective:Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition that is associated with significant difficulties in adaptive behavior and variation in clinical outcomes across the life span. Some individuals with ASD improve, whereas others may not change significantly, or regress. Hence, the development of “personalized medicine” approaches is essential. However, this requires an understanding of the biological processes underpinning differences in clinical outcome, at both the individual and subgroup levels, across the lifespan.Methods:The authors conducted a longitudinal follow-up study of 483 individuals (204 with ASD and 279 neurotypical individuals, ages 6–30 years), with assessment time points separated by ∼12–24 months. Data collected included behavioral data (Vineland Adaptive Behavior Scale–II), neuroanatomical data (structural MRI), and genetic data (DNA). Individuals with ASD were grouped into clinically meaningful “increasers,” “no-changers,” and “decreasers” in adaptive behavior. First, the authors compared neuroanatomy between outcome groups. Next, they examined whether deviations from the neurotypical neuroanatomical profile were associated with outcome at the individual level. Finally, they explored the observed neuroanatomical differences’ potential genetic underpinnings.Results:Outcome groups differed in neuroanatomical features (cortical volume and thickness, surface area), including in “social brain” regions previously implicated in ASD. Also, deviations of neuroanatomical features from the neurotypical profile predicted outcome at the individual level. Moreover, neuroanatomical differences were associated with genetic processes relevant to neuroanatomical phenotypes (e.g., synaptic development).Conclusions:This study demonstrates, for the first time, that variation in clinical (adaptive) outcome is associated with both group- and individual-level variation in anatomy of brain regions enriched for genes relevant to ASD. This may facilitate the move toward better targeted/precision medicine approaches.
Published: 2022

27. Resting state EEG power spectrum and functional connectivity in autism: a cross-sectional analysis

Author: Garcés, Pilar, Baumeister, Sarah, Mason, Luke, Chatham, Christopher, Holiga, Stefan, Dukart, Juergen, Jones, Emily, Banaschewski, Tobias, Baron-Cohen, Simon, Bölte, Sven, Buitelaar, Jan, Durston, Sarah, Oranje, Bob, Persico, Antonio, Beckmann, Christian, Bougeron, Thomas, Dell’acqua, Flavio, Ecker, Christine, Moessnang, Carolin, Charman, Tony, Tillmann, Julian, Murphy, Declan, Johnson, Mark, Loth, Eva, Brandeis, Daniel, Hipp, Joerg, Ahmad, Jumana, Ambrosino, Sara, Auyeung, Bonnie, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brogna, Claudia, de Bruijn, Yvette, Chakrabarti, Bhismadev, Cornelissen, Ineke, Crawley, Daisy, Dumas, Guillaume, Faulkner, Jessica, Frouin, Vincent, Goyard, David, Ham, Lindsay, Hayward, Hannah, Holt, Rosemary, Kundu, Prantik, Lai, Meng-Chuan, Ardhuy, Xavier Liogier D’, Lombardo, Michael, Lythgoe, David, Mandl, René, Marquand, Andre, Mennes, Maarten, Meyer-Lindenberg, Andreas, Mueller, Nico, Oakley, Bethany, O’dwyer, Laurence, Oldehinkel, Marianne, Pandina, Gahan, Ruggeri, Barbara, Ruigrok, Amber, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Spooren, Will, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve, Wooldridge, Caroline, Zwiers, Marcel, Leap Group, The Eu-Aims, Garcés, Pilar [0000-0003-4989-0123], Apollo - University of Cambridge Repository, Roche Innovation Center [Basel, Switzerland], Heidelberg University, University Hospital Mannheim | Universitätsmedizin Mannheim, University of London [London], Institute of Neuroscience and Medicine, Brain and Behaviour [Jülich, Germany] (INM-7), Jülich Research Centre, Autism Research Centre [Cambridge, Royaume-Uni], University of Cambridge [UK] (CAM), Centre for Psychiatry Research [Stockholm], Karolinska Institutet [Stockholm], Curtin University [Perth], Planning and Transport Research Centre (PATREC), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], University Medical Center [Utrecht], Università degli Studi di Messina = University of Messina (UniMe), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), King‘s College London, Goethe-University Frankfurt am Main, Central Institute of Mental Health [Mannheim], This work was supported by EU-AIMS (European Autism Interventions), which receives support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115300, the resources of which are composed of financial contributions from the European Union’s Seventh Framework Programme (grant FP7/2007–2013), from the European Federation of Pharmaceutical Industries and Associations companies’ in-kind contributions and from Autism Speaks. AIMS-2-TRIALS is funded by the Innovative Medicines Initiative 2 Joint Undertaking (IMI 2 JU) under grant agreement no. 777394. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation program, EFPIA, Autism Speaks, Autistica, and SFARI. PG was supported by the Roche Postdoctoral Fellowship (RPF) program., European Project: 115300,EC:FP7:SP1-JTI,IMI-JU-03-2010,EU-AIMS(2012), European Project: 777394,H2020-JTI-IMI2-2016-10-two-stage,AIMS-2-TRIALS(2018), and University of Zurich
Subjects: Adult, Adolescent, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Autism spectrum disorder, EEG, Resting state, Power spectrum, Functional connectivity, 610 Medicine & health, 1309 Developmental Biology, 2806 Developmental Neuroscience, 2738 Psychiatry and Mental Health, Developmental Neuroscience, 130 000 Cognitive Neurology & Memory, 1312 Molecular Biology, Humans, ddc:610, 10064 Neuroscience Center Zurich, Autistic Disorder, Child, Molecular Biology, Brain Mapping, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Research, 220 Statistical Imaging Neuroscience, Brain, Reproducibility of Results, Electroencephalography, 10058 Department of Child and Adolescent Psychiatry, Magnetic Resonance Imaging, Psychiatry and Mental health, Cross-Sectional Studies, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Developmental Biology
Abstract: Background Understanding the development of the neuronal circuitry underlying autism spectrum disorder (ASD) is critical to shed light into its etiology and for the development of treatment options. Resting state EEG provides a window into spontaneous local and long-range neuronal synchronization and has been investigated in many ASD studies, but results are inconsistent. Unbiased investigation in large and comprehensive samples focusing on replicability is needed. Methods We quantified resting state EEG alpha peak metrics, power spectrum (PS, 2–32 Hz) and functional connectivity (FC) in 411 children, adolescents and adults (n = 212 ASD, n = 199 neurotypicals [NT], all with IQ > 75). We performed analyses in source-space using individual head models derived from the participants’ MRIs. We tested for differences in mean and variance between the ASD and NT groups for both PS and FC using linear mixed effects models accounting for age, sex, IQ and site effects. Then, we used machine learning to assess whether a multivariate combination of EEG features could better separate ASD and NT participants. All analyses were embedded within a train-validation approach (70%–30% split). Results In the training dataset, we found an interaction between age and group for the reactivity to eye opening (p = .042 uncorrected), and a significant but weak multivariate ASD vs. NT classification performance for PS and FC (sensitivity 0.52–0.62, specificity 0.59–0.73). None of these findings replicated significantly in the validation dataset, although the effect size in the validation dataset overlapped with the prediction interval from the training dataset. Limitations The statistical power to detect weak effects—of the magnitude of those found in the training dataset—in the validation dataset is small, and we cannot fully conclude on the reproducibility of the training dataset’s effects. Conclusions This suggests that PS and FC values in ASD and NT have a strong overlap, and that differences between both groups (in both mean and variance) have, at best, a small effect size. Larger studies would be needed to investigate and replicate such potential effects., Molecular Autism, 13
Published: 2022

28. Decoding the microstructural properties of white matter using realistic models

Author: Kwok-Shing Chan, Riccardo Metere, Jeroen Mollink, Christian Licht, José P. Marques, Anne-Marie van Cappellen van Walsum, Renaud Hédouin, Neuroimagerie: méthodes et applications (Empenn), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], Medical Faculty [Mannheim], hedouin, renaud, University Hospital Mannheim | Universitätsmedizin Mannheim, Empenn, Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), and Radboud university [Nijmegen]
Subjects: Work (thermodynamics), Cognitive Neuroscience, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, Neuroimaging, Neurosciences. Biological psychiatry. Neuropsychiatry, Signal, 050105 experimental psychology, 150 000 MR Techniques in Brain Function, 030218 nuclear medicine & medical imaging, Overdetermined system, Magnetic susceptibility, 03 medical and health sciences, 0302 clinical medicine, Deep Learning, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, 0501 psychology and cognitive sciences, Computer Simulation, White matter models, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Anisotropy, 320 000 MR Structural Quantitative Imaging, Physics, Aged, 80 and over, Pixel, Orientation (computer vision), 05 social sciences, Models, Theoretical, Magnetostatics, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Magnetic Resonance Imaging, White Matter, Magnetic field, Microscopy, Electron, Deep learning network, Neurology, Feasibility Studies, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Autopsy, Biological system, 030217 neurology & neurosurgery, Decoding methods, RC321-571, Microstructural properties
Abstract: Multi-echo gradient echo (ME-GRE) magnetic resonance signal evolution in white matter has a strong dependence on the orientation of myelinated axons with respect to the main static field. Although analytical solutions have been able to predict some of the white matter (WM) signal behaviour of the hollow cylinder model, it has been shown that realistic models of WM offer a better description of the signal behaviour observed.In this work, we present a pipeline to (i) generate realistic 2D WM models with their microstructure based on real axon morphology with adjustable fiber volume fraction (FVF) and g-ratio. We (ii) simulate their interaction with the static magnetic field to be able to simulate their MR signal. For the first time, we (iii) demonstrate that realistic 2D WM models can be used to simulate a MR signal that provides a good approximation of the signal obtained from a real 3D WM model derived from electron microscopy. We then (iv) demonstrate in silico that 2D WM models can be used to predict microstructural parameters in a robust way if ME-GRE multi-orientation data is available and the main fiber orientation in each pixel is known using DTI. A deep learning network was trained and characterized in its ability to recover the desired microstructural parameters such as FVF, g-ratio, free and bound water transverse relaxation and magnetic susceptibility. Finally, the network was trained to recover these micro-structural parameters from an ex vivo dataset acquired in 9 orientations with respect to the magnetic field and 12 echo times. We demonstrate that this is an overdetermined problem and that as few as 3 orientations can already provide comparable results for some of the decoded metrics.[Highlights] - A pipeline to generate realistic white models of arbitrary fiber volume fraction and g-ratio is presented; - We present a methodology to simulated the gradient echo signal from segmented 2D and 3D models of white matter, which takes into account the interaction of the static magnetic field with the anisotropic susceptibility of the myelin phospholipids; - Deep Learning Networks can be used to decode microstructural white matter parameters from the signal of multi-echo multi-orientation data
Published: 2021

29. Fractionating autism based on neuroanatomical normative modeling

Author: Zabihi, Mariam, Floris, Dorothea L, Kia, Seyed Mostafa, Wolfers, Thomas, Tillmann, Julian, Arenas, Alberto Llera, Moessnang, Carolin, Banaschewski, Tobias, Holt, Rosemary, Baron-Cohen, Simon, Loth, Eva, Charman, Tony, Bourgeron, Thomas, Murphy, Declan, Ecker, Christine, Buitelaar, Jan K, Beckmann, Christian F, Marquand, Andre, EU-AIMS LEAP Group, Zabihi, Mariam [0000-0002-7083-2318], Kia, Seyed Mostafa [0000-0002-7128-814X], Banaschewski, Tobias [0000-0003-4595-1144], Charman, Tony [0000-0003-1993-6549], Murphy, Declan [0000-0002-6664-7451], Buitelaar, Jan K [0000-0001-8288-7757], Apollo - University of Cambridge Repository, TILT, Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Radboud University Medical Center [Nijmegen], University of Oslo (UiO), Oslo University Hospital [Oslo], King‘s College London, University of Vienna [Vienna], Universität Heidelberg [Heidelberg], Medical Faculty [Mannheim], University of Cambridge [UK] (CAM), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Goethe-Universität Frankfurt am Main, Karakter Child and Adolescent Psychiatry University Centre [Nijmegen], University of Oxford [Oxford], The work is supported by the Netherlands Organization for Scientific Research VIDI Grant Nos. 016.156.415 (to A.F.M.) and 864.12.003 (to C.F.B.), European Union Seventh Framework Program Grant Nos. 602805 (AGGRESSOTYPE) (to J.K.B.), 603016 (MATRICS) (to J.K.B.), and 278948 (TACTICS) (to J.K.B.), European Community’s Horizon 2020 Program (H2020/2014–2020) Grant Nos. 643051 (MiND) (to J.K.B.) and 642996 (BRAINVIEW) (to J.K.B.), Wellcome Trust UK Strategic Award Grant No. 098369/Z/12/Z (to C.F.B.), and EU-AIMS (European Autism Interventions), which receives support from Innovative Medicines Initiative Joint Undertaking Grant No. 115300, the resources of which are composed of financial contributions from the European Union’s Seventh Framework Program (Grant No. FP7/2007–2013), from the European Federation of Pharmaceutical Industries and Associations companies’ in-kind contributions and Innovative Medicines Initiative 2 Joint Undertaking Grant No. 777394 for the project AIMS-2-TRIALS. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA and AUTISM SPEAKS, Autistica, SFARI. D.M. was also supported by the NIHR Maudsley Biomedical Research Centre. S.B.-C. was funded by the Wellcome Trust and the Autism Research Trust during the period of this work., European Project: 602805,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,AGGRESSOTYPE(2013), European Project: 603016,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,MATRICS(2014), European Project: 278948,EC:FP7:HEALTH,FP7-HEALTH-2011-two-stage,TACTICS(2012), European Project: 643051,H2020,H2020-MSCA-ITN-2014,MiND(2015), European Project: 642996,H2020,H2020-MSCA-ITN-2014,BRAINVIEW(2015), European Project: 115300,EC:FP7:SP1-JTI,IMI-JU-03-2010,EU-AIMS(2012), Radboud University [Nijmegen], Universität Heidelberg [Heidelberg] = Heidelberg University, University Hospital Mannheim | Universitätsmedizin Mannheim, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of Oxford, Buitelaar, Jan K. [0000-0001-8288-7757], and Baron-Cohen, Simon [0000-0001-9217-2544]
Subjects: Autism Spectrum Disorder, Autism, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], MESH: Magnetic Resonance Imaging, 0302 clinical medicine, Neurobiology, MESH: Child, Psychology, Young adult, Child, EU-AIMS LEAP Group, MESH: Autism Spectrum Disorder, Cortical Thickness, 0303 health sciences, 220 Statistical Imaging Neuroscience, Cognition, Autism spectrum disorders, MESH: Case-Control Studies, 692/699/476/1373, Magnetic Resonance Imaging, Psychiatry and Mental health, MESH: Young Adult, Autism spectrum disorder, 9, Female, Neurotypical, Clinical psychology, Adult, Adolescent, MESH: Autistic Disorder, Biology, Predictive markers, Article, lcsh:RC321-571, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, All institutes and research themes of the Radboud University Medical Center, MESH: Neurobiology, 692/53/2423, Neurodevelopmental Condition, medicine, Humans, Autistic Disorder, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, 030304 developmental biology, MESH: Adolescent, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], MESH: Humans, [SCCO.NEUR]Cognitive science/Neuroscience, Case-control study, MESH: Adult, medicine.disease, Case-Control Studies, 59/57, Normative, Polygenic risk score, 631/477, MESH: Female, 030217 neurology & neurosurgery
Abstract: Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440, Funder: SBC was funded by the Wellcome Trust and the Autism Research Trust during the period of this work., Funder: DM was supported by the NIHR Maudsley Biomedical Research Centre., Autism is a complex neurodevelopmental condition with substantial phenotypic, biological, and etiologic heterogeneity. It remains a challenge to identify biomarkers to stratify autism into replicable cognitive or biological subtypes. Here, we aim to introduce a novel methodological framework for parsing neuroanatomical subtypes within a large cohort of individuals with autism. We used cortical thickness (CT) in a large and well-characterized sample of 316 participants with autism (88 female, age mean: 17.2 ± 5.7) and 206 with neurotypical development (79 female, age mean: 17.5 ± 6.1) aged 6–31 years across six sites from the EU-AIMS multi-center Longitudinal European Autism Project. Five biologically based putative subtypes were derived using normative modeling of CT and spectral clustering. Three of these clusters showed relatively widespread decreased CT and two showed relatively increased CT. These subtypes showed morphometric differences from one another, providing a potential explanation for inconsistent case–control findings in autism, and loaded differentially and more strongly onto symptoms and polygenic risk, indicating a dilution of clinical effects across heterogeneous cohorts. Our results provide an important step towards parsing the heterogeneous neurobiology of autism.
Published: 2020

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

Author: Dimitri Papadopoulos Orfanos, Michael N. Smolka, Juliane H. Fröhner, Robert Whelan, Chao Xie, Gareth J. Barker, Andreas Heinz, Tianye Jia, Frauke Nees, Erin Burke Quinlan, Penny A. Gowland, Tobias Banaschewski, Bernd Ittermann, Gunter Schumann, Henrik Walter, Marie-Laure Paillère Martinot, Herta Flor, Antoine Grigis, Trevor W. Robbins, Christian Büchel, Hugh Garavan, Luise Poustka, Sylvane Desrivières, Arun L.W. Bokde, Jianfeng Feng, Jean-Luc Martinot, Gestionnaire, Hal Sorbonne Université, Fudan University [Shanghai], King‘s College London, Heidelberg University, Trinity College Dublin, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), University of Mannheim, 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), University of Vermont [Burlington], University of Nottingham, UK (UON), Humboldt University Of Berlin, Physikalisch-Technische Bundesanstalt [Berlin] (PTB), CB - Centre Borelli - UMR 9010 (CB), Service de Santé des Armées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay)-Université Paris Cité (UPCité), Service de Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière] (SPEA), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universität Heidelberg [Heidelberg], University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, University Medical Center Göttingen (UMG), Technische Universität Dresden = Dresden University of Technology (TU Dresden), University of Potsdam = Universität Potsdam, University of Cambridge [UK] (CAM), University of Warwick [Coventry], Zhejiang Normal University, Humboldt-Universität zu Berlin, Service de Santé des Armées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay)-Université de Paris (UP), University of Potsdam, Universität Mannheim, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Universität Heidelberg [Heidelberg] = Heidelberg University
Subjects: Adolescent, [SDV]Life Sciences [q-bio], Prefrontal Cortex, Biology, Nucleus accumbens, Impulsivity, Periaqueductal gray, 03 medical and health sciences, 0302 clinical medicine, Biological neural network, medicine, Humans, Periaqueductal Gray, Research Articles, Cerebral Cortex, Multidisciplinary, medicine.diagnostic_test, Central nucleus of the amygdala, Alcohol dependence, SciAdv r-articles, Magnetic Resonance Imaging, 030227 psychiatry, [SDV] Life Sciences [q-bio], Alcoholism, Orbitofrontal cortex, Neural Networks, Computer, medicine.symptom, Functional magnetic resonance imaging, Neuroscience, 030217 neurology & neurosurgery, Research Article
Abstract: Neuroimaging data from 1890 adolescents implicated an orbitofronto-amygdalo-periaqueductal gray network in early alcohol abuse., 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: 2020

31. Dissecting the heterogeneous cortical anatomy of autism spectrum disorder using normative models

Author: David Goyard, Tony Charman, Sarah Durston, Marianne Oldehinkel, Vincent Frouin, Sven Bölte, Andre F. Marquand, Christine Ecker, Simon Baron-Cohen, Mariam Zabihi, Christian F. Beckmann, Tobias Banaschewski, Jan K. Buitelaar, Rosemary Holt, Guillaume Dumas, Eva Loth, Declan G. Murphy, Thomas Wolfers, Julian Tillmann, Radboud University Medical Center [Nijmegen], Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Service NEUROSPIN (NEUROSPIN), 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, Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim], Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), University of Cambridge [UK] (CAM), University Medical Center [Utrecht], Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt am Main, Stockholm County Council, Sackler Institute of Translational Neurodevelopment, Institute of Psychiatry, King's College London, Goethe-University Frankfurt am Main, Department of Psychiatry, The work is supported by the Netherlands Organization for Scientific Research VIDI Grant Nos. 016.156.415 (to AFM) and 864.12.003 (to CFB), European Union Seventh Framework Programme Grant Nos. 602805 (AGGRESSOTYPE) (to JKB), 603016 (MATRICS) (to JKB), and 278948 (TACTICS) (to JKB), European Community’s Horizon 2020 Programme (H2020/2014-2020) Grant Nos. 643051 (MiND) (to JKB) and 642996 (BRAINVIEW) (to JKB), Wellcome Trust UK Strategic Award Grant No. 098369/Z/12/Z (to CFB), and EU-AIMS (European Autism Interventions), which receives support from Innovative Medicines Initiative Joint Undertaking Grant No. 115300, the resources of which are composed of financial contributions from the European Union’s Seventh Framework Programme (Grant No. FP7/2007-2013), from the European Federation of Pharmaceutical Industries and Associations companies’ in-kind contributions., JKB has been a consultant to, advisory board member of, and a speaker for Janssen Cilag BV, Eli Lilly, Shire, Lundbeck, Roche, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents or royalties. CFB is director and shareholder in SBGNeuro Ltd. SB discloses that he has in the last 5 years acted as an author, consultant or lecturer for Shire, Medice, Roche, Eli Lilly, Prima Psychiatry, GLGroup, System Analytic, Ability Partner, Kompetento, Expo Medica, and Prophase. He receives royalties for text books and diagnostic tools from Huber/Hogrefe, Kohlhammer, and UTB. TB served in an advisory or consultancy role for Actelion, Hexal Pharma, Lilly, Lundbeck, Medice, Novartis, and 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 and Vifor Pharma. He received royalities from Hogrefe, Kohlhammer, CIP Medien, and Oxford University Press. The present work is unrelated to the above grants and relationships. The other authors report no biomedical financial interests or potential conflicts of interest., We gratefully acknowledge the support of the EU-AIMS (European Autism Interventions) Longitudinal European Autism Project study team for data acquisition, quality control, and preprocessing., European Project: 602805,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,AGGRESSOTYPE(2013), European Project: 603016,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,MATRICS(2014), European Project: 278948,EC:FP7:HEALTH,FP7-HEALTH-2011-two-stage,TACTICS(2012), European Project: 643051,H2020,H2020-MSCA-ITN-2014,MiND(2015), European Project: 115300,EC:FP7:SP1-JTI,IMI-JU-03-2010,EU-AIMS(2012), Radboud University [Nijmegen], 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), University Hospital Mannheim | Universitätsmedizin Mannheim, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Sackler Institute of Translational Neurodevelopment [London]
Subjects: Male, 0301 basic medicine, Autism Spectrum Disorder, Autism, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Neuroimaging biomarkers, 0302 clinical medicine, Child, Cerebral Cortex, 0303 health sciences, 220 Statistical Imaging Neuroscience, Magnetic Resonance Imaging, medicine.anatomical_structure, Autism spectrum disorder, Homogeneous, Radiology Nuclear Medicine and imaging, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Biological psychiatry, Psychology, Normative modeling, Cognitive psychology, Adult, Brain development, Adolescent, Cognitive Neuroscience, Models, Neurological, Clinical Neurology, Cognitive neuroscience, behavioral disciplines and activities, Article, Cortical thickness, Young Adult, 03 medical and health sciences, Clinical heterogeneity, Image Interpretation, Computer-Assisted, mental disorders, medicine, Journal Article, Outlier detection, Humans, Radiology, Nuclear Medicine and imaging, Gaussian process, Biological Psychiatry, 030304 developmental biology, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], cortical thickness, medicine.disease, Cross-Sectional Studies, 030104 developmental biology, Case-Control Studies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Multiple comparisons problem, Normative, Neurology (clinical), Heterogeneity, heterogeneity, 030217 neurology & neurosurgery, Neuroanatomy
Abstract: BackgroundThe neuroanatomical basis of autism spectrum disorder (ASD) has remained elusive, mostly due to high biological and clinical heterogeneity among diagnosed individuals. Despite considerable effort towards understanding ASD using neuroimaging biomarkers, heterogeneity remains a barrier, partly because studies mostly employ case-control approaches, which assume that the clinical group is homogeneous.MethodsHere, we used an innovative normative modelling approach to parse biological heterogeneity in ASD. We aimed to dissect the neuroanatomy of ASD by mapping the deviations from a typical pattern of neuroanatomical development at the level of the individual and to show the necessity to look beyond the case-control paradigm to understand the neurobiology of ASD. We first estimated a vertex-wise normative model of cortical thickness development using Gaussian process regression, then mapped the deviation of each participant from the typical pattern. For this we employed a heterogeneous cross-sectional sample of 206 typically developing (TD) individuals (127 male), and 321 individuals (232 male) with ASD (aged 6-31).ResultsWe found few case-control differences but the ASD cohort showed highly individualized patterns of deviations in cortical thickness that were widespread across the brain. These deviations correlated with severity of repetitive behaviors and social communicative symptoms, although only repetitive behaviors survived corrections for multiple testing.ConclusionsOur results: (i) reinforce the notion that individuals with ASD show distinct, highly individualized trajectories of brain development and (ii) show that by focusing on common effects (i.e. the ‘average ASD participant’), the case-control approach disguises considerable inter-individual variation crucial for precision medicine.
Published: 2019

32. Adolescent binge drinking disrupts normal trajectories of brain functional organization and personality maturation

Author: Zhaowen Liu, Herta Flor, Frauke Nees, Gabriel Robert, Christian Büchel, Juliane H. Fröhner, Tobias Banaschewski, Yunyi Zhou, Michael N. Smolka, Sylvane Desrivières, Fei Li, Qiang Luo, Robert Whelan, Andreas Heinz, Arun L.W. Bokde, Gunter Schumann, Luise Poustka, Erin Burke Quinlan, Marie-Laure Paillère Martinot, Henrik Walter, Penny A. Gowland, Vincent Frouin, Jianfeng Feng, Hongtao Ruan, Bernd Ittermann, Hugh Garavan, Jean-Luc Martinot, Dimitri Papadopoulos Orfanos, Uli Bromberg, Sarah Hohmann, Jonchère, Laurent, Santé Mentale et Addictions - Dépression à l'Adolescence: Structure cérébrale et myélinisation - - ADODEP2012 - ANR-12-SAMA-0004 - SAMENTA - VALID, Fudan University [Shanghai], Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Xidian University, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim], Discipline of Psychiatry [Dublin], School of Medicine [Dublin], Trinity College Dublin-Trinity College Dublin, 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), University of Vermont [Burlington], University of Nottingham, UK (UON), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Physikalisch-Technische Bundesanstalt [Braunschweig] (PTB), Neuroimagerie en psychiatrie (U1000), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Heidelberg University, University Medical Center Göttingen (UMG), Technische Universität Dresden = Dresden University of Technology (TU Dresden), MR/N000390/1, Medical Research Council Canada, 20152234, Shanghai Municipal Education Commission, AERIAL 01EE1406A, Bundesministeriumfür Bildung und Forschung, ANR-12-SAMA-0004, ANR, Shanghai AI Platform for Diagnosis and Treatment of Brain Diseases, Fondation pour la Recherche Médicale, Assistance-Publique-Hôpitaux-de-Paris, 16/ERCD/3797, National Institutes of Health, Science Foundation Ireland, IDEX 2012, Université Paris-Sud, RO1 MH085772-01A1, U.S.A., U54 EB020403, NIH, National Institute for Health Research, MR/N027558/1, BRIDGET, 81761128035, National Natural Science Foundation of China, Fondation de France, LSHM-CT- 2007-037286, European Commission, 2016-17, Project of Zhangjiang Hi-Tech District Management Committee, Shanghai, SFB 940/1, Deutsche Forschungsgemeinschaft, 695313, Horizon 2020 Framework Programme, Mission Interministérielle de Lutte Contre les Drogues et les Conduites Addictives, 17ZR1444400, Natural Science Foundation of Shanghai, Svenska Forskningsrådet Formas, 2018SHZDZX01, Shanghai Municipal Science and Technology, 602450, FP7, Zhangjiang Lab, 16JC1420402, Shanghai Science and Technology Innovation Plan, B18015, Higher Education Discipline Innovation Project, GDEK201709, Shanghai Municipal Commission of Health and Family Planning, 16CR2025B, Shanghai Shenkang Hospital Development Center, 17XD1403200, Shanghai Committee of Science and Technology, 2018YJRC03, Xinhua Hospital of Shanghai Jiao Tong University School of Medicine, PR-ST-0416-10004, ERANID, Institut National de la Santé et de la Recherche Médicale, 603016, MATRICS, 115300-2, Innovative Medicine Initiative Project EU-AIMS, Maudsley NHS Foundation Trust, 2018YFC0910503, National Basic Research Program of China (973 Program), King's College London, ANR-12-SAMA-0004,ADODEP,Dépression à l'Adolescence: Structure cérébrale et myélinisation(2012), Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), University Hospital Mannheim | Universitätsmedizin Mannheim, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), 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, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11)
Subjects: Male, Support Vector Machine, Time Factors, Co-development, [SDV]Life Sciences [q-bio], iFC, increased rsFC, Binge drinking, Underage Drinking, Adolescent, Genome, Personality, Resting state, lcsh:RC346-429, 0302 clinical medicine, rsFC, resting-state functional connectivity, Longitudinal Studies, Cantab, Cambridge Neuropsychological Test Automated Battery, Age of Onset, Big Five personality traits, media_common, rsfMRI, resting-state fMRI, ANOVA, Analysis of Variance, NEO-PI-R, Revised NEO Personality Inventory, 05 social sciences, Brain, Regular Article, SNP, single nucleotide polymorphism, Magnetic Resonance Imaging, [SDV] Life Sciences [q-bio], ESPAD, European School Survey Project on Alcohol and Drugs, Neurology, lcsh:R858-859.7, Female, Functional organization, medicine.symptom, Psychology, Alcohol consumption, Clinical psychology, Adult, FDR, false discovery rate, Cognitive Neuroscience, media_common.quotation_subject, SVM, support-vector machine, AUC, area under curve, Impulsivity, lcsh:Computer applications to medicine. Medical informatics, 050105 experimental psychology, Young Adult, 03 medical and health sciences, Connectome, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, pSNP, protective SNP, ROC, receiver operational characteristic, lcsh:Neurology. Diseases of the nervous system, rSNP, risk SNP, dFC, decreased rsFC, Resting state fMRI, Adolescent Development, Mental health, LOO, leave-one-out, NRI, net reclassification improvement, Personality Development, Impulsive Behavior, Neurology (clinical), SURPS, Substance Use Risk Profile Scale, 030217 neurology & neurosurgery
Abstract: Adolescent binge drinking has been associated with higher risks for the development of many health problems throughout the lifespan. Adolescents undergo multiple changes that involve the co-development processes of brain, personality and behavior; therefore, certain behavior, such as alcohol consumption, can have disruptive effects on both brain development and personality maturation. However, these effects remain unclear due to the scarcity of longitudinal studies. In the current study, we used multivariate approaches to explore discriminative features in brain functional architecture, personality traits, and genetic variants in 19-year-old individuals (n = 212). Taking advantage of a longitudinal design, we selected features that were more drastically altered in drinkers with an earlier onset of binge drinking. With the selected features, we trained a hierarchical model of support vector machines using a training sample (n = 139). Using an independent sample (n = 73), we tested the model and achieved a classification accuracy of 71.2%. We demonstrated longitudinally that after the onset of binge drinking the developmental trajectory of improvement in impulsivity slowed down. This study identified the disrupting effects of adolescent binge drinking on the developmental trajectories of both brain and personality., Highlights • History of binge drinking could be identified by multivariate features at age 19. • Adolescent binge drinking disrupted frontal connectivity maturation in the brain. • Impulsivity improvement slowed down after the onset of adolescent binge drinking.
Published: 2019

33. Diagnosis and management of Aspergillus diseases: Executive summary of the 2017 ESCMID-ECMM-ERS guideline

Author: János Sinkó, Roger J. M. Brüggemann, Catherine Beigelman-Aubry, Jesús Fortún, Olivier Lortholary, Livio Pagano, Donald C. Sheppard, J Maertens, Murat Akova, Werner J. Heinz, Claudio Viscoli, Florence Ader, O. Marchetti, Katrien Lagrou, Bart Jan Kullberg, Paul E. Verweij, Oliver A. Cornely, Christoph Lange, Russell E. Lewis, Maria J G T Vehreschild, Patricia Muñoz, Manuel Cuenca-Estrella, Emilio Bouza, Thomas Lehrnbecher, Stijn Blot, José María Aguado, Elio Castagnola, Claus Peter Heussel, Jacques Cadranel, Malcolm Richardson, Christopher C. Kibbler, Jean-Pierre Gangneux, S. Arikan-Akdagli, George Dimopoulos, Raoul Herbrecht, Cornelia Lass-Flörl, Maurizio Sanguinetti, Rosemary Ann Barnes, Jürgen Löffler, David W. Denning, Anna Skiada, Jorge Garbino, Jacques F. Meis, Maiken Cavling Arendrup, Andrew J. Ullmann, Andreas H. Groll, Patricia Ribaud, Adilia Warris, Nikolay Klimko, Arunaloke Chakrabarti, Dieter Buchheidt, Emmanuel Roilides, Markus Ruhnke, A J Ullmann, J M Aguado, S Arikan-Akdagli, D W Denning, A H Groll, K Lagrou, C Lass-Flörl, R E Lewis, P Munoz, P E Verweij, A Warris, F Ader, M Akova, M C Arendrup, R A Barnes, C Beigelman-Aubry, S Blot, E Bouza, R J M Brüggemann, D Buchheidt, J Cadranel, E Castagnola, A Chakrabarti, M Cuenca-Estrella, G Dimopoulos, J Fortun, J-P Gangneux, J Garbino, W J Heinz, R Herbrecht, C P Heussel, C C Kibbler, N Klimko, B J Kullberg, C Lange, T Lehrnbecher, J Löffler, O Lortholary, J Maertens, O Marchetti, J F Meis, L Pagano, P Ribaud, M Richardson, E Roilides, M Ruhnke, M Sanguinetti, D C Sheppard, J Sinkó, A Skiada, M, J G T Vehreschild, C Viscoli, O A Cornely, University Hospital of Würzburg, Division of Infectious Diseases (Department of Medicine), Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, Wythenshawe Hospital Manchester UK, University Children's Hospital, Munster, Leuven University Hospital, Innsbruck Medical University [Austria] (IMU), University of Bologna, Hospital General Universitario 'Gregorio Marañón' [Madrid], Department of Medical Microbiology, Radboud University Medical Center [Nijmegen], Institute of Medical Sciences, University of Aberdeen, Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Statens Serum Institute [Copenhagen], School of Medicine [Cardiff], Cardiff University-Institute of Medical Genetics [Cardiff], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Faculty of Medicine and Health Science, University of Ghent, Ghent, Belgium, University Hospital Mannheim, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Istituto Giannina Gaslini, Institute of Post Graduate Medical Education & Research [Calcutta] (IPGMER), Instituto de Salud Carlos III [Madrid] (ISC), 'Attikon' University Hospital, Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University Hospital of Geneva, University Hospital of Strasbourg (CIC), University Hospital of Strasbourg, Heidelberg University Hospital [Heidelberg], University College of London [London] (UCL), Russian State Medical University, Universität zu Lübeck [Lübeck], Clinic of Johann Wolfgang von Goethe University, Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University Hospitals Leuven [Leuven], Canisius-Wilhelmina Hospital [Nijmegen, The Netherlands], Università cattolica del Sacro Cuore [Roma] (Unicatt), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Wythenshawe Hospital [Manchester, UK], University of South Manchester, Aristotle University of Thessaloniki, Paracelsus-Elena-Hospital, Department of Medecine [Montréal], McGill University = Université McGill [Montréal, Canada], Szent László Hospital, National and Kapodistrian University of Athens (NKUA), University Hospital of Cologne [Cologne], University of Genova [Genova, Italy], Actelion Pharmaceuticals, Astellas Pharma Canada, AstraZeneca, Bayer HealthCare, Cidara Therapeutics, NIH UM1AI104681, Duke University, Amplyx, Arsanis, Basilea, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), University of Bologna/Università di Bologna, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University (UGENT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Universität zu Lübeck = University of Lübeck [Lübeck], Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Pathogenèse des légionelles- Legionella pathogenesis, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [APHP], Institute of Post Graduate Medical Education & Research, Calcutta, Instituto de Salud Carlos III (ISC), Universität zu Lübeck [Lübeck] - University of Lübeck [Lübeck], Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]-Institut des Maladies Génétiques Imagine [Paris], Università Cattolica del Sacro Cuore [Roma] (Unicatt), Hopital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), McGill University, and National and Kapodistrian University of Athens
Subjects: 0301 basic medicine, Myeloid, Posaconazole, Antifungal Agents, Pyridines, Biopsy, Pyridine, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Flucytosine, Aspergillosis, Bronchoalveolar Lavage, Mannans, chemistry.chemical_compound, 0302 clinical medicine, Invasive fungal infection, Early Diagnosi, Diagnosis, Haematology, Transplantation, Treatment, Antibodies, Fungal, Aspergillus, Early Diagnosis, Humans, Immunocompromised Host, Immunologic Tests, Invasive Pulmonary Aspergillosis, Itraconazole, Leukemia, Myeloid, Acute, Magnetic Resonance Imaging, Microbial Sensitivity Tests, Myelodysplastic Syndromes, Nitriles, Tomography, X-Ray Computed, Triazoles, Voriconazole, Disease Management, Antifungal Agent, Immunologic Test, 030212 general & internal medicine, Tomography, ComputingMilieux_MISCELLANEOUS, Leukemia, Microbial Sensitivity Test, General Medicine, Mannan, 3. Good health, X-Ray Computed, Fungal, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Nitrile, medicine.drug, Diagnosi, Human, Microbiology (medical), medicine.medical_specialty, Echinocandin, Aspergillosi, 030106 microbiology, Invasive Pulmonary Aspergillosi, Myelodysplastic Syndrome, Acute, Antibodies, Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA, 03 medical and health sciences, Internal medicine, medicine, business.industry, Micafungin, Induction chemotherapy, Galactose, medicine.disease, Aspergillu, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Settore MED/15 - MALATTIE DEL SANGUE, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], chemistry, Triazole, Caspofungin, business
Abstract: Contains fulltext : 193204.pdf (Publisher’s version ) (Closed access) The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.
Published: 2018

34. Associations of the Intellectual Disability Gene MYT1L with Helix–Loop–Helix Gene Expression, Hippocampus Volume and Hippocampus Activation During Memory Retrieval

Author: Christian P. Müller, Gunter Schumann, Roberto Toro, Susanne Erk, Stephanie H. Witt, Cathy Fernandes, Jean Christophe Poncer, Franziska Degenhardt, Andreas Meyer-Lindenberg, Deepak Srivastava, Barbara Ruggeri, A. Fernandes, Marie-Laure Paillère Martinot, Andreas Heinz, Lourdes Martinez Medina, Agnieszka Kepa, Henrik Walter, Sylvane Desrivières, Sabine Lévi, Jean-Luc Martinot, Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Gènes, Synapses et Cognition, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut du Fer à Moulin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), University of Bonn, Universität Heidelberg [Heidelberg], Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim], Neuroimagerie en psychiatrie (U1000), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Maison de Solenn [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Friedrich Alexander University [Erlangen-Nürnberg], This work was funded by Wellcome Trust grant reference 090532/Z/09/Z and MRC Hub grant G0900747 91070. This work received further support from the European Union-funded FP6 Integrated Project IMAGEN (reinforcement-related behavior in normal brain function and psychopathology, LSHM-CT- 2007-037286). S.D and G.S. are also supported in part by the NIH BD2K award, U54EB020403, the FP7 projects IMAGEMEND (602450, IMAging GEnetics for MENtal Disorders) and MATRICS (603016), the Innovative Medicine Initiative Project EU-AIMS (115300-2), a Medical Research Council Programme Grant ‘Developmental pathways into adolescent substance abuse’ (93558), the Swedish funding agency FORMAS, the Medical Research Council and the Wellcome Trust (Behavioural and Clinical Neuroscience Institute, University of Cambridge), the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, the Bundesministeriumfür Bildung und Forschung (BMBF grants 01GS08152, 01EV0711, eMED SysAlc01ZX1311A, Forschungsnetze AERIAL and BipoLife) and the Deutsche Forschungsgemeinschaft (DFG grants FOR 1617, SFB 940 and SM 80/5-2)., European Project: 39513,IMAGEN, European Project: 602450,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,IMAGEMEND(2013), European Project: 603016,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,MATRICS(2014), European Project: 115300,EC:FP7:SP1-JTI,IMI-JU-03-2010,EU-AIMS(2012), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], 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), Universität Bonn = University of Bonn, Universität Heidelberg [Heidelberg] = Heidelberg University, University Hospital Mannheim | Universitätsmedizin Mannheim, Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Department of Genomics, Génétique humaine et Fonctions cognitives - Human Genetics and Cognitive Functions, Centre National de la Recherche Scientifique ( CNRS ) -Institut Pasteur [Paris], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), King's College, Department of Genomics, Life and Brain Center, Université de Bonn, Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Sorbonne Université, Neuroimagerie en psychiatrie ( U1000 ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), IFR49, Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Service Hospitalier Frédéric Joliot ( SHFJ ), 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, Université Paris-Sud - Paris 11 ( UP11 ), Université Paris Descartes - Paris 5 ( UPD5 ), Université Sorbonne Paris Cité ( USPC ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Institut für Chemie und Biochemie, Anorganische Chemie, Freie Universität Berlin, and MRC- SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK
Subjects: Adult, Inhibitor of Differentiation Protein 1, Male, 0301 basic medicine, Neurogenesis, [SDV]Life Sciences [q-bio], Gene Expression, Hippocampus, Nerve Tissue Proteins, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, Neural Stem Cells, Memory, Gene expression, Journal Article, Basic Helix-Loop-Helix Transcription Factors, Humans, Transcription factor, ComputingMilieux_MISCELLANEOUS, Genetic Association Studies, Pharmacology, Gene knockdown, [ SDV ] Life Sciences [q-bio], Long-term potentiation, Organ Size, TCF4, Magnetic Resonance Imaging, Neural stem cell, Neoplasm Proteins, Psychiatry and Mental health, HEK293 Cells, 030104 developmental biology, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Gene Knockdown Techniques, Female, Inhibitor of Differentiation Proteins, Neuroscience, 030217 neurology & neurosurgery, Transcription Factors
Abstract: The fundamental role of the brain-specific myelin transcription factor 1-like (MYT1L) gene in cases of intellectual disability and in the aetiology of neurodevelopmental disorders is increasingly recognised. Yet, its function remains under-investigated. Here, we identify a network of helix-loop-helix (HLH) transcriptional regulators controlled by MYT1L, as indicated by our analyses in human neural stem cells and in the human brain. Using cell-based knockdown approaches and microarray analyses we found that (i) MYT1L is required for neuronal differentiation and identified ID1, a HLH inhibitor of premature neurogenesis, as a target. (2) While MYT1L prevented expression of ID1, it induced expression of a large number of terminal differentiation genes. (3) Consistently, expression of MYT1L in the human brain coincided with neuronal maturation and inversely correlated with that of ID1 and ID3 throughout the lifespan. (4) Genetic polymorphisms that reduced expression of MYT1L in the hippocampus resulted in increased expression of ID1 and ID3, decreased levels of the proneural basic HLH (bHLH) transcriptional regulators TCF4 and NEUROD6 and decreased expression of genes involved in long-term potentiation and synaptic transmission, cancer and neurodegeneration. Furthermore, our neuroimaging analyses indicated that MYT1L expression associated with hippocampal volume and activation during episodic memory recall, as measured by blood-oxygen-level dependent (BOLD) signals. Overall, our findings suggest that MYT1L influences memory-related processes by controlling a neuronal proliferation/differentiation switch of ID-bHLH factors.Neuropsychopharmacology accepted article preview online, 04 May 2017. doi:10.1038/npp.2017.91.
Published: 2017

35. Association of a Schizophrenia-Risk Nonsynonymous Variant With Putamen Volume in Adolescents

Author: Lena Palaniyappan, Qiang Luo, Christian Büchel, Daniel R. Weinberger, Vincent Frouin, Ferath Kherif, Jean-François Dartigues, Marie Laure Paillère-Martinot, Christine Macare, Jianfeng Feng, Mickaël Guedj, Michael N. Smolka, Tomáš Paus, Erin Burke Quinlan, Tianye Jia, Robin M. Murray, Joseph H. Callicott, Dimitri Papadopoulos Orfanos, Karen F. Berman, Jean-Luc Martinot, Christophe Tzourio, Wenjia Wang, Fabrice Crivello, Bernd Ittermann, Eric Artiges, Jing Cui, Gunter Schumann, Sylvane Desrivières, Frauke Nees, Venkata S. Mattay, Robert Whelan, Qiang Chen, Andreas Heinz, Arun L.W. Bokde, Fei Li, Penny A. Gowland, Zdenka Pausova, Luise Poustka, Herta Flor, Henrik Walter, Hugh Garavan, Gabriel Robert, Tobias Banaschewski, Juliane H. Fröhner, Fudan University [Shanghai], King‘s College London, Lieber Institute for Brain Development [Baltimore] (LIBD), Pharnext SAS, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of Western Ontario (UWO), Universität Heidelberg [Heidelberg], Trinity College Dublin, University of Mannheim, Service NEUROSPIN (NEUROSPIN), 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, University of Vermont [Burlington], University of Nottingham, UK (UON), Service Hospitalier Frédéric Joliot (SHFJ), Maison de Solenn [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neuroimagerie en psychiatrie (U1000), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Airbus [France], University Medical Center Göttingen (UMG), Medizinische Universität Wien = Medical University of Vienna, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Johns Hopkins University School of Medicine [Baltimore], University of Toronto, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Bloorview Research Institute, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, University of Warwick [Coventry], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Universität Heidelberg [Heidelberg] = Heidelberg University, Universität Mannheim, 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-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences Cliniques de Rennes (INCR)-CHU Pontchaillou [Rennes]-Université européenne de Bretagne - European University of Brittany (UEB)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), University Medical Centre Göttingen, Medical University of Vienna, Technische Universität Dresden (TUD), and IMAGEN consortium
Subjects: 0303 health sciences, medicine.medical_specialty, Psychosis, business.industry, [SDV]Life Sciences [q-bio], Putamen, Genome-wide association study, medicine.disease, 3. Good health, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Internal medicine, Cohort, medicine, Etiology, Missense mutation, Allele, Adolescent, Adult, Case-Control Studies, Cation Transport Proteins/biosynthesis, Cation Transport Proteins/genetics, Female, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study, Gray Matter/pathology, Humans, Hypertrophy/genetics, Hypertrophy/pathology, Magnetic Resonance Imaging, Male, Mutation, Missense/genetics, Neuroimaging, Putamen/pathology, Schizophrenia/genetics, Schizophrenia/pathology, Siblings, business, 030217 neurology & neurosurgery, 030304 developmental biology, Psychopathology
Abstract: 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..
Published: 2019

36. Genomic architecture of human neuroanatomical diversity

Author: Gunter Schumann, Thomas Bourgeron, Bernd Ittermann, Zdenka Pausova, Roberto Toro, Fabiana M. Carvalho, Marcella Rietschel, Patricia J. Conrod, Karl Mann, J-B Poline, Hugh Garavan, Penny A. Gowland, Eva Loth, Mira Fauth-Bühler, Tomáš Paus, Herta Flor, Andreas Ströhle, Arun L.W. Bokde, Trevor W. Robbins, Claire Lawrence, Christian Büchel, Andreas Heinz, Michael N. Smolka, Tobias Banaschewski, Gareth J. Barker, Guillaume Huguet, Vincent Frouin, Frauke Nees, Jürgen Gallinat, Herve Lemaitre, 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), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), 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), Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, University Hospital Mannheim | Universitätsmedizin Mannheim, Universität Heidelberg [Heidelberg] = Heidelberg University, Trinity College Dublin, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), CHU Sainte Justine [Montréal], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Vermont [Burlington], Physikalisch-Technische Bundesanstalt [Berlin] (PTB), University of Nottingham, UK (UON), Neuroimagerie en psychiatrie (U1000), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maison de Solenn [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rotman Research Institute at the Baycrest Centre (RRI), University of Toronto, University of Cambridge [UK] (CAM), Technische Universität Dresden = Dresden University of Technology (TU Dresden), Fondation FondaMental [Créteil], This work was supported by the European Union-funded FP6 Integrated Project IMAGEN (Reinforcement-related behaviour in normal brain function and psychopathology, LSHM-CT-2007-037286), the FP7 projects ADAMS (Genomic variations underlying common neuropsychiatric diseases and diseases related to cognitive traits in different human populations, 242257), the Innovative Medicine Initiative Project EU-AIMS (115300-2), the Medical Research Council Programme Grant ‘Developmental pathways into adolescent substance abuse’ (93558), the Swedish Funding Agency FORMAS, the German Bundesministerium und Forschung (FKZ: 01EV0711), Institut Pasteur, CNRS, Université Paris Diderot, the Bettencourt-Schueller Foundation, the Conny-Maeva Foundation, the Orange Foundation, the FondaMental Foundation and the Cognacq-Jay Foundation., European Project: 39513,IMAGEN, European Project: 242257,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,ADAMS(2009), European Project: 115300,EC:FP7:SP1-JTI,IMI-JU-03-2010,EU-AIMS(2012), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], 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, Medical Faculty [Mannheim], Universität Heidelberg [Heidelberg], Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Technische Universität Dresden (TUD), Université de Montréal. Faculté de médecine. Département de psychiatrie et d'addictologie, Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11)
Subjects: Male, Adolescent, Genotyping Techniques, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Genome-wide association study, Single-nucleotide polymorphism, Neuroimaging, Biology, Genome, Polymorphism, Single Nucleotide, Cohort Studies, Heritability, Cellular and Molecular Neuroscience, 03 medical and health sciences, 0302 clinical medicine, medicine, Genetics, Humans, Computer Simulation, Molecular Biology, Gene, Genotyping, 030304 developmental biology, media_common, 0303 health sciences, Models, Genetic, Brain, Human brain, Organ Size, Magnetic Resonance Imaging, Psychiatry and Mental health, Neuroanatomy, medicine.anatomical_structure, Phenotype, Evolutionary biology, Female, 030217 neurology & neurosurgery, Diversity (politics), Genome-Wide Association Study
Abstract: International audience; Human brain anatomy is strikingly diverse and highly inheritable: genetic factors may explain up to 80% of its variability. Prior studies have tried to detect genetic variants with a large effect on neuroanatomical diversity, but those currently identified account for
Published: 2015

37. Single nucleotide polymorphism in the neuroplastin locus associates with cortical thickness and intellectual ability in adolescents

Author: Marcella Rietschel, Patricia J. Conrod, Jean-Baptiste Poline, Tobias Banaschewski, Michael N. Smolka, Roberto Toro, Chenyang Tao, Frauke Nees, Lourdes Martinez Medina, Gareth J. Barker, Juergen Gallinat, Christian Büchel, Zdenka Pausova, A. Fernandes, Marie-Laure Paillère Martinot, Tomáš Paus, Tianye Jia, Agnieszka Kepa, Andreas Heinz, Gunter Schumann, Barbara Ruggeri, Eva Loth, Mira Fauth-Bühler, Claire Lawrence, Fabiana M. Carvalho, Mark Lathrop, Herta Flor, Hugh Garavan, Graham Cocks, Anbarasu Lourdusamy, Penny A. Gowland, Rüdiger Brühl, Karl Mann, Sylvane Desrivières, Arun L.W. Bokde, Paul M. Thompson, Jianfeng Feng, Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Fudan University [Shanghai], Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim], University of Heidelberg, Medical Faculty, Trinity College Dublin, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), CHU Sainte Justine [Montréal], Université de Montréal (UdeM), Universität Heidelberg [Heidelberg], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Vermont [Burlington], Physikalisch-Technische Bundesanstalt [Berlin] (PTB), University of Nottingham, UK (UON), Neuroimagerie en psychiatrie (U1000), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Maison de Solenn [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), 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), School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Technische Universität Dresden = Dresden University of Technology (TU Dresden), University of Toronto, McGill University = Université McGill [Montréal, Canada], University of Warwick [Coventry], This work was supported by the European Union-funded FP6 Integrated Project IMAGEN (Reinforcement-related behavior in normal brain function and psychopathology) (LSHM-CT- 2007-037286), the German Ministry of Education and Research (BMBF Grant # 01EV0711 and eMED ‘Alcoholism’), the FP7 project IMAGEMEND (Development of effective imaging tools for diagnosis, monitoring and management of mental disorders) and the Innovative Medicine Initiative Project EU-AIMS (115300-2), as well as the Medical Research Council Programme Grant ‘Developmental pathways into adolescent substance abuse’ (G93558), the Swedish Research Council (FORMAS) and the United Kingdom National Institute for Health Research (NIHR) Biomedical Research Centre Mental Health., European Project: 39513,IMAGEN, European Project: 602450,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,IMAGEMEND(2013), European Project: 115300,EC:FP7:SP1-JTI,IMI-JU-03-2010,EU-AIMS(2012), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Université de Montréal [Montréal], Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], 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, Technische Universität Dresden (TUD), McGill University, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), University Hospital Mannheim | Universitätsmedizin Mannheim, Universität Heidelberg [Heidelberg] = Heidelberg University, Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and University of California (UC)-University of California (UC)
Subjects: Male, [SDV]Life Sciences [q-bio], Locus (genetics), Single-nucleotide polymorphism, Mice, Transgenic, Neuropsychological Tests, Polymorphism, Single Nucleotide, Lateralization of brain function, 03 medical and health sciences, Cellular and Molecular Neuroscience, Mice, neural stem cell, 0302 clinical medicine, Cognition, Meta-Analysis as Topic, Neural Stem Cells, medicine, Image Processing, Computer-Assisted, SNP, Animals, Humans, lateralization, Molecular Biology, Gene, Cells, Cultured, Genetic Association Studies, 030304 developmental biology, Genetics, QM, 0303 health sciences, Membrane Glycoproteins, neuroimaging, Brain, Human brain, intelligence, cortical thickness, Microarray Analysis, Magnetic Resonance Imaging, Neural stem cell, Psychiatry and Mental health, medicine.anatomical_structure, adolescent, Linear Models, Female, Original Article, Psychology, Neuroplastin, Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; Despite the recognition that cortical thickness is heritable and correlates with intellectual ability in children and adolescents, the genes contributing to individual differences in these traits remain unknown. We conducted a large-scale association study in 1583 adolescents to identify genes affecting cortical thickness. Single-nucleotide polymorphisms (SNPs; n = 54 837) within genes whose expression changed between stages of growth and differentiation of a human neural stem cell line were selected for association analyses with average cortical thickness. We identified a variant, rs7171755, associating with thinner cortex in the left hemisphere (P = 1.12 × 10 −7), particularly in the frontal and temporal lobes. Localized effects of this SNP on cortical thickness differently affected verbal and nonverbal intellectual abilities. The rs7171755 polymorphism acted in cis to affect expression in the human brain of the synaptic cell adhesion glycoprotein-encoding gene NPTN. We also found that cortical thickness and NPTN expression were on average higher in the right hemisphere, suggesting that asymmetric NPTN expression may render the left hemisphere more sensitive to the effects of NPTN mutations, accounting for the lateralized effect of rs7171755 found in our study. Altogether, our findings support a potential role for regional synaptic dysfunctions in forms of intellectual deficits.
Published: 2015

38. Apolipoprotein E-dependent load of white matter hyperintensities in Alzheimer’s disease: a voxel-based lesion mapping study

Author: Lutz Frölich, Michael Schneider, Eckart Rüther, Hermann-Josef Gertz, Stefan J. Teipel, Michael Hüll, Fabian Rakebrandt, Harald Hampel, Holger Jahn, Heike Kölsch, Michael M. Plichta, Johannes Pantel, Wolfgang Maier, Johannes Schröder, Katrin Morgen, Frank Jessen, Andreas Meyer-Lindenberg, Johannes Kornhuber, Christian Luckhaus, Oliver Peters, Isabella Heuser, Heike Tost, Jens Wiltfang, Otto Rienhoff, Medical Faculty [Mannheim], AHG-Klinik für Psychosomatik, University of Bonn, University of Göttigen, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Hamburg, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], University of Freiburg [Freiburg], Universität Leipzig [Leipzig], Universität Heidelberg [Heidelberg], Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), University of Rostock, University of Frankfurt, Universität Duisburg-Essen [Essen], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), University Hospital Mannheim | Universitätsmedizin Mannheim, Universität Bonn = University of Bonn, Universität Leipzig, Universität Heidelberg [Heidelberg] = Heidelberg University, Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Universität Duisburg-Essen = University of Duisburg-Essen [Essen]
Subjects: Apolipoprotein E, medicine.medical_specialty, Pathology, Neurology, Cognitive Neuroscience, Medizin, Clinical Neurology, White matter, Lesion, 03 medical and health sciences, 610 Medical sciences Medicine, 0302 clinical medicine, Medizinische Fakultät, mental disorders, medicine, Dementia, ddc:610, 030304 developmental biology, 0303 health sciences, medicine.diagnostic_test, business.industry, Research, Neuropsychology, Magnetic resonance imaging, medicine.disease, Hyperintensity, 3. Good health, medicine.anatomical_structure, lipids (amino acids, peptides, and proteins), Neurology (clinical), medicine.symptom, Function and Dysfunction of the Nervous System, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: Introduction White matter (WM) magnetic resonance imaging (MRI) hyperintensities are common in Alzheimer’s disease (AD), but their pathophysiological relevance and relationship to genetic factors are unclear. In the present study, we investigated potential apolipoprotein E (APOE)-dependent effects on the extent and cognitive impact of WM hyperintensities in patients with AD. Methods WM hyperintensity volume on fluid-attenuated inversion recovery images of 201 patients with AD (128 carriers and 73 non-carriers of the APOE ε4 risk allele) was determined globally as well as regionally with voxel-based lesion mapping. Clinical, neuropsychological and MRI data were collected from prospective multicenter trials conducted by the German Dementia Competence Network. Results WM hyperintensity volume was significantly greater in non-carriers of the APOE ε4 allele. Lesion distribution was similar among ε4 carriers and non-carriers. Only ε4 non-carriers showed a correlation between lesion volume and cognitive performance. Conclusion The current findings indicate an increased prevalence of WM hyperintensities in non-carriers compared with carriers of the APOE ε4 allele among patients with AD. This is consistent with a possibly more pronounced contribution of heterogeneous vascular risk factors to WM damage and cognitive impairment in patients with AD without APOE ε4-mediated risk. Electronic supplementary material The online version of this article (doi:10.1186/s13195-015-0111-8) contains supplementary material, which is available to authorized users.
Published: 2015

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