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1. Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup

Author: Huggins, Ashley A, Baird, C Lexi, Briggs, Melvin, Laskowitz, Sarah, Hussain, Ahmed, Fouda, Samar, Haswell, Courtney, Sun, Delin, Salminen, Lauren E, Jahanshad, Neda, Thomopoulos, Sophia I, Veltman, Dick J, Frijling, Jessie L, Olff, Miranda, van Zuiden, Mirjam, Koch, Saskia BJ, Nawjin, Laura, Wang, Li, Zhu, Ye, Li, Gen, Stein, Dan J, Ipser, Jonathan, Seedat, Soraya, du Plessis, Stefan, van den Heuvel, Leigh L, Suarez-Jimenez, Benjamin, Zhu, Xi, Kim, Yoojean, He, Xiaofu, Zilcha-Mano, Sigal, Lazarov, Amit, Neria, Yuval, Stevens, Jennifer S, Ressler, Kerry J, Jovanovic, Tanja, van Rooij, Sanne JH, Fani, Negar, Hudson, Anna R, Mueller, Sven C, Sierk, Anika, Manthey, Antje, Walter, Henrik, Daniels, Judith K, Schmahl, Christian, Herzog, Julia I, Říha, Pavel, Rektor, Ivan, Lebois, Lauren AM, Kaufman, Milissa L, Olson, Elizabeth A, Baker, Justin T, Rosso, Isabelle M, King, Anthony P, Liberzon, Isreal, Angstadt, Mike, Davenport, Nicholas D, Sponheim, Scott R, Disner, Seth G, Straube, Thomas, Hofmann, David, Qi, Rongfeng, Lu, Guang Ming, Baugh, Lee A, Forster, Gina L, Simons, Raluca M, Simons, Jeffrey S, Magnotta, Vincent A, Fercho, Kelene A, Maron-Katz, Adi, Etkin, Amit, Cotton, Andrew S, O’Leary, Erin N, Xie, Hong, Wang, Xin, Quidé, Yann, El-Hage, Wissam, Lissek, Shmuel, Berg, Hannah, Bruce, Steven, Cisler, Josh, Ross, Marisa, Herringa, Ryan J, Grupe, Daniel W, Nitschke, Jack B, Davidson, Richard J, Larson, Christine L, deRoon-Cassini, Terri A, Tomas, Carissa W, Fitzgerald, Jacklynn M, Blackford, Jennifer Urbano, Olatunji, Bunmi O, Kremen, William S, Lyons, Michael J, Franz, Carol E, Gordon, Evan M, May, Geoffrey, Nelson, Steven M, Abdallah, Chadi G, Levy, Ifat, and Harpaz-Rotem, Ilan
Subjects: Clinical and Health Psychology, Psychology, Brain Disorders, Neurosciences, Mental Illness, Mind and Body, Behavioral and Social Science, Mental Health, Anxiety Disorders, Post-Traumatic Stress Disorder (PTSD), Mental health, Humans, Stress Disorders, Post-Traumatic, Cerebellum, Female, Male, Adult, Magnetic Resonance Imaging, Middle Aged, White Matter, Gray Matter, Organ Size, Deep Learning, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract: Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR
Published: 2024

2. Synthesizing study-specific controls using generative models on open access datasets for harmonized multi-study analyses

Author: Gadewar, Shruti P., Zhu, Alyssa H., Gari, Iyad Ba, Somu, Sunanda, Thomopoulos, Sophia I., Thompson, Paul M., Nir, Talia M., and Jahanshad, Neda
Subjects: Quantitative Biology - Quantitative Methods
Abstract: Neuroimaging consortia can enhance reliability and generalizability of findings by pooling data across studies to achieve larger sample sizes. To adjust for site and MRI protocol effects, imaging datasets are often harmonized based on healthy controls. When data from a control group were not collected, statistical harmonization options are limited as patient characteristics and acquisition-related variables may be confounded. Here, in a multi-study neuroimaging analysis of Alzheimer's patients and controls, we tested whether it is possible to generate synthetic control MRIs. For one case-control study, we used a generative adversarial model for style-based harmonization to generate site-specific controls. Downstream feature extraction, statistical harmonization and group-level multi-study case-control and case-only analyses were performed twice, using either true or synthetic controls. All effect sizes using synthetic controls overlapped with those based on true study controls. This line of work may facilitate wider inclusion of case-only studies in multi-study consortia.
Published: 2024

3. Cortical microstructural associations with CSF amyloid and pTau

Author: Nir, Talia M, Villalón-Reina, Julio E, Salminen, Lauren E, Haddad, Elizabeth, Zheng, Hong, Thomopoulos, Sophia I, Jack, Clifford R, Weiner, Michael W, Thompson, Paul M, and Jahanshad, Neda
Subjects: Biomedical and Clinical Sciences, Biological Psychology, Clinical and Health Psychology, Clinical Sciences, Psychology, Brain Disorders, Behavioral and Social Science, Clinical Research, Basic Behavioral and Social Science, Acquired Cognitive Impairment, Aging, Dementia, Neurodegenerative, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurosciences, Biomedical Imaging, 2.1 Biological and endogenous factors, Aetiology, Neurological, Aged, Aged, 80 and over, Female, Humans, Male, Alzheimer Disease, Amyloid, Amyloid beta-Peptides, Biomarkers, Brain, Cerebral Cortex, Cognitive Dysfunction, Diffusion Magnetic Resonance Imaging, Gray Matter, Neuroimaging, Peptide Fragments, tau Proteins, Middle Aged, Alzheimer’s Disease Neuroimaging Initiative, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract: Diffusion MRI (dMRI) can be used to probe microstructural properties of brain tissue and holds great promise as a means to non-invasively map Alzheimer's disease (AD) pathology. Few studies have evaluated multi-shell dMRI models such as neurite orientation dispersion and density imaging (NODDI) and mean apparent propagator (MAP)-MRI in cortical gray matter where many of the earliest histopathological changes occur in AD. Here, we investigated the relationship between CSF pTau181 and Aβ1-42 burden and regional cortical NODDI and MAP-MRI indices in 46 cognitively unimpaired individuals, 18 with mild cognitive impairment, and two with dementia (mean age: 71.8 ± 6.2 years) from the Alzheimer's Disease Neuroimaging Initiative. We compared findings to more conventional cortical thickness measures. Lower CSF Aβ1-42 and higher pTau181 were associated with cortical dMRI measures reflecting less hindered or restricted diffusion and greater diffusivity. Cortical dMRI measures, but not cortical thickness measures, were more widely associated with Aβ1-42 than pTau181 and better distinguished Aβ+ from Aβ- participants than pTau+ from pTau- participants. dMRI associations mediated the relationship between CSF markers and delayed logical memory performance, commonly impaired in early AD. dMRI metrics sensitive to early AD pathogenesis and microstructural damage may be better measures of subtle neurodegeneration in comparison to standard cortical thickness and help to elucidate mechanisms underlying cognitive decline.
Published: 2024

4. DenseNet and Support Vector Machine classifications of major depressive disorder using vertex-wise cortical features

Author: Belov, Vladimir, Erwin-Grabner, Tracy, Zeng, Ling-Li, Ching, Christopher R. K., Aleman, Andre, Amod, Alyssa R., Basgoze, Zeynep, Benedetti, Francesco, Besteher, Bianca, Brosch, Katharina, Bülow, Robin, Colle, Romain, Connolly, Colm G., Corruble, Emmanuelle, Couvy-Duchesne, Baptiste, Cullen, Kathryn, Dannlowski, Udo, Davey, Christopher G., Dols, Annemiek, Ernsting, Jan, Evans, Jennifer W., Fisch, Lukas, Fuentes-Claramonte, Paola, Gonul, Ali Saffet, Gotlib, Ian H., Grabe, Hans J., Groenewold, Nynke A., Grotegerd, Dominik, Hahn, Tim, Hamilton, J. Paul, Han, Laura K. M., Harrison, Ben J, Ho, Tiffany C., Jahanshad, Neda, Jamieson, Alec J., Karuk, Andriana, Kircher, Tilo, Klimes-Dougan, Bonnie, Koopowitz, Sheri-Michelle, Lancaster, Thomas, Leenings, Ramona, Li, Meng, Linden, David E. J., MacMaster, Frank P., Mehler, David M. A., Meinert, Susanne, Melloni, Elisa, Mueller, Bryon A., Mwangi, Benson, Nenadić, Igor, Ojha, Amar, Okamoto, Yasumasa, Oudega, Mardien L., Penninx, Brenda W. J. H., Poletti, Sara, Pomarol-Clotet, Edith, Portella, Maria J., Pozzi, Elena, Radua, Joaquim, Rodríguez-Cano, Elena, Sacchet, Matthew D., Salvador, Raymond, Schrantee, Anouk, Sim, Kang, Soares, Jair C., Solanes, Aleix, Stein, Dan J., Stein, Frederike, Stolicyn, Aleks, Thomopoulos, Sophia I., Toenders, Yara J., Uyar-Demir, Aslihan, Vieta, Eduard, Vives-Gilabert, Yolanda, Völzke, Henry, Walter, Martin, Whalley, Heather C., Whittle, Sarah, Winter, Nils, Wittfeld, Katharina, Wright, Margaret J., Wu, Mon-Ju, Yang, Tony T., Zarate, Carlos, Veltman, Dick J., Schmaal, Lianne, Thompson, Paul M., and Goya-Maldonado, Roberto
Subjects: Quantitative Biology - Quantitative Methods, Computer Science - Machine Learning, Quantitative Biology - Neurons and Cognition
Abstract: Major depressive disorder (MDD) is a complex psychiatric disorder that affects the lives of hundreds of millions of individuals around the globe. Even today, researchers debate if morphological alterations in the brain are linked to MDD, likely due to the heterogeneity of this disorder. The application of deep learning tools to neuroimaging data, capable of capturing complex non-linear patterns, has the potential to provide diagnostic and predictive biomarkers for MDD. However, previous attempts to demarcate MDD patients and healthy controls (HC) based on segmented cortical features via linear machine learning approaches have reported low accuracies. In this study, we used globally representative data from the ENIGMA-MDD working group containing an extensive sample of people with MDD (N=2,772) and HC (N=4,240), which allows a comprehensive analysis with generalizable results. Based on the hypothesis that integration of vertex-wise cortical features can improve classification performance, we evaluated the classification of a DenseNet and a Support Vector Machine (SVM), with the expectation that the former would outperform the latter. As we analyzed a multi-site sample, we additionally applied the ComBat harmonization tool to remove potential nuisance effects of site. We found that both classifiers exhibited close to chance performance (balanced accuracy DenseNet: 51%; SVM: 53%), when estimated on unseen sites. Slightly higher classification performance (balanced accuracy DenseNet: 58%; SVM: 55%) was found when the cross-validation folds contained subjects from all sites, indicating site effect. In conclusion, the integration of vertex-wise morphometric features and the use of the non-linear classifier did not lead to the differentiability between MDD and HC. Our results support the notion that MDD classification on this combination of features and classifiers is unfeasible.
Published: 2023

5. Video and Synthetic MRI Pre-training of 3D Vision Architectures for Neuroimage Analysis

Author: Dhinagar, Nikhil J., Singh, Amit, Ozarkar, Saket, Buwa, Ketaki, Thomopoulos, Sophia I., Owens-Walton, Conor, Laltoo, Emily, Chen, Yao-Liang, Cook, Philip, McMillan, Corey, Tsai, Chih-Chien, Wang, J-J, Wu, Yih-Ru, and Thompson, Paul M.
Subjects: Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Artificial Intelligence, Computer Science - Computer Vision and Pattern Recognition
Abstract: Transfer learning represents a recent paradigm shift in the way we build artificial intelligence (AI) systems. In contrast to training task-specific models, transfer learning involves pre-training deep learning models on a large corpus of data and minimally fine-tuning them for adaptation to specific tasks. Even so, for 3D medical imaging tasks, we do not know if it is best to pre-train models on natural images, medical images, or even synthetically generated MRI scans or video data. To evaluate these alternatives, here we benchmarked vision transformers (ViTs) and convolutional neural networks (CNNs), initialized with varied upstream pre-training approaches. These methods were then adapted to three unique downstream neuroimaging tasks with a range of difficulty: Alzheimer's disease (AD) and Parkinson's disease (PD) classification, "brain age" prediction. Experimental tests led to the following key observations: 1. Pre-training improved performance across all tasks including a boost of 7.4% for AD classification and 4.6% for PD classification for the ViT and 19.1% for PD classification and reduction in brain age prediction error by 1.26 years for CNNs, 2. Pre-training on large-scale video or synthetic MRI data boosted performance of ViTs, 3. CNNs were robust in limited-data settings, and in-domain pretraining enhanced their performances, 4. Pre-training improved generalization to out-of-distribution datasets and sites. Overall, we benchmarked different vision architectures, revealing the value of pre-training them with emerging datasets for model initialization. The resulting pre-trained models can be adapted to a range of downstream neuroimaging tasks, even when training data for the target task is limited.
Published: 2023

6. Linking Symptom Inventories using Semantic Textual Similarity

Author: Kennedy, Eamonn, Vadlamani, Shashank, Lindsey, Hannah M, Peterson, Kelly S, OConnor, Kristen Dams, Murray, Kenton, Agarwal, Ronak, Amiri, Houshang H, Andersen, Raeda K, Babikian, Talin, Baron, David A, Bigler, Erin D, Caeyenberghs, Karen, Delano-Wood, Lisa, Disner, Seth G, Dobryakova, Ekaterina, Eapen, Blessen C, Edelstein, Rachel M, Esopenko, Carrie, Genova, Helen M, Geuze, Elbert, Goodrich-Hunsaker, Naomi J, Grafman, Jordan, Haberg, Asta K, Hodges, Cooper B, Hoskinson, Kristen R, Hovenden, Elizabeth S, Irimia, Andrei, Jahanshad, Neda, Jha, Ruchira M, Keleher, Finian, Kenney, Kimbra, Koerte, Inga K, Liebel, Spencer W, Livny, Abigail, Lovstad, Marianne, Martindale, Sarah L, Max, Jeffrey E, Mayer, Andrew R, Meier, Timothy B, Menefee, Deleene S, Mohamed, Abdalla Z, Mondello, Stefania, Monti, Martin M, Morey, Rajendra A, Newcombe, Virginia, Newsome, Mary R, Olsen, Alexander, Pastorek, Nicholas J, Pugh, Mary Jo, Razi, Adeel, Resch, Jacob E, Rowland, Jared A, Russell, Kelly, Ryan, Nicholas P, Scheibel, Randall S, Schmidt, Adam T, Spitz, Gershon, Stephens, Jaclyn A, Tal, Assaf, Talbert, Leah D, Tartaglia, Maria Carmela, Taylor, Brian A, Thomopoulos, Sophia I, Troyanskaya, Maya, Valera, Eve M, van der Horn, Harm Jan, Van Horn, John D, Verma, Ragini, Wade, Benjamin SC, Walker, Willian SC, Ware, Ashley L, Werner Jr, J Kent, Yeates, Keith Owen, Zafonte, Ross D, Zeineh, Michael M, Zielinski, Brandon, Thompson, Paul M, Hillary, Frank G, Tate, David F, Wilde, Elisabeth A, and Dennis, Emily L
Subjects: Computer Science - Computation and Language, Computer Science - Artificial Intelligence
Abstract: An extensive library of symptom inventories has been developed over time to measure clinical symptoms, but this variety has led to several long standing issues. Most notably, results drawn from different settings and studies are not comparable, which limits reproducibility. Here, we present an artificial intelligence (AI) approach using semantic textual similarity (STS) to link symptoms and scores across previously incongruous symptom inventories. We tested the ability of four pre-trained STS models to screen thousands of symptom description pairs for related content - a challenging task typically requiring expert panels. Models were tasked to predict symptom severity across four different inventories for 6,607 participants drawn from 16 international data sources. The STS approach achieved 74.8% accuracy across five tasks, outperforming other models tested. This work suggests that incorporating contextual, semantic information can assist expert decision-making processes, yielding gains for both general and disease-specific clinical assessment.
Published: 2023

7. White matter diffusion estimates in obsessive-compulsive disorder across 1653 individuals: machine learning findings from the ENIGMA OCD Working Group

Author: Kim, Bo-Gyeom, Kim, Gakyung, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie, Anticevic, Alan, Arnold, Paul D., Balachander, Srinivas, Banaj, Nerisa, Bargalló, Nuria, Batistuzzo, Marcelo C., Benedetti, Francesco, Bertolín, Sara, Beucke, Jan Carl, Bollettini, Irene, Brem, Silvia, Brennan, Brian P., Buitelaar, Jan K., Calvo, Rosa, Castelo-Branco, Miguel, Cheng, Yuqi, Chhatkuli, Ritu Bhusal, Ciullo, Valentina, Coelho, Ana, Couto, Beatriz, Dallaspezia, Sara, Ely, Benjamin A., Ferreira, Sónia, Fontaine, Martine, Fouche, Jean-Paul, Grazioplene, Rachael, Gruner, Patricia, Hagen, Kristen, Hansen, Bjarne, Hanna, Gregory L., Hirano, Yoshiyuki, Höxter, Marcelo Q., Hough, Morgan, Hu, Hao, Huyser, Chaim, Ikuta, Toshikazu, Jahanshad, Neda, James, Anthony, Jaspers-Fayer, Fern, Kasprzak, Selina, Kathmann, Norbert, Kaufmann, Christian, Kim, Minah, Koch, Kathrin, Kvale, Gerd, Kwon, Jun Soo, Lazaro, Luisa, Lee, Junhee, Lochner, Christine, Lu, Jin, Manrique, Daniela Rodriguez, Martínez-Zalacaín, Ignacio, Masuda, Yoshitada, Matsumoto, Koji, Maziero, Maria Paula, Menchón, Jose M., Minuzzi, Luciano, Moreira, Pedro Silva, Morgado, Pedro, Narayanaswamy, Janardhanan C., Narumoto, Jin, Ortiz, Ana E., Ota, Junko, Pariente, Jose C., Perriello, Chris, Picó-Pérez, Maria, Pittenger, Christopher, Poletti, Sara, Real, Eva, Reddy, Y. C. Janardhan, van Rooij, Daan, Sakai, Yuki, Sato, João Ricardo, Segalas, Cinto, Shavitt, Roseli G., Shen, Zonglin, Shimizu, Eiji, Shivakumar, Venkataram, Soreni, Noam, Soriano-Mas, Carles, Sousa, Nuno, Sousa, Mafalda Machado, Spalletta, Gianfranco, Stern, Emily R., Stewart, S. Evelyn, Szeszko, Philip R., Thomas, Rajat, Thomopoulos, Sophia I., Vecchio, Daniela, Venkatasubramanian, Ganesan, Vriend, Chris, Walitza, Susanne, Wang, Zhen, Watanabe, Anri, Wolters, Lidewij, Xu, Jian, Yamada, Kei, Yun, Je-Yeon, Zarei, Mojtaba, Zhao, Qing, Zhu, Xi, Thompson, Paul M., Bruin, Willem B., van Wingen, Guido A., Piras, Federica, Piras, Fabrizio, Stein, Dan J., van den Heuvel, Odile A., Simpson, Helen Blair, Marsh, Rachel, and Cha, Jiook
Published: 2024
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8. Determinants of cognitive and brain resilience to tau pathology: a longitudinal analysis

Author: Bocancea, Diana I, Svenningsson, Anna L, van Loenhoud, Anna C, Groot, Colin, Barkhof, Frederik, Strandberg, Olof, Smith, Ruben, Weiner, Michael W, Aisen, Paul, Petersen, Ronald, Jack, Clifford R, Jagust, William, Trojanowki, John Q, Toga, Arthur W, Beckett, Laurel, Green, Robert C, Saykin, Andrew J, Morris, John C, Perrin, Richard J, Shaw, Leslie M, Khachaturian, Zaven, Carrillo, Maria, Potter, William, Barnes, Lisa, Bernard, Marie, González, Hector, Ho, Carole, Hsiao, John K, Jackson, Jonathan, Masliah, Eliezer, Masterman, Donna, Okonkwo, Ozioma, Ryan, Laurie, Silverberg, Nina, Fleisher, Adam, Sacrey, Diana Truran, Fockler, Juliet, Conti, Cat, Veitch, Dallas, Neuhaus, John, Jin, Chengshi, Nosheny, Rachel, Ashford, Miriam, Flenniken, Derek, Kormo, Adrienne, Montine, Tom, Conti, Cat B, Rafii, Michael, Raman, Rema, Jimenez, Gustavo, Donohue, Michael, Gessert, Devon, Salazar, Jennifer, Zimmerman, Caileigh, Cabrera, Yuliana, Walter, Sarah, Miller, Garrett, Coker, Godfrey, Clanton, Taylor, Hergesheimer, Lindsey, Smith, Stephanie, Adegoke, Olusegun, Mahboubi, Payam, Moore, Shelley, Pizzola, Jeremy, Shaffer, Elizabeth, Harvey, Danielle, Forghanian-Arani, Arvin, Borowski, Bret, Ward, Chad, Schwarz, Christopher, Jones, David, Gunter, Jeff, Kantarci, Kejal, Senjem, Matthew, Vemuri, Prashanthi, Reid, Robert, Fox, Nick C, Malone, Ian, Thompson, Paul, Thomopoulos, Sophia I, Nir, Talia M, Jahanshad, Neda, DeCarli, Charles, Knaack, Alexander, Fletcher, Evan, Tosun-Turgut, Duygu, Chen, Stephanie Rossi, Choe, Mark, and Crawfor, Karen
Subjects: Health Sciences, Dementia, Vascular Cognitive Impairment/Dementia, Biomedical Imaging, Aging, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Behavioral and Social Science, Alzheimer's Disease, Neurodegenerative, Cerebrovascular, Alzheimer's Disease Related Dementias (ADRD), Clinical Research, Brain Disorders, Neurosciences, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Neurological, Mental health, Humans, Alzheimer Disease, Longitudinal Studies, tau Proteins, Cross-Sectional Studies, Cerebral Cortical Thinning, Positron-Emission Tomography, Brain, Cognition, Apolipoproteins E, Alzheimer's disease, tau, resilience, cognition, PET, MRI, Alzheimer’s Disease Neuroimaging Initiative, Alzheimer’s disease, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences, Psychology
Abstract: Mechanisms of resilience against tau pathology in individuals across the Alzheimer's disease spectrum are insufficiently understood. Longitudinal data are necessary to reveal which factors relate to preserved cognition (i.e. cognitive resilience) and brain structure (i.e. brain resilience) despite abundant tau pathology, and to clarify whether these associations are cross-sectional or longitudinal. We used a longitudinal study design to investigate the role of several demographic, biological and brain structural factors in yielding cognitive and brain resilience to tau pathology as measured with PET. In this multicentre study, we included 366 amyloid-β-positive individuals with mild cognitive impairment or Alzheimer's disease dementia with baseline 18F-flortaucipir-PET and longitudinal cognitive assessments. A subset (n = 200) additionally underwent longitudinal structural MRI. We used linear mixed-effects models with global cognition and cortical thickness as dependent variables to investigate determinants of cognitive resilience and brain resilience, respectively. Models assessed whether age, sex, years of education, APOE-ε4 status, intracranial volume (and cortical thickness for cognitive resilience models) modified the association of tau pathology with cognitive decline or cortical thinning. We found that the association between higher baseline tau-PET levels (quantified in a temporal meta-region of interest) and rate of cognitive decline (measured with repeated Mini-Mental State Examination) was adversely modified by older age (Stβinteraction = -0.062, P = 0.032), higher education level (Stβinteraction = -0.072, P = 0.011) and higher intracranial volume (Stβinteraction = -0.07, P = 0.016). Younger age, higher education and greater cortical thickness were associated with better cognitive performance at baseline. Greater cortical thickness was furthermore associated with slower cognitive decline independent of tau burden. Higher education also modified the negative impact of tau-PET on cortical thinning, while older age was associated with higher baseline cortical thickness and slower rate of cortical thinning independent of tau. Our analyses revealed no (cross-sectional or longitudinal) associations for sex and APOE-ε4 status on cognition and cortical thickness. In this longitudinal study of clinically impaired individuals with underlying Alzheimer's disease neuropathological changes, we identified education as the most robust determinant of both cognitive and brain resilience against tau pathology. The observed interaction with tau burden on cognitive decline suggests that education may be protective against cognitive decline and brain atrophy at lower levels of tau pathology, with a potential depletion of resilience resources with advancing pathology. Finally, we did not find major contributions of sex to brain nor cognitive resilience, suggesting that previous links between sex and resilience might be mainly driven by cross-sectional differences.
Published: 2023

9. The ENIGMA-Neuroendocrinology working group to bridge gaps in female mental health research

Author: Heller, Carina, Barth, Claudia, Silk, Tim J., Vijayakumar, Nandita, Carmona, Susana, Martínez-García, Magdalena, Kikinis, Zora, Thomopoulos, Sophia I., Jahanshad, Neda, Salminen, Lauren, Lawrence, Katherine, Thompson, Paul M., and Petersen, Nicole
Published: 2024
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10. Efficiently Training Vision Transformers on Structural MRI Scans for Alzheimer's Disease Detection

Author: Dhinagar, Nikhil J., Thomopoulos, Sophia I., Laltoo, Emily, and Thompson, Paul M.
Subjects: Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Artificial Intelligence, Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning, Quantitative Biology - Quantitative Methods
Abstract: Neuroimaging of large populations is valuable to identify factors that promote or resist brain disease, and to assist diagnosis, subtyping, and prognosis. Data-driven models such as convolutional neural networks (CNNs) have increasingly been applied to brain images to perform diagnostic and prognostic tasks by learning robust features. Vision transformers (ViT) - a new class of deep learning architectures - have emerged in recent years as an alternative to CNNs for several computer vision applications. Here we tested variants of the ViT architecture for a range of desired neuroimaging downstream tasks based on difficulty, in this case for sex and Alzheimer's disease (AD) classification based on 3D brain MRI. In our experiments, two vision transformer architecture variants achieved an AUC of 0.987 for sex and 0.892 for AD classification, respectively. We independently evaluated our models on data from two benchmark AD datasets. We achieved a performance boost of 5% and 9-10% upon fine-tuning vision transformer models pre-trained on synthetic (generated by a latent diffusion model) and real MRI scans, respectively. Our main contributions include testing the effects of different ViT training strategies including pre-training, data augmentation and learning rate warm-ups followed by annealing, as pertaining to the neuroimaging domain. These techniques are essential for training ViT-like models for neuroimaging applications where training data is usually limited. We also analyzed the effect of the amount of training data utilized on the test-time performance of the ViT via data-model scaling curves.
Published: 2023

11. Normative Aging for an Individual’s Full Brain MRI Using Style GANs to Detect Localized Neurodegeneration

Author: Gadewar, Shruti P., Zhu, Alyssa H., Somu, Sunanda, Ramesh, Abhinaav, Gari, Iyad Ba, Thomopoulos, Sophia I., Thompson, Paul M., Nir, Talia M., Jahanshad, Neda, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Cao, Xiaohuan, editor, Xu, Xuanang, editor, Rekik, Islem, editor, Cui, Zhiming, editor, and Ouyang, Xi, editor
Published: 2024
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12. Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study

Author: Si, Shuqing, Bi, Anbreen, Yu, Zhaoying, See, Cheryl, Kelly, Sinead, Ambrogi, Sonia, Arango, Celso, Baeza, Inmaculada, Banaj, Nerisa, Berk, Michael, Castro-Fornieles, Josefina, Crespo-Facorro, Benedicto, Crouse, Jacob J., Díaz-Caneja, Covadonga M., Fett, Anne-Kathrin, Fortea, Adriana, Frangou, Sophia, Goldstein, Benjamin I., Hickie, Ian B., Janssen, Joost, Kennedy, Kody G., Krabbendam, Lydia, Kyriakopoulos, Marinos, MacIntosh, Bradley J., Morgado, Pedro, Nerland, Stener, Pascual-Diaz, Saül, Picó-Pérez, Maria, Piras, Fabrizio, Rund, Bjørn Rishovd, de la Serna, Elena, Spalletta, Gianfranco, Sugranyes, Gisela, Suo, Chao, Tordesillas-Gutiérrez, Diana, Vecchio, Daniela, Radua, Joaquim, McGuire, Philip, Thomopoulos, Sophia I., Jahanshad, Neda, Thompson, Paul M., Barth, Claudia, Agartz, Ingrid, James, Anthony, and Kempton, Matthew J.
Published: 2024
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13. Examining the association between posttraumatic stress disorder and disruptions in cortical networks identified using data-driven methods

Author: Yang, Jin, Huggins, Ashley A., Sun, Delin, Baird, C. Lexi, Haswell, Courtney C., Frijling, Jessie L., Olff, Miranda, van Zuiden, Mirjam, Koch, Saskia B. J., Nawijn, Laura, Veltman, Dick J., Suarez-Jimenez, Benjamin, Zhu, Xi, Neria, Yuval, Hudson, Anna R., Mueller, Sven C., Baker, Justin T., Lebois, Lauren A. M., Kaufman, Milissa L., Qi, Rongfeng, Lu, Guang Ming, Říha, Pavel, Rektor, Ivan, Dennis, Emily L., Ching, Christopher R. K., Thomopoulos, Sophia I., Salminen, Lauren E., Jahanshad, Neda, Thompson, Paul M., Stein, Dan J., Koopowitz, Sheri M., Ipser, Jonathan C., Seedat, Soraya, du Plessis, Stefan, van den Heuvel, Leigh L., Wang, Li, Zhu, Ye, Li, Gen, Sierk, Anika, Manthey, Antje, Walter, Henrik, Daniels, Judith K., Schmahl, Christian, Herzog, Julia I., Liberzon, Israel, King, Anthony, Angstadt, Mike, Davenport, Nicholas D., Sponheim, Scott R., Disner, Seth G., Straube, Thomas, Hofmann, David, Grupe, Daniel W., Nitschke, Jack B., Davidson, Richard J., Larson, Christine L., deRoon-Cassini, Terri A., Blackford, Jennifer U., Olatunji, Bunmi O., Gordon, Evan M., May, Geoffrey, Nelson, Steven M., Abdallah, Chadi G., Levy, Ifat, Harpaz-Rotem, Ilan, Krystal, John H., Morey, Rajendra A., and Sotiras, Aristeidis
Published: 2024
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14. Brain-based classification of youth with anxiety disorders: transdiagnostic examinations within the ENIGMA-Anxiety database using machine learning

Author: Bruin, Willem B., Zhutovsky, Paul, van Wingen, Guido A., Bas-Hoogendam, Janna Marie, Groenewold, Nynke A., Hilbert, Kevin, Winkler, Anderson M., Zugman, Andre, Agosta, Federica, Åhs, Fredrik, Andreescu, Carmen, Antonacci, Chase, Asami, Takeshi, Assaf, Michal, Barber, Jacques P., Bauer, Jochen, Bavdekar, Shreya Y., Beesdo-Baum, Katja, Benedetti, Francesco, Bernstein, Rachel, Björkstrand, Johannes, Blair, Robert J., Blair, Karina S., Blanco-Hinojo, Laura, Böhnlein, Joscha, Brambilla, Paolo, Bressan, Rodrigo A., Breuer, Fabian, Cano, Marta, Canu, Elisa, Cardinale, Elise M., Cardoner, Narcís, Cividini, Camilla, Cremers, Henk, Dannlowski, Udo, Diefenbach, Gretchen J., Domschke, Katharina, Doruyter, Alexander G. G., Dresler, Thomas, Erhardt, Angelika, Filippi, Massimo, Fonzo, Gregory A., Freitag, Gabrielle F., Furmark, Tomas, Ge, Tian, Gerber, Andrew J., Gosnell, Savannah N., Grabe, Hans J., Grotegerd, Dominik, Gur, Ruben C., Gur, Raquel E., Hamm, Alfons O., Han, Laura K. M., Harper, Jennifer C., Harrewijn, Anita, Heeren, Alexandre, Hofmann, David, Jackowski, Andrea P., Jahanshad, Neda, Jett, Laura, Kaczkurkin, Antonia N., Khosravi, Parmis, Kingsley, Ellen N., Kircher, Tilo, Kostic, Milutin, Larsen, Bart, Lee, Sang-Hyuk, Leehr, Elisabeth J., Leibenluft, Ellen, Lochner, Christine, Lui, Su, Maggioni, Eleonora, Manfro, Gisele G., Månsson, Kristoffer N. T., Marino, Claire E., Meeten, Frances, Milrod, Barbara, Jovanovic, Ana Munjiza, Mwangi, Benson, Myers, Michael J., Neufang, Susanne, Nielsen, Jared A., Ohrmann, Patricia A., Ottaviani, Cristina, Paulus, Martin P., Perino, Michael T., Phan, K. Luan, Poletti, Sara, Porta-Casteràs, Daniel, Pujol, Jesus, Reinecke, Andrea, Ringlein, Grace V., Rjabtsenkov, Pavel, Roelofs, Karin, Salas, Ramiro, Salum, Giovanni A., Satterthwaite, Theodore D., Schrammen, Elisabeth, Sindermann, Lisa, Smoller, Jordan W., Soares, Jair C., Stark, Rudolf, Stein, Frederike, Straube, Thomas, Straube, Benjamin, Strawn, Jeffrey R., Suarez-Jimenez, Benjamin, Sylvester, Chad M., Talati, Ardesheer, Thomopoulos, Sophia I., Tükel, Raşit, van Nieuwenhuizen, Helena, Werwath, Kathryn, Wittfeld, Katharina, Wright, Barry, Wu, Mon-Ju, Yang, Yunbo, Zilverstand, Anna, Zwanzger, Peter, Blackford, Jennifer U., Avery, Suzanne N., Clauss, Jacqueline A., Lueken, Ulrike, Thompson, Paul M., Pine, Daniel S., Stein, Dan J., van der Wee, Nic J. A., Veltman, Dick J., and Aghajani, Moji
Published: 2024
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15. Altered lateralization of the cingulum in deployment‐related traumatic brain injury: An ENIGMA military‐relevant brain injury study

Author: Dennis, Emily L, Newsome, Mary R, Lindsey, Hannah M, Adamson, Maheen, Austin, Tara A, Disner, Seth G, Eapen, Blessen C, Esopenko, Carrie, Franz, Carol E, Geuze, Elbert, Haswell, Courtney, Hinds, Sidney R, Hodges, Cooper B, Irimia, Andrei, Kenney, Kimbra, Koerte, Inga K, Kremen, William S, Levin, Harvey S, Morey, Rajendra A, Ollinger, John, Rowland, Jared A, Scheibel, Randall S, Shenton, Martha E, Sullivan, Danielle R, Talbert, Leah D, Thomopoulos, Sophia I, Troyanskaya, Maya, Walker, William C, Wang, Xin, Ware, Ashley L, Werner, John Kent, Williams, Wright, Thompson, Paul M, Tate, David F, and Wilde, Elisabeth A
Subjects: Traumatic Head and Spine Injury, Brain Disorders, Biomedical Imaging, Neurosciences, Traumatic Brain Injury (TBI), Mental Health, Physical Injury - Accidents and Adverse Effects, Evaluation of treatments and therapeutic interventions, 6.6 Psychological and behavioural, Neurological, Mental health, Humans, Adult, White Matter, Neuropsychological Tests, Brain Injuries, Brain Injuries, Traumatic, Brain, DTI, military, traumatic brain injury, Cognitive Sciences, Experimental Psychology
Abstract: Traumatic brain injury (TBI) in military populations can cause disruptions in brain structure and function, along with cognitive and psychological dysfunction. Diffusion magnetic resonance imaging (dMRI) can detect alterations in white matter (WM) microstructure, but few studies have examined brain asymmetry. Examining asymmetry in large samples may increase sensitivity to detect heterogeneous areas of WM alteration in mild TBI. Through the Enhancing Neuroimaging Genetics Through Meta-Analysis Military-Relevant Brain Injury working group, we conducted a mega-analysis of neuroimaging and clinical data from 16 cohorts of Active Duty Service Members and Veterans (n = 2598). dMRI data were processed together along with harmonized demographic, injury, psychiatric, and cognitive measures. Fractional anisotropy in the cingulum showed greater asymmetry in individuals with deployment-related TBI, driven by greater left lateralization in TBI. Results remained significant after accounting for potentially confounding variables including posttraumatic stress disorder, depression, and handedness, and were driven primarily by individuals whose worst TBI occurred before age 40. Alterations in the cingulum were also associated with slower processing speed and poorer set shifting. The results indicate an enhancement of the natural left laterality of the cingulum, possibly due to vulnerability of the nondominant hemisphere or compensatory mechanisms in the dominant hemisphere. The cingulum is one of the last WM tracts to mature, reaching peak FA around 42 years old. This effect was primarily detected in individuals whose worst injury occurred before age 40, suggesting that the protracted development of the cingulum may lead to increased vulnerability to insults, such as TBI.
Published: 2023

16. In vivo white matter microstructure in adolescents with early-onset psychosis: a multi-site mega-analysis

Author: Barth, Claudia, Kelly, Sinead, Nerland, Stener, Jahanshad, Neda, Alloza, Clara, Ambrogi, Sonia, Andreassen, Ole A, Andreou, Dimitrios, Arango, Celso, Baeza, Inmaculada, Banaj, Nerisa, Bearden, Carrie E, Berk, Michael, Bohman, Hannes, Castro-Fornieles, Josefina, Chye, Yann, Crespo-Facorro, Benedicto, de la Serna, Elena, Díaz-Caneja, Covadonga M, Gurholt, Tiril P, Hegarty, Catherine E, James, Anthony, Janssen, Joost, Johannessen, Cecilie, Jönsson, Erik G, Karlsgodt, Katherine H, Kochunov, Peter, Lois, Noemi G, Lundberg, Mathias, Myhre, Anne M, Pascual-Diaz, Saül, Piras, Fabrizio, Smelror, Runar E, Spalletta, Gianfranco, Stokkan, Therese S, Sugranyes, Gisela, Suo, Chao, Thomopoulos, Sophia I, Tordesillas-Gutiérrez, Diana, Vecchio, Daniela, Wedervang-Resell, Kirsten, Wortinger, Laura A, Thompson, Paul M, and Agartz, Ingrid
Subjects: Brain Disorders, Serious Mental Illness, Pediatric, Biomedical Imaging, Clinical Research, Neurosciences, Mental Health, Schizophrenia, Mental health, Good Health and Well Being, Female, Humans, Male, Adolescent, White Matter, Diffusion Tensor Imaging, Brain, Psychotic Disorders, Anisotropy, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset
Published: 2023

17. Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium.

Author: Constantinides, Constantinos, Han, Laura KM, Alloza, Clara, Antonucci, Linda Antonella, Arango, Celso, Ayesa-Arriola, Rosa, Banaj, Nerisa, Bertolino, Alessandro, Borgwardt, Stefan, Bruggemann, Jason, Bustillo, Juan, Bykhovski, Oleg, Calhoun, Vince, Carr, Vaughan, Catts, Stanley, Chung, Young-Chul, Crespo-Facorro, Benedicto, Díaz-Caneja, Covadonga M, Donohoe, Gary, Plessis, Stefan Du, Edmond, Jesse, Ehrlich, Stefan, Emsley, Robin, Eyler, Lisa T, Fuentes-Claramonte, Paola, Georgiadis, Foivos, Green, Melissa, Guerrero-Pedraza, Amalia, Ha, Minji, Hahn, Tim, Henskens, Frans A, Holleran, Laurena, Homan, Stephanie, Homan, Philipp, Jahanshad, Neda, Janssen, Joost, Ji, Ellen, Kaiser, Stefan, Kaleda, Vasily, Kim, Minah, Kim, Woo-Sung, Kirschner, Matthias, Kochunov, Peter, Kwak, Yoo Bin, Kwon, Jun Soo, Lebedeva, Irina, Liu, Jingyu, Mitchie, Patricia, Michielse, Stijn, Mothersill, David, Mowry, Bryan, de la Foz, Víctor Ortiz-García, Pantelis, Christos, Pergola, Giulio, Piras, Fabrizio, Pomarol-Clotet, Edith, Preda, Adrian, Quidé, Yann, Rasser, Paul E, Rootes-Murdy, Kelly, Salvador, Raymond, Sangiuliano, Marina, Sarró, Salvador, Schall, Ulrich, Schmidt, André, Scott, Rodney J, Selvaggi, Pierluigi, Sim, Kang, Skoch, Antonin, Spalletta, Gianfranco, Spaniel, Filip, Thomopoulos, Sophia I, Tomecek, David, Tomyshev, Alexander S, Tordesillas-Gutiérrez, Diana, van Amelsvoort, Therese, Vázquez-Bourgon, Javier, Vecchio, Daniela, Voineskos, Aristotle, Weickert, Cynthia S, Weickert, Thomas, Thompson, Paul M, Schmaal, Lianne, van Erp, Theo GM, Turner, Jessica, Cole, James H, ENIGMA Schizophrenia Consortium, Dima, Danai, and Walton, Esther
Subjects: ENIGMA Schizophrenia Consortium, Brain, Humans, Magnetic Resonance Imaging, Prospective Studies, Schizophrenia, Aging, Adolescent, Adult, Aged, Middle Aged, Female, Male, Young Adult, Mental Health, Serious Mental Illness, Brain Disorders, Neurosciences, Biomedical Imaging, Clinical Research, Behavioral and Social Science, Neurological, Mental health, Good Health and Well Being, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18-72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18-73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen's d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.
Published: 2023

18. Preliminary validation of a structural magnetic resonance imaging metric for tracking dementia-related neurodegeneration and future decline

Author: Kress, Gavin T, Popa, Emily S, Thompson, Paul M, Bookheimer, Susan Y, Thomopoulos, Sophia I, Ching, Christopher RK, Zheng, Hong, Hirsh, Daniel A, Merrill, David A, Panos, Stella E, Raji, Cyrus A, Siddarth, Prabha, and Bramen, Jennifer E
Subjects: Biological Psychology, Psychology, Biomedical Imaging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Neurosciences, Aging, Dementia, Alzheimer's Disease, Neurodegenerative, Behavioral and Social Science, Acquired Cognitive Impairment, 4.1 Discovery and preclinical testing of markers and technologies, 2.1 Biological and endogenous factors, Neurological, Humans, Aged, Alzheimer Disease, Neurodegenerative Diseases, Temporal Lobe, Magnetic Resonance Imaging, Cognitive Dysfunction, Atrophy, Disease Progression, Mild cognitive impairment, Alzheimer's disease, Magnetic resonance imaging, Biomarker, Alzheimer’s disease, Biological psychology, Clinical and health psychology
Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline and atrophy in the medial temporal lobe (MTL) and subsequent brain regions. Structural magnetic resonance imaging (sMRI) has been widely used in research and clinical care for diagnosis and monitoring AD progression. However, atrophy patterns are complex and vary by patient. To address this issue, researchers have made efforts to develop more concise metrics that can summarize AD-specific atrophy. Many of these methods can be difficult to interpret clinically, hampering adoption. In this study, we introduce a novel index which we call an "AD-NeuroScore," that uses a modified Euclidean-inspired distance function to calculate differences between regional brain volumes associated with cognitive decline. The index is adjusted for intracranial volume (ICV), age, sex, and scanner model. We validated AD-NeuroScore using 929 older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, with a mean age of 72.7 years (SD = 6.3; 55.1-91.5) and cognitively normal (CN), mild cognitive impairment (MCI), or AD diagnoses. Our validation results showed that AD-NeuroScore was significantly associated with diagnosis and disease severity scores (measured by MMSE, CDR-SB, and ADAS-11) at baseline. Furthermore, baseline AD-NeuroScore was associated with both changes in diagnosis and disease severity scores at all time points with available data. The performance of AD-NeuroScore was equivalent or superior to adjusted hippocampal volume (AHV), a widely used metric in AD research. Further, AD-NeuroScore typically performed as well as or sometimes better when compared to other existing sMRI-based metrics. In conclusion, we have introduced a new metric, AD-NeuroScore, which shows promising results in detecting AD, benchmarking disease severity, and predicting disease progression. AD-NeuroScore differentiates itself from other metrics by being clinically practical and interpretable.
Published: 2023

19. Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures

Author: Belov, Vladimir, Erwin-Grabner, Tracy, Gonul, Ali Saffet, Amod, Alyssa R., Ojha, Amar, Aleman, Andre, Dols, Annemiek, Scharntee, Anouk, Uyar-Demir, Aslihan, Harrison, Ben J, Irungu, Benson M., Besteher, Bianca, Klimes-Dougan, Bonnie, Penninx, Brenda W. J. H., Mueller, Bryon A., Zarate, Carlos, Davey, Christopher G., Ching, Christopher R. K., Connolly, Colm G., Fu, Cynthia H. Y., Stein, Dan J., Dima, Danai, Linden, David E. J., Mehler, David M. A., Pomarol-Clotet, Edith, Pozzi, Elena, Melloni, Elisa, Benedetti, Francesco, MacMaster, Frank P., Grabe, Hans J., Völzke, Henry, Gotlib, Ian H., Soares, Jair C., Evans, Jennifer W., Sim, Kang, Wittfeld, Katharina, Cullen, Kathryn, Reneman, Liesbeth, Oudega, Mardien L., Wright, Margaret J., Portella, Maria J., Sacchet, Matthew D., Li, Meng, Aghajani, Moji, Wu, Mon-Ju, Jaworska, Natalia, Jahanshad, Neda, van der Wee, Nic J. A., Groenewold, Nynke, Hamilton, Paul J., Saemann, Philipp, Bülow, Robin, Poletti, Sara, Whittle, Sarah, Thomopoulos, Sophia I., van, Steven J. A., Werff, der, Koopowitz, Sheri-Michelle, Lancaster, Thomas, Ho, Tiffany C., Yang, Tony T., Basgoze, Zeynep, Veltman, Dick J., Schmaal, Lianne, Thompson, Paul M., and Goya-Maldonado, Roberto
Subjects: Quantitative Biology - Quantitative Methods
Abstract: Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (n=5,356) to provide a generalizable ML classification benchmark of major depressive disorder (MDD). Using brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD vs healthy controls (HC) with around 62% balanced accuracy, but when harmonizing the data using ComBat balanced accuracy dropped to approximately 52%. Similar results were observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may achieve more encouraging prospects., Comment: main document 37 pages; supplementary material 24 pages
Published: 2022

20. Cortical morphology in patients with the deficit and non-deficit syndrome of schizophrenia: a worldwide meta- and mega-analyses

Author: Banaj, Nerisa, Vecchio, Daniela, Piras, Fabrizio, De Rossi, Pietro, Bustillo, Juan, Ciufolini, Simone, Dazzan, Paola, Di Forti, Marta, Dickie, Erin W., Ford, Judith M., Fuentes-Claramonte, Paola, Gruber, Oliver, Guerrero-Pedraza, Amalia, Hamilton, Holly K., Howells, Fleur M., Kraemer, Bernd, Lawrie, Stephen M., Mathalon, Daniel H., Murray, Robin, Pomarol-Clotet, Edith, Potkin, Steven G., Preda, Adrian, Radua, Joaquim, Richter, Anja, Salvador, Raymond, Sawa, Akira, Scheffler, Freda, Sim, Kang, Spaniel, Filip, Stein, Dan J., Temmingh, Henk S., Thomopoulos, Sophia I., Tomecek, David, Uhlmann, Anne, Voineskos, Aristotle, Yang, Kun, Jahanshad, Neda, Thompson, Paul M., Van Erp, Theo G. M., Turner, Jessica A., Spalletta, Gianfranco, and Piras, Federica
Published: 2023
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21. The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium

Author: Bruin, Willem B., Abe, Yoshinari, Alonso, Pino, Anticevic, Alan, Backhausen, Lea L., Balachander, Srinivas, Bargallo, Nuria, Batistuzzo, Marcelo C., Benedetti, Francesco, Bertolin Triquell, Sara, Brem, Silvia, Calesella, Federico, Couto, Beatriz, Denys, Damiaan A. J. P., Echevarria, Marco A. N., Eng, Goi Khia, Ferreira, Sónia, Feusner, Jamie D., Grazioplene, Rachael G., Gruner, Patricia, Guo, Joyce Y., Hagen, Kristen, Hansen, Bjarne, Hirano, Yoshiyuki, Hoexter, Marcelo Q., Jahanshad, Neda, Jaspers-Fayer, Fern, Kasprzak, Selina, Kim, Minah, Koch, Kathrin, Bin Kwak, Yoo, Kwon, Jun Soo, Lazaro, Luisa, Li, Chiang-Shan R., Lochner, Christine, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Menchon, Jose M., Moreira, Pedro S., Morgado, Pedro, Nakagawa, Akiko, Nakao, Tomohiro, Narayanaswamy, Janardhanan C., Nurmi, Erika L., Zorrilla, Jose C. Pariente, Piacentini, John, Picó-Pérez, Maria, Piras, Fabrizio, Piras, Federica, Pittenger, Christopher, Reddy, Janardhan Y. C., Rodriguez-Manrique, Daniela, Sakai, Yuki, Shimizu, Eiji, Shivakumar, Venkataram, Simpson, Blair H., Soriano-Mas, Carles, Sousa, Nuno, Spalletta, Gianfranco, Stern, Emily R., Evelyn Stewart, S., Szeszko, Philip R., Tang, Jinsong, Thomopoulos, Sophia I., Thorsen, Anders L., Yoshida, Tokiko, Tomiyama, Hirofumi, Vai, Benedetta, Veer, Ilya M., Venkatasubramanian, Ganesan, Vetter, Nora C., Vriend, Chris, Walitza, Susanne, Waller, Lea, Wang, Zhen, Watanabe, Anri, Wolff, Nicole, Yun, Je-Yeon, Zhao, Qing, van Leeuwen, Wieke A., van Marle, Hein J. F., van de Mortel, Laurens A., van der Straten, Anouk, van der Werf, Ysbrand D., Thompson, Paul M., Stein, Dan J., van den Heuvel, Odile A., and van Wingen, Guido A.
Published: 2023
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22. A comparison of methods to harmonize cortical thickness measurements across scanners and sites

Author: Sun, Delin, Rakesh, Gopalkumar, Haswell, Courtney C, Logue, Mark, Baird, C Lexi, O'Leary, Erin N, Cotton, Andrew S, Xie, Hong, Tamburrino, Marijo, Chen, Tian, Dennis, Emily L, Jahanshad, Neda, Salminen, Lauren E, Thomopoulos, Sophia I, Rashid, Faisal, Ching, Christopher RK, Koch, Saskia BJ, Frijling, Jessie L, Nawijn, Laura, van Zuiden, Mirjam, Zhu, Xi, Suarez-Jimenez, Benjamin, Sierk, Anika, Walter, Henrik, Manthey, Antje, Stevens, Jennifer S, Fani, Negar, van Rooij, Sanne JH, Stein, Murray, Bomyea, Jessica, Koerte, Inga K, Choi, Kyle, van der Werff, Steven JA, Vermeiren, Robert RJM, Herzog, Julia, Lebois, Lauren AM, Baker, Justin T, Olson, Elizabeth A, Straube, Thomas, Korgaonkar, Mayuresh S, Andrew, Elpiniki, Zhu, Ye, Li, Gen, Ipser, Jonathan, Hudson, Anna R, Peverill, Matthew, Sambrook, Kelly, Gordon, Evan, Baugh, Lee, Forster, Gina, Simons, Raluca M, Simons, Jeffrey S, Magnotta, Vincent, Maron-Katz, Adi, du Plessis, Stefan, Disner, Seth G, Davenport, Nicholas, Grupe, Daniel W, Nitschke, Jack B, deRoon-Cassini, Terri A, Fitzgerald, Jacklynn M, Krystal, John H, Levy, Ifat, Olff, Miranda, Veltman, Dick J, Wang, Li, Neria, Yuval, De Bellis, Michael D, Jovanovic, Tanja, Daniels, Judith K, Shenton, Martha, van de Wee, Nic JA, Schmahl, Christian, Kaufman, Milissa L, Rosso, Isabelle M, Sponheim, Scott R, Hofmann, David Bernd, Bryant, Richard A, Fercho, Kelene A, Stein, Dan J, Mueller, Sven C, Hosseini, Bobak, Phan, K Luan, McLaughlin, Katie A, Davidson, Richard J, Larson, Christine L, May, Geoffrey, Nelson, Steven M, Abdallah, Chadi G, Gomaa, Hassaan, Etkin, Amit, Seedat, Soraya, Harpaz-Rotem, Ilan, Liberzon, Israel, van Erp, Theo GM, Quidé, Yann, Wang, Xin, Thompson, Paul M, and Morey, Rajendra A
Subjects: Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Child, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Stress Disorders, Post-Traumatic, Young Adult, Data Harmonization, Scanner Effects, Site Effects, Cortical Thickness, ComBat, ComBat-GAM, Linear Mixed-Effects Model, General Additive Model, PTSD, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract: Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants' demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LMEINT), (2) LME that models both site-specific random intercepts and age-related random slopes (LMEINT+SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2-81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3-85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (Χ2(3) = 63.704, p < 0.001) as well as case-control differences in age-related cortical thinning (Χ2(3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (Χ2(3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects.
Published: 2022

23. Multiscale neural gradients reflect transdiagnostic effects of major psychiatric conditions on cortical morphology

Author: Park, Bo-yong, Kebets, Valeria, Larivière, Sara, Hettwer, Meike D, Paquola, Casey, van Rooij, Daan, Buitelaar, Jan, Franke, Barbara, Hoogman, Martine, Schmaal, Lianne, Veltman, Dick J, van den Heuvel, Odile A, Stein, Dan J, Andreassen, Ole A, Ching, Christopher RK, Turner, Jessica A, van Erp, Theo GM, Evans, Alan C, Dagher, Alain, Thomopoulos, Sophia I, Thompson, Paul M, Valk, Sofie L, Kirschner, Matthias, and Bernhardt, Boris C
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Depression, Neurosciences, Behavioral and Social Science, Serious Mental Illness, Mental Health, Brain Disorders, Schizophrenia, 2.1 Biological and endogenous factors, Aetiology, Neurological, Mental health, Good Health and Well Being, Autism Spectrum Disorder, Connectome, Dopamine, Humans, Neural Pathways, Serotonin, Biological sciences, Biomedical and clinical sciences
Abstract: It is increasingly recognized that multiple psychiatric conditions are underpinned by shared neural pathways, affecting similar brain systems. Here, we carried out a multiscale neural contextualization of shared alterations of cortical morphology across six major psychiatric conditions (autism spectrum disorder, attention deficit/hyperactivity disorder, major depression disorder, obsessive-compulsive disorder, bipolar disorder, and schizophrenia). Our framework cross-referenced shared morphological anomalies with respect to cortical myeloarchitecture and cytoarchitecture, as well as connectome and neurotransmitter organization. Pooling disease-related effects on MRI-based cortical thickness measures across six ENIGMA working groups, including a total of 28,546 participants (12,876 patients and 15,670 controls), we identified a cortex-wide dimension of morphological changes that described a sensory-fugal pattern, with paralimbic regions showing the most consistent alterations across conditions. The shared disease dimension was closely related to cortical gradients of microstructure as well as neurotransmitter axes, specifically cortex-wide variations in serotonin and dopamine. Multiple sensitivity analyses confirmed robustness with respect to slight variations in analytical choices. Our findings embed shared effects of common psychiatric conditions on brain structure in multiple scales of brain organization, and may provide insights into neural mechanisms of transdiagnostic vulnerability.
Published: 2022

24. Normative Aging for an Individual’s Full Brain MRI Using Style GANs to Detect Localized Neurodegeneration

Author: Gadewar, Shruti P., primary, Zhu, Alyssa H., additional, Somu, Sunanda, additional, Ramesh, Abhinaav, additional, Gari, Iyad Ba, additional, Thomopoulos, Sophia I., additional, Thompson, Paul M., additional, Nir, Talia M., additional, and Jahanshad, Neda, additional
Published: 2023
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25. Correction: White matter diffusion estimates in obsessive-compulsive disorder across 1653 individuals: machine learning findings from the ENIGMA OCD Working Group

Author: Kim, Bo-Gyeom, Kim, Gakyung, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie, Anticevic, Alan, Arnold, Paul D., Balachander, Srinivas, Banaj, Nerisa, Bargalló, Nuria, Batistuzzo, Marcelo C., Benedetti, Francesco, Bertolín, Sara, Beucke, Jan Carl, Bollettini, Irene, Brem, Silvia, Brennan, Brian P., Buitelaar, Jan K., Calvo, Rosa, Castelo-Branco, Miguel, Cheng, Yuqi, Chhatkuli, Ritu Bhusal, Ciullo, Valentina, Coelho, Ana, Couto, Beatriz, Dallaspezia, Sara, Ely, Benjamin A., Ferreira, Sónia, Fontaine, Martine, Fouche, Jean-Paul, Grazioplene, Rachael, Gruner, Patricia, Hagen, Kristen, Hansen, Bjarne, Hanna, Gregory L., Hirano, Yoshiyuki, Höxter, Marcelo Q., Hough, Morgan, Hu, Hao, Huyser, Chaim, Ikuta, Toshikazu, Jahanshad, Neda, James, Anthony, Jaspers-Fayer, Fern, Kasprzak, Selina, Kathmann, Norbert, Kaufmann, Christian, Kim, Minah, Koch, Kathrin, Kvale, Gerd, Kwon, Jun Soo, Lazaro, Luisa, Lee, Junhee, Lochner, Christine, Lu, Jin, Manrique, Daniela Rodriguez, Martínez-Zalacaín, Ignacio, Masuda, Yoshitada, Matsumoto, Koji, Maziero, Maria Paula, Menchón, Jose M., Minuzzi, Luciano, Moreira, Pedro Silva, Morgado, Pedro, Narayanaswamy, Janardhanan C., Narumoto, Jin, Ortiz, Ana E., Ota, Junko, Pariente, Jose C., Perriello, Chris, Picó-Pérez, Maria, Pittenger, Christopher, Poletti, Sara, Real, Eva, Reddy, Y. C. Janardhan, van Rooij, Daan, Sakai, Yuki, Sato, João Ricardo, Segalas, Cinto, Shavitt, Roseli G., Shen, Zonglin, Shimizu, Eiji, Shivakumar, Venkataram, Soreni, Noam, Soriano-Mas, Carles, Sousa, Nuno, Sousa, Mafalda Machado, Spalletta, Gianfranco, Stern, Emily R., Stewart, S. Evelyn, Szeszko, Philip R., Thomas, Rajat, Thomopoulos, Sophia I., Vecchio, Daniela, Venkatasubramanian, Ganesan, Vriend, Chris, Walitza, Susanne, Wang, Zhen, Watanabe, Anri, Wolters, Lidewij, Xu, Jian, Yamada, Kei, Yun, Je-Yeon, Zarei, Mojtaba, Zhao, Qing, Zhu, Xi, Thompson, Paul M., Bruin, Willem B., van Wingen, Guido A., Piras, Federica, Piras, Fabrizio, Stein, Dan J., van den Heuvel, Odile A., Simpson, Helen Blair, Marsh, Rachel, and Cha, Jiook
Published: 2024
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26. Event‐based modeling in temporal lobe epilepsy demonstrates progressive atrophy from cross‐sectional data

Author: Lopez, Seymour M, Aksman, Leon M, Oxtoby, Neil P, Vos, Sjoerd B, Rao, Jun, Kaestner, Erik, Alhusaini, Saud, Alvim, Marina, Bender, Benjamin, Bernasconi, Andrea, Bernasconi, Neda, Bernhardt, Boris, Bonilha, Leonardo, Caciagli, Lorenzo, Caldairou, Benoit, Caligiuri, Maria Eugenia, Calvet, Angels, Cendes, Fernando, Concha, Luis, Conde‐Blanco, Estefania, Davoodi‐Bojd, Esmaeil, de Bézenac, Christophe, Delanty, Norman, Desmond, Patricia M, Devinsky, Orrin, Domin, Martin, Duncan, John S, Focke, Niels K, Foley, Sonya, Fortunato, Francesco, Galovic, Marian, Gambardella, Antonio, Gleichgerrcht, Ezequiel, Guerrini, Renzo, Hamandi, Khalid, Ives‐Deliperi, Victoria, Jackson, Graeme D, Jahanshad, Neda, Keller, Simon S, Kochunov, Peter, Kotikalapudi, Raviteja, Kreilkamp, Barbara AK, Labate, Angelo, Larivière, Sara, Lenge, Matteo, Lui, Elaine, Malpas, Charles, Martin, Pascal, Mascalchi, Mario, Medland, Sarah E, Meletti, Stefano, Morita‐Sherman, Marcia E, Owen, Thomas W, Richardson, Mark, Riva, Antonella, Rüber, Theodor, Sinclair, Ben, Soltanian‐Zadeh, Hamid, Stein, Dan J, Striano, Pasquale, Taylor, Peter N, Thomopoulos, Sophia I, Thompson, Paul M, Tondelli, Manuela, Vaudano, Anna Elisabetta, Vivash, Lucy, Wang, Yujiang, Weber, Bernd, Whelan, Christopher D, Wiest, Roland, Winston, Gavin P, Yasuda, Clarissa Lin, McDonald, Carrie R, Alexander, Daniel C, Sisodiya, Sanjay M, Altmann, Andre, Bargalló, Núria, Bartolini, Emanuele, O’Brien, Terence J, and Thomas, Rhys H
Subjects: Brain Disorders, Epilepsy, Neurodegenerative, Neurosciences, Clinical Research, Biomedical Imaging, Aetiology, 2.1 Biological and endogenous factors, Neurological, Good Health and Well Being, Atrophy, Biomarkers, Cross-Sectional Studies, Epilepsy, Temporal Lobe, Hippocampus, Humans, Magnetic Resonance Imaging, Sclerosis, disease progression, duration of illness, event-based model, MTLE, patient staging, ENIGMA-Epilepsy Working Group, Clinical Sciences, Neurology & Neurosurgery
Abstract: ObjectiveRecent work has shown that people with common epilepsies have characteristic patterns of cortical thinning, and that these changes may be progressive over time. Leveraging a large multicenter cross-sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) correlate with clinical features.MethodsWe extracted regional measures of cortical thickness, surface area, and subcortical brain volumes from T1-weighted (T1W) magnetic resonance imaging (MRI) scans collected by the ENIGMA-Epilepsy consortium, comprising 804 people with MTLE-HS and 1625 healthy controls from 25 centers. Features with a moderate case-control effect size (Cohen d ≥ .5) were used to train an event-based model (EBM), which estimates a sequence of disease-specific biomarker changes from cross-sectional data and assigns a biomarker-based fine-grained disease stage to individual patients. We tested for associations between EBM disease stage and duration of epilepsy, age at onset, and antiseizure medicine (ASM) resistance.ResultsIn MTLE-HS, decrease in ipsilateral hippocampal volume along with increased asymmetry in hippocampal volume was followed by reduced thickness in neocortical regions, reduction in ipsilateral thalamus volume, and finally, increase in ipsilateral lateral ventricle volume. EBM stage was correlated with duration of illness (Spearman ρ = .293, p = 7.03 × 10-16 ), age at onset (ρ = -.18, p = 9.82 × 10-7 ), and ASM resistance (area under the curve = .59, p = .043, Mann-Whitney U test). However, associations were driven by cases assigned to EBM Stage 0, which represents MTLE-HS with mild or nondetectable abnormality on T1W MRI.SignificanceFrom cross-sectional MRI, we reconstructed a disease progression model that highlights a sequence of MRI changes that aligns with previous longitudinal studies. This model could be used to stage MTLE-HS subjects in other cohorts and help establish connections between imaging-based progression staging and clinical features.
Published: 2022

27. Cross disorder comparisons of brain structure in schizophrenia, bipolar disorder, major depressive disorder, and 22q11.2 deletion syndrome: A review of ENIGMA findings

Author: Cheon, Eun‐Jin, Bearden, Carrie E, Sun, Daqiang, Ching, Christopher RK, Andreassen, Ole A, Schmaal, Lianne, Veltman, Dick J, Thomopoulos, Sophia I, Kochunov, Peter, Jahanshad, Neda, Thompson, Paul M, Turner, Jessica A, and van Erp, Theo GM
Subjects: Depression, Neurosciences, Schizophrenia, Genetics, Clinical Research, Biomedical Imaging, Serious Mental Illness, Brain Disorders, Bipolar Disorder, Mental Health, Aetiology, 2.3 Psychological, social and economic factors, 2.1 Biological and endogenous factors, Mental health, Brain, Depressive Disorder, Major, DiGeorge Syndrome, Diffusion Tensor Imaging, Humans, Magnetic Resonance Imaging, bipolar disorder, ENIGMA, major depressive disorder, schizophrenia, velocardiofacial, Clinical Sciences, Cognitive Sciences
Abstract: This review compares the main brain abnormalities in schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and 22q11.2 Deletion Syndrome (22q11DS) determined by ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) consortium investigations. We obtained ranked effect sizes for subcortical volumes, regional cortical thickness, cortical surface area, and diffusion tensor imaging abnormalities, comparing each of these disorders relative to healthy controls. In addition, the studies report on significant associations between brain imaging metrics and disorder-related factors such as symptom severity and treatments. Visual comparison of effect size profiles shows that effect sizes are generally in the same direction and scale in severity with the disorders (in the order SZ > BD > MDD). The effect sizes for 22q11DS, a rare genetic syndrome that increases the risk for psychiatric disorders, appear to be much larger than for either of the complex psychiatric disorders. This is consistent with the idea of generally larger effects on the brain of rare compared to common genetic variants. Cortical thickness and surface area effect sizes for 22q11DS with psychosis compared to 22q11DS without psychosis are more similar to those of SZ and BD than those of MDD; a pattern not observed for subcortical brain structures and fractional anisotropy effect sizes. The observed similarities in effect size profiles for cortical measures across the psychiatric disorders mimic those observed for shared genetic variance between these disorders reported based on family and genetic studies and are consistent with shared genetic risk for SZ and BD and structural brain phenotypes.
Published: 2022

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

Author: Brouwer, Rachel M, Klein, Marieke, Grasby, Katrina L, Schnack, Hugo G, Jahanshad, Neda, Teeuw, Jalmar, Thomopoulos, Sophia I, Sprooten, Emma, Franz, Carol E, Gogtay, Nitin, Kremen, William S, Panizzon, Matthew S, Olde Loohuis, Loes M, Whelan, Christopher D, Aghajani, Moji, Alloza, Clara, Alnæs, Dag, Artiges, Eric, Ayesa-Arriola, Rosa, Barker, Gareth J, Bastin, Mark E, Blok, Elisabet, Bøen, Erlend, Breukelaar, Isabella A, Bright, Joanna K, Buimer, Elizabeth EL, Bülow, Robin, Cannon, Dara M, Ciufolini, Simone, Crossley, Nicolas A, Damatac, Christienne G, Dazzan, Paola, de Mol, Casper L, de Zwarte, Sonja MC, Desrivières, Sylvane, Díaz-Caneja, Covadonga M, Doan, Nhat Trung, Dohm, Katharina, Fröhner, Juliane H, Goltermann, Janik, Grigis, Antoine, Grotegerd, Dominik, Han, Laura KM, Harris, Mathew A, Hartman, Catharina A, Heany, Sarah J, Heindel, Walter, Heslenfeld, Dirk J, Hohmann, Sarah, Ittermann, Bernd, Jansen, Philip R, Janssen, Joost, Jia, Tianye, Jiang, Jiyang, Jockwitz, Christiane, Karali, Temmuz, Keeser, Daniel, Koevoets, Martijn GJC, Lenroot, Rhoshel K, Malchow, Berend, Mandl, René CW, Medel, Vicente, Meinert, Susanne, Morgan, Catherine A, Mühleisen, Thomas W, Nabulsi, Leila, Opel, Nils, de la Foz, Víctor Ortiz-García, Overs, Bronwyn J, Paillère Martinot, Marie-Laure, Redlich, Ronny, Marques, Tiago Reis, Repple, Jonathan, Roberts, Gloria, Roshchupkin, Gennady V, Setiaman, Nikita, Shumskaya, Elena, Stein, Frederike, Sudre, Gustavo, Takahashi, Shun, Thalamuthu, Anbupalam, Tordesillas-Gutiérrez, Diana, van der Lugt, Aad, van Haren, Neeltje EM, Wardlaw, Joanna M, Wen, Wei, Westeneng, Henk-Jan, Wittfeld, Katharina, Zhu, Alyssa H, Zugman, Andre, Armstrong, Nicola J, Bonfiglio, Gaia, Bralten, Janita, Dalvie, Shareefa, Davies, Gail, Di Forti, Marta, Ding, Linda, Donohoe, Gary, Forstner, Andreas J, and Gonzalez-Peñas, Javier
Subjects: Biological Psychology, Psychology, Genetics, Biomedical Imaging, Mental Health, Biotechnology, Human Genome, Prevention, Aging, Brain Disorders, Neurosciences, 2.1 Biological and endogenous factors, Aetiology, Mental health, Neurological, Brain, Genome-Wide Association Study, Humans, Longevity, Magnetic Resonance Imaging, IMAGEN Consortium, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract: Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.
Published: 2022

29. The ENIGMA‐Epilepsy working group: Mapping disease from large data sets

Author: Sisodiya, Sanjay M, Whelan, Christopher D, Hatton, Sean N, Huynh, Khoa, Altmann, Andre, Ryten, Mina, Vezzani, Annamaria, Caligiuri, Maria Eugenia, Labate, Angelo, Gambardella, Antonio, Ives‐Deliperi, Victoria, Meletti, Stefano, Munsell, Brent C, Bonilha, Leonardo, Tondelli, Manuela, Rebsamen, Michael, Rummel, Christian, Vaudano, Anna Elisabetta, Wiest, Roland, Balachandra, Akshara R, Bargalló, Núria, Bartolini, Emanuele, Bernasconi, Andrea, Bernasconi, Neda, Bernhardt, Boris, Caldairou, Benoit, Carr, Sarah JA, Cavalleri, Gianpiero L, Cendes, Fernando, Concha, Luis, Desmond, Patricia M, Domin, Martin, Duncan, John S, Focke, Niels K, Guerrini, Renzo, Hamandi, Khalid, Jackson, Graeme D, Jahanshad, Neda, Kälviäinen, Reetta, Keller, Simon S, Kochunov, Peter, Kowalczyk, Magdalena A, Kreilkamp, Barbara AK, Kwan, Patrick, Lariviere, Sara, Lenge, Matteo, Lopez, Seymour M, Martin, Pascal, Mascalchi, Mario, Moreira, José CV, Morita‐Sherman, Marcia E, Pardoe, Heath R, Pariente, Jose C, Raviteja, Kotikalapudi, Rocha, Cristiane S, Rodríguez‐Cruces, Raúl, Seeck, Margitta, Semmelroch, Mira KHG, Sinclair, Benjamin, Soltanian‐Zadeh, Hamid, Stein, Dan J, Striano, Pasquale, Taylor, Peter N, Thomas, Rhys H, Thomopoulos, Sophia I, Velakoulis, Dennis, Vivash, Lucy, Weber, Bernd, Yasuda, Clarissa Lin, Zhang, Junsong, Thompson, Paul M, McDonald, Carrie R, Abela, Eugenio, Absil, Julie, Adams, Sophia, Alhusaini, Saud, Alvim, Marina, Balestrini, Simona, Bender, Benjamin, Bergo, Felipe, Bernardes, Tauana, Calvo, Anna, Carreno, Mar, Cherubini, Andrea, David, Philippe, Davoodi‐Bojd, Esmaeil, Delanty, Norman, Depondt, Chantal, Devinsky, Orrin, Doherty, Colin, França, Wendy Caroline, Franceschet, Leticia, Hibar, Derrek P, Ishikawa, Akari, Kaestner, Erik, Langner, Soenke, Liu, Min, Mirandola, Laura, Naylor, Jillian, and Nazem‐Zadeh, Mohammad‐reza
Subjects: Brain Disorders, Biomedical Imaging, Neurosciences, Epilepsy, Neurodegenerative, 2.1 Biological and endogenous factors, Aetiology, Neurological, covariance, deep learning, DTI, event-based modeling, gene expression, genetics, imaging, MRI, quantitative, rsfMRI, ENIGMA Consortium Epilepsy Working Group, Cognitive Sciences, Experimental Psychology
Abstract: Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller-scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well-established by the ENIGMA Consortium, ENIGMA-Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event-based modeling analysis. We explore age of onset- and duration-related features, as well as phenomena-specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA-Epilepsy.
Published: 2022

30. Intelligence, educational attainment, and brain structure in those at familial high‐risk for schizophrenia or bipolar disorder

Author: Zwarte, Sonja MC, Brouwer, Rachel M, Agartz, Ingrid, Alda, Martin, Alonso‐Lana, Silvia, Bearden, Carrie E, Bertolino, Alessandro, Bonvino, Aurora, Bramon, Elvira, Buimer, Elizabeth EL, Cahn, Wiepke, Canales‐Rodríguez, Erick J, Cannon, Dara M, Cannon, Tyrone D, Caseras, Xavier, Castro‐Fornieles, Josefina, Chen, Qiang, Chung, Yoonho, De la Serna, Elena, Bonnin, Caterina Mar, Demro, Caroline, Di Giorgio, Annabella, Doucet, Gaelle E, Eker, Mehmet Cagdas, Erk, Susanne, Fatjó‐Vilas, Mar, Fears, Scott C, Foley, Sonya F, Frangou, Sophia, Fullerton, Janice M, Glahn, David C, Goghari, Vina M, Goikolea, Jose M, Goldman, Aaron L, Gonul, Ali Saffet, Gruber, Oliver, Hajek, Tomas, Hawkins, Emma L, Heinz, Andreas, Ongun, Ceren Hidiroglu, Hillegers, Manon HJ, Houenou, Josselin, Pol, Hilleke E Hulshoff, Hultman, Christina M, Ingvar, Martin, Johansson, Viktoria, Jönsson, Erik G, Kane, Fergus, Kempton, Matthew J, Koenis, Marinka MG, Kopecek, Miloslav, Krämer, Bernd, Lawrie, Stephen M, Lenroot, Rhoshel K, Marcelis, Machteld, Mattay, Venkata S, McDonald, Colm, Meyer‐Lindenberg, Andreas, Michielse, Stijn, Mitchell, Philip B, Moreno, Dolores, Murray, Robin M, Mwangi, Benson, Nabulsi, Leila, Newport, Jason, Olman, Cheryl A, Os, Jim, Overs, Bronwyn J, Ozerdem, Aysegul, Pergola, Giulio, Picchioni, Marco M, Piguet, Camille, Pomarol‐Clotet, Edith, Radua, Joaquim, Ramsay, Ian S, Richter, Anja, Roberts, Gloria, Salvador, Raymond, Aydogan, Aybala Saricicek, Sarró, Salvador, Schofield, Peter R, Simsek, Esma M, Simsek, Fatma, Soares, Jair C, Sponheim, Scott R, Sugranyes, Gisela, Toulopoulou, Timothea, Tronchin, Giulia, Vieta, Eduard, Walter, Henrik, Weinberger, Daniel R, Whalley, Heather C, Wu, Mon‐Ju, Yalin, Nefize, Andreassen, Ole A, Ching, Christopher RK, Thomopoulos, Sophia I, Erp, Theo GM, Jahanshad, Neda, and Thompson, Paul M
Subjects: Biological Psychology, Biomedical and Clinical Sciences, Psychology, Brain Disorders, Bipolar Disorder, Clinical Research, Serious Mental Illness, Neurosciences, Schizophrenia, Mental Health, Aetiology, 2.3 Psychological, social and economic factors, 2.1 Biological and endogenous factors, Mental health, Cognitive Dysfunction, Educational Status, Family, Genetic Predisposition to Disease, Humans, Intelligence, Magnetic Resonance Imaging, Neuroimaging, bipolar disorder, education, intelligence, neuroimaging, relatives, schizophrenia, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
Abstract: First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.
Published: 2022

31. In vivo hippocampal subfield volumes in bipolar disorder—A mega‐analysis from The Enhancing Neuro Imaging Genetics through Meta‐Analysis Bipolar Disorder Working Group

Author: Haukvik, Unn K, Gurholt, Tiril P, Nerland, Stener, Elvsåshagen, Torbjørn, Akudjedu, Theophilus N, Alda, Martin, Alnæs, Dag, Alonso‐Lana, Silvia, Bauer, Jochen, Baune, Bernhard T, Benedetti, Francesco, Berk, Michael, Bettella, Francesco, Bøen, Erlend, Bonnín, Caterina M, Brambilla, Paolo, Canales‐Rodríguez, Erick J, Cannon, Dara M, Caseras, Xavier, Dandash, Orwa, Dannlowski, Udo, Delvecchio, Giuseppe, Díaz‐Zuluaga, Ana M, Erp, Theo GM, Fatjó‐Vilas, Mar, Foley, Sonya F, Förster, Katharina, Fullerton, Janice M, Goikolea, José M, Grotegerd, Dominik, Gruber, Oliver, Haarman, Bartholomeus CM, Haatveit, Beathe, Hajek, Tomas, Hallahan, Brian, Harris, Mathew, Hawkins, Emma L, Howells, Fleur M, Hülsmann, Carina, Jahanshad, Neda, Jørgensen, Kjetil N, Kircher, Tilo, Krämer, Bernd, Krug, Axel, Kuplicki, Rayus, Lagerberg, Trine V, Lancaster, Thomas M, Lenroot, Rhoshel K, Lonning, Vera, López‐Jaramillo, Carlos, Malt, Ulrik F, McDonald, Colm, McIntosh, Andrew M, McPhilemy, Genevieve, Meer, Dennis, Melle, Ingrid, Melloni, Elisa MT, Mitchell, Philip B, Nabulsi, Leila, Nenadić, Igor, Oertel, Viola, Oldani, Lucio, Opel, Nils, Otaduy, Maria CG, Overs, Bronwyn J, Pineda‐Zapata, Julian A, Pomarol‐Clotet, Edith, Radua, Joaquim, Rauer, Lisa, Redlich, Ronny, Repple, Jonathan, Rive, Maria M, Roberts, Gloria, Ruhe, Henricus G, Salminen, Lauren E, Salvador, Raymond, Sarró, Salvador, Savitz, Jonathan, Schene, Aart H, Sim, Kang, Soeiro‐de‐Souza, Marcio G, Stäblein, Michael, Stein, Dan J, Stein, Frederike, Tamnes, Christian K, Temmingh, Henk S, Thomopoulos, Sophia I, Veltman, Dick J, Vieta, Eduard, Waltemate, Lena, Westlye, Lars T, Whalley, Heather C, Sämann, Philipp G, Thompson, Paul M, Ching, Christopher RK, Andreassen, Ole A, Agartz, Ingrid, and Group, ENIGMA Bipolar Disorder Working
Subjects: Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Brain Disorders, Mental Health, Serious Mental Illness, Neurosciences, Biomedical Imaging, Bipolar Disorder, Mental health, Genetics, Hippocampus, Humans, Magnetic Resonance Imaging, Neuroimaging, ENIGMA Bipolar Disorder Working Group, bipolar disorder subtype, hippocampus, large-scale, lithium, psychosis, structural brain MRI, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
Abstract: The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta-Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1-weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed-effects models and mega-analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = -0.20), cornu ammonis (CA)1 (d = -0.18), CA2/3 (d = -0.11), CA4 (d = -0.19), molecular layer (d = -0.21), granule cell layer of dentate gyrus (d = -0.21), hippocampal tail (d = -0.10), subiculum (d = -0.15), presubiculum (d = -0.18), and hippocampal amygdala transition area (d = -0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non-users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD.
Published: 2022

32. Local molecular and global connectomic contributions to cross-disorder cortical abnormalities

Author: Hansen, Justine Y, Shafiei, Golia, Vogel, Jacob W, Smart, Kelly, Bearden, Carrie E, Hoogman, Martine, Franke, Barbara, van Rooij, Daan, Buitelaar, Jan, McDonald, Carrie R, Sisodiya, Sanjay M, Schmaal, Lianne, Veltman, Dick J, van den Heuvel, Odile A, Stein, Dan J, van Erp, Theo GM, Ching, Christopher RK, Andreassen, Ole A, Hajek, Tomas, Opel, Nils, Modinos, Gemma, Aleman, André, van der Werf, Ysbrand, Jahanshad, Neda, Thomopoulos, Sophia I, Thompson, Paul M, Carson, Richard E, Dagher, Alain, and Misic, Bratislav
Subjects: Neurosciences, Pediatric, Brain Disorders, Mental Health, Aetiology, Underpinning research, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Mental health, Neurological, Brain, Brain Diseases, Connectome, Humans, Magnetic Resonance Imaging, Neural Pathways
Abstract: Numerous brain disorders demonstrate structural brain abnormalities, which are thought to arise from molecular perturbations or connectome miswiring. The unique and shared contributions of these molecular and connectomic vulnerabilities to brain disorders remain unknown, and has yet to be studied in a single multi-disorder framework. Using MRI morphometry from the ENIGMA consortium, we construct maps of cortical abnormalities for thirteen neurodevelopmental, neurological, and psychiatric disorders from N = 21,000 participants and N = 26,000 controls, collected using a harmonised processing protocol. We systematically compare cortical maps to multiple micro-architectural measures, including gene expression, neurotransmitter density, metabolism, and myelination (molecular vulnerability), as well as global connectomic measures including number of connections, centrality, and connection diversity (connectomic vulnerability). We find a relationship between molecular vulnerability and white-matter architecture that drives cortical disorder profiles. Local attributes, particularly neurotransmitter receptor profiles, constitute the best predictors of both disorder-specific cortical morphology and cross-disorder similarity. Finally, we find that cross-disorder abnormalities are consistently subtended by a small subset of network epicentres in bilateral sensory-motor, inferior temporal lobe, precuneus, and superior parietal cortex. Collectively, our results highlight how local molecular attributes and global connectivity jointly shape cross-disorder cortical abnormalities.
Published: 2022

33. Mapping brain asymmetry in health and disease through the ENIGMA consortium

Author: Kong, Xiang‐Zhen, Postema, Merel C, Guadalupe, Tulio, de Kovel, Carolien, Boedhoe, Premika SW, Hoogman, Martine, Mathias, Samuel R, van Rooij, Daan, Schijven, Dick, Glahn, David C, Medland, Sarah E, Jahanshad, Neda, Thomopoulos, Sophia I, Turner, Jessica A, Buitelaar, Jan, van Erp, Theo GM, Franke, Barbara, Fisher, Simon E, van den Heuvel, Odile A, Schmaal, Lianne, Thompson, Paul M, and Francks, Clyde
Subjects: Biological Psychology, Psychology, Brain Disorders, Mental Health, Neurosciences, Clinical Research, Mental health, Neurological, Autism Spectrum Disorder, Cerebral Cortex, Depressive Disorder, Major, Gray Matter, Humans, Magnetic Resonance Imaging, Multicenter Studies as Topic, Neuroimaging, Obsessive-Compulsive Disorder, autism spectrum disorder, brain asymmetry, brain laterality, major depressive disorder, mega-analysis, meta-analysis, obsessive-compulsive disorder, structural imaging, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
Abstract: Left-right asymmetry of the human brain is one of its cardinal features, and also a complex, multivariate trait. Decades of research have suggested that brain asymmetry may be altered in psychiatric disorders. However, findings have been inconsistent and often based on small sample sizes. There are also open questions surrounding which structures are asymmetrical on average in the healthy population, and how variability in brain asymmetry relates to basic biological variables such as age and sex. Over the last 4 years, the ENIGMA-Laterality Working Group has published six studies of gray matter morphological asymmetry based on total sample sizes from roughly 3,500 to 17,000 individuals, which were between one and two orders of magnitude larger than those published in previous decades. A population-level mapping of average asymmetry was achieved, including an intriguing fronto-occipital gradient of cortical thickness asymmetry in healthy brains. ENIGMA's multi-dataset approach also supported an empirical illustration of reproducibility of hemispheric differences across datasets. Effect sizes were estimated for gray matter asymmetry based on large, international, samples in relation to age, sex, handedness, and brain volume, as well as for three psychiatric disorders: autism spectrum disorder was associated with subtly reduced asymmetry of cortical thickness at regions spread widely over the cortex; pediatric obsessive-compulsive disorder was associated with altered subcortical asymmetry; major depressive disorder was not significantly associated with changes of asymmetry. Ongoing studies are examining brain asymmetry in other disorders. Moreover, a groundwork has been laid for possibly identifying shared genetic contributions to brain asymmetry and disorders.
Published: 2022

34. An overview of the first 5 years of the ENIGMA obsessive–compulsive disorder working group: The power of worldwide collaboration

Author: van den Heuvel, Odile A, Boedhoe, Premika SW, Bertolin, Sara, Bruin, Willem B, Francks, Clyde, Ivanov, Iliyan, Jahanshad, Neda, Kong, Xiang‐Zhen, Kwon, Jun Soo, O'Neill, Joseph, Paus, Tomas, Patel, Yash, Piras, Fabrizio, Schmaal, Lianne, Soriano‐Mas, Carles, Spalletta, Gianfranco, van Wingen, Guido A, Yun, Je‐Yeon, Vriend, Chris, Simpson, H Blair, van Rooij, Daan, Hoexter, Marcelo Q, Hoogman, Martine, Buitelaar, Jan K, Arnold, Paul, Beucke, Jan C, Benedetti, Francesco, Bollettini, Irene, Bose, Anushree, Brennan, Brian P, De Nadai, Alessandro S, Fitzgerald, Kate, Gruner, Patricia, Grünblatt, Edna, Hirano, Yoshiyuki, Huyser, Chaim, James, Anthony, Koch, Kathrin, Kvale, Gerd, Lazaro, Luisa, Lochner, Christine, Marsh, Rachel, Mataix‐Cols, David, Morgado, Pedro, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C, Nurmi, Erika, Pittenger, Christopher, Reddy, YC Janardhan, Sato, João R, Soreni, Noam, Stewart, S Evelyn, Taylor, Stephan F, Tolin, David, Thomopoulos, Sophia I, Veltman, Dick J, Venkatasubramanian, Ganesan, Walitza, Susanne, Wang, Zhen, Thompson, Paul M, Stein, Dan J, Abe, Yoshinari, Alonso, Pino, Assogna, Francesca, Banaj, Nerisa, Batistuzzo, Marcelo C, Brem, Silvia, Ciullo, Valentina, Feusner, Jamie, Martínez‐Zalacaín, Ignacio, Menchón, José M, Miguel, Euripedes C, Piacentini, John, Piras, Federica, Sakai, Yuki, Wolters, Lidewij, and Yamada, Kei
Subjects: Biological Psychology, Psychology, Brain Disorders, Clinical Research, Serious Mental Illness, Pediatric, Neurosciences, Mental Health, Mental health, Neurological, Cerebral Cortex, Humans, Machine Learning, Multicenter Studies as Topic, Neuroimaging, Obsessive-Compulsive Disorder, cortical thickness, ENIGMA, mega-analysis, meta-analysis, MRI, obsessive-compulsive disorder, surface area, volume, ENIGMA-OCD working group, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
Abstract: Neuroimaging has played an important part in advancing our understanding of the neurobiology of obsessive-compulsive disorder (OCD). At the same time, neuroimaging studies of OCD have had notable limitations, including reliance on relatively small samples. International collaborative efforts to increase statistical power by combining samples from across sites have been bolstered by the ENIGMA consortium; this provides specific technical expertise for conducting multi-site analyses, as well as access to a collaborative community of neuroimaging scientists. In this article, we outline the background to, development of, and initial findings from ENIGMA's OCD working group, which currently consists of 47 samples from 34 institutes in 15 countries on 5 continents, with a total sample of 2,323 OCD patients and 2,325 healthy controls. Initial work has focused on studies of cortical thickness and subcortical volumes, structural connectivity, and brain lateralization in children, adolescents and adults with OCD, also including the study on the commonalities and distinctions across different neurodevelopment disorders. Additional work is ongoing, employing machine learning techniques. Findings to date have contributed to the development of neurobiological models of OCD, have provided an important model of global scientific collaboration, and have had a number of clinical implications. Importantly, our work has shed new light on questions about whether structural and functional alterations found in OCD reflect neurodevelopmental changes, effects of the disease process, or medication impacts. We conclude with a summary of ongoing work by ENIGMA-OCD, and a consideration of future directions for neuroimaging research on OCD within and beyond ENIGMA.
Published: 2022

35. Effects of copy number variations on brain structure and risk for psychiatric illness: Large‐scale studies from the ENIGMA working groups on CNVs

Author: Sønderby, Ida E, Ching, Christopher RK, Thomopoulos, Sophia I, van der Meer, Dennis, Sun, Daqiang, Villalon‐Reina, Julio E, Agartz, Ingrid, Amunts, Katrin, Arango, Celso, Armstrong, Nicola J, Ayesa‐Arriola, Rosa, Bakker, Geor, Bassett, Anne S, Boomsma, Dorret I, Bülow, Robin, Butcher, Nancy J, Calhoun, Vince D, Caspers, Svenja, Chow, Eva WC, Cichon, Sven, Ciufolini, Simone, Craig, Michael C, Crespo‐Facorro, Benedicto, Cunningham, Adam C, Dale, Anders M, Dazzan, Paola, de Zubicaray, Greig I, Djurovic, Srdjan, Doherty, Joanne L, Donohoe, Gary, Draganski, Bogdan, Durdle, Courtney A, Ehrlich, Stefan, Emanuel, Beverly S, Espeseth, Thomas, Fisher, Simon E, Ge, Tian, Glahn, David C, Grabe, Hans J, Gur, Raquel E, Gutman, Boris A, Haavik, Jan, Håberg, Asta K, Hansen, Laura A, Hashimoto, Ryota, Hibar, Derrek P, Holmes, Avram J, Hottenga, Jouke‐Jan, Pol, Hilleke E Hulshoff, Jalbrzikowski, Maria, Knowles, Emma EM, Kushan, Leila, Linden, David EJ, Liu, Jingyu, Lundervold, Astri J, Martin‐Brevet, Sandra, Martínez, Kenia, Mather, Karen A, Mathias, Samuel R, McDonald‐McGinn, Donna M, McRae, Allan F, Medland, Sarah E, Moberget, Torgeir, Modenato, Claudia, Sánchez, Jennifer Monereo, Moreau, Clara A, Mühleisen, Thomas W, Paus, Tomas, Pausova, Zdenka, Prieto, Carlos, Ragothaman, Anjanibhargavi, Reinbold, Céline S, Marques, Tiago Reis, Repetto, Gabriela M, Reymond, Alexandre, Roalf, David R, Rodriguez‐Herreros, Borja, Rucker, James J, Sachdev, Perminder S, Schmitt, James E, Schofield, Peter R, Silva, Ana I, Stefansson, Hreinn, Stein, Dan J, Tamnes, Christian K, Tordesillas‐Gutiérrez, Diana, Ulfarsson, Magnus O, Vajdi, Ariana, van 't Ent, Dennis, van den Bree, Marianne BM, Vassos, Evangelos, Vázquez‐Bourgon, Javier, Vila‐Rodriguez, Fidel, Walters, G Bragi, Wen, Wei, Westlye, Lars T, Wittfeld, Katharina, Zackai, Elaine H, Stefánsson, Kári, and Jacquemont, Sebastien
Subjects: Biological Psychology, Biomedical and Clinical Sciences, Psychology, Mental Health, Clinical Research, Pediatric, Genetics, Basic Behavioral and Social Science, Human Genome, Prevention, Brain Disorders, Behavioral and Social Science, Neurosciences, Aetiology, 2.1 Biological and endogenous factors, Mental health, Neurological, Brain, DNA Copy Number Variations, Humans, Magnetic Resonance Imaging, Mental Disorders, Multicenter Studies as Topic, Neurodevelopmental Disorders, Neuroimaging, brain structural imaging, copy number variant, diffusion tensor imaging, evolution, genetics-first approach, neurodevelopmental disorders, psychiatric disorders, ENIGMA-CNV Working Group, ENIGMA 22q11.2 Deletion Syndrome Working Group, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
Abstract: The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype-phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This "genotype-first" approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.
Published: 2022

36. ENIGMA + COINSTAC: Improving Findability, Accessibility, Interoperability, and Re-usability.

Author: Turner, Jessica A, Calhoun, Vince D, Thompson, Paul M, Jahanshad, Neda, Ching, Christopher RK, Thomopoulos, Sophia I, Verner, Eric, Strauss, Gregory P, Ahmed, Anthony O, Turner, Matthew D, Basodi, Sunitha, Ford, Judith M, Mathalon, Daniel H, Preda, Adrian, Belger, Aysenil, Mueller, Bryon A, Lim, Kelvin O, and van Erp, Theo GM
Subjects: Humans, Female, Male, Neuroimaging, COINSTAC, Data privacy, Decentralized, ENIGMA, Meta-analysis, Biochemistry and Cell Biology, Neurosciences, Neurology & Neurosurgery
Abstract: The FAIR principles, as applied to clinical and neuroimaging data, reflect the goal of making research products Findable, Accessible, Interoperable, and Reusable. The use of the Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymized Computation (COINSTAC) platform in the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium combines the technological approach of decentralized analyses with the sociological approach of sharing data. In addition, ENIGMA + COINSTAC provides a platform to facilitate the use of machine-actionable data objects. We first present how ENIGMA and COINSTAC support the FAIR principles, and then showcase their integration with a decentralized meta-analysis of sex differences in negative symptom severity in schizophrenia, and finally present ongoing activities and plans to advance FAIR principles in ENIGMA + COINSTAC. ENIGMA and COINSTAC currently represent efforts toward improved Access, Interoperability, and Reusability. We highlight additional improvements needed in these areas, as well as future connections to other resources for expanded Findability.
Published: 2022

37. Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis

Author: Baldwin, Helen, Radua, Joaquim, Antoniades, Mathilde, Haas, Shalaila S, Frangou, Sophia, Agartz, Ingrid, Allen, Paul, Andreassen, Ole A, Atkinson, Kimberley, Bachman, Peter, Baeza, Inmaculada, Bartholomeusz, Cali F, Chee, Michael WL, Colibazzi, Tiziano, Cooper, Rebecca E, Corcoran, Cheryl M, Cropley, Vanessa L, Ebdrup, Bjørn H, Fortea, Adriana, Glenthøj, Louise Birkedal, Hamilton, Holly K, Haut, Kristen M, Hayes, Rebecca A, He, Ying, Heekeren, Karsten, Kaess, Michael, Kasai, Kiyoto, Katagiri, Naoyuki, Kim, Minah, Kindler, Jochen, Klaunig, Mallory J, Koike, Shinsuke, Koppel, Alex, Kristensen, Tina D, Bin Kwak, Yoo, Kwon, Jun Soo, Lawrie, Stephen M, Lebedeva, Irina, Lee, Jimmy, Lin, Ashleigh, Loewy, Rachel L, Mathalon, Daniel H, Michel, Chantal, Mizrahi, Romina, Møller, Paul, Nelson, Barnaby, Nemoto, Takahiro, Nordholm, Dorte, Omelchenko, Maria A, Pantelis, Christos, Raghava, Jayachandra M, Røssberg, Jan I, Rössler, Wulf, Salisbury, Dean F, Sasabayashi, Daiki, Schall, Ulrich, Smigielski, Lukasz, Sugranyes, Gisela, Suzuki, Michio, Takahashi, Tsutomu, Tamnes, Christian K, Tang, Jinsong, Theodoridou, Anastasia, Thomopoulos, Sophia I, Tomyshev, Alexander S, Uhlhaas, Peter J, Værnes, Tor G, van Amelsvoort, Therese AMJ, Van Erp, Theo GM, Waltz, James A, Westlye, Lars T, Wood, Stephen J, Zhou, Juan H, McGuire, Philip, Thompson, Paul M, Jalbrzikowski, Maria, Hernaus, Dennis, and Fusar-Poli, Paolo
Subjects: Serious Mental Illness, Prevention, Biomedical Imaging, Mental Health, Clinical Research, Neurosciences, Brain, Humans, Magnetic Resonance Imaging, Psychotic Disorders, ENIGMA Clinical High Risk for Psychosis Working Group, Clinical Sciences, Public Health and Health Services, Psychology
Abstract: Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the 'normativeness' of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation.
Published: 2022

38. What we learn about bipolar disorder from large‐scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group

Author: Ching, Christopher RK, Hibar, Derrek P, Gurholt, Tiril P, Nunes, Abraham, Thomopoulos, Sophia I, Abé, Christoph, Agartz, Ingrid, Brouwer, Rachel M, Cannon, Dara M, Zwarte, Sonja MC, Eyler, Lisa T, Favre, Pauline, Hajek, Tomas, Haukvik, Unn K, Houenou, Josselin, Landén, Mikael, Lett, Tristram A, McDonald, Colm, Nabulsi, Leila, Patel, Yash, Pauling, Melissa E, Paus, Tomas, Radua, Joaquim, Soeiro‐de‐Souza, Marcio G, Tronchin, Giulia, Haren, Neeltje EM, Vieta, Eduard, Walter, Henrik, Zeng, Ling‐Li, Alda, Martin, Almeida, Jorge, Alnæs, Dag, Alonso‐Lana, Silvia, Altimus, Cara, Bauer, Michael, Baune, Bernhard T, Bearden, Carrie E, Bellani, Marcella, Benedetti, Francesco, Berk, Michael, Bilderbeck, Amy C, Blumberg, Hilary P, Bøen, Erlend, Bollettini, Irene, Bonnin, Caterina Mar, Brambilla, Paolo, Canales‐Rodríguez, Erick J, Caseras, Xavier, Dandash, Orwa, Dannlowski, Udo, Delvecchio, Giuseppe, Díaz‐Zuluaga, Ana M, Dima, Danai, Duchesnay, Édouard, Elvsåshagen, Torbjørn, Fears, Scott C, Frangou, Sophia, Fullerton, Janice M, Glahn, David C, Goikolea, Jose M, Green, Melissa J, Grotegerd, Dominik, Gruber, Oliver, Haarman, Bartholomeus CM, Henry, Chantal, Howells, Fleur M, Ives‐Deliperi, Victoria, Jansen, Andreas, Kircher, Tilo TJ, Knöchel, Christian, Kramer, Bernd, Lafer, Beny, López‐Jaramillo, Carlos, Machado‐Vieira, Rodrigo, MacIntosh, Bradley J, Melloni, Elisa MT, Mitchell, Philip B, Nenadic, Igor, Nery, Fabiano, Nugent, Allison C, Oertel, Viola, Ophoff, Roel A, Ota, Miho, Overs, Bronwyn J, Pham, Daniel L, Phillips, Mary L, Pineda‐Zapata, Julian A, Poletti, Sara, Polosan, Mircea, Pomarol‐Clotet, Edith, Pouchon, Arnaud, Quidé, Yann, Rive, Maria M, Roberts, Gloria, Ruhe, Henricus G, Salvador, Raymond, Sarró, Salvador, Satterthwaite, Theodore D, Schene, Aart H, and Sim, Kang
Subjects: Serious Mental Illness, Brain Disorders, Biomedical Imaging, Bipolar Disorder, Clinical Research, Behavioral and Social Science, Mental Health, Neurosciences, Mental health, Neurological, Good Health and Well Being, Cerebral Cortex, Humans, Magnetic Resonance Imaging, Meta-Analysis as Topic, Multicenter Studies as Topic, Neuroimaging, bipolar disorder, cortical surface area, cortical thickness, ENIGMA, mega-analysis, meta-analysis, MRI, neuroimaging, psychiatry, volume, ENIGMA Bipolar Disorder Working Group, Cognitive Sciences, Experimental Psychology
Abstract: MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.
Published: 2022

39. Intracranial and subcortical volumes in adolescents with early-onset psychosis: A multisite mega-analysis from the ENIGMA consortium.

Author: Gurholt, Tiril P, Lonning, Vera, Nerland, Stener, Jørgensen, Kjetil N, Haukvik, Unn K, Alloza, Clara, Arango, Celso, Barth, Claudia, Bearden, Carrie E, Berk, Michael, Bohman, Hannes, Dandash, Orwa, Díaz-Caneja, Covadonga M, Edbom, Carl T, van Erp, Theo GM, Fett, Anne-Kathrin J, Frangou, Sophia, Goldstein, Benjamin I, Grigorian, Anahit, Jahanshad, Neda, James, Anthony C, Janssen, Joost, Johannessen, Cecilie, Karlsgodt, Katherine H, Kempton, Matthew J, Kochunov, Peter, Krabbendam, Lydia, Kyriakopoulos, Marinos, Lundberg, Mathias, MacIntosh, Bradley J, Rund, Bjørn Rishovd, Smelror, Runar E, Sultan, Alysha, Tamnes, Christian K, Thomopoulos, Sophia I, Vajdi, Ariana, Wedervang-Resell, Kirsten, Myhre, Anne M, Andreassen, Ole A, Thompson, Paul M, Agartz, Ingrid, and ENIGMA-EOP Working Group
Subjects: ENIGMA-EOP Working Group, Brain, Hippocampus, Globus Pallidus, Humans, Magnetic Resonance Imaging, Adolescent Development, Affective Disorders, Psychotic, Psychotic Disorders, Schizophrenia, Age of Onset, Adolescent, adolescence, antipsychotics, brain structure, early-onset, intracranial volume, psychosis spectrum, Mental Health, Clinical Research, Serious Mental Illness, Biomedical Imaging, Brain Disorders, Pediatric, Pediatric Research Initiative, Neurosciences, Mental health, Good Health and Well Being, Cognitive Sciences, Experimental Psychology
Abstract: Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = -0.39) and hippocampal (d = -0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = -0.34) and affective psychosis (d = -0.42), and early-onset schizophrenia showed lower hippocampal (d = -0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = -0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis.
Published: 2022

40. BundleCleaner: Unsupervised Denoising and Subsampling of Diffusion MRI-Derived Tractography Data

Author: Feng, Yixue, Chandio, Bramsh Q., Villalón-Reina, Julio E., Thomopoulos, Sophia I., Joshi, Himanshu, Nair, Gauthami, Joshi, Anand A., Venkatasubramanian, Ganesan, John, John P., Thompson, Paul M., Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Karaman, Muge, editor, Mito, Remika, editor, Powell, Elizabeth, editor, Rheault, Francois, editor, and Winzeck, Stefan, editor
Published: 2023
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41. Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group

Author: Groenewold, Nynke A., Bas-Hoogendam, Janna Marie, Amod, Alyssa R., Laansma, Max A., Van Velzen, Laura S., Aghajani, Moji, Hilbert, Kevin, Oh, Hyuntaek, Salas, Ramiro, Jackowski, Andrea P., Pan, Pedro M., Salum, Giovanni A., Blair, James R., Blair, Karina S., Hirsch, Joy, Pantazatos, Spiro P., Schneier, Franklin R., Talati, Ardesheer, Roelofs, Karin, Volman, Inge, Blanco-Hinojo, Laura, Cardoner, Narcís, Pujol, Jesus, Beesdo-Baum, Katja, Ching, Christopher R. K., Thomopoulos, Sophia I., Jansen, Andreas, Kircher, Tilo, Krug, Axel, Nenadić, Igor, Stein, Frederike, Dannlowski, Udo, Grotegerd, Dominik, Lemke, Hannah, Meinert, Susanne, Winter, Alexandra, Erb, Michael, Kreifelts, Benjamin, Gong, Qiyong, Lui, Su, Zhu, Fei, Mwangi, Benson, Soares, Jair C., Wu, Mon-Ju, Bayram, Ali, Canli, Mesut, Tükel, Raşit, Westenberg, P. Michiel, Heeren, Alexandre, Cremers, Henk R., Hofmann, David, Straube, Thomas, Doruyter, Alexander G. G., Lochner, Christine, Peterburs, Jutta, Van Tol, Marie-José, Gur, Raquel E., Kaczkurkin, Antonia N., Larsen, Bart, Satterthwaite, Theodore D., Filippi, Courtney A., Gold, Andrea L., Harrewijn, Anita, Zugman, André, Bülow, Robin, Grabe, Hans J., Völzke, Henry, Wittfeld, Katharina, Böhnlein, Joscha, Dohm, Katharina, Kugel, Harald, Schrammen, Elisabeth, Zwanzger, Peter, Leehr, Elisabeth J., Sindermann, Lisa, Ball, Tali M., Fonzo, Gregory A., Paulus, Martin P., Simmons, Alan, Stein, Murray B., Klumpp, Heide, Phan, K. Luan, Furmark, Tomas, Månsson, Kristoffer N. T., Manzouri, Amirhossein, Avery, Suzanne N., Blackford, Jennifer Urbano, Clauss, Jacqueline A., Feola, Brandee, Harper, Jennifer C., Sylvester, Chad M., Lueken, Ulrike, Veltman, Dick J., Winkler, Anderson M., Jahanshad, Neda, Pine, Daniel S., Thompson, Paul M., Stein, Dan J., and Van der Wee, Nic J. A.
Published: 2023
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42. Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group

Author: Han, Laura KM, Dinga, Richard, Hahn, Tim, Ching, Christopher RK, Eyler, Lisa T, Aftanas, Lyubomir, Aghajani, Moji, Aleman, André, Baune, Bernhard T, Berger, Klaus, Brak, Ivan, Filho, Geraldo Busatto, Carballedo, Angela, Connolly, Colm G, Couvy-Duchesne, Baptiste, Cullen, Kathryn R, Dannlowski, Udo, Davey, Christopher G, Dima, Danai, Duran, Fabio LS, Enneking, Verena, Filimonova, Elena, Frenzel, Stefan, Frodl, Thomas, Fu, Cynthia HY, Godlewska, Beata R, Gotlib, Ian H, Grabe, Hans J, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Hall, Geoffrey B, Harrison, Ben J, Hatton, Sean N, Hermesdorf, Marco, Hickie, Ian B, Ho, Tiffany C, Hosten, Norbert, Jansen, Andreas, Kähler, Claas, Kircher, Tilo, Klimes-Dougan, Bonnie, Krämer, Bernd, Krug, Axel, Lagopoulos, Jim, Leenings, Ramona, MacMaster, Frank P, MacQueen, Glenda, McIntosh, Andrew, McLellan, Quinn, McMahon, Katie L, Medland, Sarah E, Mueller, Bryon A, Mwangi, Benson, Osipov, Evgeny, Portella, Maria J, Pozzi, Elena, Reneman, Liesbeth, Repple, Jonathan, Rosa, Pedro GP, Sacchet, Matthew D, Sämann, Philipp G, Schnell, Knut, Schrantee, Anouk, Simulionyte, Egle, Soares, Jair C, Sommer, Jens, Stein, Dan J, Steinsträter, Olaf, Strike, Lachlan T, Thomopoulos, Sophia I, van Tol, Marie-José, Veer, Ilya M, Vermeiren, Robert RJM, Walter, Henrik, van der Wee, Nic JA, van der Werff, Steven JA, Whalley, Heather, Winter, Nils R, Wittfeld, Katharina, Wright, Margaret J, Wu, Mon-Ju, Völzke, Henry, Yang, Tony T, Zannias, Vasileios, de Zubicaray, Greig I, Zunta-Soares, Giovana B, Abé, Christoph, Alda, Martin, Andreassen, Ole A, Bøen, Erlend, Bonnin, Caterina M, Canales-Rodriguez, Erick J, Cannon, Dara, Caseras, Xavier, Chaim-Avancini, Tiffany M, Elvsåshagen, Torbjørn, Favre, Pauline, Foley, Sonya F, and Fullerton, Janice M
Subjects: Depression, Aging, Brain Disorders, Biomedical Imaging, Serious Mental Illness, Mental Health, Major Depressive Disorder, Behavioral and Social Science, Clinical Research, Neurosciences, 2.3 Psychological, social and economic factors, Aetiology, Mental health, Adolescent, Adult, Aged, Brain, Depressive Disorder, Major, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Young Adult, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d = 0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.
Published: 2021

43. Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium

Author: Zhu, Xi, Kim, Yoojean, Ravid, Orren, He, Xiaofu, Suarez-Jimenez, Benjamin, Zilcha-Mano, Sigal, Lazarov, Amit, Lee, Seonjoo, Abdallah, Chadi G., Angstadt, Michael, Averill, Christopher L., Baird, C. Lexi, Baugh, Lee A., Blackford, Jennifer U., Bomyea, Jessica, Bruce, Steven E., Bryant, Richard A., Cao, Zhihong, Choi, Kyle, Cisler, Josh, Cotton, Andrew S., Daniels, Judith K., Davenport, Nicholas D., Davidson, Richard J., DeBellis, Michael D., Dennis, Emily L., Densmore, Maria, deRoon-Cassini, Terri, Disner, Seth G., Hage, Wissam El, Etkin, Amit, Fani, Negar, Fercho, Kelene A., Fitzgerald, Jacklynn, Forster, Gina L., Frijling, Jessie L., Geuze, Elbert, Gonenc, Atilla, Gordon, Evan M., Gruber, Staci, Grupe, Daniel W, Guenette, Jeffrey P., Haswell, Courtney C., Herringa, Ryan J., Herzog, Julia, Hofmann, David Bernd, Hosseini, Bobak, Hudson, Anna R., Huggins, Ashley A., Ipser, Jonathan C., Jahanshad, Neda, Jia-Richards, Meilin, Jovanovic, Tanja, Kaufman, Milissa L., Kennis, Mitzy, King, Anthony, Kinzel, Philipp, Koch, Saskia B.J., Koerte, Inga K., Koopowitz, Sheri M., Korgaonkar, Mayuresh S., Krystal, John H., Lanius, Ruth, Larson, Christine L., Lebois, Lauren A.M., Li, Gen, Liberzon, Israel, Lu, Guang Ming, Luo, Yifeng, Magnotta, Vincent A., Manthey, Antje, Maron-Katz, Adi, May, Geoffery, McLaughlin, Katie, Mueller, Sven C., Nawijn, Laura, Nelson, Steven M., Neufeld, Richard W.J., Nitschke, Jack B, O'Leary, Erin M., Olatunji, Bunmi O., Olff, Miranda, Peverill, Matthew, Phan, K. Luan, Qi, Rongfeng, Quidé, Yann, Rektor, Ivan, Ressler, Kerry, Riha, Pavel, Ross, Marisa, Rosso, Isabelle M., Salminen, Lauren E., Sambrook, Kelly, Schmahl, Christian, Shenton, Martha E., Sheridan, Margaret, Shih, Chiahao, Sicorello, Maurizio, Sierk, Anika, Simmons, Alan N., Simons, Raluca M., Simons, Jeffrey S., Sponheim, Scott R., Stein, Murray B., Stein, Dan J., Stevens, Jennifer S., Straube, Thomas, Sun, Delin, Théberge, Jean, Thompson, Paul M., Thomopoulos, Sophia I., van der Wee, Nic J.A., van der Werff, Steven J.A., van Erp, Theo G.M., van Rooij, Sanne J.H., van Zuiden, Mirjam, Varkevisser, Tim, Veltman, Dick J., Vermeiren, Robert R.J.M., Walter, Henrik, Wang, Li, Wang, Xin, Weis, Carissa, Winternitz, Sherry, Xie, Hong, Zhu, Ye, Wall, Melanie, Neria, Yuval, and Morey, Rajendra A.
Published: 2023
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44. Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis

Author: Wang, Xin, Xie, Hong, Chen, Tian, Cotton, Andrew S, Salminen, Lauren E, Logue, Mark W, Clarke-Rubright, Emily K, Wall, John, Dennis, Emily L, O’Leary, Brian M, Abdallah, Chadi G, Andrew, Elpiniki, Baugh, Lee A, Bomyea, Jessica, Bruce, Steven E, Bryant, Richard, Choi, Kyle, Daniels, Judith K, Davenport, Nicholas D, Davidson, Richard J, DeBellis, Michael, deRoon-Cassini, Terri, Disner, Seth G, Fani, Negar, Fercho, Kelene A, Fitzgerald, Jacklynn, Forster, Gina L, Frijling, Jessie L, Geuze, Elbert, Gomaa, Hassaan, Gordon, Evan M, Grupe, Dan, Harpaz-Rotem, Ilan, Haswell, Courtney C, Herzog, Julia I, Hofmann, David, Hollifield, Michael, Hosseini, Bobak, Hudson, Anna R, Ipser, Jonathan, Jahanshad, Neda, Jovanovic, Tanja, Kaufman, Milissa L, King, Anthony P, Koch, Saskia BJ, Koerte, Inga K, Korgaonkar, Mayuresh S, Krystal, John H, Larson, Christine, Lebois, Lauren AM, Levy, Ifat, Li, Gen, Magnotta, Vincent A, Manthey, Antje, May, Geoffrey, McLaughlin, Katie A, Mueller, Sven C, Nawijn, Laura, Nelson, Steven M, Neria, Yuval, Nitschke, Jack B, Olff, Miranda, Olson, Elizabeth A, Peverill, Matthew, Phan, K Luan, Rashid, Faisal M, Ressler, Kerry, Rosso, Isabelle M, Sambrook, Kelly, Schmahl, Christian, Shenton, Martha E, Sierk, Anika, Simons, Jeffrey S, Simons, Raluca M, Sponheim, Scott R, Stein, Murray B, Stein, Dan J, Stevens, Jennifer S, Straube, Thomas, Suarez-Jimenez, Benjamin, Tamburrino, Marijo, Thomopoulos, Sophia I, van der Wee, Nic JA, van der Werff, Steven JA, van Erp, Theo GM, van Rooij, Sanne JH, van Zuiden, Mirjam, Varkevisser, Tim, Veltman, Dick J, Vermeiren, Robert RJM, Walter, Henrik, Wang, Li, Zhu, Ye, Zhu, Xi, Thompson, Paul M, Morey, Rajendra A, and Liberzon, Israel
Subjects: Clinical Research, Behavioral and Social Science, Mental Health, Post-Traumatic Stress Disorder (PTSD), Neurosciences, Brain Disorders, Mental health, Cerebral Cortex, Genomics, Humans, Magnetic Resonance Imaging, Stress Disorders, Post-Traumatic, Temporal Lobe, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = -0.111 to -0.068, FDR corrected P values
Published: 2021

45. Challenges and opportunities for neuroimaging in young patients with traumatic brain injury: a coordinated effort towards advancing discovery from the ENIGMA pediatric moderate/severe TBI group

Author: Dennis, Emily L, Caeyenberghs, Karen, Asarnow, Robert F, Babikian, Talin, Bartnik-Olson, Brenda, Bigler, Erin D, Figaji, Anthony, Giza, Christopher C, Goodrich-Hunsaker, Naomi J, Hodges, Cooper B, Hoskinson, Kristen R, Königs, Marsh, Levin, Harvey S, Lindsey, Hannah M, Livny, Abigail, Max, Jeffrey E, Merkley, Tricia L, Newsome, Mary R, Olsen, Alexander, Ryan, Nicholas P, Spruiell, Matthew S, Suskauer, Stacy J, Thomopoulos, Sophia I, Ware, Ashley L, Watson, Christopher G, Wheeler, Anne L, Yeates, Keith Owen, Zielinski, Brandon A, Thompson, Paul M, Tate, David F, and Wilde, Elisabeth A
Subjects: Brain Disorders, Clinical Research, Neurosciences, Biomedical Imaging, Physical Injury - Accidents and Adverse Effects, Pediatric, Childhood Injury, Pediatric Research Initiative, Unintentional Childhood Injury, Traumatic Brain Injury (TBI), Traumatic Head and Spine Injury, Injuries and accidents, Adolescent, Adult, Biomarkers, Brain Injuries, Traumatic, Child, Humans, Magnetic Resonance Imaging, Neuroimaging, traumatic brain injury, ENIGMA, Moderate-severe TBI, Medical and Health Sciences, Psychology and Cognitive Sciences, Experimental Psychology
Abstract: Traumatic brain injury (TBI) is a major cause of death and disability in children in both developed and developing nations. Children and adolescents suffer from TBI at a higher rate than the general population, and specific developmental issues require a unique context since findings from adult research do not necessarily directly translate to children. Findings in pediatric cohorts tend to lag behind those in adult samples. This may be due, in part, both to the smaller number of investigators engaged in research with this population and may also be related to changes in safety laws and clinical practice that have altered length of hospital stays, treatment, and access to this population. The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Pediatric Moderate/Severe TBI (msTBI) group aims to advance research in this area through global collaborative meta-analysis of neuroimaging data. In this paper, we discuss important challenges in pediatric TBI research and opportunities that we believe the ENIGMA Pediatric msTBI group can provide to address them. With the paucity of research studies examining neuroimaging biomarkers in pediatric patients with TBI and the challenges of recruiting large numbers of participants, collaborating to improve statistical power and to address technical challenges like lesions will significantly advance the field. We conclude with recommendations for future research in this field of study.
Published: 2021

46. A worldwide study of white matter microstructural alterations in people living with Parkinson’s disease

Author: Owens-Walton, Conor, Nir, Talia M., Al-Bachari, Sarah, Ambrogi, Sonia, Anderson, Tim J., Aventurato, Ítalo Karmann, Cendes, Fernando, Chen, Yao-Liang, Ciullo, Valentina, Cook, Phil, Dalrymple-Alford, John C., Dirkx, Michiel F., Druzgal, Jason, Emsley, Hedley C. A., Guimarães, Rachel, Haroon, Hamied A., Helmich, Rick C., Hu, Michele T., Johansson, Martin E., Kim, Ho Bin, Klein, Johannes C., Laansma, Max, Lawrence, Katherine E., Lochner, Christine, Mackay, Clare, McMillan, Corey T., Melzer, Tracy R., Nabulsi, Leila, Newman, Ben, Opriessnig, Peter, Parkes, Laura M., Pellicano, Clelia, Piras, Fabrizio, Piras, Federica, Pirpamer, Lukas, Pitcher, Toni L., Poston, Kathleen L., Roos, Annerine, Silva, Lucas Scárdua, Schmidt, Reinhold, Schwingenschuh, Petra, Shahid-Besanti, Marian, Spalletta, Gianfranco, Stein, Dan J., Thomopoulos, Sophia I., Tosun, Duygu, Tsai, Chih-Chien, van den Heuvel, Odile A., van Heese, Eva, Vecchio, Daniela, Villalón-Reina, Julio E., Vriend, Chris, Wang, Jiun-Jie, Wu, Yih-Ru, Yasuda, Clarissa Lin, Thompson, Paul M., Jahanshad, Neda, and van der Werf, Ysbrand
Published: 2024
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47. Neurostructural subgroup in 4291 individuals with schizophrenia identified using the subtype and stage inference algorithm

Author: Jiang, Yuchao, Luo, Cheng, Wang, Jijun, Palaniyappan, Lena, Chang, Xiao, Xiang, Shitong, Zhang, Jie, Duan, Mingjun, Huang, Huan, Gaser, Christian, Nemoto, Kiyotaka, Miura, Kenichiro, Hashimoto, Ryota, Westlye, Lars T., Richard, Genevieve, Fernandez-Cabello, Sara, Parker, Nadine, Andreassen, Ole A., Kircher, Tilo, Nenadić, Igor, Stein, Frederike, Thomas-Odenthal, Florian, Teutenberg, Lea, Usemann, Paula, Dannlowski, Udo, Hahn, Tim, Grotegerd, Dominik, Meinert, Susanne, Lencer, Rebekka, Tang, Yingying, Zhang, Tianhong, Li, Chunbo, Yue, Weihua, Zhang, Yuyanan, Yu, Xin, Zhou, Enpeng, Lin, Ching-Po, Tsai, Shih-Jen, Rodrigue, Amanda L., Glahn, David, Pearlson, Godfrey, Blangero, John, Karuk, Andriana, Pomarol-Clotet, Edith, Salvador, Raymond, Fuentes-Claramonte, Paola, Garcia-León, María Ángeles, Spalletta, Gianfranco, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Cheng, Jingliang, Liu, Zhening, Yang, Jie, Gonul, Ali Saffet, Uslu, Ozgul, Burhanoglu, Birce Begum, Uyar Demir, Aslihan, Rootes-Murdy, Kelly, Calhoun, Vince D., Sim, Kang, Green, Melissa, Quidé, Yann, Chung, Young Chul, Kim, Woo-Sung, Sponheim, Scott R., Demro, Caroline, Ramsay, Ian S., Iasevoli, Felice, de Bartolomeis, Andrea, Barone, Annarita, Ciccarelli, Mariateresa, Brunetti, Arturo, Cocozza, Sirio, Pontillo, Giuseppe, Tranfa, Mario, Park, Min Tae M., Kirschner, Matthias, Georgiadis, Foivos, Kaiser, Stefan, Van Rheenen, Tamsyn E., Rossell, Susan L., Hughes, Matthew, Woods, William, Carruthers, Sean P., Sumner, Philip, Ringin, Elysha, Spaniel, Filip, Skoch, Antonin, Tomecek, David, Homan, Philipp, Homan, Stephanie, Omlor, Wolfgang, Cecere, Giacomo, Nguyen, Dana D., Preda, Adrian, Thomopoulos, Sophia I., Jahanshad, Neda, Cui, Long-Biao, Yao, Dezhong, Thompson, Paul M., Turner, Jessica A., van Erp, Theo G. M., Cheng, Wei, and Feng, Jianfeng
Published: 2024
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48. Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures

Author: Belov, Vladimir, Erwin-Grabner, Tracy, Aghajani, Moji, Aleman, Andre, Amod, Alyssa R., Basgoze, Zeynep, Benedetti, Francesco, Besteher, Bianca, Bülow, Robin, Ching, Christopher R. K., Connolly, Colm G., Cullen, Kathryn, Davey, Christopher G., Dima, Danai, Dols, Annemiek, Evans, Jennifer W., Fu, Cynthia H. Y., Gonul, Ali Saffet, Gotlib, Ian H., Grabe, Hans J., Groenewold, Nynke, Hamilton, J Paul, Harrison, Ben J., Ho, Tiffany C., Mwangi, Benson, Jaworska, Natalia, Jahanshad, Neda, Klimes-Dougan, Bonnie, Koopowitz, Sheri-Michelle, Lancaster, Thomas, Li, Meng, Linden, David E. J., MacMaster, Frank P., Mehler, David M. A., Melloni, Elisa, Mueller, Bryon A., Ojha, Amar, Oudega, Mardien L., Penninx, Brenda W. J. H., Poletti, Sara, Pomarol-Clotet, Edith, Portella, Maria J., Pozzi, Elena, Reneman, Liesbeth, Sacchet, Matthew D., Sämann, Philipp G., Schrantee, Anouk, Sim, Kang, Soares, Jair C., Stein, Dan J., Thomopoulos, Sophia I., Uyar-Demir, Aslihan, van der Wee, Nic J. A., van der Werff, Steven J. A., Völzke, Henry, Whittle, Sarah, Wittfeld, Katharina, Wright, Margaret J., Wu, Mon-Ju, Yang, Tony T., Zarate, Carlos, Veltman, Dick J., Schmaal, Lianne, Thompson, Paul M., and Goya-Maldonado, Roberto
Published: 2024
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49. Circular-SWAT for deep learning based diagnostic classification of Alzheimer's disease: application to metabolome data

Author: Kaddurah-Daouk, Rima, Kueider-Paisley, Alexandra, Doraiswamy, P. Murali, Blach, Colette, Moseley, Arthur, Thompson, Will, St John-Williams, Lisa, Mahmoudiandehkhordi, Siamak, Tenenbaum, Jessica, Welsh-Balmer, Kathleen, Plassman, Brenda, Saykin, Andrew J., Nho, Kwangsik, Risacher, Shannon L., Kastenmüller, Gabi, Arnold, Matthias, Han, Xianlin, Baillie, Rebecca, Knight, Rob, Dorrestein, Pieter, Brewer, James, Mayer, Emeran, Labus, Jennifer, Baldi, Pierre, Gupta, Arpana, Fiehn, Oliver, Barupal, Dinesh, Meikle, Peter, Mazmanian, Sarkis, Rader, Dan, Kling, Mitchel, Shaw, Leslie, Trojanowski, John, van Duijin, Cornelia, Nevado-Holgado, Alejo, Bennett, David, Krishnan, Ranga, Keshavarzian, Ali, Vogt, Robin, Ikram, Arfan, Hankemeier, Thomas, Thiele, Ines, Price, Nathan, Funk, Cory, Baloni, Priyanka, Jia, Wei, Wishart, David, Brinton, Roberta, Chang, Rui, Farrer, Lindsay, Au, Rhoda, Qiu, Wendy, Würtz, Peter, Koal, Therese, Mangravite, Lara, Krumsiek, Jan, Suhre, Karsten, Newman, John, Moreno, Herman, Foroud, Tatania, Sacks, Frank, Jansson, Janet, Weiner, Michael W., Aisen, Paul, Petersen, Ronald, Jack, Clifford R., Jr., Jagust, William, Trojanowki, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Morris, John C., Perrin, Richard J., Shaw, Leslie M., Khachaturian, Zaven, Carrillo, Maria, Potter, William, Barnes, Lisa, Bernard, Marie, Gonzalez, Hector, Ho, Carole, Hsiao, John K., Jackson, Jonathan, Masliah, Eliezer, Masterman, Donna, Okonkwo, Ozioma, Perrin, Richard, Ryan, Laurie, Silverberg, Nina, Fleisher, Adam, Sacrey, Diana Truran, Fockler, Juliet, Conti, Cat, Veitch, Dallas, Neuhaus, John, Jin, Chengshi, Nosheny, Rachel, Ashford, Miriam, Flenniken, Derek, Kormos, Adrienne, Montine, Tom, Rafii, Michael, Raman, Rema, Jimenez, Gustavo, Donohue, Michael, Gessert, Devon, Salazar, Jennifer, Zimmerman, Caileigh, Cabrera, Yuliana, Walter, Sarah, Miller, Garrett, Coker, Godfrey, Clanton, Taylor, Hergesheimer, Lindsey, Smith, Stephanie, Adegoke, Olusegun, Mahboubi, Payam, Moore, Shelley, Pizzola, Jeremy, Shaffer, Elizabeth, Sloan, Brittany, Harvey, Danielle, Forghanian-Arani, Arvin, Borowski, Bret, Ward, Chad, Schwarz, Christopher, Jones, David, Gunter, Jeff, Kantarci, Kejal, Senjem, Matthew, Vemuri, Prashanthi, Reid, Robert, Fox, Nick C., Malone, Ian, Thompson, Paul, Thomopoulos, Sophia I., Nir, Talia M., Jahanshad, Neda, DeCarli, Charles, Knaack, Alexander, Fletcher, Evan, Tosun-Turgut, Duygu, Chen, Stephanie Rossi, Choe, Mark, Crawford, Karen, Yushkevich, Paul A., Das, Sandhitsu, Koeppe, Robert A., Reiman, Eric M., Chen, Kewei, Mathis, Chet, Landau, Susan, Cairns, Nigel J., Householder, Erin, Franklin, Erin, Bernhardt, Haley, Taylor-Reinwald, Lisa, Korecka, Magdalena, Figurski, Michal, Neu, Scott, Apostolova, Liana G., Shen, Li, Foroud, Tatiana M., Nudelman, Kelly, Faber, Kelley, Wilmes, Kristi, Thal, Leon, Silbert, Lisa C., Lind, Betty, Crissey, Rachel, Kaye, Jeffrey A., Carter, Raina, Dolen, Sara, Quinn, Joseph, Schneider, Lon S., Pawluczyk, Sonia, Becerra, Mauricio, Teodoro, Liberty, Dagerman, Karen, Spann, Bryan M., Vanderswag, Helen, Ziolkowski, Jaimie, Heidebrink, Judith L., Zbizek-Nulph, Lisa, Lord, Joanne L., Mason, Sara S., Albers, Colleen S., Knopman, David, Johnson, Kris, Villanueva-Meyer, Javier, Pavlik, Valory, Pacini, Nathaniel, Lamb, Ashley, Kass, Joseph S., Doody, Rachelle S., Shibley, Victoria, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S., Mintz, Akiva, Ances, Beau, Winkfield, David, Carroll, Maria, Stobbs-Cucchi, Georgia, Oliver, Angela, Creech, Mary L., Mintun, Mark A., Schneider, Stacy, Geldmacher, David, Love, Marissa Natelson, Griffith, Randall, Clark, David, Brockington, John, Marson, Daniel, Grossman, Hillel, Goldstein, Martin A., Greenberg, Jonathan, Mitsis, Effie, Shah, Raj C., Lamar, Melissa, Samuels, Patricia, Duara, Ranjan, Greig-Custo, Maria T., Rodriguez, Rosemarie, Albert, Marilyn, Onyike, Chiadi, Farrington, Leonie, Rudow, Scott, Brichko, Rottislav, Kielb, Stephanie, Smith, Amanda, Raj, Balebail Ashok, Fargher, Kristin, Sadowski, Martin, Wisniewski, Thomas, Shulman, Melanie, Faustin, Arline, Rao, Julia, Castro, Karen M., Ulysse, Anaztasia, Chen, Shannon, Sheikh, Mohammed O., Singleton-Garvin, Jamika, Petrella, JeffreyR., James, Olga, Wong, Terence Z., Borges-Neto, Salvador, Karlawish, Jason H., Wolk, David A., Vaishnavi, Sanjeev, Clark, Christopher M., Arnold, Steven E., Smith, Charles D., Jicha, Gregory A., Raslau, Flavius D., Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Porsteinsson, Anton P., Martin, Kim, Kowalski, Nancy, Keltz, Melanie, Goldstein, Bonnie S., Makino, Kelly M., Ismail, M. Saleem, Brand, Connie, Thai, Gaby, Pierce, Aimee, Yanez, Beatriz, Sosa, Elizabeth, Witbracht, Megan, Kelley, Brendan, Nguyen, Trung, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Levey, Allan I., Lah, James J., Hajjar, Ihab, Cellar, Janet S., Burns, Jeffrey M., Swerdlow, Russell H., Brooks, William M., Silverman, Daniel H.S., Kremen, Sarah, Apostolova, Liana, Tingus, Kathleen, Lu, Po H., Bartzokis, George, Woo, Ellen, Teng, Edmond, Graff-Radford, Neill R., Parfitt, Francine, Poki-Walker, Kim, Farlow, Martin R., Hake, Ann Marie, Matthews, Brandy R., Brosch, Jared R., Herring, Scott, van, Christopher H., Mecca, Adam P., Good, Susan P., MacAvoy, Martha G., Carson, Richard E., Varma, Pradeep, Chertkow, Howard, Vaitekunis, Susan, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Heyn, Chris (Chinthaka), Robin Hsiung, Ging-Yuek, Kim, Ellen, Mudge, Benita, Sossi, Vesna, Feldman, Howard, Assaly, Michele, Finger, Elizabeth, Pasternak, Stephen, Rachinsky, Irina, Kertesz, Andrew, Drost, Dick, Rogers, John, Grant, Ian, Muse, Brittanie, Rogalski, Emily, Robson, Jordan, Mesulam, M.-Marsel, Kerwin, Diana, Wu, Chuang-Kuo, Johnson, Nancy, Lipowski, Kristine, Weintraub, Sandra, Bonakdarpour, Borna, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Rosen, Howard J., Miller, Bruce L., Perry, David, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, MCCann, Kelly, Poe, Jessica, Sperling, Reisa A., Johnson, Keith A., Marshall, Gad A., Yesavage, Jerome, Taylor, Joy L., Chao, Steven, Coleman, Jaila, White, Jessica D., Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Belden, Christine M., Atri, Alireza, Clark, Kelly A., Zamrini, Edward, Sabbagh, Marwan, Killiany, Ronald, Stern, Robert, Mez, Jesse, Kowall, Neil, Budson, Andrew E., Obisesan, Thomas O., Ntekim, Oyonumo E., Wolday, Saba, Khan, Javed I., Nwulia, Evaristus, Nadarajah, Sheeba, Lerner, Alan, Ogrocki, Paula, Tatsuoka, Curtis, Fatica, Parianne, Maillard, Pauline, Olichney, John, Carmichael, Owen, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Borrie, Michael, Lee, T.-Y., Bartha, Dr Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Perrin, Allison, Burke, Anna, Scharre, Douglas W., Kataki, Maria, Tarawneh, Rawan, Hart, David, Zimmerman, Earl A., Celmins, Dzintra, Miller, Delwyn D., BolesPonto, Laura L., Smith, Karen Ekstam, Koleva, Hristina, Shim, Hyungsub, Nam, Ki Won, Schultz, Susan K., Williamson, Jeff D., Craft, Suzanne, Cleveland, Jo, Yang, Mia, Sink, Kaycee M., Ott, Brian R., Drake, Jonathan, Tremont, Geoffrey, Daiello, Lori A., Drake, Jonathan D., Ritter, Aaron, Bernick, Charles, Munic, Donna, O'Connelll, Abigail, Mintzer, Jacobo, Wiliams, Arthur, Masdeu, Joseph, Shi, Jiong, Garcia, Angelica, Newhouse, Paul, Potkin, Steven, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Kittur, Smita, Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Flashman, Laura A., Seltzer, Marc, Hynes, Mary L., Santulli, Robert B., Relkin, Norman, Chiang, Gloria, Lee, Athena, Lin, Michael, Ravdin, Lisa, Petersen, Ron, Neylan, Thomas, Grafman, Jordan, Danowski, Sarah, Nguyen-Barrera, Catherine, Hayes, Jacqueline, Finley, Shannon, Bernstein, Matthew, Senjem, Matt, Foster, Norm, Kim, Sungeun, Sood, Ajay, Blanchard, Kimberly S., Fleischman, Debra, Arfanakis, Konstantinos, Varon, Daniel, Greig, Maria T., Petrella, Jeffrey R., Goldstein, Bonnie, Martin, Kimberly S., Reist, Christopher, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Rosen, Howard, Marshall, Gad, Peskind, Elaine R., Petrie, Eric C., Li, Gail, Mackin, Scott, Jimenez-Maggiora, Gustavo, Drake, Erin, Donohue, Mike, Nelson, Craig, Bickford, David, Butters, Meryl, Zmuda, Michelle, Reyes, Denise, Faber, Kelley M., Nudelman, Kelly N., Au, Yiu Ho, Scherer, Kelly, Catalinotto, Daniel, Stark, Samuel, Ong, Elise, Fernandez, Dariella, Jo, Taeho, Kim, Junpyo, Bice, Paula, Huynh, Kevin, Wang, Tingting, Meikle, Peter J., and Giles, Corey
Published: 2023
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50. Cortical and Subcortical Brain Alterations in Specific Phobia and Its Animal and Blood-Injection-Injury Subtypes: A Mega-Analysis From the ENIGMA Anxiety Working Group

Author: Hilbert, Kevin, primary, Boeken, Ole Jonas, additional, Langhammer, Till, additional, Groenewold, Nynke A., additional, Bas-Hoogendam, Janna Marie, additional, Aghajani, Moji, additional, Zugman, André, additional, Åhs, Fredrik, additional, Arolt, Volker, additional, Beesdo-Baum, Katja, additional, Björkstrand, Johannes, additional, Blackford, Jennifer U., additional, Blanco-Hinojo, Laura, additional, Böhnlein, Joscha, additional, Bülow, Robin, additional, Cano, Marta, additional, Cardoner, Narcis, additional, Caseras, Xavier, additional, Dannlowski, Udo, additional, Domschke, Katharina, additional, Fehm, Lydia, additional, Feola, Brandee, additional, Fredrikson, Mats, additional, Goossens, Liesbet, additional, Grabe, Hans J., additional, Grotegerd, Dominik, additional, Gur, Raquel E., additional, Hamm, Alfons O., additional, Harrewijn, Anita, additional, Heinig, Ingmar, additional, Herrmann, Martin J., additional, Hofmann, David, additional, Jackowski, Andrea P., additional, Jansen, Andreas, additional, Kaczkurkin, Antonia N., additional, Kindt, Merel, additional, Kingsley, Ellen N., additional, Kircher, Tilo, additional, Klahn, Anna L., additional, Koelkebeck, Katja, additional, Krug, Axel, additional, Kugel, Harald, additional, Larsen, Bart, additional, Leehr, Elisabeth J., additional, Leonhardt, Lieselotte, additional, Lotze, Martin, additional, Margraf, Jürgen, additional, Michałowski, Jarosław, additional, Muehlhan, Markus, additional, Nenadić, Igor, additional, Pan, Pedro M., additional, Pauli, Paul, additional, Peñate, Wenceslao, additional, Pittig, Andre, additional, Plag, Jens, additional, Pujol, Jesus, additional, Richter, Jan, additional, Rivero, Francisco L., additional, Salum, Giovanni A., additional, Satterthwaite, Theodore D., additional, Schäfer, Axel, additional, Schäfer, Judith, additional, Schienle, Anne, additional, Schneider, Silvia, additional, Schrammen, Elisabeth, additional, Schruers, Koen, additional, Schulz, Stefan M., additional, Seidl, Esther, additional, Stark, Rudolf M., additional, Stein, Frederike, additional, Straube, Benjamin, additional, Straube, Thomas, additional, Ströhle, Andreas, additional, Suchan, Boris, additional, Thomopoulos, Sophia I., additional, Ventura-Bort, Carlos, additional, Visser, Renee, additional, Völzke, Henry, additional, Wabnegger, Albert, additional, Wannemüller, André, additional, Wendt, Julia, additional, Wiemer, Julian, additional, Wittchen, Hans-Ulrich, additional, Wittfeld, Katharina, additional, Wright, Barry, additional, Yang, Yunbo, additional, Zilverstand, Anna, additional, Zwanzger, Peter, additional, Veltman, Dick J., additional, Winkler, Anderson M., additional, Pine, Daniel S., additional, Jahanshad, Neda, additional, Thompson, Paul M., additional, Stein, Dan J., additional, Van der Wee, Nic J.A., additional, and Lueken, Ulrike, additional
Published: 2024
Full Text: View/download PDF

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