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1. Investigating grey matter volumetric trajectories through the lifespan at the individual level

Author: Runye Shi, Shitong Xiang, Tianye Jia, Trevor W. Robbins, Jujiao Kang, Tobias Banaschewski, Gareth J. Barker, Arun L. W. Bokde, Sylvane Desrivières, Herta Flor, Antoine Grigis, Hugh Garavan, Penny Gowland, Andreas Heinz, Rüdiger Brühl, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Eric Artiges, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomáš Paus, Luise Poustka, Sarah Hohmann, Sabina Millenet, Juliane H. Fröhner, Michael N. Smolka, Nilakshi Vaidya, Henrik Walter, Robert Whelan, Gunter Schumann, Xiaolei Lin, Barbara J. Sahakian, Jianfeng Feng, and IMAGEN Consortium
Subjects: Science
Abstract: 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.
Published: 2024
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2. Whole exome sequencing analysis identifies genes for alcohol consumption

Author: Jujiao Kang, Yue-Ting Deng, Bang-Sheng Wu, Wei-Shi Liu, Ze-Yu Li, Shitong Xiang, Liu Yang, Jia You, Xiaohong Gong, Tianye Jia, Jin-Tai Yu, Wei Cheng, and Jianfeng Feng
Subjects: Science
Abstract: Abstract Alcohol consumption is a heritable behavior seriously endangers human health. However, genetic studies on alcohol consumption primarily focuses on common variants, while insights from rare coding variants are lacking. Here we leverage whole exome sequencing data across 304,119 white British individuals from UK Biobank to identify protein-coding variants associated with alcohol consumption. Twenty-five variants are associated with alcohol consumption through single variant analysis and thirteen genes through gene-based analysis, ten of which have not been reported previously. Notably, the two unreported alcohol consumption-related genes GIGYF1 and ANKRD12 show enrichment in brain function-related pathways including glial cell differentiation and are strongly expressed in the cerebellum. Phenome-wide association analyses reveal that alcohol consumption-related genes are associated with brain white matter integrity and risk of digestive and neuropsychiatric diseases. In summary, this study enhances the comprehension of the genetic architecture of alcohol consumption and implies biological mechanisms underlying alcohol-related adverse outcomes.
Published: 2024
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3. The impact of REM sleep loss on human brain connectivity

Author: Tianqi Di, Libo Zhang, Shiqiu Meng, Wangyue Liu, Yang Guo, Enyu Zheng, Chao Xie, Shitong Xiang, Tianye Jia, Lin Lu, Yan Sun, and Jie Shi
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Brain function is vulnerable to the consequences of inadequate sleep, an adverse trend that is increasingly prevalent. The REM sleep phase has been implicated in coordinating various brain structures and is hypothesized to have potential links to brain variability. However, traditional imaging research have encountered challenges in attributing specific brain region activity to REM sleep, remained understudied at the whole-brain connectivity level. Through the spilt-night paradigm, distinct patterns of REM sleep phases were observed among the full-night sleep group (n = 36), the early-night deprivation group (n = 41), and the late-night deprivation group (n = 36). We employed connectome-based predictive modeling (CPM) to delineate the effects of REM sleep deprivation on the functional connectivity of the brain (REM connectome) during its resting state. The REM sleep-brain connectome was characterized by stronger connectivity within the default mode network (DMN) and between the DMN and visual networks, while fewer predictive edges were observed. Notably, connections such as those between the cingulo-opercular network (CON) and the auditory network, as well as between the subcortex and visual networks, also made significant contributions. These findings elucidate the neural signatures of REM sleep loss and reveal common connectivity patterns across individuals, validated at the group level.
Published: 2024
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4. A neural signature for the subjective experience of threat anticipation under uncertainty

Author: Xiqin Liu, Guojuan Jiao, Feng Zhou, Keith M. Kendrick, Dezhong Yao, Qiyong Gong, Shitong Xiang, Tianye Jia, Xiao-Yong Zhang, Jie Zhang, Jianfeng Feng, and Benjamin Becker
Subjects: Science
Abstract: Abstract Uncertainty about potential future threats and the associated anxious anticipation represents a key feature of anxiety. However, the neural systems that underlie the subjective experience of threat anticipation under uncertainty remain unclear. Combining an uncertainty-variation threat anticipation paradigm that allows precise modulation of the level of momentary anxious arousal during functional magnetic resonance imaging (fMRI) with multivariate predictive modeling, we train a brain model that accurately predicts subjective anxious arousal intensity during anticipation and test it across 9 samples (total n = 572, both gender). Using publicly available datasets, we demonstrate that the whole-brain signature specifically predicts anxious anticipation and is not sensitive in predicting pain, general anticipation or unspecific emotional and autonomic arousal. The signature is also functionally and spatially distinguishable from representations of subjective fear or negative affect. We develop a sensitive, generalizable, and specific neuroimaging marker for the subjective experience of uncertain threat anticipation that can facilitate model development.
Published: 2024
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5. Association between vmPFC gray matter volume and smoking initiation in adolescents

Author: Shitong Xiang, Tianye Jia, Chao Xie, Wei Cheng, Bader Chaarani, Tobias Banaschewski, Gareth J. Barker, Arun L. W. Bokde, Christian Büchel, Sylvane Desrivières, Herta Flor, Antoine Grigis, Penny A. Gowland, Rüdiger Brühl, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Luise Poustka, Sarah Hohmann, Juliane H. Fröhner, Michael N. Smolka, Nilakshi Vaidya, Henrik Walter, Robert Whelan, Hugh Garavan, Gunter Schumann, Barbara J. Sahakian, Trevor W. Robbins, Jianfeng Feng, and IMAGEN Consortium
Subjects: Science
Abstract: Abstract Smoking of cigarettes among young adolescents is a pressing public health issue. However, the neural mechanisms underlying smoking initiation and sustenance during adolescence, especially the potential causal interactions between altered brain development and smoking behaviour, remain elusive. Here, using large longitudinal adolescence imaging genetic cohorts, we identify associations between left ventromedial prefrontal cortex (vmPFC) gray matter volume (GMV) and subsequent self-reported smoking initiation, and between right vmPFC GMV and the maintenance of smoking behaviour. Rule-breaking behaviour mediates the association between smaller left vmPFC GMV and smoking behaviour based on longitudinal cross-lagged analysis and Mendelian randomisation. In contrast, smoking behaviour associated longitudinal covariation of right vmPFC GMV and sensation seeking (especially hedonic experience) highlights a potential reward-based mechanism for sustaining addictive behaviour. Taken together, our findings reveal vmPFC GMV as a possible biomarker for the early stages of nicotine addiction, with implications for its prevention and treatment.
Published: 2023
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6. Fractionation of neural reward processing into independent components by novel decoding principle

Author: Shitong Xiang, Tianye Jia, Chao Xie, Zhichao Zhu, Wei Cheng, Gunter Schumann, Trevor W. Robbins, and Jianfeng Feng
Subjects: Reward/punishment anticipation, Orthogonal decoding, Task fMRI, Evaluation, Salience, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: How to retrieve latent neurobehavioural processes from complex neurobiological signals is an important yet unresolved challenge. Here, we develop a novel approach, orthogonal-Decoding multi-Cognitive Processes (DeCoP), to reveal underlying latent neurobehavioural processing and show that its performance is superior to traditional non-orthogonal decoding in terms of both false inference and robustness. Processing value and salience information are two fundamental but mutually confounded pathways of reward reinforcement essential for decision making. During reward/punishment anticipation, we applied DeCoP to decode brain-wide responses into spatially overlapping, yet functionally independent, evaluation and readiness processes, which are modulated differentially by meso‑limbic vs nigro-striatal dopamine systems. Using DeCoP, we further demonstrated that most brain regions only encoded abstract information but not the exact input, except for dorsal anterior cingulate cortex and insula. Furthermore, we anticipate our novel analytical principle to be applied generally in decoding multiple latent neurobehavioral processes and thus advance both the design and hypothesis testing for cognitive tasks.
Published: 2023
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7. Intersecting distributed networks support convergent linguistic functioning across different languages in bilinguals

Author: Shujie Geng, Wanwan Guo, Edmund T. Rolls, Kunyu Xu, Tianye Jia, Wei Zhou, Colin Blakemore, Li-Hai Tan, Miao Cao, and Jianfeng Feng
Subjects: Biology (General), QH301-705.5
Abstract: Functional MRI data from Chinese-English bilingual participants during a reading task reveals linguistic feature-specific accommodation and assimilation between first and second languages.
Published: 2023
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8. Clinical and genomic analysis of hypermucoviscous Klebsiella pneumoniae isolates: Identification of new hypermucoviscosity associated genes

Author: Meiling Jin, Tianye Jia, Xiong Liu, Meitao Yang, Na Zhang, Jiali Chen, Xiaojing Yang, Shiyu Qin, Fangni Liu, Yue Tang, Yong Wang, Jinpeng Guo, Yong Chen, Boan Li, and Changjun Wang
Subjects: Klebsiella pneumonia, hypermucoviscosity, invasive infection, risk factors, genomic analysis, Microbiology, QR1-502
Abstract: IntroductionHypermucoviscous Klebsiella pneumoniae (HmKp) poses an emerging and highly pathogenic global health threat. This study aimed to investigate the clinical and genomic characteristics of HmKp isolates to better understand the virulence mechanisms of the hypermucoviscous (HMV) phenotype.MethodsFrom May 2018 to August 2021, 203 non-repeat K. pneumoniae isolates causing invasive infections were collected from a hospital in Beijing, China. Isolates were divided into HmKp (n=90, 44.3%) and non-HmKp (n=113, 55.7%) groups according to string test results.ResultsMultivariate regression showed that diabetes mellitus (odds ratio [OR]=2.20, 95% confidence interval (CI): 1.20-4.05, p=0.010) and liver abscess (OR=2.93, CI 95%:1.29-7.03, p=0.012) were associated with HmKp infections. K. pneumoniae was highly diverse, comprising 87 sequence types (STs) and 54 serotypes. Among HmKp isolates, ST23 was the most frequent ST (25/90, 27.8%), and the most prevalent serotypes were KL2 (31/90, 34.4%) and KL1 (27/90, 30.0%). Thirteen virulence genes were located on the capsular polysaccharide synthesis region of KL1 strains. HmKp isolates were sensitive to multiple antibiotics but carried more SHV-type extended spectrum β-lactamase (ESBL) resistance genes (p
Published: 2023
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9. A model-based approach to assess reproducibility for large-scale high-throughput MRI-based studies

Author: Zeyu Jiao, Yinglei Lai, Jujiao Kang, Weikang Gong, Liang Ma, Tianye Jia, Chao Xie, Shitong Xiang, Wei Cheng, Andreas Heinz, Sylvane Desrivières, Gunter Schumann, Fengzhu Sun, and Jianfeng Feng
Subjects: Reproducibility, Association studies, MRI (magnetic resonance imaging), Sample size, Heterogeneity, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Magnetic Resonance Imaging (MRI) technology has been increasingly used in neuroscience studies. Reproducibility of statistically significant findings generated by MRI-based studies, especially association studies (phenotype vs. MRI metric) and task-induced brain activation, has been recently heavily debated. However, most currently available reproducibility measures depend on thresholds for the test statistics and cannot be use to evaluate overall study reproducibility. It is also crucial to elucidate the relationship between overall study reproducibility and sample size in an experimental design. In this study, we proposed a model-based reproducibility index to quantify reproducibility which could be used in large-scale high-throughput MRI-based studies including both association studies and task-induced brain activation. We performed the model-based reproducibility assessments for a few association studies and task-induced brain activation by using several recent large sMRI/fMRI databases. For large sample size association studies between brain structure/function features and some basic physiological phenotypes (i.e. Sex, BMI), we demonstrated that the model-based reproducibility of these studies is more than 0.99. For MID task activation, similar results could be observed. Furthermore, we proposed a model-based analytical tool to evaluate minimal sample size for the purpose of achieving a desirable model-based reproducibility. Additionally, we evaluated the model-based reproducibility of gray matter volume (GMV) changes for UK Biobank (UKB) vs. Parkinson Progression Marker Initiative (PPMI) and UK Biobank (UKB) vs. Human Connectome Project (HCP). We demonstrated that both sample size and study-specific experimental factors play important roles in the model-based reproducibility assessments for different experiments. In summary, a systematic assessment of reproducibility is fundamental and important in the current large-scale high-throughput MRI-based studies.
Published: 2022
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10. Association between childhood trauma and risk for obesity: a putative neurocognitive developmental pathway

Author: Qiang Luo, Lingli Zhang, Chu-Chung Huang, Yan Zheng, Jonathan W. Kanen, Qi Zhao, Ye Yao, Erin B. Quinlan, Tianye Jia, Tobias Banaschewski, Arun L. W. Bokde, Uli Bromberg, Christian Büchel, Herta Flor, Vincent Frouin, Hugh Garavan, Penny Gowland, Andreas Heinz, Bernd Ittermann, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Luise Poustka, Sarah Hohmann, Juliane H. Fröhner, Michael N. Smolka, Henrik Walter, Robert Whelan, Barbara J. Sahakian, Gunter Schumann, Fei Li, Jianfeng Feng, Sylvane Desrivières, Trevor W. Robbins, and for the IMAGEN consortium
Subjects: Childhood trauma, Adult obesity, Neurocognitive control pathway, Structural brain imaging, Medicine
Abstract: Abstract Background Childhood trauma increases the risk for adult obesity through multiple complex pathways, and the neural substrates are yet to be determined. Methods Participants from three population-based neuroimaging cohorts, including the IMAGEN cohort, the UK Biobank (UKB), and the Human Connectome Project (HCP), were recruited. Voxel-based morphometry analysis of both childhood trauma and body mass index (BMI) was performed in the longitudinal IMAGEN cohort; validation of the findings was performed in the UKB. White-matter connectivity analysis was conducted to study the structural connectivity between the identified brain region and subdivisions of the hypothalamus in the HCP. Results In IMAGEN, a smaller frontopolar cortex (FPC) was associated with both childhood abuse (CA) (β = − .568, 95%CI − .942 to − .194; p = .003) and higher BMI (β = − .086, 95%CI − .128 to − .043; p
Published: 2020
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11. Longitudinal Metabolomics Reveals Ornithine Cycle Dysregulation Correlates With Inflammation and Coagulation in COVID-19 Severe Patients

Author: Tao Li, Nianzhi Ning, Bo Li, Deyan Luo, Enqiang Qin, Wenjing Yu, Jianxin Wang, Guang Yang, Nan Nan, Zhili He, Ning Yang, Saisai Gong, Jiajia Li, Aixia Liu, Yakun Sun, Zhan Li, Tianye Jia, Jie Gao, Wang Zhang, Yanyu Huang, Jun Hou, Ying Xue, Deyu Li, Zhen Wei, Liangyan Zhang, Boan Li, and Hui Wang
Subjects: COVID-19, metabolomics, inflammation, ornithine cycle, SARS-CoV-2, Microbiology, QR1-502
Abstract: COVID-19 is a severe disease in humans, as highlighted by the current global pandemic. Several studies about the metabolome of COVID-19 patients have revealed metabolic disorders and some potential diagnostic markers during disease progression. However, the longitudinal changes of metabolomics in COVID-19 patients, especially their association with disease progression, are still unclear. Here, we systematically analyzed the dynamic changes of the serum metabolome of COVID-19 patients, demonstrating that most of the metabolites did not recover by 1–3 days before discharge. A prominent signature in COVID-19 patients comprised metabolites of amino acids, peptides, and analogs, involving nine essential amino acids, 10 dipeptides, and four N-acetylated amino acids. The levels of 12 metabolites in amino acid metabolism, especially three metabolites of the ornithine cycle, were significantly higher in severe patients than in mild ones, mainly on days 1–3 or 4–6 since onset. Integrating blood metabolomic, biochemical, and cytokine data, we uncovered a highly correlated network, including 6 cytokines, 13 biochemical parameters, and 49 metabolites. Significantly, five ornithine cycle-related metabolites (ornithine, N-acetylornithine, 3-amino-2-piperidone, aspartic acid, and asparagine) highly correlated with “cytokine storms” and coagulation index. We discovered that the ornithine cycle dysregulation significantly correlated with inflammation and coagulation in severe patients, which may be a potential mechanism of COVID-19 pathogenicity. Our study provided a valuable resource for detailed exploration of metabolic factors in COVID-19 patients, guiding metabolic recovery, understanding the pathogenic mechanisms, and creating drugs against SARS-CoV-2 infection.
Published: 2021
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12. Neural Biomarkers Distinguish Severe From Mild Autism Spectrum Disorder Among High-Functioning Individuals

Author: Di Chen, Tianye Jia, Yuning Zhang, Miao Cao, Eva Loth, Chun-Yi Zac Lo, Wei Cheng, Zhaowen Liu, Weikang Gong, Barbara Jacquelyn Sahakian, and Jianfeng Feng
Subjects: autism spectrum disorder, functional magnetic resonance imaging, high-functioning autism, neural biomarker, autism diagnostic observation schedule, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Several previous studies have reported atypicality in resting-state functional connectivity (FC) in autism spectrum disorder (ASD), yet the relatively small effect sizes prevent us from using these characteristics for diagnostic purposes. Here, canonical correlation analysis (CCA) and hierarchical clustering were used to partition the high-functioning ASD group (i.e., the ASD discovery group) into subgroups. A support vector machine (SVM) model was trained through the 10-fold strategy to predict Autism Diagnostic Observation Schedule (ADOS) scores within the ASD discovery group (r = 0.30, P < 0.001, n = 260), which was further validated in an independent sample (i.e., the ASD validation group) (r = 0.35, P = 0.031, n = 29). The neuroimage-based partition derived two subgroups representing severe versus mild autistic patients. We identified FCs that show graded changes in strength from ASD-severe, through ASD-mild, to controls, while the same pattern cannot be observed in partitions based on ADOS score. We also identified FCs that are specific for ASD-mild, similar to a partition based on ADOS score. The current study provided multiple pieces of evidence with replication to show that resting-state functional magnetic resonance imaging (rsfMRI) FCs could serve as neural biomarkers in partitioning high-functioning autistic individuals based on their symptom severity and showing advantages over traditional partition based on ADOS score. Our results also indicate a compensatory role for a frontocortical network in patients with mild ASD, indicating potential targets for future clinical treatments.
Published: 2021
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13. Clinical and Molecular Analysis of ST11-K47 Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae: A Strain Causing Liver Abscess

Author: Zhen Cai, Tianye Jia, Mingfang Pu, Shuyong Zhang, Jingxia Zhang, Ronghua Geng, Suming Chen, Yahao Li, Huahao Fan, Yigang Tong, and Fen Qu
Subjects: Klebsiella pneumoniae, liver abscess, hypervirulent, virulence genes, carbapenem resistance, ST11-K47, Medicine
Abstract: Klebsiella pneumoniae has been the predominant pathogen of liver abscess, but ST11-K47 carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) has rarely been studied as the causative organism. We identified an ST11-K47 CR-hvKP (HvKp-su1) from the drainage fluid of a liver abscess in a Chinese man who was diagnosed with liver abscess combined with diabetes, pneumonia, pleural infection, abdominal abscess, and splenic abscess. HvKp-su1 was non-hypermucoviscous and lacked the magA and rmpA genes and pLVPK plasmid but exhibited high virulence, with a high mortality rate (90%) to wax moth larvae (G. mellonella), similar to the hypervirulent Klebsiella pneumoniae ATCC43816 (91.67%). Whole-genome sequencing and bioinformatics analysis indicated that HvKp-su1 possesses a plasmid similar to a type of pLVPK-like plasmid (JX-CR-hvKP-2-P2), which is an uncommon plasmid in CR-hvKP. HvKp-su1 carried multiple resistance genes, including blaKPC-2. blaTEM-1, blaSHV-55, and blaCTX-M-65; hypervirulence genes such as aerobactin (iutA), salmochelin (iroEN), and yersiniabactin (ybtAEPQSTUX); and the type 3 fimbriae-encoding system (mrkACDF). Moreover, v_5377 and v_5429 (cofT, CFA/III (CS8)) located on plasmid 1 were simultaneously predicted to be virulence genes. After the long-term combination use of antibiotics, the patient successfully recovered. In summary, our study clarified the clinical and molecular characteristics of a rare ST11-K47 CR-hvKP (HvKp-su1), raising great concerns about the emergence of ST11-K47 CR-hvKP with multidrug resistance and hypervirulence, and providing insights into the control and treatment of liver abscess caused by ST11-K47 CR-hvKP.
Published: 2022
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14. Letter response to the brain after COVID-19: Compensatory neurogenesis or persistent neuroinflammation?

Author: Yiping Lu, Xuanxuan Li, Daoying Geng, Nan Mei, Pu-Yeh Wu, Chu-Chung Huang, Tianye Jia, Yajing Zhao, Dongdong Wang, Anling Xiao, and Bo Yin
Subjects: Medicine (General), R5-920
Published: 2021
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15. Cerebral Micro-Structural Changes in COVID-19 Patients – An MRI-based 3-month Follow-up Study

Author: Yiping Lu, MD, Xuanxuan Li, MD, Daoying Geng, MD, Nan Mei, MD, Pu-Yeh Wu, PhD, Chu-Chung Huang, PhD, Tianye Jia, PhD, Yajing Zhao, MD, Dongdong Wang, MD, Anling Xiao, MD, and Bo Yin, PhD
Subjects: COVID-19, Neuroimaging, Central Nervous System Diseases, Prospective studies, Diffusion Tensor Imaging, Medicine (General), R5-920
Abstract: Background: Increasing evidence supported the possible neuro-invasion potential of SARS-CoV-2. However, no studies were conducted to explore the existence of the micro-structural changes in the central nervous system after infection. We aimed to identify the existence of potential brain micro-structural changes related to SARS-CoV-2. Methods: In this prospective study, diffusion tensor imaging (DTI) and 3D high-resolution T1WI sequences were acquired in 60 recovered COVID-19 patients (56.67% male; age: 44.10 ± 16.00) and 39 age- and sex-matched non-COVID-19 controls (56.41% male; age: 45.88 ± 13.90). Registered fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were quantified for DTI, and an index score system was introduced. Regional volumes derived from Voxel-based Morphometry (VBM) and DTI metrics were compared using analysis of covariance (ANCOVA). Two sample t-test and Spearman correlation were conducted to assess the relationships among imaging indices, index scores and clinical information. Findings: In this follow-up stage, neurological symptoms were presented in 55% COVID-19 patients. COVID-19 patients had statistically significantly higher bilateral gray matter volumes (GMV) in olfactory cortices, hippocampi, insulas, left Rolandic operculum, left Heschl's gyrus and right cingulate gyrus and a general decline of MD, AD, RD accompanied with an increase of FA in white matter, especially AD in the right CR, EC and SFF, and MD in SFF compared with non-COVID-19 volunteers (corrected p value
Published: 2020
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16. Novel genetic loci associated with hippocampal volume

Author: Derrek P. Hibar, Hieab H. H. Adams, Neda Jahanshad, Ganesh Chauhan, Jason L. Stein, Edith Hofer, Miguel E. Renteria, Joshua C. Bis, Alejandro Arias-Vasquez, M. Kamran Ikram, Sylvane Desrivières, Meike W. Vernooij, Lucija Abramovic, Saud Alhusaini, Najaf Amin, Micael Andersson, Konstantinos Arfanakis, Benjamin S. Aribisala, Nicola J. Armstrong, Lavinia Athanasiu, Tomas Axelsson, Ashley H. Beecham, Alexa Beiser, Manon Bernard, Susan H. Blanton, Marc M. Bohlken, Marco P. Boks, Janita Bralten, Adam M. Brickman, Owen Carmichael, M. Mallar Chakravarty, Qiang Chen, Christopher R. K. Ching, Vincent Chouraki, Gabriel Cuellar-Partida, Fabrice Crivello, Anouk Den Braber, Nhat Trung Doan, Stefan Ehrlich, Sudheer Giddaluru, Aaron L. Goldman, Rebecca F. Gottesman, Oliver Grimm, Michael E. Griswold, Tulio Guadalupe, Boris A. Gutman, Johanna Hass, Unn K. Haukvik, David Hoehn, Avram J. Holmes, Martine Hoogman, Deborah Janowitz, Tianye Jia, Kjetil N. Jørgensen, Nazanin Karbalai, Dalia Kasperaviciute, Sungeun Kim, Marieke Klein, Bernd Kraemer, Phil H. Lee, David C. M. Liewald, Lorna M. Lopez, Michelle Luciano, Christine Macare, Andre F. Marquand, Mar Matarin, Karen A. Mather, Manuel Mattheisen, David R. McKay, Yuri Milaneschi, Susana Muñoz Maniega, Kwangsik Nho, Allison C. Nugent, Paul Nyquist, Loes M. Olde Loohuis, Jaap Oosterlaan, Martina Papmeyer, Lukas Pirpamer, Benno Pütz, Adaikalavan Ramasamy, Jennifer S. Richards, Shannon L. Risacher, Roberto Roiz-Santiañez, Nanda Rommelse, Stefan Ropele, Emma J. Rose, Natalie A. Royle, Tatjana Rundek, Philipp G. Sämann, Arvin Saremi, Claudia L. Satizabal, Lianne Schmaal, Andrew J. Schork, Li Shen, Jean Shin, Elena Shumskaya, Albert V. Smith, Emma Sprooten, Lachlan T. Strike, Alexander Teumer, Diana Tordesillas-Gutierrez, Roberto Toro, Daniah Trabzuni, Stella Trompet, Dhananjay Vaidya, Jeroen Van der Grond, Sven J. Van der Lee, Dennis Van der Meer, Marjolein M. J. Van Donkelaar, Kristel R. Van Eijk, Theo G. M. Van Erp, Daan Van Rooij, Esther Walton, Lars T. Westlye, Christopher D. Whelan, Beverly G. Windham, Anderson M. Winkler, Katharina Wittfeld, Girma Woldehawariat, Christiane Wolf, Thomas Wolfers, Lisa R. Yanek, Jingyun Yang, Alex Zijdenbos, Marcel P. Zwiers, Ingrid Agartz, Laura Almasy, David Ames, Philippe Amouyel, Ole A. Andreassen, Sampath Arepalli, Amelia A. Assareh, Sandra Barral, Mark E. Bastin, Diane M. Becker, James T. Becker, David A. Bennett, John Blangero, Hans van Bokhoven, Dorret I. Boomsma, Henry Brodaty, Rachel M. Brouwer, Han G. Brunner, Randy L. Buckner, Jan K. Buitelaar, Kazima B. Bulayeva, Wiepke Cahn, Vince D. Calhoun, Dara M. Cannon, Gianpiero L. Cavalleri, Ching-Yu Cheng, Sven Cichon, Mark R. Cookson, Aiden Corvin, Benedicto Crespo-Facorro, Joanne E. Curran, Michael Czisch, Anders M. Dale, Gareth E. Davies, Anton J. M. De Craen, Eco J. C. De Geus, Philip L. De Jager, Greig I. De Zubicaray, Ian J. Deary, Stéphanie Debette, Charles DeCarli, Norman Delanty, Chantal Depondt, Anita DeStefano, Allissa Dillman, Srdjan Djurovic, Gary Donohoe, Wayne C. Drevets, Ravi Duggirala, Thomas D. Dyer, Christian Enzinger, Susanne Erk, Thomas Espeseth, Iryna O. Fedko, Guillén Fernández, Luigi Ferrucci, Simon E. Fisher, Debra A. Fleischman, Ian Ford, Myriam Fornage, Tatiana M. Foroud, Peter T. Fox, Clyde Francks, Masaki Fukunaga, J. Raphael Gibbs, David C. Glahn, Randy L. Gollub, Harald H. H. Göring, Robert C. Green, Oliver Gruber, Vilmundur Gudnason, Sebastian Guelfi, Asta K. Håberg, Narelle K. Hansell, John Hardy, Catharina A. Hartman, Ryota Hashimoto, Katrin Hegenscheid, Andreas Heinz, Stephanie Le Hellard, Dena G. Hernandez, Dirk J. Heslenfeld, Beng-Choon Ho, Pieter J. Hoekstra, Wolfgang Hoffmann, Albert Hofman, Florian Holsboer, Georg Homuth, Norbert Hosten, Jouke-Jan Hottenga, Matthew Huentelman, Hilleke E. Hulshoff Pol, Masashi Ikeda, Clifford R. Jack Jr, Mark Jenkinson, Robert Johnson, Erik G. Jönsson, J. Wouter Jukema, René S. Kahn, Ryota Kanai, Iwona Kloszewska, David S. Knopman, Peter Kochunov, John B. Kwok, Stephen M. Lawrie, Hervé Lemaître, Xinmin Liu, Dan L. Longo, Oscar L. Lopez, Simon Lovestone, Oliver Martinez, Jean-Luc Martinot, Venkata S. Mattay, Colm McDonald, Andrew M. McIntosh, Francis J. McMahon, Katie L. McMahon, Patrizia Mecocci, Ingrid Melle, Andreas Meyer-Lindenberg, Sebastian Mohnke, Grant W. Montgomery, Derek W. Morris, Thomas H. Mosley, Thomas W. Mühleisen, Bertram Müller-Myhsok, Michael A. Nalls, Matthias Nauck, Thomas E. Nichols, Wiro J. Niessen, Markus M. Nöthen, Lars Nyberg, Kazutaka Ohi, Rene L. Olvera, Roel A. Ophoff, Massimo Pandolfo, Tomas Paus, Zdenka Pausova, Brenda W. J. H. Penninx, G. Bruce Pike, Steven G. Potkin, Bruce M. Psaty, Simone Reppermund, Marcella Rietschel, Joshua L. Roffman, Nina Romanczuk-Seiferth, Jerome I. Rotter, Mina Ryten, Ralph L. Sacco, Perminder S. Sachdev, Andrew J. Saykin, Reinhold Schmidt, Helena Schmidt, Peter R. Schofield, Sigurdur Sigursson, Andrew Simmons, Andrew Singleton, Sanjay M. Sisodiya, Colin Smith, Jordan W. Smoller, Hilkka Soininen, Vidar M. Steen, David J. Stott, Jessika E. Sussmann, Anbupalam Thalamuthu, Arthur W. Toga, Bryan J. Traynor, Juan Troncoso, Magda Tsolaki, Christophe Tzourio, Andre G. Uitterlinden, Maria C. Valdés Hernández, Marcel Van der Brug, Aad van der Lugt, Nic J. A. van der Wee, Neeltje E. M. Van Haren, Dennis van ’t Ent, Marie-Jose Van Tol, Badri N. Vardarajan, Bruno Vellas, Dick J. Veltman, Henry Völzke, Henrik Walter, Joanna M. Wardlaw, Thomas H. Wassink, Michael E. Weale, Daniel R. Weinberger, Michael W. Weiner, Wei Wen, Eric Westman, Tonya White, Tien Y. Wong, Clinton B. Wright, Ronald H. Zielke, Alan B. Zonderman, Nicholas G. Martin, Cornelia M. Van Duijn, Margaret J. Wright, W. T. Longstreth, Gunter Schumann, Hans J. Grabe, Barbara Franke, Lenore J. Launer, Sarah E. Medland, Sudha Seshadri, Paul M. Thompson, and M. Arfan Ikram
Subjects: Science
Abstract: The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.
Published: 2017
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17. A robust statistical method for association-based eQTL analysis.

Author: Ning Jiang, Minghui Wang, Tianye Jia, Lin Wang, Lindsey Leach, Christine Hackett, David Marshall, and Zewei Luo
Subjects: Medicine, Science
Abstract: It has been well established that theoretical kernel for recently surging genome-wide association study (GWAS) is statistical inference of linkage disequilibrium (LD) between a tested genetic marker and a putative locus affecting a disease trait. However, LD analysis is vulnerable to several confounding factors of which population stratification is the most prominent. Whilst many methods have been proposed to correct for the influence either through predicting the structure parameters or correcting inflation in the test statistic due to the stratification, these may not be feasible or may impose further statistical problems in practical implementation.We propose here a novel statistical method to control spurious LD in GWAS from population structure by incorporating a control marker into testing for significance of genetic association of a polymorphic marker with phenotypic variation of a complex trait. The method avoids the need of structure prediction which may be infeasible or inadequate in practice and accounts properly for a varying effect of population stratification on different regions of the genome under study. Utility and statistical properties of the new method were tested through an intensive computer simulation study and an association-based genome-wide mapping of expression quantitative trait loci in genetically divergent human populations.The analyses show that the new method confers an improved statistical power for detecting genuine genetic association in subpopulations and an effective control of spurious associations stemmed from population structure when compared with other two popularly implemented methods in the literature of GWAS.
Published: 2011
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18. Associations of DNA Methylation With Behavioral Problems, Gray Matter Volumes, and Negative Life Events Across Adolescence: Evidence From the Longitudinal IMAGEN Study

Author: Yan Sun, Tianye Jia, Edward D. Barker, Di Chen, Zuo Zhang, Jiayuan Xu, Suhua Chang, Guangdong Zhou, Yun Liu, Nicole Tay, Qiang Luo, Xiao Chang, Tobias Banaschewski, Arun L.W. Bokde, Herta Flor, Antoine Grigis, Hugh Garavan, Andreas Heinz, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Eric Artiges, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomáš Paus, Luise Poustka, Sarah Hohmann, Sabina Millenet, Juliane H. Fröhner, Michael N. Smolka, Henrik Walter, Robert Whelan, Lin Lu, Jie Shi, Gunter Schumann, and Sylvane Desrivières
Subjects: Biological Psychiatry
Abstract: Negative life events (NLEs) increase the risk for externalizing behaviors (EBs) and internalizing behaviors (IBs) in adolescence and adult psychopathology. DNA methylation associated with behavioral problems may reflect this risk and long-lasting effects of NLEs.To identify consistent associations between blood DNA methylation and EBs or IBs across adolescence, we conducted longitudinal epigenome-wide association studies (EWASs) using data from the IMAGEN cohort, collected at ages 14 and 19 years (n = 506). Significant findings were validated in a separate subsample (n = 823). Methylation risk scores were generated by 10-fold cross-validation and further tested for their associations with gray matter volumes and NLEs.No significant findings were obtained for the IB-EWAS. The EB-EWAS identified a genome-wide significant locus in a gene linked to attention-deficit/hyperactivity disorder (ADHD) (IQSEC1, cg01460382; p = 1.26 × 10Our findings suggest that novel epigenetic mechanisms through which NLEs exert short and longer-term effects on behavior may contribute to ADHD.
Published: 2023

19. Global diversity in individualized cortical network topography

Author: Guoyuan Yang, Jelena Bozek, Stephanie Noble, Meizhen Han, Xinyu Wu, Mufan Xue, Jujiao Kang, Tianye Jia, Jilian Fu, Jianqiao Ge, Zaixu Cui, Xuesong Li, Jianfeng Feng, and Jia-Hong Gao
Subjects: Cellular and Molecular Neuroscience, ethnicity, individualized parcellation, functional brain networks, resting state, variability, Cognitive Neuroscience
Abstract: Individualized cortical network topography (ICNT) varies between people and exhibits great variability in the association networks in the human brain. However, these findings were mainly discovered in Western populations. It remains unclear whether and how ICNT is shaped by the non-Western populations. Here, we leveraged a multisession hierarchical Bayesian model to define individualized functional networks in White American and Han Chinese populations with data from both US and Chinese Human Connectome Projects. We found that both the size and spatial topography of individualized functional networks differed between White American and Han Chinese groups, especially in the heteromodal association cortex (including the ventral attention, control, language, dorsal attention, and default mode networks). Employing a support vector machine, we then demonstrated that ethnicity-related ICNT diversity can be used to identify an individual’s ethnicity with high accuracy (74%, pperm
Published: 2023

20. Increased brain volume from higher cereal and lower coffee intake: shared genetic determinants and impacts on cognition and metabolism

Author: Jujiao Kang, Tianye Jia, Zeyu Jiao, Chun Shen, Chao Xie, Wei Cheng, Barbara J Sahakian, David Waxman, and Jianfeng Feng
Subjects: Adult, QH, Cognitive Neuroscience, COVID-19, Brain, Mendelian Randomization Analysis, QP, Coffee, Cellular and Molecular Neuroscience, Cognition, Risk Factors, Humans, RB, Edible Grain, Genome-Wide Association Study
Abstract: It is unclear how different diets may affect human brain development and if genetic and environmental factors play a part. We investigated diet effects in the UK Biobank data from 18,879 healthy adults and discovered anticorrelated brain-wide gray matter volume (GMV)-association patterns between coffee and cereal intake, coincidence with their anticorrelated genetic constructs. The Mendelian randomization approach further indicated a causal effect of higher coffee intake on reduced total GMV, which is likely through regulating the expression of genes responsible for synaptic development in the brain. The identified genetic factors may further affect people’s lifestyle habits and body/blood fat levels through the mediation of cereal/coffee intake, and the brain-wide expression pattern of gene CPLX3, a dedicated marker of subplate neurons that regulate cortical development and plasticity, may underlie the shared GMV-association patterns among the coffee/cereal intake and cognitive functions. All the main findings were successfully replicated. Our findings thus revealed that high-cereal and low-coffee diets shared similar brain and genetic constructs, leading to long-term beneficial associations regarding cognitive, body mass index (BMI), and other metabolic measures. This study has important implications for public health, especially during the pandemic, given the poorer outcomes of COVID-19 patients with greater BMIs.
Published: 2022

21. Association between obesity, brain atrophy and accelerated brain aging and their genetic mechanisms

Author: Jujiao Kang, Tianye Jia, Zeqiang Linli, Yuzhu Li, Wei Cheng, Shuixia Guo, and Jianfeng Feng
Abstract: ObjectiveTo investigate the causal relationship and the underlying biological mechanisms between body mass index (BMI) and grey matter volume (GMV).MethodsWe applied Mendelian randomization analyses utilizing 33,6514 individuals from the UK Biobank cohort to establish the causal relationship between BMI and GMV. We also quantified obesity-related accelerated brain aging using an XGBoost prediction paradigm. Then, mediation analyses were performed to test the association between BMI, brain atrophy, brain aging and cognitive function. Finally, the gene expression data from the Allen Human Brain Atlas were used to identify genes contributing to the BMI-GMV association.ResultsA causal effect of increased BMI on decreased GMV was established using multiple Mendelian randomization methods. The brain age prediction paradigm achieved appreciable performance in both training (R = 0.725, mean-absolute-error (MAE) = 4.130) and test data (R= 0.71, MAE = 4.239). On average, overweight and obese individuals exhibited significantly accelerated brain aging by +0.59 years and +1.7 years, respectively. Further, the accelerated brain age and total GMV mediated 18% of the association of higher BMI with poorer cognitive function. BMI-associated lower GMVs were related to the over-expression of gene TRIM27 and other genes involved in the autophagy biological process.ConclusionObesity led to GMV decline and accelerated brain aging. Genes including TRIM27 and biological process pathways involved in autophagy may contribute to the BMI-GMV association.
Published: 2022

22. Neutral sphingomyelinase is a major driver of sex-differences in depression and alcohol-abuse

Author: Christian Müller, Christiane Mühle, Tianye Jia, Erich Gulbins, Bernd Lenz, Gunter Schumann, Johannes Kornhuber, and LiubovS Kalinichenko
Published: 2022

23. Interdigitated distributed networks support convergent linguistic functioning across different languages in bilinguals

Author: Shujie Geng, Wanan Guo, Edmund Rolls, Kunyu Xu, Tianye Jia, Wei Zhou, Colin Blakemore, Li-Hai Tan, Miao Cao, and Jianfeng Feng
Abstract: How bilingual brains accomplish the processing of more than one language has been widely investigated by neuroimaging studies. The assimilation-accommodation hypothesis holds that both the same brain neural networks supporting the native language and additional new neural networks are utilized to implement second language processing. However, whether and how this hypothesis applies at the finer-grained levels of both brain anatomical organization and linguistic functions remain unknown. To address this issue, we scanned Chinese-English bilinguals during an implicit reading task involving Chinese words, English words and Chinese pinyin. We observed broad brain cortical regions wherein interdigitated distributed neural populations supporting the same cognitive components of different languages. Although spatially separate, regions including the opercular and triangular parts of the inferior frontal gyrus, temporal pole, superior and middle temporal gyrus, precentral gyrus and supplementary motor areas were found to perform the same linguistic functions across languages, indicating regional-level functional assimilation supported by voxel-wise anatomical accommodation. Taken together, the findings not only verify the functional independence of neural representations of different languages, but show co-representation organization of both languages in most language regions, revealing linguistic-feature specific accommodation and assimilation between first and second languages.
Published: 2022

24. Substance Use Initiation, Particularly Alcohol, in Drug-Naive Adolescents: Possible Predictors and Consequences From a Large Cohort Naturalistic Study

Author: Iliyan Ivanov, Muhammad A. Parvaz, Eva Velthorst, Riaz B. Shaik, Sven Sandin, Gabriela Gan, Philip Spechler, Matthew D. Albaugh, Bader Chaarani, Scott Mackey, Tobias Banaschewski, Arun L.W. Bokde, Uli Bromberg, Christian Büchel, Erin Burke Quinlan, Sylvane Desrivières, Herta Flor, Antoine Grigis, Penny Gowland, Andreas Heinz, Bernd Ittermann, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Eric Artiges, Herve Lemaitre, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomáš Paus, Luise Poustka, Sarah Hohmann, Sabina Millenet, Juliane H. Fröhner, Michael N. Smolka, Henrik Walter, Robert Whelan, Gunter Schumann, Hugh Garavan, Michael Rapp, Sophia Schneider, Tomas Paus, Alexis Barbot, Gareth Barker, Arun Bokde, Nora Vetter, Anna Cattrell, Patrick Constant, Hans Crombag, Jeffrey Dalley, Benjamin Decideur, Tade Spranger, Tamzin Ripley, Nadja Heym, Wolfgang Sommer, Birgit Fuchs, Jürgen Gallinat, Rainer Spanagel, Mehri Kaviani, Bert Heinrichs, null Andreas Heinz, Naresh Subramaniam, Tianye Jia, Albrecht Ihlenfeld, James Ireland, Patricia Conrod, Jennifer Jones, Arno Klaassen, Christophe Lalanne, Dirk Lanzerath, Claire Lawrence, Hervé Lemaitre, Sylvane Desrivieres, Catherine Mallik, Karl Mann, Adam Mar, Lourdes Martinez-Medina, Eva Mennigen, Fabiana Mesquita de Carvahlo, Yannick Schwartz, Ruediger Bruehl, Kathrin Müller, Charlotte Nymberg, Mark Lathrop, Trevor Robbins, Zdenka Pausova, Jani Pentilla, Francesca Biondo, Jean-Baptiste Poline, Michael Smolka, Juliane Fröhner, Maren Struve, Steve Williams, Thomas Hübner, Semiha Aydin, John Rogers, Alexander Romanowski, Christine Schmäl, Dirk Schmidt, Stephan Ripke, Mercedes Arroyo, Florian Schubert, Yolanda Pena-Oliver, Mira Fauth-Bühler, Xavier Mignon, Claudia Speiser, Tahmine Fadai, Dai Stephens, Andreas Ströhle, Marie-Laure Paillere, Nicole Strache, David Theobald, Sarah Jurk, Helene Vulser, Ruben Miranda, Juliana Yacubilin, Vincent Frouin, Alexander Genauck, Caroline Parchetka, Isabel Gemmeke, Johann Kruschwitz, Katharina WeiB, Jianfeng Feng, Dimitri Papadopoulos, Irina Filippi, Alex Ing, Barbara Ruggeri, Bing Xu, Christine Macare, Congying Chu, Eanna Hanratty, Gabriel Robert, Tao Yu, Veronika Ziesch, and Alicia Stedman
Subjects: Adolescent, Substance-Related Disorders, Impulsivity, Naturalistic observation, Reward, Neuroimaging, Intervention (counseling), Developmental and Educational Psychology, medicine, Humans, 0501 psychology and cognitive sciences, business.industry, 05 social sciences, Brain, medicine.disease, Magnetic Resonance Imaging, Substance abuse, Psychiatry and Mental health, Drug-naïve, Pharmaceutical Preparations, Trait, Orbitofrontal cortex, medicine.symptom, business, 050104 developmental & child psychology, Clinical psychology, medicine.drug
Abstract: It is unclear whether deviations in brain and behavioral development, which may underpin elevated substance use during adolescence, are predispositions for or consequences of substance use initiation. Here, we examine behavioral and neuroimaging indices at early and mid-adolescence in drug-naive youths to identify possible predisposing factors for substance use initiation and its possible consequences.Among 304 drug-naive adolescents at baseline (age 14 years) from the IMAGEN dataset, 83 stayed drug-naive, 133 used alcohol on 1 to 9 occasions, 42 on 10 to 19 occasions, 27 on 20 to 39 occasions, and 19 on40 occasions at follow-up (age 16 years). Baseline measures included brain activation during the Monetary Incentive Delay task. Data at both baseline and follow-up included measures of trait impulsivity and delay discounting.From baseline to follow-up, impulsivity decreased in the 0 and 1- to 9-occasions groups (p .004), did not change in the 10- to 19-occasions and 20- to 29-occasions groups (p.294), and uncharacteristically increased in the40-occasions group (p = .046). Furthermore, blunted medial orbitofrontal cortex activation during reward outcome at baseline significantly predicted higher alcohol use frequency at follow-up, above and beyond behavioral and clinical variables (p = .008).These results suggest that the transition from no use to frequent drinking in early to mid-adolescence may disrupt normative developmental changes in behavioral control. In addition, blunted activity of the medial orbitofrontal cortex during reward outcome may underscore a predisposition toward the development of more severe alcohol use in adolescents. This distinction is clinically important, as it informs early intervention efforts in preventing the onset of substance use disorder in adolescents.
Published: 2021

25. Brain charts for the human lifespan

Author: Armin Raznahan, Eric Courchesne, Andrea Parolin Jackowski, Kamen A. Tsvetanov, Cameron T. Ellis, R.C. Gur, Bin Bae J, Park Mtm, Pedro A. Valdes-Sosa, Simon N. Vandekar, Jacob W. Vogel, Juan Zhou, Machteld Marcelis, Kiho Im, Patricia Ellen Grant, Minhui Ouyang, Blesa Cabez M, Michael V. Lombardo, Sarah E. Morgan, James P. Boardman, Adamson C, Calhoun Vd, Delarue M, James H. Cole, Pichet Binette A, Roberto Toro, David H. Rowitch, Nynke A. Groenewold, Kevin M. Anderson, David T.W. Jones, Michael Schöll, Wang Ys, Aiden Corvin, R.E. Gur, Damien A. Fair, Gareth Ball, Herma Lina Schaare, Andrew Zalesky, Evdokia Anagnostou, Michael J. Meaney, Taki Y, Gareth J. Sullivan, Warrier, Petra E. Vértes, Chixiang Chen, Lisa T. Eyler, Wei Liao, Tomáš Paus, Jeremy A. Elman, Phillip McGuire, Hisham Ziauddeen, William S. Kremen, Etienne Vachon-Presseau, E.T. Bullmore, Christophe Tzourio, White, Hammill Cf, Mothersill D, Richard N. Henson, Jiang Qiu, Duncan E. Astle, Fabrice Crivello, Paul C. Fletcher, Chertavian C, Kim K, Jennifer Crosbie, Russell Schachar, Gabriel A. Devenyi, Manfred G. Kitzbichler, Tianye Jia, Trey Hedden, Sang Jae Lee, Ross D. Markello, Silke Kern, Ian M. Goodyer, Keith A. Johnson, Frauke Beyer, Bernard Mazoyer, A. Heinz, Sylvane Desrivières, Rosenberg, Gary Donohoe, Ong Mq, Alexander D. Edwards, Dan J. Stein, Nenad Medic, Zuo Xn, Travis T. Mallard, Peter Fonagy, Lindsay W. Victoria, Ingmar Skoog, Avram J. Holmes, Jason P. Lerch, Jed T. Elison, Jianfu Li, John H. Gilmore, Rosemary Holt, Caitlin K. Rollins, Carol E. Franz, Pedro Mario Pan, Saashi A Bedford, Yang N, Jonathan C Ipser, Richard A. I. Bethlehem, Tuulari Jj, Stolicyn A, Hua Huang, Bratislav Misic, Conor Liston, Ayub M, Lisa Ronan, Yeo Bt, Sophie Adler, Charles J. Lynch, Faith M. Gunning, Konrad Wagstyl, M. Mallar Chakravarty, John Suckling, Theodore D. Satterthwaite, Bharath Holla, Yap Seng Chong, Jinglei Lv, Jakob Seidlitz, Niall J Bourke, Xinlei Qian, Simon Baron-Cohen, Cynthia M. Ortinau, Deirel Paz Linares, Thyreau B, René S. Kahn, Aaron P. Schultz, Vanessa Cropley, Eric Westman, Mitchell Valdés-Sosa, Rik Ossenkoppele, André Zugman, Hasse Karlsson, Sylvia Villeneuve, Katja Heuer, Di Biase Ma, Margaret L. Westwater, Sofie L. Valk, David J. Sharp, Brigitte Landeau, Matthew Borzage, Kirsten A. Donald, Timothy Rittman, Richard Beare, Giovanni Abrahão Salum, Gunter Schumann, Ryuta Kawashima, Romero-Garcia R, John Blangero, Yun Hj, Russel T. Shinohara, Nicolas Crossley, Simon K. Warfield, Karen Pierce, George S. Alexopoulos, Katharine Dunlop, David C. Glahn, Francois Lalonde, Anqi Qiu, Lana Vasung, Gaël Chételat, Lídice Galán-García, Clifford R. Jack, Reisa A. Sperling, Anna Zettergren, Elizabeth Kelley, Arno Villringer, Andrea Mechelli, Benegal, Aaron Alexander-Bloch, Nicholas B. Turk-Browne, van Amelsvoort T, John D. Lewis, Heather C. Whalley, A. V. Witte, Zdenka Pausova, Joel T. Nigg, Heather J. Zar, Raymond J. Dolan, Christopher D. Smyser, Jay N. Giedd, Lena Palaniyappan, Ali Gholipour, Areces-Gonzalez A, Peter B. Jones, Jacqueline Hoare, Oskar Hansson, Linnea Karlsson, C Pantelis, Paly L, Bonnie Auyeung, Jorge Bosch-Bayard, Bethlehem, Richard [0000-0002-0714-0685], White, Simon [0000-0001-8642-7037], Astle, Duncan [0000-0002-7042-5392], Baron-Cohen, Simon [0000-0001-9217-2544], Henson, Rik [0000-0002-0712-2639], Jones, Peter [0000-0002-0387-880X], Kitzbichler, Manfred [0000-0002-4494-0753], Rittman, Timothy [0000-0003-1063-6937], Rowitch, David [0000-0002-0079-0060], Tsvetanov, Kamen A. [0000-0002-3178-6363], Westwater-Wozniak, Margaret [0000-0002-2918-0979], Ziauddeen, Hisham [0000-0003-4044-1719], Apollo - University of Cambridge Repository, British Academy, Autism Research Trust, National Institute of Mental Health (US), UK Research and Innovation, Medical Research Council (UK), National Institute for Health and Care Research (US), Wellcome Trust, University of Cambridge, Cambridge Biomedical Research Centre, University of Cambridge [UK] (CAM), University of Pennsylvania, Yale University [New Haven], Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Child and Adolescent Psychiatry Department [AP- HP Hôpital Robert Debré], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Neuroscience - Department of Neuroscience, Centre de Recherche Interdisciplinaire / Center for Research and Interdisciplinarity [Paris, France] (CRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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), Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: MA Med Staf Spec Psychiatrie (9), Neurology, Amsterdam Neuroscience - Neurodegeneration, 3R-BRAIN, AIBL, Alzheimer’s Disease Neuroimaging Initiative, Alzheimer’s Disease Repository Without Borders Investigators, CALM Team, Cam-CAN, CCNP, COBRE, cVEDA, ENIGMA Developmental Brain Age Working Group, Developing Human Connectome Project, FinnBrain, Harvard Aging Brain Study, IMAGEN, KNE96, The Mayo Clinic Study of Aging, NSPN, POND, The PREVENT-AD Research Group, VETSA, [Bethlehem, R. A. I.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Auyeung, B.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Baron-Cohen, S.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Bedford, S. A.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Holt, R.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Lombardo, M. V.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Bethlehem, R. A. I.] Univ Cambridge, Dept Psychiat, Brain Mapping Unit, Cambridge, England, [Kitzbichler, M. G.] Univ Cambridge, Dept Psychiat, Brain Mapping Unit, Cambridge, England, [Seidlitz, J.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Vogel, J. W.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Gur, R. E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Gur, R. C.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Jackowski, A. P.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Satterthwaite, T. D.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Alexander-Bloch, A. F.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Seidlitz, J.] Childrens Hosp Philadelphia, Dept Child & Adolescent Psychiat & Behav Sci, Philadelphia, PA 19104 USA, [Alexander-Bloch, A. F.] Childrens Hosp Philadelphia, Dept Child & Adolescent Psychiat & Behav Sci, Philadelphia, PA 19104 USA, [Seidlitz, J.] Childrens Hosp Philadelphia & Penn Med, Lifespan Brain Inst, Philadelphia, PA USA, [Chertavian, C.] Childrens Hosp Philadelphia & Penn Med, Lifespan Brain Inst, Philadelphia, PA USA, [Gur, R. E.] Childrens Hosp Philadelphia & Penn Med, Lifespan Brain Inst, Philadelphia, PA USA, [Gur, R. C.] Childrens Hosp Philadelphia & Penn Med, Lifespan Brain Inst, Philadelphia, PA USA, [Alexander-Bloch, A. F.] Childrens Hosp Philadelphia & Penn Med, Lifespan Brain Inst, Philadelphia, PA USA, [White, S. R.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Goodyer, I. M.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Henson, R. N.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Jones, P. B.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Kitzbichler, M. G.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Medic, N.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Morgan, S. E.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Romero-Garcia, R.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Ronan, L.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Suckling, J.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Vertes, P. E.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Warrier, V.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Westwater, M. L.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Ziauddeen, H.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Bullmore, E. T.] Univ Cambridge, Dept Psychiat, Cambridge, England, [White, S. R.] Univ Cambridge, MRC Biostat Unit, Cambridge, England, [Vogel, J. W.] Univ Penn, Lifespan Informat & Neuroimaging Ctr, Philadelphia, PA 19104 USA, [Satterthwaite, T. D.] Univ Penn, Lifespan Informat & Neuroimaging Ctr, Philadelphia, PA 19104 USA, [Anderson, K. M.] Yale Univ, Dept Psychol, New Haven, CT USA, [Ellis, C. T.] Yale Univ, Dept Psychol, New Haven, CT USA, [Turk-Browne, N. B.] Yale Univ, Dept Psychol, New Haven, CT USA, [Adamson, C.] Murdoch Childrens Res Inst, Dev Imaging, Melbourne, Vic, Australia, [Ball, G.] Murdoch Childrens Res Inst, Dev Imaging, Melbourne, Vic, Australia, [Beare, R.] Murdoch Childrens Res Inst, Dev Imaging, Melbourne, Vic, Australia, [Jackowski, A. P.] Murdoch Childrens Res Inst, Dev Imaging, Melbourne, Vic, Australia, [Adamson, C.] Monash Univ, Dept Med, Melbourne, Vic, Australia, [Beare, R.] Monash Univ, Dept Med, Melbourne, Vic, Australia, [Adler, S.] UCL Great Ormond St Inst Child Hlth, London, England, [Alexopoulos, G. S.] Weill Cornell Med, Dept Psychiat, Weill Cornell Inst Geriatr Psychiat, New York, NY USA, [Anagnostou, E.] Univ Toronto, Dept Pediat, Toronto, ON, Canada, [Anagnostou, E.] Holland Bloorview Kids Rehabil Hosp, Toronto, ON, Canada, [Pierce, K.] Holland Bloorview Kids Rehabil Hosp, Toronto, ON, Canada, [Areces-Gonzalez, A.] Univ Elect Sci & Technol China, MOE Key Lab NeuroInformat, Clin Hosp, Chengdu Brain Sci Inst, Chengdu, Peoples R China, [Paz-Linares, D.] Univ Elect Sci & Technol China, MOE Key Lab NeuroInformat, Clin Hosp, Chengdu Brain Sci Inst, Chengdu, Peoples R China, [Areces-Gonzalez, A.] Univ Pinar del Rio Hermanos Saiz Montes de Oca, Pinar Del Rio, Cuba, [Astle, D. E.] Univ Cambridge, MRC Cognit & Brain Sci Unit, Cambridge, England, [Henson, R. N.] Univ Cambridge, MRC Cognit & Brain Sci Unit, Cambridge, England, [Whalley, H. C.] Univ Cambridge, MRC Cognit & Brain Sci Unit, Cambridge, England, [Auyeung, B.] Univ Edinburgh, Sch Philosophy Psychol & Language Sci, Dept Psychol, Edinburgh, Midlothian, Scotland, [Pausova, Z.] Univ Edinburgh, Sch Philosophy Psychol & Language Sci, Dept Psychol, Edinburgh, Midlothian, Scotland, [Ayub, M.] Queens Univ, Dept Psychiat, Ctr Neurosci Studies, Kingston, ON, Canada, [Ayub, M.] UCL, Mental Hlth Neurosci Res Dept, Div Psychiat, London, England, [Bae, J.] Seoul Natl Univ, Bundang Hosp, Dept Neuropsychiat, Seongnam, South Korea, [Ball, G.] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia, [Baron-Cohen, S.] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge Lifetime Asperger Syndrome Serv CLASS, Cambridge, England, [Benegal, V.] Natl Inst Mental Hlth & Neurosci NIMHANS, Ctr Addict Med, Bengaluru, India, [Beyer, F.] Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, Leipzig, Germany, [Villringer, A.] Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, Leipzig, Germany, [Witte, A. V.] Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, Leipzig, Germany, [Blangero, J.] Univ Texas Rio Grande Valley, South Texas Diabet & Obes Inst, Dept Human Genet, Edinburg, TX USA, [Blesa Cabez, M.] Univ Edinburgh, MRC Ctr Reprod Hlth, Edinburgh, Midlothian, Scotland, [Boardman, J. P.] Univ Edinburgh, MRC Ctr Reprod Hlth, Edinburgh, Midlothian, Scotland, [Sullivan, G.] Univ Edinburgh, MRC Ctr Reprod Hlth, Edinburgh, Midlothian, Scotland, [Borzage, M.] Univ Southern Calif, Childrens Hosp Los Angeles, Keck Sch Med, Fetal & Neonatal Inst,Div Neonatol,Dept Pediat, Los Angeles, CA 90007 USA, [Bosch-Bayard, J. F.] Montreal Neurol Inst, Ludmer Ctr Neuroinformat & Mental Hlth, McGill Ctr Integrat Neurosci, Montreal, PQ, Canada, [Bosch-Bayard, J. F.] McGill Univ, Montreal, PQ, Canada, [Chakravarty, M. 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E.] Alan Turing Inst, London, England, [Mothersill, D.] Natl Coll Ireland, Sch Business, Dept Psychol, Dublin, Ireland, [Mothersill, D.] Natl Univ Ireland Galway, Sch Psychol, Galway, Ireland, [Mothersill, D.] Natl Univ Ireland Galway, Ctr Neuroimaging & Cognit Genom, Galway, Ireland, [Mothersill, D.] Trinity Coll Dublin, Dept Psychiat, Dublin, Ireland, [Nigg, J.] Oregon Hlth & Sci Univ, Dept Psychiat, Sch Med, Portland, OR 97201 USA, [Ong, M. Q. W.] Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Sleep & Cognit, Singapore, Singapore, [Qian, X.] Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Sleep & Cognit, Singapore, Singapore, [Zhou, J. 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M.] Natl Inst Dev Psychiat Children & Adolescents INP, Sao Poalo, Brazil, [Zugman, A.] Natl Inst Dev Psychiat Children & Adolescents INP, Sao Poalo, Brazil, [Pantelis, C.] Univ Melbourne, Dept Psychiat, Melbourne Neuropsychiat Ctr, Carlton, Vic, Australia, [Pantelis, C.] Melbourne Hlth, Carlton, Vic, Australia, [Pantelis, C.] Univ Melbourne, Melbourne Sch Engn, Parkville, Vic, Australia, [Pantelis, C.] Florey Inst Neurosci & Mental Hlth, Parkville, Vic, Australia, [Park, M. M.] Western Univ, Schulich Sch Med & Dent, Dept Psychiat, London, ON, Canada, [Rollins, C. K.] Univ Montreal, Dept Psychiat, Fac Med, Montreal, PQ, Canada, [Rollins, C. K.] Univ Montreal, CHU St Justine, Montreal, PQ, Canada, [Romero-Garcia, R.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada, [Romero-Garcia, R.] Univ Toronto, Dept Psychol, Toronto, ON, Canada, [Rosenberg, M. D.] Univ Toronto, Dept Physiol, Toronto, ON, Canada, [Rosenberg, M. 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P.] Massachusetts Gen Hosp, Dept Radiol, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA, [Schumann, G.] Fudan Univ, Inst Sci & Technol Brain Inspired Intelligence, Ctr Populat Neurosci & Stratified Med PONS, Shanghai, Peoples R China, [Schumann, G.] Charite Campus Mitte, Dept Psychiat & Psychotherapy, Charite Mental Hlth, PONS Ctr, Berlin, Germany, [Scholl, M.] Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, Gothenburg, Sweden, [Scholl, M.] Univ Gothenburg, Dept Psychiat & Neurochem, Gothenburg, Sweden, [Scholl, M.] UCL, Queens Sq Inst Neurol, Dementia Res Ctr, London, England, [Sharp, D.] UK Dementia Res Inst, Care Res & Technol Ctr, London, England, [Shinohara, R. T.] Univ Penn, Perelman Sch Med, Dept Radiol, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA, [Smyser, C. D.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA, [Smyser, C. D.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA, [Smyser, C. D.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA, [Stein, D. J.] Univ Cape Town, Dept Psychiat, SA MRC Unit Risk & Resilience Mental Disorders, Cape Town, South Africa, [Stein, D. J.] Univ Cape Town, Neurosci Inst, Cape Town, South Africa, [Stolicyn, A.] Univ Edinburgh, Ctr Clin Brain Sci, Div Psychiat, Edinburgh, Midlothian, Scotland, [Whalley, H. C.] Univ Edinburgh, Ctr Clin Brain Sci, Div Psychiat, Edinburgh, Midlothian, Scotland, [Toro, R.] Inst Pasteur, Dept Neurosci, Paris, France, [Traut, N.] Inst Pasteur, Dept Neurosci, Paris, France, [Traut, N.] Univ Paris 05, Ctr Res & Interdisciplinar CRI, Paris, France, [Tsvetanov, K. A.] Univ Cambridge, Dept Psychol, Cambridge, England, [Turk-Browne, N. B.] Yale Univ, Wu Tsai Inst, New Haven, CT USA, [Tuulari, J. J.] Univ Turku, Dept Clin Med, Turku, Finland, [Tuulari, J. J.] Univ Turku, Turku Coll Sci Med & Technol, Turku, Finland, [Tzourio, C.] Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, CHU Bordeaux, U1219,INSERM, Bordeaux, France, [Vachon-Presseau, E.] McGill Univ, Fac Dent Med & Oral Hlth Sci, Montreal, PQ, Canada, [Valdes-Sosa, P. A.] McGill Univ, Alan Edwards Ctr Res Pain AECRP, Montreal, PQ, Canada, [Valk, S. L.] Forschungszentrum Julich, Inst Neurosci & Med 7, Julich, Germany, [Valk, S. L.] Max Planck Inst Human Cognit & Brain Sci, Leipzig, Germany, [van Amelsvoort, T.] Maastricht Univ, Dept Psychiat & Neurosychol, Maastricht, Netherlands, [Vandekar, S. N.] Vanderbilt Univ, Dept Biostat, 221 Kirkland Hall, Nashville, TN 37235 USA, [Villeneuve, S.] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN USA, [Villringer, A.] Univ Leipzig, Clin Cognit Neurol, Med Ctr, Leipzig, Germany, [Witte, A. V.] Univ Leipzig, Clin Cognit Neurol, Med Ctr, Leipzig, Germany, [Zuo, X. N.] Univ Leipzig, Clin Cognit Neurol, Med Ctr, Leipzig, Germany, [Wang, Y. S.] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China, [Yang, N.] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China, [Yeo, B.] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China, [Zuo, X. N.] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China, [Wang, Y. S.] Beijing Normal Univ, IDG McGovern Inst Brain Res, Dev Populat Neuroscience Res Ctr, Beijing, Peoples R China, [Yang, N.] Beijing Normal Univ, IDG McGovern Inst Brain Res, Dev Populat Neuroscience Res Ctr, Beijing, Peoples R China, [Zuo, X. N.] Beijing Normal Univ, IDG McGovern Inst Brain Res, Dev Populat Neuroscience Res Ctr, Beijing, Peoples R China, [Wang, Y. S.] Natl Basic Sci Data Ctr, Beijing, Peoples R China, [Yang, N.] Natl Basic Sci Data Ctr, Beijing, Peoples R China, [Zuo, X. N.] Natl Basic Sci Data Ctr, Beijing, Peoples R China, [Wang, Y. S.] Chinese Acad Sci, Res Ctr Lifespan Dev Brain & Mind, Inst Psychol, Beijing, Peoples R China, [Yang, N.] Chinese Acad Sci, Res Ctr Lifespan Dev Brain & Mind, Inst Psychol, Beijing, Peoples R China, [Westman, E.] Karolinska Inst, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Div Clin Geriatr, Stockholm, Sweden, [Witte, A. V.] Univ Leipzig, CRC 1052 Obes Mech, Fac Med, Leipzig, Germany, [Zhou, J. H.] Natl Univ Singapore, Dept Elect & Comp Engn, Singapore, Singapore, [Yeo, B.] Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Sleep & Cognit, Singapore, Singapore, [Yeo, B.] Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Translat MR Res, Singapore, Singapore, [Yeo, B.] Natl Univ Singapore, N1 Inst Hlth, Singapore, Singapore, [Yeo, B.] Natl Univ Singapore, Inst Digital Med, Singapore, Singapore, [Yun, H.] Natl Univ Singapore, Integrat Sci & Engn Programme ISEP, Singapore, Singapore, [Zar, H. J.] Univ Melbourne, Dept Biomed Engn, Melbourne, Vic, Australia, [Zhou, J. H.] Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Translat Magnet Resonance Res, Singapore, Singapore, [Ziauddeen, H.] Univ Cambridge, Wellcome Trust MRC Inst Metab Sci, Cambridge, England, [Zugman, A.] NIMH, NIH, Bethesda, MD 20892 USA, [Zugman, A.] Escola Paulista Med, Dept Psychiat, Sao Paulo, Brazil, [Zuo, X. N.] Nanning Normal Univ, Sch Educ Sci, Key Lab Brain & Educ, Nanning, Peoples R China, British Academy Postdoctoral fellowship, NIMH, UKRI Medical Research Council, NIHR Cambridge Biomedical Research Centre, NIHR Senior Investigator award, MRC research infrastructure award, Commonwealth Scientific and Industrial Research Organisation (CSIRO), and Ontario Brain Institute
Subjects: 631/378/2649, OpenPain Project, KNE96, Growth, Psychiatric-disorders, DISEASE, 3R-BRAIN, Brain charts, MRI Brain, OASIS-3, Disease, CCNP, 631/378/2571, UMN BCP, Multidisciplinary, medicine.diagnostic_test, PSYCHIATRIC-DISORDERS, article, Brain, Human brain, ASSOCIATION, Magnetic Resonance Imaging, Harvard Aging Brain Study, The Mayo Clinic Study of Aging, NSPN, medicine.anatomical_structure, GROWTH, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], ddc:500, BURDEN, WHITE-MATTER, FinnBrain, Harvard Aging Brain Study, Organization, Mri, MRI, medicine.medical_specialty, Concurrent validity, MODELS, Cam-CAN, Longevity, CALM Team, POND, Neuroimaging, Burden, ORGANIZATION, AIBL, The PREVENT-AD Research Group, VETSA, Cortical thickness, Association, Physical medicine and rehabilitation, FinnBrain, IMAGEN, KNE96, White-matter, medicine, Humans, ASRB, 631/378/1689, COBRE, business.industry, 631/378/2611, Brain morphometry, Neurosciences, Alzheimer’s Disease Repository Without Borders Investigators, Magnetic resonance imaging, Alzheimer’s Disease Neuroimaging Initiative, Anthropometry, Body Height, Brain growth, Birth, 59/57, Normative, IMAGEN, ENIGMA Developmental Brain Age working group, NSPN, business, CCNP, 3R-BRAIN, CORTICAL THICKNESS, Developing Human Connectome Project, ENIGMA Developmental Brain Age working group, The PREVENT-AD Research Group, VETSA, Bullmore, E.T
Abstract: Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes., R.A.I.B. was supported by a British Academy Postdoctoral fellowship and by the Autism Research Trust. J. Seidlitz was supported by NIMH T32MH019112-29 and K08MH120564. S.R.W. was funded by UKRI Medical Research Council MC_UU_00002/2 and was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). E.T.B. was supported by an NIHR Senior Investigator award and the Wellcome Trust collaborative award for the Neuroscience in Psychiatry Network. A.F.A.-B. was supported by NIMH K08MH120564. Data were curated and analysed using a computational facility funded by an MRC research infrastructure award (MR/M009041/1) to the School of Clinical Medicine, University of Cambridge and supported by the mental health theme of the NIHR Cambridge Biomedical Research Centre.
Published: 2022

26. Fractionation of reward processing into independent neural representations by novel decoding principle

Author: Tianye Jia, Shitong Xiang, Chao Xie, Zhichao Zhu, Jujiao Kang, Wei Cheng, Gunter Schumann, Trevor Robbins, and Jianfeng Feng
Abstract: How to retrieve latent neurobehavioural processes from complex human neurobiological signals is an important yet unresolved challenge. Processing value and salience information are fundamental yet mutually confounded pathways of reward reinforcement. Here, we develop a novel analytical approach, orthogonal-Decoding multi-Cognitive Processes (DeCoP), to decode brain-wide responses into spatially overlapping, yet functionally independent, evaluation and readiness networks during the anticipation of reward or punishment. Our findings indicate that this functional independence is modulated differentially by those neural systems innervated by the cortico-mesolimbic and nigro-striatal dopamine projections. The segregation of evaluation and readiness neural responses from a unified input signal was also achievable using a theoretical neuronal population-coding model, hence further advancing our understanding of the neural basis involved in motivational processing. Furthermore, our novel theoretical approach could potentially be applied more generally to decode multiple latent neurobehavioral processes and thus advance both the design and hypothesis testing in cognitive task paradigms.
Published: 2022

27. Neural Correlates of Adolescent Irritability and Its Comorbidity With Psychiatric Disorders

Author: Bader Chaarani, Kees-Jan Kan, Scott Mackey, Philip A. Spechler, Alexandra Potter, Tobias Banaschewski, Sabina Millenet, Arun L.W. Bokde, Uli Bromberg, Christian Büchel, Anna Cattrell, Patricia J. Conrod, Sylvane Desrivières, Herta Flor, Vincent Frouin, Jürgen Gallinat, Penny Gowland, Andreas Heinz, Bernd Ittermann, Jean-Luc Martinot, Frauke Nees, Tomáš Paus, Luise Poustka, Michael N. Smolka, Henrik Walter, Robert Whelan, Argyris Stringaris, Stephen T. Higgins, Gunter Schumann, Hugh Garavan, Robert R. Althoff, Dr. Michael Rapp, Dr. Eric Artiges, Sophia Schneider, Christine Bach, Dr. Tomas Paus, Alexis Barbot, Dr. Gareth Barker, Dr. Arun Bokde, Dr. Nora Vetter, Dr. Christian Büchel, Dr. Anna Cattrell, Patrick Constant, Dr. Hans Crombag, Katharina Czech, Dr. Jeffrey Dalley, Benjamin Decideur, Tade Spranger, Dr. Tamzin Ripley, Dr. Nadja Heym, Dr. Wolfgang Sommer, Birgit Fuchs, Dr. Jürgen Gallinat, Dr. Hugh Garavan, Dr. Rainer Spanagel, Mehri Kaviani, Dr. Bert Heinrichs, Dr. Andreas Heinz, Naresh Subramaniam, Dr. Tianye Jia, Albrecht Ihlenfeld, James Ireland, Dr. Bernd Ittermann, Dr. Patricia Conrod, Dr. Tobias Banaschewski, Jennifer Jones, Dr. Arno Klaassen, Christophe Lalanne, Dr. Dirk Lanzerath, Dr. Claire Lawrence, Dr. Hervé Lemaitre, Dr. Sylvane Desrivieres, Catherine Mallik, Dr. Karl Mann, Dr. Adam Mar, Lourdes Martinez-Medina, Dr. Jean-Luc Martinot, Eva Mennigen, Dr. Fabiana Mesquita de Carvahlo, Yannick Schwartz, Dr. Ruediger Bruehl, Kathrin Müller, Charlotte Nymberg, Dr. Mark Lathrop, Dr. Trevor Robbins, Dr. Zdenka Pausova, Dr. Jani Pentilla, Dr. Francesca Biondo, Dr. Jean-Baptiste Poline, Dr. Luise Poustka, Dr. Michael Smolka, Juliane Fröhner, Dr. Maren Struve, Dr. Steve Williams, Dr. Thomas Hübner, Semiha Aydin, John Rogers, Alexander Romanowski, Dr. Christine Schmäl, Dirk Schmidt, Stephan Ripke, Dr. Mercedes Arroyo, Dr. Florian Schubert, Dr. Yolanda Pena-Oliver, Mira Fauth-Bühler, Xavier Mignon, Dr. Robert Whelan, Dr. Claudia Speiser, Tahmine Fadai, Dr. Dai Stephens, Dr. Andreas Ströhle, Dr. Marie-Laure Paillere, Nicole Strache, David Theobald, Sarah Jurk, Dr. Helene Vulser, Ruben Miranda, Dr. Juliana Yacubilin, Alexander Genauck, Caroline Parchetka, Isabel Gemmeke, Johann Kruschwitz, Katharina Weiss, Dr. Henrik Walter, Jianfeng Feng, Dimitri Papadopoulos, Irina Filippi, Alex Ing, Dr. Barbara Ruggeri, Bing Xu, Christine Macare, Dr. Congying Chu, Eanna Hanratty, Dr. Erin Burke Quinlan, Dr. Gabriel Robert, Dr. Gunter Schumann, Dr. Tao Yu, Veronika Ziesch, and Alicia Stedman
Subjects: Neural correlates of consciousness, medicine.medical_specialty, Generalized anxiety disorder, medicine.diagnostic_test, business.industry, 05 social sciences, medicine.disease, Irritability, Comorbidity, Psychiatry and Mental health, Developmental and Educational Psychology, medicine, Major depressive disorder, 0501 psychology and cognitive sciences, Irritable Mood, medicine.symptom, Psychiatry, Functional magnetic resonance imaging, business, 050104 developmental & child psychology, Psychopathology
Abstract: Objective Irritable mood, a common and impairing symptom in psychopathology, has been proposed to underlie the developmental link between oppositional problems in youth and depression in adulthood. We examined the neural correlates of adolescent irritability in IMAGEN, a sample of 2,024 14-year-old adolescents from 5 European countries. Method The Development and Well-Being Assessment (DAWBA) was used to assess attention-deficit/hyperactivity disorder, major depressive disorder, oppositional defiant disorder, and generalized anxiety disorder. Three items from the DAWBA, selected as close matches to the Affective Reactivity Index, were used to assess irritability. Structural magnetic resonance imaging was examined using whole-brain voxel-based morphometry analysis, and functional magnetic resonance imaging was examined during a stop signal task of inhibitory control. Imaging data were included in structural equation models to examine the direct and indirect associations between irritable mood and comorbid DSM diagnoses. Results Whole-brain voxelwise analysis showed that adolescent irritable mood was associated with less gray matter volume and less neural activation underlying inhibitory control in frontal and temporal cortical areas (cluster-correction at p Conclusion This study identifies adolescent irritability as an independent construct and points to a neurobiological correlate to irritability that is an important contributing feature to many psychopathological disorders.
Published: 2020

28. How cognitive neuroscience can enhance education and population mental health

Author: Tianye, Jia and Gunter, Schumann
Subjects: Mental Health, Cognition, Multidisciplinary, Population Health, Cognitive Neuroscience, Educational Status
Published: 2022

29. Adult alcohol drinking and emotional tone are mediated by neutral sphingomyelinase during development in males

Author: Liubov S Kalinichenko, Christiane Mühle, Tianye Jia, Felix Anderheiden, Maria Datz, Anna-Lisa Eberle, Volker Eulenburg, Jonas Granzow, Martin Hofer, Julia Hohenschild, Sabine E Huber, Stefanie Kämpf, Georgios Kogias, Laura Lacatusu, Charlotte Lugmair, Stephen Mbu Taku, Doris Meixner, Nina-Kristin Sembritzki, Marc Praetner, Cosima Rhein, Christina Sauer, Jessica Scholz, Franziska Ulrich, Florian Valenta, Esther Weigand, Markus Werner, Nicole Tay, Conor J Mc Veigh, Jana Haase, An-Li Wang, Laila Abdel-Hafiz, Joseph P Huston, Irena Smaga, Malgorzata Frankowska, Malgorzata Filip, Anbarasu Lourdusamy, Philipp Kirchner, Arif B Ekici, Lena M Marx, Neeraja Puliparambil Suresh, Renato Frischknecht, Anna Fejtova, Essa M Saied, Christoph Arenz, Aline Bozec, Isabel Wank, Silke Kreitz, Andreas Hess, Tobias Bäuerle, Maria Dolores Ledesma, Daniel N Mitroi, André M Miranda, Tiago Gil Oliveira, Bernd Lenz, Gunter Schumann, Johannes Kornhuber, and Christian P Müller
Subjects: Cellular and Molecular Neuroscience, Cognitive Neuroscience, ddc:610
Abstract: Alcohol use, abuse, and addiction, and resulting health hazards are highly sex-dependent with unknown mechanisms. Previously, strong links between the SMPD3 gene and its coded protein neutral sphingomyelinase 2 (NSM) and alcohol abuse, emotional behavior, and bone defects were discovered and multiple mechanisms were identified for females. Here we report strong sex-dimorphisms for central, but not for peripheral mechanisms of NSM action in mouse models. Reduced NSM activity resulted in enhanced alcohol consumption in males, but delayed conditioned rewarding effects. It enhanced the acute dopamine response to alcohol, but decreased monoaminergic systems adaptations to chronic alcohol. Reduced NSM activity increased depression- and anxiety-like behavior, but was not involved in alcohol use for the self-management of the emotional state. Constitutively reduced NSM activity impaired structural development in the brain and enhanced lipidomic sensitivity to chronic alcohol. While the central effects were mostly opposite to NSM function in females, similar roles in bone-mediated osteocalcin release and its effects on alcohol drinking and emotional behavior were observed. These findings support the view that the NSM and multiple downstream mechanism may be a source of the sex-differences in alcohol use and emotional behavior.
Published: 2022

30. Interference of Default Mode on Attention in Adults with Attention-Deficit/Hyperactivity Disorder and its Association with Genetic Variations and Treatment Outcomes

Author: Lu Liu, Di Chen, Fang Huang, Tianye Jia, Wei Cheng, Meirong Pan, Mengjie Zhao, Xuan Bu, Xuhong Liao, Yufeng Wang, Miao Cao, Qiujin Qian, and Jianfeng Feng
Subjects: History, Polymers and Plastics, Business and International Management, Industrial and Manufacturing Engineering
Published: 2022

31. Big Data Analysis and Application of Liver Cancer Gene Sequence Based on Second-Generation Sequencing Technology

Author: Chaohui Xiao, Fuchuan Wang, Tianye Jia, Liru Pan, and Zhaohai Wang
Subjects: Data Analysis, Technology, General Immunology and Microbiology, Article Subject, Applied Mathematics, Modeling and Simulation, Liver Neoplasms, Cluster Analysis, Humans, Bayes Theorem, General Medicine, General Biochemistry, Genetics and Molecular Biology, Algorithms
Abstract: In big data analysis with the rapid improvement of computer storage capacity and the rapid development of complex algorithms, the exponential growth of massive data has also made science and technology progress with each passing day. Based on omics data such as mRNA data, microRNA data, or DNA methylation data, this study uses traditional clustering methods such as kmeans, K-nearest neighbors, hierarchical clustering, affinity propagation, and nonnegative matrix decomposition to classify samples into categories, obtained: (1) The assumption that the attributes are independent of each other reduces the classification effect of the algorithm to a certain extent. According to the idea of multilevel grid, there is a one-to-one mapping from high-dimensional space to one-dimensional. The complexity is greatly simplified by encoding the one-dimensional grid of the hierarchical grid. The logic of the algorithm is relatively simple, and it also has a very stable classification efficiency. (2) Convert the two-dimensional representation of the data into the one-dimensional representation of the binary, realize the dimensionality reduction processing of the data, and improve the organization and storage efficiency of the data. The grid coding expresses the spatial position of the data, maintains the original organization method of the data, and does not make the abstract expression of the data object. (3) The data processing of nondiscrete and missing values provides a new opportunity for the identification of protein targets of small molecule therapy and obtains a better classification effect. (4) The comparison of the three models shows that Naive Bayes is the optimal model. Each iteration is composed of alternately expected steps and maximal steps and then identified and quantified by MS.
Published: 2022
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32. Neural Correlates of the Dual-Pathway Model for ADHD in Adolescents

Author: Barbara J. Sahakian, Herta Flor, Qi Zhao, Christian Büchel, Qiang Luo, Gunter Schumann, Juliane H. Fröhner, Tomáš Paus, Sylvane Desrivières, Penny A. Gowland, Frauke Nees, Sabina Millenet, Arun L.W. Bokde, Michael N. Smolka, Andreas Heinz, Jianfeng Feng, Tobias Banaschewski, Dimitri Papadopoulos Orfanos, Marie-Laure Paillère-Martinot, Tianye Jia, Jean-Luc Martinot, Eric Artiges, Fei Li, Robert Whelan, Erin Burke Quinlan, Chun Shen, Vincent Frouin, Hugh Garavan, Luise Poustka, Henrik Walter, and Bernd Ittermann
Subjects: Male, Adolescent, Prefrontal Cortex, Neuroimaging, Behavioral Symptoms, Neuropsychological Tests, Risk Assessment, 03 medical and health sciences, Cognition, 0302 clinical medicine, mental disorders, medicine, Humans, Attention deficit hyperactivity disorder, Longitudinal Studies, Gray Matter, Dual pathway, Motivation, Neural correlates of consciousness, Biobehavioral Sciences, Organ Size, medicine.disease, 030227 psychiatry, Neuroanatomical Tract-Tracing Techniques, Psychiatry and Mental health, medicine.anatomical_structure, Attention Deficit Disorder with Hyperactivity, Female, Occipital Lobe, Psychology, Neuroscience, 030217 neurology & neurosurgery, Neuroanatomy
Abstract: Objective: The dual-pathway model has been proposed to explain the heterogeneity in symptoms of attention deficit hyperactivity disorder (ADHD) by two independent psychological pathways based on distinct brain circuits. The authors sought to test whether the hypothesized cognitive and motivational pathways have separable neural correlates. Methods: In a longitudinal community-based cohort of 1,963 adolescents, the neuroanatomical correlates of ADHD were identified by a voxel-wise association analysis and then validated using an independent clinical sample (99 never-medicated patients with ADHD, 56 medicated patients with ADHD, and 267 healthy control subjects). The cognitive and motivational pathways were assessed by neuropsychological tests of working memory, intrasubject variability, stop-signal reaction time, and delay discounting. The associations were tested between the identified neuroanatomical correlates and both ADHD symptoms 2 years later and the polygenic risk score for ADHD. Results: Gray matter volumes of both a prefrontal cluster and a posterior occipital cluster were negatively associated with inattention. Compared with healthy control subjects, never-medicated patients, but not medicated patients, had significantly lower gray matter volumes in these two clusters. Working memory and intrasubject variability were associated with the posterior occipital cluster, and delay discounting was independently associated with both clusters. The baseline gray matter volume of the posterior occipital cluster predicted the inattention symptoms in a 2-year follow-up and was associated with the genetic risk for ADHD. Conclusions: The dual-pathway model has both shared and separable neuroanatomical correlates, and the shared correlate in the occipital cortex has the potential to serve as an imaging trait marker of ADHD, especially the inattention symptom domain.
Published: 2020

33. Neurobehavioural characterisation and stratification of reinforcement-related behaviour

Author: Alex Ing, Luise Poustka, Erin Burke Quinlan, Frauke Nees, Tianye Jia, Andreas Heinz, Bernd Ittermann, Biondo Francesca, Michael N. Smolka, Sylvane Desrivières, Tobias Banaschewski, Arun L.W. Bokde, Robert Whelan, Henrik Walter, Jianfeng Feng, Gareth J. Barker, Tomáš Paus, Qiang Luo, Jean-Luc Martinot, Uli Bromberg, Marie-Laure Paillère Martinot, Juliane H. Fröhner, Hugh Garavan, Nicole Tay, Penny A. Gowland, Dimitri Papadopoulos Orfanos, Herta Flor, Antoine Grigis, Christian Büchel, and Gunter Schumann
Subjects: Male, Elementary cognitive task, Adolescent, Social Psychology, Experimental and Cognitive Psychology, Emotional processing, Impulsivity, Developmental psychology, Reward processing, Functional brain, 03 medical and health sciences, Behavioral Neuroscience, Cognition, 0302 clinical medicine, Reward, Neuroimaging, Functional neuroimaging, medicine, Humans, Attention, Child, Reinforcement, 030304 developmental biology, 0303 health sciences, Facial expression, Functional Neuroimaging, Brain, Anticipation, Psychological, medicine.disease, Magnetic Resonance Imaging, Comorbidity, Anticipation, Facial Expression, Impulsive Behavior, Female, Nerve Net, medicine.symptom, Psychology, Reinforcement, Psychology, 030217 neurology & neurosurgery, Cognitive psychology
Abstract: Reinforcement-related cognitive processes, such as reward processing, inhibitory control and social–emotional regulation are critical components of externalising and internalising behaviours. It is unclear to what extent the deficit in each of these processes contributes to individual behavioural symptoms, how their neural substrates give rise to distinct behavioural outcomes and whether neural activation profiles across different reinforcement-related processes might differentiate individual behaviours. We created a statistical framework that enabled us to directly compare functional brain activation during reward anticipation, motor inhibition and viewing emotional faces in the European IMAGEN cohort of 2,000 14-year-old adolescents. We observe significant correlations and modulation of reward anticipation and motor inhibition networks in hyperactivity, impulsivity, inattentive behaviour and conduct symptoms, and we describe neural signatures across cognitive tasks that differentiate these behaviours. We thus characterise shared and distinct functional brain activation patterns underling different externalising symptoms and identify neural stratification markers, while accounting for clinically observed comorbidity. On the basis of the IMAGEN database of 2,000 Caucasian adolescents, Jia et al identify neural patterns of activity during reward anticipation and motor inhibition associated with different externalising symptoms for ADHD and conduct problems.
Published: 2020

34. Connectome-wide association analysis identified significant brain functional alteration in adults with attention-deficit/hyperactivity disorder

Author: Lu Liu, Di Chen, Fang Huang, Tianye Jia, Meirong Pan, Mengjie Zhao, Xuan Bu, Yufeng Wang, Miao Cao, Qiujin Qian, and Jianfeng Feng
Subjects: mental disorders, behavioral disciplines and activities
Abstract: Adults with attention-deficit/hyperactivity disorder (ADHD), as an extreme-phenotype of ADHD, is still facing problems of inconsistency and undeciphered mechanisms for its neuropathology. To address this matter, our present study performed connecotome-wide voxel-based analyses with the resting-state fMRI data of 84 adults with ADHD and 89 healthy controls. We found that functional connectivity patterns of the left precuneus and the left middle temporal significantly altered in ADHD populations serving as potential neural biomarkers to distinguish ADHD with healthy controls, with subsequent seed-based analysis revealing the dysfunction of functional connections both intra- and inter-default mode and attention networks, among which middle temporal gyrus plays the key role of ‘bridge’ linking the default mode and attention networks. After cognitive behavioral therapy, two of these ADHD-altered functional connections ameliorated accompanied with improvement of ADHD core symptoms. Additionally, imaging genetic analyses also revealed close relationships between the observed brain functional alterations and ADHD-risk genes. Taken together, our findings suggested the interference of default mode on attention networks in adults with ADHD, which would be severing as a potential biomarker for both ADHD pathogenesis and treatment effects.
Published: 2021

35. Isolation and characterization of fucosylated extracellular vesicles based on a novel high-throughput GlyExo-Capture technique

Author: Boan Li, Kun Hao, Cuidie Ma, Zhengtai Li, Hongjiang Li, Wenqian Du, Lijuan Sun, Tianye Jia, Aixia Liu, Yanzhao Li, Lida Xu, Qi Gao, Ruifu Yang, and Changqing Lin
Abstract: Owing to their diagnostic and therapeutic potential, extracellular vesicles (EVs) derived from tumour cells have recently garnered great interest. The presence of different glycosylation sites at the EV surface supports the need for efficient glycosylated EV isolation. Here, we developed a GlyExo-Capture technique for robustly capturing fucosylated EVs from sera and cell supernatants. Lens culinaris lectin (LCA)-immobilized magnetic complexes were found to capture approximately 60% of the total EVs from HepG2 cells. The capture efficiency was reduced to less than 40% in nontumorigenic MIHA cells. Notably, the cellular uptake pattern of highly fucosylated EVs was markedly different from that of EVs with low fucosylation. The unearthing of enriched fucosylated EV miRNA cargos by next-generation deep sequencing (NGS) revealed 75 differentially expressed miRNAs (DEMs) in hepatocellular carcinoma (HCC). Among them, a 4-miRNA panel was chosen and yielded an area under the ROC curve (AUC) of 0.86 and 0.84 for the detection of HCC from non-HCC controls in testing samples and independent validation samples, respectively. The 4-miRNA signature was independent of alpha-fetoprotein (AFP), and a combined model with AFP yielded an increased AUC of 0.92. In conclusion, we developed a high-throughput method for capturing fucosylated EVs efficiently and shed light on the use of fucosylated EVs as potential sources of miRNAs for cancer biomarker detection.
Published: 2021

36. Cortical encoding during word reading in bilinguals: parallel interdigitated distributed networks support convergent linguistic functioning

Author: Wanwan Guo, Tianye Jia, Miao Cao, Wei Zhou, Kunyu Xu, Jianfeng Feng, Colin Blakemore, Li-Hai Tan, and Shujie Geng
Subjects: Writing system, Computer science, Middle temporal gyrus, Word recognition, Pinyin, Precentral gyrus, Inferior frontal gyrus, Cognition, Lateralization of brain function, Cognitive psychology
Abstract: Word reading includes a series of cognitive processes that convert low-level visual characteristics to neural representations. However, the consistency of the neural mechanisms for processing these cognitive components across different writing systems in bilinguals remains inconclusive. Here, we explored this question by employing representational similarity analysis with a semantic access task involving Chinese words, English words and Chinese pinyin. Distinct anatomical distribution patterns were detected for each type of brain representation across ideographic and alphabetic languages, resulting in 100% classification accuracy. Meanwhile, convergent cognitive components processing was found in the core language-related regions in left hemisphere, including the inferior frontal gyrus, temporal pole, superior and middle temporal gyrus, precentral gyrus and supplementary motor areas. Broadly, our findings indicated that the neural basis for word recognition of different writing systems in bilinguals was divergent in anatomical locations of neural representations for specialized processing but convergent in cognitive domains, which supported and enriched the assimilation-accommodation hypothesis.TeaserCortical encoding linguistic processing across languages was support by parallel interdigitated distributed networks but convergent in cognitive domains.
Published: 2021

37. Anxiety-impulsivity subtypes in adolescent internalizing disorder are characterized by distinguishable neurodevelopmental, neurocognitive and clinical trajectory signatures

Author: Tianye Jia, Trevor W. Robbins, Jie Zhang, Benjamin Becker, Huaxin Fan, Gunter Schumann, Barbara J. Sahakian, Gechang Yu, Nanyu Kuang, Xinran Wu, and Jianfeng Feng
Subjects: business.industry, Internalizing disorder, Cognition, Impulsivity, medicine.disease, Medicine, Sensation seeking, Anxiety, medicine.symptom, business, Neurocognitive, Suicidal ideation, Psychopathology, Clinical psychology
Abstract: Background Anxiety and impulsivity represent transdiagnostic pathology dimensions yet their interaction and contribution to emotional disorders in adolescence and to disease development remain controversial, and previous studies indicate heterogeneity within the broad category of internalizing disorders. Methods A combination of hierarchical and non-hierarchical clustering strategies was employed to determine impulsivity-related subtypes (based on the facets of negative urgency, lack of planning, lack of perseverance, sensation seeking and positive urgency in UPPS-P scales) in a large cohort of adolescents with internalizing disorders (n=2437) from Adolescent Brain Cognitive Development (ABCD) Study. Linear mixed-effect models were employed to determine cortical thickness alterations of the subtypes. Results Data-driven clustering identified two distinct subtypes of internalizing patients (subtype 1/subtype 2) with comparable levels of increased anxiety yet distinguishable levels of impulsivity, i.e., enhanced (subtype 1) or decreased (subtype 2) compared to healthy controls. Subtype 1 was further characterized by thicker prefrontal and temporal cortical regions involved in regulatory control and fear processing, while subtype 2 did not demonstrate significant thickness alterations. The differential neuroanatomical profiles remained stable over the two-year follow-up, while the two subtypes had different neurodevelopmental trajectories. Subtype 1 additionally reported more psychopathology and dysfunctionality including higher suicidal ideation, depressive symptoms and transition rates to externalizing disorders during follow-up as well as impaired neurocognitive and educational performance compared to subtype 2. Moreover, for subtype 1, anxiety at baseline (9-10 years) was significantly positively associated with impulsivity (lack of perseverance) at 2-year follow-up, while in subtype 2, baseline anxiety was significantly negatively associated with impulsivity (sensation seeking) at 2-year follow-up. Conclusions Our results demonstrate an impulsivity-dependent heterogeneity in adolescent internalizing disorders, with high-impulsivity patients being characterized by neurodevelopmental delay at the neural and cognitive levels. Individuals with elevated impulsivity are at a greater risk to develop behavioral dysregulation over the following two years and may thus require specific early interventions.
Published: 2021

38. Fractionation of neural reward processing into independent components by novel decoding principle

Author: Jianfeng Feng, Jujiao Kang, Gunter Schumann, Wei Cheng, Trevor W. Robbins, Chao Xie, Tianye Jia, Shitong Xiang, and Zhichao Zhu
Subjects: medicine.anatomical_structure, Punishment (psychology), medicine, Cognition, Valence (psychology), Psychology, Amygdala, Anticipation, Cognitive psychology, Statistical hypothesis testing, Arousal, Task (project management)
Abstract: Brain, as a complex cognitive system, often processes multiple dimension information synchronously and integrate them to adapt dynamic environments and make effective decisions.1–3 How to retrieve latent neurobehavioral processes from complex human neurobiological signals is an important yet previously unresolved challenge.4,5 For instance, the previous literature has proposed two fundamental yet mutually confounded processes during the decision making and affective processing, i.e. valance and arousal.6,7 Here, we develop a novel analytical approach, orthogonal-Decoding multi-Cognitive Processes (DeCoP), with which we dissociate neural responses in processing valence and arousal information during tests of motivational and emotional function. During reward/punishment anticipation, we decode brain-wide responses into spatially overlapping, yet functionally independent, evaluation and readiness networks, i.e., motivational valence and arousal processing, which are modulated differentially by the meso-limbic vs nigro-striatal dopamine systems. Similarly, during emotional reactivity, we decompose amygdala response into independent emotional valence and facial arousal processing features. We demonstrate that DeCoP can resolve paradoxically unexpected brain ‘inactivation’, and be applied more generally to decode multiple latent neurobehavioral processes. Furthermore, we anticipate our approach to advance both the design and hypothesis testing of cognitive experimental task paradigms.
Published: 2021

39. Neutral sphingomyelinase mediates the co-morbidity trias of alcohol abuse, major depression and bone defects

Author: Christina Sauer, André Miguel Lopes Miranda, Anna Fejtova, Doris Meixner, Christiane Mühle, Aline Bozec, Nina Tesch, Georgios Kogias, Christian P. Müller, Bernd Lenz, Daniel N Mitroi, Julia Hohenschild, Irena Smaga, Christoph Arenz, Jana Haase, Felix Anderheiden, Renato Frischknecht, Anbarasu Lourdusamy, Sabine E. Huber, Laila Abdel-Hafiz, Małgorzata Frankowska, Tianye Jia, Nicole Tay, An-Li Wang, Charlotte Lugmair, Gunter Schumann, Neeraja Puliparambil Suresh, Cosima Rhein, Lena M. Marx, Anna-Lisa Eberle, Essa M. Saied, Volker Eulenburg, Esther Weigand, Marc Praetner, Erich Gulbins, Martin Hofer, Laura Lacatusu, Jessica Scholz, Florian Valenta, Stefanie Kämpf, Philipp Kirchner, Arif B. Ekici, Conor J Mc Veigh, Tobias Bäuerle, Johannes Kornhuber, Franziska Ulrich, Silke Kreitz, Maria Dolores Ledesma, Isabel Wank, Jonas Granzow, Joseph P. Huston, Markus Werner, Tiago Gil Oliveira, Maria Datz, Andreas Hess, Małgorzata Filip, Stephen Mbu Taku, and Liubov S. Kalinichenko
Subjects: medicine.medical_specialty, Medizin, Alcohol abuse, Addiction, Alcohol, Comorbidity, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Mice, Internal medicine, Monoaminergic, medicine, Animals, Humans, ddc:610, Molecular Biology, Depression (differential diagnoses), Depressive Disorder, Major, biology, business.industry, Haplotype, Genetic disorder, medicine.disease, Psychiatry and Mental health, Alcoholism, Endocrinology, Sphingomyelin Phosphodiesterase, chemistry, Osteocalcin, biology.protein, Bone Diseases, Morbidity, Sphingomyelin, business, 610 Medizin und Gesundheit, Neuroscience
Abstract: Mental disorders are highly comorbid and occur together with physical diseases, which are often considered to arise from separate pathogenic pathways. We observed in alcohol-dependent patients increased serum activity of neutral sphingomyelinase. A genetic association analysis in 456,693 volunteers found associations of haplotypes of SMPD3 coding for NSM-2 (NSM) with alcohol consumption, but also with affective state, and bone mineralisation. Functional analysis in mice showed that NSM controls alcohol consumption, affective behaviour, and their interaction by regulating hippocampal volume, cortical connectivity, and monoaminergic responses. Furthermore, NSM controlled bone–brain communication by enhancing osteocalcin signalling, which can independently supress alcohol consumption and reduce depressive behaviour. Altogether, we identified a single gene source for multiple pathways originating in the brain and bone, which interlink disorders of a mental–physical co-morbidity trias of alcohol abuse—depression/anxiety—bone disorder. Targeting NSM and osteocalcin signalling may, thus, provide a new systems approach in the treatment of a mental–physical co-morbidity trias. Deutsche Forschungsgemeinschaft (German Research Foundation) https://doi.org/10.13039/501100001659
Published: 2021

40. Low Smoking Exposure, the Adolescent Brain, and the Modulating Role of CHRNA5 Polymorphisms

Author: Stephan Ripke, Anna Cattrell, Christophe Lalanne, Patricia J. Conrod, Tomáš Paus, Gunter Schumann, Jennifer Jones, K. Mann, Dirk Schmidt, Scott Mackey, Vincent Frouin, Eva Loth, Rainer Spanagel, Mira Fauth-Bühler, Andreas Ströhle, Jürgen Gallinat, Hélène Vulser, Jan Reuter, Catherine Mallik, Kelsey Hudson, Herta Flor, Amir M. Tahmasebi, Elliot A. Stein, Lindsay Smith, Philip A. Spechler, Bernadeta Walaszek, Kay Head, Tahmine Fadai, Frauke Nees, Bader Chaarani, Jani Pentilla, Michael A. Rapp, Uli Bromberg, Stephen T. Higgins, Argyris Stringaris, Kees-Jan Kan, Kathrin U. Müller, Craig Newman, Michael N. Smolka, Nicholas D'Alberto, Patrick Constant, Jean-Luc Martinot, Robert Whelan, Helen Werts, Claire Lawrence, Sylvane Desrivières, Nicole Strache, Laurence J. Reed, Arun L.W. Bokde, Zuleima Bricaud, Maren Struve, Jean-Baptiste Poline, Sabina Millenet, Ruediger Brühl, Tobias Banaschewski, Barbara Ruggeri, Andreas Heinz, Sophia Schneider, Kerstin Stueber, Charlotte Nymberg, Hugh Garavan, Christian Büchel, Zdenka Pausova, Robert R. Althoff, Albrecht Ihlenfeld, Catherine Orr, Eva Mennigen, Marcella Rietschel, Alexis Barbot, Alexandra Potter, Veronika Ziesch, Penny A. Gowland, Yvonne Grimmer, Jessica Massicotte, Nikolay Ivanov, Sarah Rodehacke, Yannick Schwartz, Stephanie Havatzias, Benjamin Thyreau, Chris Andrew, Juliana Yacubian, Luise Poustka, Nadja Heym, Thomas Hübner, André Galinowski, Dimitri Papadopoulos-Orfanos, L. Topper, Nora C. Vetter, Herve Lemaitre, Henrik Walter, Tianye Jia, Fanny Gollier Briand, and Bernd Ittermann
Subjects: Male, Adolescent, Cognitive Neuroscience, media_common.quotation_subject, Ventromedial prefrontal cortex, Nerve Tissue Proteins, Neuropsychological Tests, Receptors, Nicotinic, Corpus callosum, Bioinformatics, Polymorphism, Single Nucleotide, Article, 050105 experimental psychology, Cigarette Smoking, Nicotine, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Biological Psychiatry, media_common, biology, business.industry, Mechanism (biology), Addiction, CHRNA5, 05 social sciences, Brain, Tobacco Use Disorder, White Matter, Diffusion Tensor Imaging, Nicotinic agonist, medicine.anatomical_structure, biology.protein, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background Studying the neural consequences of tobacco smoking during adolescence, including those associated with early light use, may help expose the mechanisms that underlie the transition from initial use to nicotine dependence in adulthood. However, only a few studies in adolescents exist, and they include small samples. In addition, the neural mechanism, if one exists, that links nicotinic receptor genes to smoking behavior in adolescents is still unknown. Methods Structural and diffusion tensor magnetic resonance imaging data were acquired from a large sample of 14-year-old adolescents who completed an extensive battery of neuropsychological, clinical, personality, and drug-use assessments. Additional assessments were conducted at 16 years of age. Results Exposure to smoking in adolescents, even at low doses, is linked to volume changes in the ventromedial prefrontal cortex and to altered neuronal connectivity in the corpus callosum. The longitudinal analyses strongly suggest that these effects are not preexisting conditions in those who progress to smoking. There was a genetic contribution wherein the volume reduction effects were magnified in smokers who were carriers of the high-risk genotype of the alpha 5 nicotinic receptor subunit gene, rs16969968. Conclusions These findings give insight into a mechanism involving genes, brain structure, and connectivity underlying why some adolescents find nicotine especially addictive.
Published: 2019

41. Allele-Specific Methylation of SPDEF: A Novel Moderator of Psychosocial Stress and Substance Abuse

Author: Congying Chu, Nicole Tay, Eric Artiges, Sarah Hohmann, Qiang Luo, Vincent Frouin, Dimitri Papadopoulos Orfanos, Penny A. Gowland, Edward D. Barker, Juliane H. Fröhner, Luise Poustka, Christine Macare, Sylvane Desrivières, Erin Burke Quinlan, Joëlle Rüegg, Georgy Bakalkin, Francesca Biondo, Arun L.W. Bokde, Robert Whelan, Gunter Schumann, Tobias Banaschewski, Tianye Jia, Barbara Ruggeri, Tomáš Paus, Bernd Ittermann, Stefan Bleich, Ann-Christine Syvänen, Hugh Garavan, Helge Frieling, Herta Flor, Christian Büchel, Andreas Heinz, Uli Bromberg, Henrik Walter, Gareth J. Barker, Michael N. Smolka, Alex Ing, Tomas J. Ekström, Yun Liu, Jean-Luc Martinot, Daniil Sarkysian, and Frauke Nees
Subjects: Psychiatry, Allele specific methylation, business.industry, Moderation, medicine.disease, Psykiatri, 3. Good health, 030227 psychiatry, Substance abuse, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, DNA methylation, Psychosocial stress, Medicine, Epigenetics, Risk factor, Substance use, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract: Objective: Psychosocial stress is a key risk factor for substance abuse among adolescents. Recently, epigenetic processes such as DNA methylation have emerged as potential mechanisms that could mediate this relationship. The authors conducted a genome-wide methylation analysis to investigate whether differentially methylated regions are associated with psychosocial stress in an adolescent population. Methods: A methylome-wide analysis of differentially methylated regions was used to examine a sample of 1,287 14-year-old adolescents (50.7% of them female) from the European IMAGEN study. The Illumina 450k array was used to assess DNA methylation, pyrosequencing was used for technical replication, and linear regression analyses were used to identify associations with psychosocial stress and substance use (alcohol and tobacco). Findings were replicated by pyrosequencing a test sample of 413 participants from the IMAGEN study. Results: Hypermethylation in the sterile alpha motif/pointed domain containing the ETS transcription factor (SPDEF) gene locus was associated with a greater number of stressful life events in an allele-dependent way. Among individuals with the minor G-allele, SPDEF methylation moderated the association between psychosocial stress and substance abuse. SPDEF methylation interacted with lifetime stress in gray matter volume in the right cuneus, which in turn was associated with the frequency of alcohol and tobacco use. SPDEF was involved in the regulation of trans-genes linked to substance use. Conclusions: Taken together, the study findings describe a novel epigenetic mechanism that helps explain how psychosocial stress exposure influences adolescent substance abuse.
Published: 2019

42. Sex differences in neural correlates of common psychopathological symptoms in early adolescence

Author: Michael N. Smolka, Penny A. Gowland, Tobias Banaschewski, Jean-Luc Martinot, Francesca Biondo, Dimitri Papadopoulos Orfanos, Gunter Schumann, Robert Whelan, Vincent Frouin, Luise Poustka, Charlotte Nymberg Thunell, Tianye Jia, Congying Chu, Herta Flor, Bing Xu, Christian Büchel, Herve Lemaitre, Frauke Nees, Bernd Ittermann, Nicole Tay, Sylvane Desrivières, Arun L.W. Bokde, Sabina Millenet, Andreas Heinz, Henrik Walter, Hugh Garavan, Erin Burke Quinlan, Edward D. Barker, Juliane H. Fröhner, and Alex Ing
Subjects: Male, Adolescent, Grey matter, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, medicine, Attention deficit hyperactivity disorder, Humans, 0501 psychology and cognitive sciences, Gray Matter, Applied Psychology, Psychomotor Agitation, Neural correlates of consciousness, Sex Characteristics, Psychopathology, 05 social sciences, Motor control, Brain, Cognition, Strengths and Difficulties Questionnaire, medicine.disease, Magnetic Resonance Imaging, Psychiatry and Mental health, medicine.anatomical_structure, Attention Deficit Disorder with Hyperactivity, Female, Psychology, 030217 neurology & neurosurgery, Clinical psychology
Abstract: BackgroundSex-related differences in psychopathology are known phenomena, with externalizing and internalizing symptoms typically more common in boys and girls, respectively. However, the neural correlates of these sex-by-psychopathology interactions are underinvestigated, particularly in adolescence.MethodsParticipants were 14 years of age and part of the IMAGEN study, a large (N = 1526) community-based sample. To test for sex-by-psychopathology interactions in structural grey matter volume (GMV), we used whole-brain, voxel-wise neuroimaging analyses based on robust non-parametric methods. Psychopathological symptom data were derived from the Strengths and Difficulties Questionnaire (SDQ).ResultsWe found a sex-by-hyperactivity/inattention interaction in four brain clusters: right temporoparietal-opercular region (p < 0.01, Cohen's d = −0.24), bilateral anterior and mid-cingulum (p < 0.05, Cohen's d = −0.18), right cerebellum and fusiform (p < 0.05, Cohen's d = −0.20) and left frontal superior and middle gyri (p < 0.05, Cohen's d = −0.26). Higher symptoms of hyperactivity/inattention were associated with lower GMV in all four brain clusters in boys, and with higher GMV in the temporoparietal-opercular and cerebellar-fusiform clusters in girls.ConclusionsUsing a large, sex-balanced and community-based sample, our study lends support to the idea that externalizing symptoms of hyperactivity/inattention may be associated with different neural structures in male and female adolescents. The brain regions we report have been associated with a myriad of important cognitive functions, in particular, attention, cognitive and motor control, and timing, that are potentially relevant to understand the behavioural manifestations of hyperactive and inattentive symptoms. This study highlights the importance of considering sex in our efforts to uncover mechanisms underlying psychopathology during adolescence.
Published: 2021

43. Brain Signatures During Reward Anticipation Predict Persistent Attention-Deficit/Hyperactivity Disorder Symptoms

Author: Di Chen, Tianye Jia, Wei Cheng, Miao Cao, Tobias Banaschewski, Gareth J. Barker, Arun L.W. Bokde, Uli Bromberg, Christian Büchel, Sylvane Desrivières, Herta Flor, Antoine Grigis, Hugh Garavan, Penny A. Gowland, Andreas Heinz, Bernd Ittermann, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomáš Paus, Luise Poustka, Juliane H. Fröhner, Michael N. Smolka, Henrik Walter, Robert Whelan, T.W. Robbins, Barbara J. Sahakian, Gunter Schumann, Jianfeng Feng, and Penny Gowland
Subjects: Adult, Psychiatry and Mental health, Brain Mapping, Adolescent, Reward, Attention Deficit Disorder with Hyperactivity, Developmental and Educational Psychology, Brain, Humans, Child, Magnetic Resonance Imaging
Abstract: Children experiencing attention-deficit/hyperactivity disorder (ADHD) symptoms may retain symptoms into adulthood, but little is known about the underlying mechanism.To identify biomarkers of persistent ADHD symptom development, we carried out whole-brain analyses of neuroimaging data during the anticipation phase of the Monetary-Incentive-Delay (MID) task in 1,368 adolescents recruited by the IMAGEN Consortium at age 14 years, whose behavioral measurements were followed up longitudinally at age 16. In particular, we focused on comparing individuals with persistent high ADHD symptoms at both ages 14 and 16 years to unaffected control individuals, but also exploring which individuals demonstrating symptom remission (with high ADHD symptoms at age 14 but much reduced at age 16).We identified reduced activations in the medial frontal cortex and the thalamus during reward anticipation as neuro-biomarkers for persistent ADHD symptoms across time. The genetic relevance of the above findings was further supported by the associations of the polygenic risk scores of ADHD with both the persistent and control status and the activations of both brain regions. Furthermore, in an exploratory analysis, the thalamic activation might also help to distinguish persons with persistent ADHD from those remitted in both an exploratory sample (odds ratio = 9.43, p .001) and an independent generalization sample (odds ratio = 4.64, p = .003).Using a well-established and widely applied functional magnetic resonance imaging task, we have identified neural biomarkers that could discriminate ADHD symptoms that persist throughout adolescence from controls and potentially those likely to remit during adolescent development as well.
Published: 2021

44. Association of Genetic and Phenotypic Assessments With Onset of Disordered Eating Behaviors and Comorbid Mental Health Problems Among Adolescents

Author: Dimitri Papadopoulos Orfanos, Andreas Becker, Iain C. Campbell, Hugh Garavan, Zuo Zhang, Jani Penttilä, Betteke van Noort, Erin Burke Quinlan, Madeleine Irish, Marina Bobou, Nicole Tay, Gunter Schumann, Andreas Heinz, Sarah Hohmann, Corinna Insensee, Tianye Jia, Antoine Grigis, Ulrike Schmidt, Michael N. Smolka, Bernd Ittermann, Lauren Robinson, Juliane H. Fröhner, Henrik Walter, Frauke Nees, Jean-Luc Martinot, Tomáš Paus, Sylvane Desrivières, Luise Poustka, Argyris Stringaris, Tobias Banaschewski, Robert Whelan, Arun L.W. Bokde, Marie-Laure Paillère Martinot, Anna Roach, Yvonne Grimmer, and Edward D. Barker
Subjects: Male, Multifactorial Inheritance, Adolescent, Comorbidity, Anxiety, Feeding and Eating Disorders, 03 medical and health sciences, 0302 clinical medicine, Adolescent Psychiatry, Risk Factors, medicine, Genetics, Humans, 030212 general & internal medicine, Longitudinal Studies, Disordered eating, Original Investigation, Psychiatry, 2. Zero hunger, Psychiatric Status Rating Scales, Binge eating, business.industry, Depression, Research, Mental Disorders, Genomics, General Medicine, medicine.disease, Neuroticism, 3. Good health, 030227 psychiatry, Substance abuse, Europe, Online Only, Eating disorders, Mental Health, Phenotype, Adolescent Behavior, Female, medicine.symptom, business, Stress, Psychological, Demography, Dieting
Abstract: Key Points Question Do associations exist between disordered eating behaviors and other mental health disorders in adolescence, and if so, to what extent are those associations genetically predisposed? Findings Longitudinal assessments in this cohort study of a population-based sample of 1623 adolescents indicated that body mass index (BMI), neuroticism, impulse control, and addiction-related behaviors at 14 years of age were differentially associated with future disordered eating behaviors and symptoms of depression and generalized anxiety. Genetic analyses suggested etiologic overlaps between BMI, neuroticism, and attention-deficit/hyperactivity disorder with dieting, binge eating, and purging, respectively. Meaning Genetic and phenotypic assessments of BMI, impulse control problems, and personality may inform early and differential diagnoses of eating disorders., Importance Eating disorders are serious mental disorders with increasing prevalence. Without early identification and treatment, eating disorders may run a long-term course. Objective To characterize any associations among disordered eating behaviors (DEBs) and other mental health disorders and to identify early associations with the development of symptoms over time. Design, Setting, and Participants This multicenter, population-based, longitudinal cohort study used data from baseline (collected in 2010), follow-up 1 (collected in 2012), and follow-up 2 (collected in 2015) of the IMAGEN Study, which included adolescents recruited from 8 European sites. The present study assessed data from 1623 healthy adolescents, aged 14 years at baseline, recruited from high schools. Data analyses were performed from January 2018 to September 2019. Main Outcomes and Measures Body mass index (BMI), mental health symptoms, substance use behaviors, and personality variables were investigated as time-varying associations of DEBs (dieting, binge eating, and purging) or change in BMI over time. Polygenic risk scores were calculated to investigate genetic contributions associated with BMI, attention-deficit/hyperactivity disorder (ADHD) and neuroticism to DEBs. Results In this cohort study of 1623 adolescents (829 girls [51.1%]) recruited at a mean (SD) age of 14.5 (0.4) years and followed up at ages 16 and 19 years, 278 adolescents (17.1%) reported binge eating, 334 adolescents (20.6%) reported purging, and 356 adolescents (21.9%) reported dieting at 14, 16, or 19 years. Among the precursors of DEBs, high BMI was associated with future dieting (OR, 3.44; 95% CI, 2.09-5.65). High levels of neuroticism (OR, 1.04; 95% CI, 1.01-1.06), conduct problems (OR, 1.41; 95% CI, 1.17-1.69), and deliberate self-harm (OR, 2.18; 95% CI, 1.37-3.45) were associated with future binge eating. Low agreeableness (OR, 0.95; 95% CI, 0.92-0.97), deliberate self-harm (OR, 2.59; 95% CI, 1.69-3.95), conduct problems (OR, 1.42; 95% CI, 1.20-1.68), alcohol misuse (OR, 1.31; 95% CI, 1.10-1.54), and drug abuse (OR, 2.91; 95% CI, 1.78-4.74) were associated with future purging. Polygenetic risk scores for BMI were associated with dieting (at 14 years: OR, 1.27; lower bound 95% CI, 1.08; at 16 years: OR, 1.38; lower bound 95% CI, 1.17); ADHD, with purging (at 16 years: OR, 1.25; lower bound 95% CI, 1.08; at 19 years, OR, 1.23; lower bound 95% CI, 1.06); and neuroticism, with binge eating (at 14 years: OR, 1.32; lower bound 95% CI, 1.11; at 16 years: OR, 1.24; lower bound 95% CI, 1.06), highlighting distinct etiologic overlaps between these traits. The DEBs predated other mental health problems, with dieting at 14 years associated with future symptoms of depression (OR, 2.53; 95% CI, 1.56-4.10), generalized anxiety (OR, 2.27; 95% CI, 1.14-4.51), deliberate self-harm (OR, 2.10; 95% CI, 1.51-4.24), emotional problems (OR, 1.24; 95% CI, 1.08-1.43), and smoking (OR, 2.16; 95% CI, 1.36-3.48). Purging at 14 years was also associated with future depression (OR, 2.87; 95% CI, 1.69-5.01) and anxiety (OR, 2.48; 95% CI, 1.49-4.12) symptoms. Conclusions and Relevance The findings of this study delineate temporal associations and shared etiologies among DEBs and other mental health disorders and emphasize the potential of genetic and phenotypical assessments of obesity, behavioral disorders, and neuroticism to improve early and differential diagnosis of eating disorders., This cohort study across numerous European sites assesses whether associations and shared etiologies exist between disordered eating behaviors (dieting, purging, and binge eating) and other mental health disorders in early adolescence.
Published: 2020

45. ENIGMA and global neuroscience:A decade of large-scale studies of the brain in health and disease across more than 40 countries

Author: Frank G. Hillary, Esther Walton, Gunter Schumann, Sophia I. Thomopoulos, Patricia J. Conrod, Nic J.A. van der Wee, Daqiang Sun, Charlotte A.M. Cecil, Robin Bülow, Henry Völzke, Rachel M. Brouwer, Yann Chye, Katrina L. Grasby, Ingrid Agartz, Bernhard T. Baune, Josselin Houenou, Simon E. Fisher, Mark S. Shiroishi, Daan van Rooij, Miguel E. Rentería, Yanli Zhang-James, Courtney A. Filippi, Stephen V. Faraone, Sara Bertolín, Elisabeth A. Wilde, Eus J.W. Van Someren, Christopher R.K. Ching, Iliyan Ivanov, Barbara Franke, Derrek P. Hibar, Tiffany C. Ho, Hilleke E. Hulshoff Pol, Norbert Hosten, Ilya M. Veer, Daniel Garijo, Jean-Paul Fouche, Inga K. Koerte, Hans J. Grabe, Carles Soriano-Mas, Lianne Schmaal, Brenda Bartnik-Olson, Amanda K. Tilot, Sinead Kelly, Ysbrand D. van der Werf, Anderson M. Winkler, Henrik Walter, Hugh Garavan, Max A. Laansma, Agnes B. McMahon, Laura K.M. Han, Natalia Shatokhina, Scott Mackey, David F. Tate, Jason L. Stein, Thomas Frodl, Tiril P. Gurholt, Carrie E. Bearden, Katharina Wittfeld, Carrie R. McDonald, Andrew R. Mayer, Yolanda Gil, Jun Soo Kwon, Tomas Hajek, Jan K. Buitelaar, Moji Aghajani, Bhim M. Adhikari, Premika S.W. Boedhoe, Graeme Fairchild, Maria Jalbrzikowski, Alexander Olsen, Carolien G.F. de Kovel, Talia M. Nir, Mojtaba Zarei, Karen Caeyenberghs, Dirk J.A. Smit, Fabio Macciardi, Jeanne Leerssen, Margaret J. Wright, Eduard T. Klapwijk, Elena Pozzi, Lisa T. Eyler, Abraham Nunes, Sanjay M. Sisodiya, Clyde Francks, Emily L. Dennis, Rajendra A. Morey, Pauline Favre, Sophia Frangou, Boris A. Gutman, Merel Postema, Ida E Sønderby, Ian H. Harding, Julio E. Villalon-Reina, Sook-Lei Liew, Peter Kochunov, Celia van der Merwe, Je-Yeon Yun, David C. Glahn, Stefan Ehrlich, George A Karkashadze, Jian Chen, Nils Opel, Tianye Jia, Peristera Paschou, Xiangzhen Kong, Marieke Klein, Leyla Namazova-Baranova, Sylvane Desrivières, Danai Dima, Masoud Tahmasian, Dennis Hernaus, Sven C. Mueller, Gemma Modinos, Guido van Wingen, Ulrike Lueken, Ole A. Andreassen, Jonathan D. Rohrer, Lauren E. Salminen, Laura A. Berner, Eileen Luders, Georg Homuth, Stephane A. De Brito, Martine Hoogman, Federica Piras, Carrie Esopenko, Laura S van Velzen, Janna Marie Bas-Hoogendam, Udo Dannlowski, Mark W. Logue, Willem B Bruin, André Aleman, Sarah E. Medland, Neeltje E.M. van Haren, Theo G.M. van Erp, Sean N. Hatton, Laurena Holleran, Gary Donohoe, Alexander P. Lin, Rebecca C. Knickmeyer, Leonardo Tozzi, Fabrizio Pizzagalli, Kevin Hilbert, Sonja M C de Zwarte, Dick J. Veltman, Gianfranco Spalletta, Daniel S. Pine, Tim Hahn, Pratik Mukherjee, Alexander Teumer, Joanna Bright, Andre Altmann, Neda Jahanshad, James H. Cole, Arielle R. Baskin-Sommers, Odile A. van den Heuvel, Dan J. Stein, Vladimir Zelman, Lei Wang, Ronald A. Cohen, Joseph O' Neill, David Baron, Fabrizio Piras, Robert R. Althoff, Nynke A. Groenewold, Philipp G. Sämann, Christopher D. Whelan, Jessica A. Turner, Janita Bralten, Guohao Zhang, Paul M. Thompson, and Netherlands Institute for Neuroscience (NIN)
Subjects: DISORDER, Scientific community, Review Article, bepress|Life Sciences|Neuroscience and Neurobiology, 0302 clinical medicine, SCHIZOPHRENIA, Medicine and Health Sciences, GENETIC INFLUENCES, ENDOPHENOTYPE CONCEPT, Cervell, VOLUMES, RISK, Psychiatry, 0303 health sciences, 05 social sciences, Brain, Genomics, Magnetic Resonance Imaging, WORKING, 3. Good health, ALZHEIMERS-DISEASE, Psychiatry and Mental health, Eating disorders, Dissociative identity disorder, Biometris, Neurology, Conduct disorder, Schizophrenia, Major depressive disorder, Anxiety, medicine.symptom, Psychology, Neuroinformatics, Neuroimaging, 050105 experimental psychology, 150 000 MR Techniques in Brain Function, lcsh:RC321-571, Neurologia, 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 3 - Good Health and Well-being, MEGA-ANALYSIS, medicine, Life Science, Humans, 0501 psychology and cognitive sciences, ddc:610, Psiquiatria, Bipolar disorder, diagnostic imaging [Brain], lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, bepress|Life Sciences|Neuroscience and Neurobiology|Other Neuroscience and Neurobiology, Biological Psychiatry, 030304 developmental biology, Depressive Disorder, Major, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], genetics [Depressive Disorder, Major], Reproducibility of Results, OBSESSIVE-COMPULSIVE DISORDER, medicine.disease, PsyArXiv|Neuroscience, PsyArXiv|Neuroscience|Other Neuroscience and Neurobiology, RC0321, HERITABILITY ANALYSIS, Autism, Psychiatric disorders, Neuroscience, Biomarkers, 030217 neurology & neurosurgery
Abstract: This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of “big data” (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA’s activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.
Published: 2020

46. Increased brain volume from higher cereal and lower coffee intake: Shared genetic determinants and impacts on cognition and metabolism

Author: Waxman D, Cong-Huan Shen, Jujiao Kang, Barbara J. Sahakian, Wei Cheng, Tianye Jia, Jianfeng Feng, Zeyu Jiao, and Xie C
Subjects: Gerontology, medicine.medical_specialty, Research ethics, Mediation (statistics), business.industry, Public health, Cognition, medicine.disease, Affect (psychology), Biobank, Informed consent, Brain size, medicine, Dementia, Psychology, business, Body mass index, Cohort study
Abstract: Background: It is unclear how different diets may affect human brain development and if genetic and environmental factors play a part. Methods: We used cross-sectional observational data from UK Biobank. Only white British individuals free of Alzheimer's or dementia diseases were included in the study. We conducted linear regression analysis and mediation models to examine the association between diets, gerey matter volume, genetic variants, lifestyle, and metabolic measures. We tested the association between the GMV-association patterns of the cereal/coffee intake, the GMV-association patterns of cognitive functions and the gene-expression patterns. Findings: Overall, 336517 participants were included in our analysis. We discovered anti-correlated brain-wide grey matter volume (GMV)-association patterns between coffee and cereal intake, coincidence with their anti-correlated genetic constructs. These genetic factors may further affect people’s lifestyle habits and body/blood fat levels through the mediation of cereal/coffee intake, and the brain-wide expression pattern of gene CPLX3, a dedicated marker of subplate neurons that regulate cortical development and plasticity, may underlie the shared GMV-association patterns among the coffee/cereal intake and cognitive functions. Interpretation: Our findings thus revealed that high-cereal and low-coffee diets shared similar brain and genetic constructs, leading to long-term beneficial associations regarding cognitive, BMI and other metabolic measures. This study has important implications for public health, especially during the pandemic, given the poorer outcomes of COVID-19 patients with greater BMIs. Funding Statement: This work received support from the following sources: the National Key Research and Development Program of China (2018YFC1312900 and 2019YFA0709502), the National Natural Science Foundation of China (91630314 and 81801773), the 111 Project (B18015), The Key Project of Shanghai Science &Technology Innovation Plan(16JC1420402), the Shanghai Municipal Science and Technology Major Project (2018SHZDZX01) and Zhangjiang Lab. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All participants provided written informed consent to UK Biobank. The UK Biobank study received ethical approval from the NHS National Research Ethics Service North West (reference number: 16/NW/0274). Data access permission was granted under UKB application 19542 (PI Jianfeng Feng).
Published: 2020

47. Multicenter Evaluation of the Xpert Carba-R Assay for Detection and Identification of Carbapenemase Genes in Sputum Specimens

Author: Mei Zhao, Xin Zhang, Bin Shan, Hongyu Fu, Wei Jia, Yi-Wei Tang, Jia Tao, Bin Huang, Hua Yu, Fen Qu, Zhen Cai, Hong Du, Liang Chen, and Tianye Jia
Subjects: Microbiology (medical), Microbiological culture, biology, Klebsiella pneumoniae, Enterobacteriaceae Infections, Sputum, Bacteriology, Klebsiella oxytoca, Carbapenem-resistant enterobacteriaceae, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, biology.organism_classification, beta-Lactamases, Citrobacter freundii, Microbiology, Carbapenem-Resistant Enterobacteriaceae, Bacterial Proteins, medicine, Humans, Multiplex, medicine.symptom, Enterobacter cloacae
Abstract: Rapid diagnosis of infections caused by carbapenem-resistant Enterobacteriaceae (CRE) is crucial for proper treatment and infection control. The Xpert Carba-R assay is a qualitative multiplex real-time PCR method that qualitatively detects and differentiates five common carbapenemase genes (bla(KPC), bla(NDM), bla(VIM), bla(OXA-48), and bla(IMP)) directly from rectal swabs or purified colonies within approximately 1 h. We performed a multicenter evaluation of the investigational use of the Carba-R assay for detection and differentiation of carbapenemase genes from sputum specimens in patients with a clinical diagnosis of pneumonia. The intra- and interassay coefficients of variation values for the Carba-R assay were 0.2% to 2.0% and 1.4% to 2.3%, respectively. A total of 301 sputum specimens were collected and tested. Compared to bacterial culture followed by PCR identification of resistance genes from colonies, the Carba-R assay reduced turnaround time from 56 to 84 h to less than 2 h. Carbapenemase genes were detected by the Carba-R assay in Klebsiella pneumoniae (n = 236), Escherichia coli (n = 22), Enterobacter cloacae (n = 23), Klebsiella oxytoca (n = 8), Serratia marcescens (n = 6), Citrobacter freundii (n = 4), and Klebsiella aerogenes (n = 2). The Carba-R assay detected 112 bla(KPC) (33.5%), 70 bla(NDM) (21.0%), 8 bla(IMP) (2.4%), and 2 bla(VIM) (0.6%) genes, with positive percent agreement, negative percent agreement, and concordance rates of 92.9%, 86.7%, and 88.3%, respectively, for the dominant bla(KPC) and 85.0%, 87.8%, and 87.4%, respectively, for the bla(NDM) genes. Neither method detected the bla(OXA-48) carbapenemase gene. The convenient, rapid, and simple characteristics of the Xpert Carba-R assay make it a potential tool for CRE detection and identification directly in sputum specimens.
Published: 2020

48. Assessing Overall Reproducibility for Large-scale High-throughput MRI-based Association Studies

Author: Jujiao Kang, Jianfeng Feng, Sylvane Desrivières, Andreas Heinz, Yinglei Lai, Gunter Schumann, Zeyu Jiao, Liang Ma, Tianye Jia, Chao Xie, Wei Cheng, Weikang Gong, and Fengzhu Sun
Subjects: Reproducibility, medicine.diagnostic_test, business.industry, Sample size determination, Medicine, Magnetic resonance imaging, business, Genetic association, Biomedical engineering
Abstract: Magnetic Resonance Imaging (MRI) technology has been increasingly used in large-scale association studies. Reproducibility of statistically significant findings generated by MRI-based association studies, especially structural MRI (sMRI) and functional MRI (fMRI), has been recently heavily debated. However, there is still a lack of overall reproducibility assessment for MRI-based association studies. It is also crucial to elucidate the relationship between overall reproducibility and sample size in an experimental design. In this study, we proposed an overall reproducibility index for large-scale high-throughput MRI-based association studies. We performed the overall reproducibility assessments for several recent large sMRI/fMRI databases and observed satisfactory overall reproducibility. Furthermore, we performed the sample size evaluation for the purpose of achieving a desirable overall reproducibility. Additionally, we evaluated the overall reproducibility of GMV changes for UKB vs. PPMI and UKB vs. HCP. We demonstrated that both sample size and some experimental factors play important roles in the overall reproducibility for different experiments. In summary, a systematic assessment of overall reproducibility is fundamental and crucial in the current large-scale high-throughput MRI-based research.
Published: 2020

49. 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

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

Author: Chao Xie, Tianye Jia, Edmund T. Rolls, Trevor W. Robbins, Barbara J. Sahakian, Jie Zhang, Zhaowen Liu, Wei Cheng, Qiang Luo, Chun-Yi Zac Lo, He Wang, Tobias Banaschewski, Gareth J. Barker, Arun L.W. Bokde, Christian Büchel, Erin Burke Quinlan, Sylvane Desrivières, Herta Flor, Antoine Grigis, Hugh Garavan, Penny Gowland, Andreas Heinz, Sarah Hohmann, Bernd Ittermann, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomáš Paus, Luise Poustka, Juliane H. Fröhner, Michael N. Smolka, Henrik Walter, Robert Whelan, Gunter Schumann, Jianfeng Feng, Eric Artiges, Semiha Aydin, Alexis Barbot, Gareth Barker, Andreas Becker, Pauline Bezivin-Frere, Francesca Biondo, Arun Bokde, Congying Chu, Patricia Conrod, Laura Daedelow, Jeffrey Dalley, Sylvane Desrivieres, Eoin Dooley, Irina Filippi, Ariane Fillmer, Juliane Fröhner, Vincent Frouin, Yvonne Grimmer, Albrecht Ihlenfeld, Alex Ing, Corinna Isensee, Hervé Lemaitre, Emma Lethbridge, Sabina Millenet, Sarah Miller, Ruben Miranda, Marie-Laure Paillere, Dimitri Papadopoulos, Zdenka Pausova, Jani Pentilla, Jean-Baptiste Poline, Erin Burke, Michael Rapp, Trevor Robbins, Gabriel Robert, John Rogers, Barbara Ruggeri, Michael Smolka, Argyris Stringaris, Betteke van Noort, Roux Simon, Steve Williams, Yuning Zhang, and IMAGEN Consortium
Subjects: Adult, medicine.medical_specialty, Adolescent, Reward anticipation, RJ, Cognitive Neuroscience, Population, Prefrontal Cortex, Audiology, Adolescents, Monetary incentive delay task, 050105 experimental psychology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Reward, Reward sensitivity, Orbitofrontal cortex, Medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, education, Biological Psychiatry, Depression (differential diagnoses), Depressive symptoms, education.field_of_study, business.industry, Depression, musculoskeletal, neural, and ocular physiology, 05 social sciences, Ventral striatum, Nonreward sensitivity, QP, Magnetic Resonance Imaging, Frontal Lobe, medicine.anatomical_structure, nervous system, Cohort, Neurology (clinical), business, psychological phenomena and processes, 030217 neurology & neurosurgery, RC
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.
Published: 2020

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