Search

Your search keyword '"National Institute for Health and Care Research (US)"' showing total 23 results
Start Over Author "National Institute for Health and Care Research (US)" Search Limiters Available in Library Collection
23 results on '"National Institute for Health and Care Research (US)"'

1. Brain tumour microstructure is associated with post-surgical cognition

Author

Cancer Research UK, Brain Tumour Charity, Ministerio de Universidades (España), Junta de Andalucía, National Institute for Health and Care Research (US), Aznarez-Sanado, Maite, Romero García, Rafael, Li, Chao, Morris, Rob C., Price, Stephen J., Manly, Thomas, Santarius, Thomas, Erez, Yaara, Hart, Michael G., Suckling, John, Cancer Research UK, Brain Tumour Charity, Ministerio de Universidades (España), Junta de Andalucía, National Institute for Health and Care Research (US), Aznarez-Sanado, Maite, Romero García, Rafael, Li, Chao, Morris, Rob C., Price, Stephen J., Manly, Thomas, Santarius, Thomas, Erez, Yaara, Hart, Michael G., and Suckling, John

Abstract

Brain tumour microstructure is potentially predictive of changes following treatment to cognitive functions subserved by the functional networks in which they are embedded. To test this hypothesis, intra-tumoural microstructure was quantified from diffusion-weighted MRI to identify which tumour subregions (if any) had a greater impact on participants' cognitive recovery after surgical resection. Additionally, we studied the role of tumour microstructure in the functional interaction between the tumour and the rest of the brain. Sixteen patients (22-56 years, 7 females) with brain tumours located in or near speech-eloquent areas of the brain were included in the analyses. Two different approaches were adopted for tumour segmentation from a multishell diffusion MRI acquisition: the first used a two-dimensional four group partition of feature space, whilst the second used data-driven clustering with Gaussian mixture modelling. For each approach, we assessed the capability of tumour microstructure to predict participants' cognitive outcomes after surgery and the strength of association between the BOLD signal of individual tumour subregions and the global BOLD signal. With both methodologies, the volumes of partially overlapped subregions within the tumour significantly predicted cognitive decline in verbal skills after surgery. We also found that these particular subregions were among those that showed greater functional interaction with the unaffected cortex. Our results indicate that tumour microstructure measured by MRI multishell diffusion is associated with cognitive recovery after surgery.

Published
2024

2. Robust estimation of cortical similarity networks from brain MRI

Author

Gates Cambridge Scholarships, Schmidt Futures, National Institute of Mental Health (US), St Catharine's College, Autism Research Trust, Junta de Andalucía, Universidad de Sevilla, National Institutes of Health (US), National Institute for Health and Care Research (US), Alan Turing Institute, Sebenius, Isaac, Seidlitz, Jakob, Warrier, Varun, Bethlehem, Richard A. I., Alexander-Bloch, Aaron, Mallard, Travis T., Romero García, Rafael, Bullmore, Edward T., Morgan, Sarah E., Gates Cambridge Scholarships, Schmidt Futures, National Institute of Mental Health (US), St Catharine's College, Autism Research Trust, Junta de Andalucía, Universidad de Sevilla, National Institutes of Health (US), National Institute for Health and Care Research (US), Alan Turing Institute, Sebenius, Isaac, Seidlitz, Jakob, Warrier, Varun, Bethlehem, Richard A. I., Alexander-Bloch, Aaron, Mallard, Travis T., Romero García, Rafael, Bullmore, Edward T., and Morgan, Sarah E.

Abstract

Structural similarity is a growing focus for magnetic resonance imaging (MRI) of connectomes. Here we propose Morphometric INverse Divergence (MIND), a new method to estimate within-subject similarity between cortical areas based on the divergence between their multivariate distributions of multiple MRI features. Compared to the prior approach of morphometric similarity networks (MSNs) on n > 11,000 scans spanning three human datasets and one macaque dataset, MIND networks were more reliable, more consistent with cortical cytoarchitectonics and symmetry and more correlated with tract-tracing measures of axonal connectivity. MIND networks derived from human T1-weighted MRI were more sensitive to age-related changes than MSNs or networks derived by tractography of diffusion-weighted MRI. Gene co-expression between cortical areas was more strongly coupled to MIND networks than to MSNs or tractography. MIND network phenotypes were also more heritable, especially edges between structurally differentiated areas. MIND network analysis provides a biologically validated lens for cortical connectomics using readily available MRI data.

Published
2023

3. Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome

Author

National Institutes of Health (US), Lundbeck Foundation, German Research Foundation, Royal Netherlands Academy of Arts and Sciences, National Science Centre (Poland), National Institute for Health and Care Research (US), NIHR Biomedical Research Centre (UK), Jain, Pritesh, Miller-Fleming, Tyne, Topaloudi, Apostolia, Yu, Dongmei, Drineas, Petros, Georgitsi, Marianthi, Yang, Zhiyu, Rizzo, Renata, Müller-Vahl, Kirsten R., Tumer, Zeynep, Mol Debes, Nanette, Hartmann, Andreas, Depienne, Christel, Worbe, Yulia, Mir, Pablo, Cath, Danielle, Boomsma, Dorret I., Roessner, Veit, Wolańczyk, Tomasz, Janik, Piotr, Szejko, Natalia, Zekanowski, Cezary, Barta, Csaba, Nemoda, Zsofia, Tarnok, Zsanett, Buxbaum, Joseph D., Grice, Dorothy, Glennon, Jeffrey, Stefansson, Hreinn, Hengerer, Bastian, Benaroya‑Milshtein, Noa, Cardona, Francesco, Hedderly, Tammy, Heyman, Isobel, Huyser, Chaim, Morer, Astrid, Mueller, Norbert, Münchau, Alexander, Plessen, Kerstin J., Porcelli, Cesare, Walitza, Susanne, Schrag, Anette, Martino, Davide, The Psychiatric Genomics Consortium Tourette Syndrome Working Group (PGC-TS), The EMTICS collaborative group, Dietrich, Andrea, The TS-EUROTRAIN Network, Mathews, Carol A., Scharf, Jeremiah M., Hoekstra, Pieter J., Davis, Lea K., Paschou, Peristera, National Institutes of Health (US), Lundbeck Foundation, German Research Foundation, Royal Netherlands Academy of Arts and Sciences, National Science Centre (Poland), National Institute for Health and Care Research (US), NIHR Biomedical Research Centre (UK), Jain, Pritesh, Miller-Fleming, Tyne, Topaloudi, Apostolia, Yu, Dongmei, Drineas, Petros, Georgitsi, Marianthi, Yang, Zhiyu, Rizzo, Renata, Müller-Vahl, Kirsten R., Tumer, Zeynep, Mol Debes, Nanette, Hartmann, Andreas, Depienne, Christel, Worbe, Yulia, Mir, Pablo, Cath, Danielle, Boomsma, Dorret I., Roessner, Veit, Wolańczyk, Tomasz, Janik, Piotr, Szejko, Natalia, Zekanowski, Cezary, Barta, Csaba, Nemoda, Zsofia, Tarnok, Zsanett, Buxbaum, Joseph D., Grice, Dorothy, Glennon, Jeffrey, Stefansson, Hreinn, Hengerer, Bastian, Benaroya‑Milshtein, Noa, Cardona, Francesco, Hedderly, Tammy, Heyman, Isobel, Huyser, Chaim, Morer, Astrid, Mueller, Norbert, Münchau, Alexander, Plessen, Kerstin J., Porcelli, Cesare, Walitza, Susanne, Schrag, Anette, Martino, Davide, The Psychiatric Genomics Consortium Tourette Syndrome Working Group (PGC-TS), The EMTICS collaborative group, Dietrich, Andrea, The TS-EUROTRAIN Network, Mathews, Carol A., Scharf, Jeremiah M., Hoekstra, Pieter J., Davis, Lea K., and Paschou, Peristera

Abstract

Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders.

Published
2023

4. Myostatin and follistatin as monitoring and prognostic biomarkers in dysferlinopathy

Author

John Walton Centre Muscular Dystrophy Research Centre, National Institute for Health and Care Research (US), Newcastle Biomedical Research Centre, Moore, Ursula, Fernández-Simón, Esther, Schiava, Marianela, Cox, Dan, Gordish-Dressman, Heather, James, Meredith K., Mayhew, Anna, Wilson, Ian, Guglieri, Michela, Rufibach, Laura, Blamire, Andrew, Carlier, Pierre G., Mori-Yoshimura, Madoka, Day, John W., Jones, Kristi J., Bharucha-Goebel, Diana X., Salort-Campana, Emmanuelle, Pestronk, Alan, Walter, Maggie C., Paradas, Carmen, Stojkovic, Tanya, Bravver, Elena, Pegoraro, Elena, Mendell, Jerry R., Bushby, Kate, Diaz-Manera, Jordi, Straub, Volker, The Jain COS Consortium, John Walton Centre Muscular Dystrophy Research Centre, National Institute for Health and Care Research (US), Newcastle Biomedical Research Centre, Moore, Ursula, Fernández-Simón, Esther, Schiava, Marianela, Cox, Dan, Gordish-Dressman, Heather, James, Meredith K., Mayhew, Anna, Wilson, Ian, Guglieri, Michela, Rufibach, Laura, Blamire, Andrew, Carlier, Pierre G., Mori-Yoshimura, Madoka, Day, John W., Jones, Kristi J., Bharucha-Goebel, Diana X., Salort-Campana, Emmanuelle, Pestronk, Alan, Walter, Maggie C., Paradas, Carmen, Stojkovic, Tanya, Bravver, Elena, Pegoraro, Elena, Mendell, Jerry R., Bushby, Kate, Diaz-Manera, Jordi, Straub, Volker, and The Jain COS Consortium

Abstract

Myostatin is a myokine which acts upon skeletal muscle to inhibit growth and regeneration. Myostatin is endogenously antagonised by follistatin. This study assessed serum myostatin and follistatin concentrations as monitoring or prognostic biomarkers in dysferlinopathy, an autosomal recessively inherited muscular dystrophy. Myostatin was quantified twice with a three-year interval in 76 patients with dysferlinopathy and 38 controls. Follistatin was quantified in 62 of these patients at the same timepoints, and in 31 controls. Correlations with motor function, muscle fat fraction and contractile cross-sectional area were performed. A regression model was used to account for confounding variables. Baseline myostatin, but not follistatin, correlated with baseline function and MRI measures. However, in individual patients, three-year change in myostatin did not correlate with functional or MRI changes. Linear modelling demonstrated that function, serum creatine kinase and C-reactive protein, but not age, were independently related to myostatin concentration. Baseline myostatin concentration predicted loss of ambulation but not rate of change of functional or MRI measures, even when relative inhibition with follistatin was considered. With adjustment for extra-muscular causes of variation, myostatin could form a surrogate measure of functional ability or muscle mass, however myostatin inhibition does not form a promising treatment target in dysferlinopathy.

Published
2023

5. Establishing an online resource to facilitate global collaboration and inclusion of underrepresented populations: Experience from the MJFF Global Genetic Parkinson's Disease Project

Author

Michael J. Fox Foundation for Parkinson's Research, Cambridge Biomedical Research Centre, National Institute for Health and Care Research (US), Vollstedt, Eva-Juliane, Madoev, Harutyun, Aasly, Anna, Ahmad-Annuar, Azlina, Al-Mubarak, Bashayer, Alcalay, Roy N., Álvarez, Victoria, Amorín, Ignacio, Annesi, Grazia, Arkadir, David, Bardien, Soraya, Barker, Roger A., Barkhuizen, Melinda, Basak, A. Nazli, Bonifati, Vincenzo, Boon, Agnita, Brighina, Laura, Brockmann, Kathrin, Carmine Belin, Andrea, Carr, Jonathan, Clarimon, Jordi, Cornejo-Olivas, Mario, Correia Guedes, Leonor, Corvol, Jean-Christophe, Crosiers, David, Damásio, Joana, Das, Parimal, Aguiar, Patricia de Carvalho, Rosa, Anna De, Dorszewska, Jolanta, Ertan, Sibel, Ferese, Rosangela, Ferreira, Joaquim, Gatto, Emilia, Genç, Gençer, Giladi, Nir, Gómez-Garre, Pilar, Hanagasi, Hasmet, Hattori, Nobutaka, Hentati, Faycal, Hoffman-Zacharska, Dorota, Illarioshkin, Sergey N., Jankovic, Joseph, Jesús Maestre, Silvia, Kaasinen, Valtteri, Kievit, Anneke, Klivenyi, Peter, Kostic, Vladimir, Koziorowski, Dariusz, Kühn, Andrea A., Lang, Anthony E., Lim, Shen-Yang, Lin, Chin-Hsien, Lohmann, Katja, Markovic, Vladana, Martikainen, Mika Henrik, Mellick, George, Merello, Marcelo, Milanowski, Lukasz, Mir, Pablo, Öztop-Çakmak, Özgür, Pimentel, Márcia Mattos Gonçalves, Pulkes, Teeratorn, Puschmann, Andreas, Rogaeva, Ekaterina, Sammler, Esther M., Skaalum Petersen, Maria, Skorvanek, Matej, Spitz, Mariana, Suchowersky, Oksana, Tan, Ai Huey, Termsarasab, Pichet, Thaler, Avner, Tumas, Vitor, Valente, Enza Maria, Warrenburg, Bart van de, Williams-Gray, Caroline H., Wu, Ruey-Mei, Zhang, Baorong, Zimprich, Alexander, Solle, Justin, Padmanabhan, Shalini, Klein, Christine, Michael J. Fox Foundation for Parkinson's Research, Cambridge Biomedical Research Centre, National Institute for Health and Care Research (US), Vollstedt, Eva-Juliane, Madoev, Harutyun, Aasly, Anna, Ahmad-Annuar, Azlina, Al-Mubarak, Bashayer, Alcalay, Roy N., Álvarez, Victoria, Amorín, Ignacio, Annesi, Grazia, Arkadir, David, Bardien, Soraya, Barker, Roger A., Barkhuizen, Melinda, Basak, A. Nazli, Bonifati, Vincenzo, Boon, Agnita, Brighina, Laura, Brockmann, Kathrin, Carmine Belin, Andrea, Carr, Jonathan, Clarimon, Jordi, Cornejo-Olivas, Mario, Correia Guedes, Leonor, Corvol, Jean-Christophe, Crosiers, David, Damásio, Joana, Das, Parimal, Aguiar, Patricia de Carvalho, Rosa, Anna De, Dorszewska, Jolanta, Ertan, Sibel, Ferese, Rosangela, Ferreira, Joaquim, Gatto, Emilia, Genç, Gençer, Giladi, Nir, Gómez-Garre, Pilar, Hanagasi, Hasmet, Hattori, Nobutaka, Hentati, Faycal, Hoffman-Zacharska, Dorota, Illarioshkin, Sergey N., Jankovic, Joseph, Jesús Maestre, Silvia, Kaasinen, Valtteri, Kievit, Anneke, Klivenyi, Peter, Kostic, Vladimir, Koziorowski, Dariusz, Kühn, Andrea A., Lang, Anthony E., Lim, Shen-Yang, Lin, Chin-Hsien, Lohmann, Katja, Markovic, Vladana, Martikainen, Mika Henrik, Mellick, George, Merello, Marcelo, Milanowski, Lukasz, Mir, Pablo, Öztop-Çakmak, Özgür, Pimentel, Márcia Mattos Gonçalves, Pulkes, Teeratorn, Puschmann, Andreas, Rogaeva, Ekaterina, Sammler, Esther M., Skaalum Petersen, Maria, Skorvanek, Matej, Spitz, Mariana, Suchowersky, Oksana, Tan, Ai Huey, Termsarasab, Pichet, Thaler, Avner, Tumas, Vitor, Valente, Enza Maria, Warrenburg, Bart van de, Williams-Gray, Caroline H., Wu, Ruey-Mei, Zhang, Baorong, Zimprich, Alexander, Solle, Justin, Padmanabhan, Shalini, and Klein, Christine

Abstract

Parkinson’s disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically heterogeneous, with at least 10% of all cases explained by a monogenic cause or strong genetic risk factor. However, the vast majority of our present data on monogenic PD is based on the investigation of patients of European White ancestry, leaving a large knowledge gap on monogenic PD in underrepresented populations. Gene-targeted therapies are being developed at a fast pace and have started entering clinical trials. In light of these developments, building a global network of centers working on monogenic PD, fostering collaborative research, and establishing a clinical trial-ready cohort is imperative. Based on a systematic review of the English literature on monogenic PD and a successful team science approach, we have built up a network of 59 sites worldwide and have collected information on the availability of data, biomaterials, and facilities. To enable access to this resource and to foster collaboration across centers, as well as between academia and industry, we have developed an interactive map and online tool allowing for a quick overview of available resources, along with an option to filter for specific items of interest. This initiative is currently being merged with the Global Parkinson’s Genetics Program (GP2), which will attract additional centers with a focus on underrepresented sites. This growing resource and tool will facilitate collaborative research and impact the development and testing of new therapies for monogenic and potentially for idiopathic PD patients.

Published
2023

6. The role of the parafascicular thalamic nucleus in action initiation and steering

Author

National Institute for Health and Care Research (US), Fallon, I.P., Hughes, R. N., Severino, F.P.U., Kim, N., Lawry, C.M., Watson, G.D.R., Roshchina, M., Yin, H.H., National Institute for Health and Care Research (US), Fallon, I.P., Hughes, R. N., Severino, F.P.U., Kim, N., Lawry, C.M., Watson, G.D.R., Roshchina, M., and Yin, H.H.

Abstract

The parafascicular (Pf) nucleus of the thalamus has been implicated in arousal and attention, but its contributions to behavior remain poorly characterized. Here, using in vivo and in vitro electrophysiology, optogenetics, and 3D motion capture, we studied the role of the Pf nucleus in behavior using a continuous reward-tracking task in freely moving mice. We found that many Pf neurons precisely represent vector components of velocity, with a strong preference for ipsiversive movements. Their activity usually leads velocity, suggesting that Pf output is critical for self-initiated orienting behavior. To test this hypothesis, we expressed excitatory or inhibitory opsins in VGlut2+ Pf neurons to manipulate neural activity bidirectionally. We found that selective optogenetic stimulation of these neurons consistently produced ipsiversive head turning, whereas inhibition stopped turning and produced downward movements. Taken together, our results suggest that the Pf nucleus can send continuous top-down commands that specify detailed action parameters (e.g., direction and speed of the head), thus providing guidance for orienting and steering during behavior.

Published
2023

7. Ex vivo, in situ perfusion protocol for human brain fixation compatible with microscopy, MRI techniques, and anatomical studies

Author

National Institute for Health and Care Research (US), Universidad de Castilla La Mancha, European Commission, Agencia Estatal de Investigación (España), Insausti, Ricardo, Insausti, A.M., Muñoz López, M., Medina Lorenzo, I., Arroyo-Jiménez, M.d.M., Marcos Rabal,M.P., de la Rosa-Prieto, C., Delgado-González, J.C., Montón Etxeberria, J., Cebada-Sánchez, S., Raspeño-García, J.F., Iñiguez de Onzoño, M.M., Molina Romero, F.J., Benavides-Piccione, Ruth, Tapia-González, Silvia, Wisse, L.E.M., Ravikumar, S., Wolk, David A., DeFelipe, Javier, Yushkevich, P., Artacho-Pérula, E., National Institute for Health and Care Research (US), Universidad de Castilla La Mancha, European Commission, Agencia Estatal de Investigación (España), Insausti, Ricardo, Insausti, A.M., Muñoz López, M., Medina Lorenzo, I., Arroyo-Jiménez, M.d.M., Marcos Rabal,M.P., de la Rosa-Prieto, C., Delgado-González, J.C., Montón Etxeberria, J., Cebada-Sánchez, S., Raspeño-García, J.F., Iñiguez de Onzoño, M.M., Molina Romero, F.J., Benavides-Piccione, Ruth, Tapia-González, Silvia, Wisse, L.E.M., Ravikumar, S., Wolk, David A., DeFelipe, Javier, Yushkevich, P., and Artacho-Pérula, E.

Abstract

We present a method for human brain fixation based on simultaneous perfusion of 4% paraformaldehyde through carotids after a flush with saline. The left carotid cannula is used to perfuse the body with 10% formalin, to allow further use of the body for anatomical research or teaching. The aim of our method is to develop a vascular fixation protocol for the human brain, by adapting protocols that are commonly used in experimental animal studies. We show that a variety of histological procedures can be carried out (cyto- and myeloarchitectonics, histochemistry, immunohistochemistry, intracellular cell injection, and electron microscopy). In addition, ex vivo, ex situ high-resolution MRI (9.4T) can be obtained in the same specimens. This procedure resulted in similar morphological features to those obtained by intravascular perfusion in experimental animals, provided that the postmortem interval was under 10 h for several of the techniques used and under 4 h in the case of intracellular injections and electron microscopy. The use of intravascular fixation of the brain inside the skull provides a fixed whole human brain, perfectly fitted to the skull, with negligible deformation compared to conventional techniques. Given this characteristic of ex vivo, in situ fixation, this procedure can probably be considered the most suitable one available for ex vivo MRI scans of the brain. We describe the compatibility of the method proposed for intravascular fixation of the human brain and fixation of the donor’s body for anatomical purposes. Thus, body donor programs can provide human brain tissue, while the remainder of the body can also be fixed for anatomical studies. Therefore, this method of human brain fixation through the carotid system optimizes the procurement of human brain tissue, allowing a greater understanding of human neurological diseases, while benefiting anatomy departments by making the remainder of the body available for teaching purposes.

Published
2023

8. Fluorescent Multifunctional Organic Nanoparticles for Drug Delivery and Bioimaging: A Tutorial Review

Author

European Commission, Ministerio de Ciencia, Innovación y Universidades (España), National Science Foundation (US), National Institute for Health and Care Research (US), Ministerio de Economía y Competitividad (España), Vargas Nadal, Guillem, Köber, Mariana, Nsamela, Audrey, Terenziani, Francesca, Sissa, Cristina, Pescina, Silvia, Sonvico, Fabio, Gazzali, Amirah Mohd, Wahab, Habibah A., Grisanti, Luca, Olivera, María Eugenia, Palena, María Celeste, Guzman, María Laura, Luciani-Giacobbe, Laura Carolina, Jiménez Kairuz, Álvaro, Ventosa, Nora, Ratera, Immaculada, Belfield, Kevin D., Maoz, Ben M., European Commission, Ministerio de Ciencia, Innovación y Universidades (España), National Science Foundation (US), National Institute for Health and Care Research (US), Ministerio de Economía y Competitividad (España), Vargas Nadal, Guillem, Köber, Mariana, Nsamela, Audrey, Terenziani, Francesca, Sissa, Cristina, Pescina, Silvia, Sonvico, Fabio, Gazzali, Amirah Mohd, Wahab, Habibah A., Grisanti, Luca, Olivera, María Eugenia, Palena, María Celeste, Guzman, María Laura, Luciani-Giacobbe, Laura Carolina, Jiménez Kairuz, Álvaro, Ventosa, Nora, Ratera, Immaculada, Belfield, Kevin D., and Maoz, Ben M.

Abstract

Fluorescent organic nanoparticles (FONs) are a large family of nanostructures constituted by organic components that emit light in different spectral regions upon excitation, due to the presence of organic fluorophores. FONs are of great interest for numerous biological and medical applications, due to their high tunability in terms of composition, morphology, surface functionalization, and optical properties. Multifunctional FONs combine several functionalities in a single nanostructure (emission of light, carriers for drug-delivery, functionalization with targeting ligands, etc.), opening the possibility of using the same nanoparticle for diagnosis and therapy. The preparation, characterization, and application of these multifunctional FONs require a multidisciplinary approach. In this review, we present FONs following a tutorial approach, with the aim of providing a general overview of the different aspects of the design, preparation, and characterization of FONs. The review encompasses the most common FONs developed to date, the description of the most important features of fluorophores that determine the optical properties of FONs, an overview of the preparation methods and of the optical characterization techniques, and the description of the theoretical approaches that are currently adopted for modeling FONs. The last part of the review is devoted to a non-exhaustive selection of some recent biomedical applications of FONs.

Published
2022

9. Assessment of neuropsychological function in brain tumor treatment: a comparison of traditional neuropsychological assessment with app-based cognitive screening

Author

Guarantors of Brain, Cancer Research UK, Junta de Andalucía, Royal Society (UK), Cambridge Trust, National Institute for Health Research (UK), National Institute for Health and Care Research (US), Brain Tumour Charity, Romero García, Rafael, Owen, Mallory, McDonald, Alexa, Woodberry, Emma, Assem, Moataz, Coelho, Pedro, Morris, Rob C., Price, Stephen J., Santarius, Thomas, Suckling, John, Manly, Tom, Erez, Yaara, Hart, Michael G., Guarantors of Brain, Cancer Research UK, Junta de Andalucía, Royal Society (UK), Cambridge Trust, National Institute for Health Research (UK), National Institute for Health and Care Research (US), Brain Tumour Charity, Romero García, Rafael, Owen, Mallory, McDonald, Alexa, Woodberry, Emma, Assem, Moataz, Coelho, Pedro, Morris, Rob C., Price, Stephen J., Santarius, Thomas, Suckling, John, Manly, Tom, Erez, Yaara, and Hart, Michael G.

Abstract

[Background] Gliomas are typically considered to cause relatively few neurological impairments. However, cognitive difficulties can arise, for example during treatment, with potential detrimental effects on quality of life. Accurate, reproducible, and accessible cognitive assessment is therefore vital in understanding the effects of both tumor and treatments. Our aim is to compare traditional neuropsychological assessment with an app-based cognitive screening tool in patients with glioma before and after surgical resection. Our hypotheses were that cognitive impairments would be apparent, even in a young and high functioning cohort, and that app-based cognitive screening would complement traditional neuropsychological assessment., [Methods] Seventeen patients with diffuse gliomas completed a traditional neuropsychological assessment and an app-based touchscreen tablet assessment pre- and post-operatively. The app assessment was also conducted at 3- and 12-month follow-up. Impairment rates, mean performance, and pre- and post-operative changes were compared using standardized Z-scores., [Results] Approximately 2–3 h of traditional assessment indicated an average of 2.88 cognitive impairments per patient, while the 30-min screen indicated 1.18. As might be expected, traditional assessment using multiple items across the difficulty range proved more sensitive than brief screening measures in areas such as memory and attention. However, the capacity of the screening app to capture reaction times enhanced its sensitivity, relative to traditional assessment, in the area of non-verbal function. Where there was overlap between the two assessments, for example digit span tasks, the results were broadly equivalent., [Conclusions] Cognitive impairments were common in this sample and app-based screening complemented traditional neuropsychological assessment. Implications for clinical assessment and follow-up are discussed.

Published
2022

10. Dipeptide repeat pathology in C9orf72-ALS is associated with redox, mitochondrial and NRF2 pathway imbalance

Author

Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundación Tatiana Pérez de Guzmán el Bueno, Medical Research Council (UK), Instituto de Salud Carlos III, Universidad Autónoma de Madrid, Motor Neuron Disease Association, National Institute for Health and Care Research (US), European Cooperation in Science and Technology, Jiménez-Villegas, José, Kirby, Janine, Mata, Ana M., Cadenas, Susana, Turner, Martin R., Malaspina, Andrea, Shaw, Pamela J., Cuadrado, Antonio, Rojo, Ana I., Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundación Tatiana Pérez de Guzmán el Bueno, Medical Research Council (UK), Instituto de Salud Carlos III, Universidad Autónoma de Madrid, Motor Neuron Disease Association, National Institute for Health and Care Research (US), European Cooperation in Science and Technology, Jiménez-Villegas, José, Kirby, Janine, Mata, Ana M., Cadenas, Susana, Turner, Martin R., Malaspina, Andrea, Shaw, Pamela J., Cuadrado, Antonio, and Rojo, Ana I.

Abstract

The hexanucleotide expansion of the C9orf72 gene is found in 40% of familial amyotrophic lateral sclerosis (ALS) patients. This genetic alteration has been connected with impaired management of reactive oxygen species. In this study, we conducted targeted transcriptional profiling in leukocytes from C9orf72 patients and control subjects by examining the mRNA levels of 84 redox-related genes. The expression of ten redox genes was altered in samples from C9orf72 ALS patients compared to healthy controls. Considering that Nuclear factor erythroid 2-Related Factor 2 (NRF2) modulates the expression of a wide range of redox genes, we further investigated its status on an in vitro model of dipeptide repeat (DPR) toxicity. This model mimics the gain of function, toxic mechanisms attributed to C9orf72 pathology. We found that exposure to DPRs increased superoxide levels and reduced mitochondrial potential as well as cell survival. Importantly, cells overexpressing DPRs exhibited reduced protein levels of NRF2 and its target genes upon inhibition of the proteasome or its canonical repressor, the E3 ligase adapter KEAP1. However, NRF2 activation was sufficient to recover cell viability and redox homeostasis. This study identifies NRF2 as a putative target in precision medicine for the therapy of ALS patients harboring C9orf72 expansion repeats.

Published
2022

11. The psychosis metabolic risk calculator (PsyMetRiC) for young people with psychosis: International external validation and site-specific recalibration in two independent European samples

Author

National Institute for Health and Care Research (US), Cambridge Biomedical Research Centre, Wellcome Trust, Swiss National Science Foundation, Instituto de Salud Carlos III, Junta de Andalucía, Fundació Seny, Fundación Marques de Valdecilla, Ministerio de Economía y Competitividad (España), Perry, Benjamin I. [0000-0002-1533-026X], Vandenberghe, Frederik [0000-0002-8964-2047], Osimo, Emanuele F. [0000-0001-6239-5691], Perry, Benjamin I., Vandenberghe, Frederik, Garrido-Torres, Nathalia, Osimo, Emanuele F., Piras, Marianna, Vázquez-Bourgon, Javier, Upthegrove, Rachel, Grosu, Claire, Ortiz-Garcia de la Foz, Victor, Jones, Peter B., Laaboub, Nermine, Ruiz-Veguilla, Miguel, Stochl, Jan, Dubath, Celine, Canal-Rivero, Manuel, Mallikarjun, Pavan, Delacrétaz, Aurélie, Ansermot, Nicolas, Fernández-Egea, Emilio, Crettol, Severine, Gamma, Franziska, Plessen, Kerstin J., Conus, Philippe, Khandaker, Golam M., Murray, Graham K., Eap, Chin B., Crespo-Facorro, Benedicto, National Institute for Health and Care Research (US), Cambridge Biomedical Research Centre, Wellcome Trust, Swiss National Science Foundation, Instituto de Salud Carlos III, Junta de Andalucía, Fundació Seny, Fundación Marques de Valdecilla, Ministerio de Economía y Competitividad (España), Perry, Benjamin I. [0000-0002-1533-026X], Vandenberghe, Frederik [0000-0002-8964-2047], Osimo, Emanuele F. [0000-0001-6239-5691], Perry, Benjamin I., Vandenberghe, Frederik, Garrido-Torres, Nathalia, Osimo, Emanuele F., Piras, Marianna, Vázquez-Bourgon, Javier, Upthegrove, Rachel, Grosu, Claire, Ortiz-Garcia de la Foz, Victor, Jones, Peter B., Laaboub, Nermine, Ruiz-Veguilla, Miguel, Stochl, Jan, Dubath, Celine, Canal-Rivero, Manuel, Mallikarjun, Pavan, Delacrétaz, Aurélie, Ansermot, Nicolas, Fernández-Egea, Emilio, Crettol, Severine, Gamma, Franziska, Plessen, Kerstin J., Conus, Philippe, Khandaker, Golam M., Murray, Graham K., Eap, Chin B., and Crespo-Facorro, Benedicto

Abstract

[Background]: Cardiometabolic dysfunction is common in young people with psychosis. Recently, the Psychosis Metabolic Risk Calculator (PsyMetRiC) was developed and externally validated in the UK, predicting up-to six-year risk of metabolic syndrome (MetS) from routinely collected data. The full-model includes age, sex, ethnicity, body-mass index, smoking status, prescription of metabolically-active antipsychotic medication, high-density lipoprotein, and triglyceride concentrations; the partial-model excludes biochemical predictors., [Methods]: To move toward a future internationally-useful tool, we externally validated PsyMetRiC in two independent European samples. We used data from the PsyMetab (Lausanne, Switzerland) and PAFIP (Cantabria, Spain) cohorts, including participants aged 16–35y without MetS at baseline who had 1–6y follow-up. Predictive performance was assessed primarily via discrimination (C-statistic), calibration (calibration plots), and decision curve analysis. Site-specific recalibration was considered., [Findings]: We included 1024 participants (PsyMetab n=558, male=62%, outcome prevalence=19%, mean follow-up=2.48y; PAFIP n=466, male=65%, outcome prevalence=14%, mean follow-up=2.59y). Discrimination was better in the full- compared with partial-model (PsyMetab=full-model C=0.73, 95% C.I., 0.68–0.79, partial-model C=0.68, 95% C.I., 0.62–0.74; PAFIP=full-model C=0.72, 95% C.I., 0.66–0.78; partial-model C=0.66, 95% C.I., 0.60–0.71). As expected, calibration plots revealed varying degrees of miscalibration, which recovered following site-specific recalibration. PsyMetRiC showed net benefit in both new cohorts, more so after recalibration., [Interpretation]: The study provides evidence of PsyMetRiC's generalizability in Western Europe, although further local and international validation studies are required. In future, PsyMetRiC could help clinicians internationally to identify young people with psychosis who are at higher cardiometabolic risk, so interventions can be directed effectively to reduce long-term morbidity and mortality.

Published
2022

12. Virtual ontogeny of cortical growth preceding mental illness

Author

German Research Foundation, University of Münster, National Health and Medical Research Council (Australia), University of Cape Town, National Research Foundation (South Africa), Swinburne University of Technology, Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L. Cooper Medical Research Foundation, Society for Mental Health Research (Australia), Swedish Research Council, Swedish Foundation for Strategic Research, Swedish Brain Foundation, Health Research Board (Ireland), Russian Foundation for Basic Research, University of Zurich, Pratt Foundation, Ramsay Health Care, Viertel Charitable Foundation, Schizophrenia Research Institute (Australia), European Commission, Australian Research Council, Instituto de Salud Carlos III, National Institute for Health and Care Research (US), National Institute for Health Research (UK), Ministry of Health of the Czech Republic, Bill & Melinda Gates Foundation, South African Medical Research Council, Carnegie Corporation of New York, Wellcome Trust, Medical Research Council (UK), Medical Research Scotland, Netherlands Organization for Scientific Research, Ambrogi, Sonia [0000-0002-2897-358X], Banaschewski, Tobias [0000-0003-4595-1144], Bandeira, Cibele Edom [0000-0003-0681-1309], Cupertino, Renata [0000-0002-3452-0632], Calderoni, Sara [0000-0002-6250-5739], Cannon, Dara [0000-0001-7378-3411], Carr, Vaughan [0000-0002-8907-5804], Chew, Qian Hui [0000-0003-0969-7994], Coghill, David [0000-0003-3017-9737], Cullen, Kathryn [0000-0001-9631-3770], Dahl, Andreas [0000-0002-8097-2082], Epstein, Jeffery [0000-0003-3464-5256], Foran, William [0000-0001-7491-9798], Fortea, Lydia [0000-0001-6778-2316], Fuentes-Claramonte, Paola [0000-0002-1428-7976], Fullerton, Janice M. [0000-0003-4014-4490], Furlong, Lisa [0000-0001-6196-4565], Gallagher, Louise [0000-0001-9462-2836], Gao, Si [0000-0002-4473-1142], Gotlib, Ian [0000-0002-3622-3199], Haavik, Jan [0000-0001-7865-2808], Henskens, Frans [0000-0003-2358-5630], Hilland, Eva [0000-0002-7102-8372], Hoekstra, Pieter J [0000-0001-7260-4119], Howells, Fleur M [0000-0001-9759-2556], Ipser, Jonathan [0000-0003-1272-0032], Jørgensen, Jes Kristian [0000-0001-9133-1670], Karantonis, James A. [0000-0003-2281-0912], Lawrie, Stephen [0000-0002-2444-5675], Patel, Yash, Shin, Jean, Abé, Christoph, Agartz, Ingrid, Alloza, Clara, Alnæs, Dag, Ambrogi, Sonia, Antonucci, Linda A., Arango, Celso, Arolt, Volker, Auzias, Guillaume, Gruber, Oliver, Haavik, Jan, McDonald, Colm, Hahn, Tim, Harrison, Ben J., Heindel, Walter, Henskens, Frans, Heslenfeld, Dirk J., Hilland, Eva, King, Joseph A., Vernooij, Meike W., Hoekstra, Pieter J., Hohmann, Sarah, Holz, Nathalie, Howells, Fleur M., McIntosh, Andrew, Ipser, Jonathan C., Meinert, Susanne, Hoogman, Martine, Kircher, Tilo, Kochunov, Peter, Vieta, Eduard, Koopowitz, Sheri-Michelle, Landén, Mikael, Landrø, Nils Inge, Lawrie, Stephen, Michie, Patricia T., Ayesa Arriola, Rosa, Mitchell, Philip, Moreno-Alcázar, Ana, Franke, Barbara, Mowry, Bryan, Bau, Claiton H. D., Muratori, Filippo, Nabulsi, Leila, Nenadić, Igor, O'Gorman Tuura, Ruth, Oosterlaan, Jaap, Overs, Bronwyn, Pantelis, Christos, Banaj, Nerisa, Parellada, Mara, van Rooij, Daan, Vilarroya, Oscar, Pariente, Jose C., Pauli, Paul, Pergola, Giulio, Piarulli, Francesco Maria, Picon, Felipe, Piras, Fabrizio, Pomarol-Clotet, Edith, Pretus, Clara, Quidé, Yann, Banaschewski, Tobias, Weickert, Cynthia, Buitelaar, Jan, Radua, Joaquim, Ramos-Quiroga, J. Antoni, Rasser, Paul E., Reif, Andreas, Retico, Alessandra, Roberts, Gloria, Rossell, Susan, Rovaris, Diego Luiz, Rubia, Katya, Weickert, Thomas, Sacchet, Matthew, Ching, Christopher R. K., Bandeira, Cibele, Salavert, Josep, Salvador, Raymond, Sarró, Salvador, Sawa, Akira, Schall, Ulrich, Scott, Rodney, Selvaggi, Pierluigi, Westlye, Lars T., Silk, Tim, Sim, Kang, Andreassen, Ole A., Skoch, Antonin, Başgöze, Zeynep, Spalletta, Gianfranco, Spaniel, Filip, Stein, Dan J., Steinsträter, Olaf, Stolicyn, Aleks, Whalley, Heather, Takayanagi, Yoichiro, Tamm, Leanne, Tavares, Maria, Pozzi, Elena, Teumer, Alexander, Thiel, Katharina, Cupertino, Renata Basso, Thomopoulos, Sophia I., Tomecek, David, Tomyshev, Alexander S., Willinger, David, Tordesillas-Gutiérrez, Diana, Tosetti, Michela, Uhlmann, Anne, Van Rheenen, Tamsyn, Veltman, Dick, Vázquez-Bourgon, Javier, Schmaal, Lianne, Jahanshad, Neda, Winter, Alexandra, Wittfeld, Katharina, Yang, Tony T., Yoncheva, Yuliya, Bauer, Jochen, Zijlmans, Jendé L., Baumeister, Sarah, Lebedeva, Irina, van Erp, Theo G. M., Turner, Jessica, Jakobi, Babette, Castellanos, F. Xavier, Pausova, Zdenka, Thompson, Paul, Paus, Tomas, Bernardoni, Fabio, Bertolino, Alessandro, Bonnin, Caterina Del Mar, Brandeis, Daniel, Luna, Beatriz, Brem, Silvia, Jansen, Andreas, Bruggemann, Jason, Bülow, Robin, Bustillo, Juan R., Calderoni, Sara, Calvo, Rosa, Canales-Rodríguez, Erick J., Cannon, Dara M., Carmona, Susanna, Carr, Vaughan J., Lundervold, Astri J., Janssen, Joost, Catts, Stanley V., Chenji, Sneha, Chew, Qian Hui, Coghill, David, Connolly, Colm G., Conzelmann, Annette, Craven, Alexander R., Crespo-Facorro, Benedicto, Cullen, Kathryn, Dahl, Andreas, Jonassen, Rune, MacMaster, Frank P., Dannlowski, Udo, Davey, Christopher G., Deruelle, Christine, Díaz-Caneja, Covadonga M., Dohm, Katharina, Ehrlich, Stefan, Epstein, Jeffery, Erwin-Grabner, Tracy, Eyler, Lisa T., Kaiser, Anna, Fedor, Jennifer, Maglanoc, Luigi A., Fitzgerald, Jacqueline, Foran, William, Ford, Judith M., Fortea, Lydia, Fuentes-Claramonte, Paola, Fullerton, Janice, Furlong, Lisa, Gallagher, Louise, Kaleda, Vasiliy, Gao, Bingchen, Gao, Si, Mathalon, Daniel H., Goikolea, Jose M., Gotlib, Ian, Goya-Maldonado, Roberto, Grabe, Hans J., Green, Melissa, Grevet, Eugenio H., Groenewold, Nynke A., Karantonis, James, Grotegerd, Dominik., German Research Foundation, University of Münster, National Health and Medical Research Council (Australia), University of Cape Town, National Research Foundation (South Africa), Swinburne University of Technology, Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L. Cooper Medical Research Foundation, Society for Mental Health Research (Australia), Swedish Research Council, Swedish Foundation for Strategic Research, Swedish Brain Foundation, Health Research Board (Ireland), Russian Foundation for Basic Research, University of Zurich, Pratt Foundation, Ramsay Health Care, Viertel Charitable Foundation, Schizophrenia Research Institute (Australia), European Commission, Australian Research Council, Instituto de Salud Carlos III, National Institute for Health and Care Research (US), National Institute for Health Research (UK), Ministry of Health of the Czech Republic, Bill & Melinda Gates Foundation, South African Medical Research Council, Carnegie Corporation of New York, Wellcome Trust, Medical Research Council (UK), Medical Research Scotland, Netherlands Organization for Scientific Research, Ambrogi, Sonia [0000-0002-2897-358X], Banaschewski, Tobias [0000-0003-4595-1144], Bandeira, Cibele Edom [0000-0003-0681-1309], Cupertino, Renata [0000-0002-3452-0632], Calderoni, Sara [0000-0002-6250-5739], Cannon, Dara [0000-0001-7378-3411], Carr, Vaughan [0000-0002-8907-5804], Chew, Qian Hui [0000-0003-0969-7994], Coghill, David [0000-0003-3017-9737], Cullen, Kathryn [0000-0001-9631-3770], Dahl, Andreas [0000-0002-8097-2082], Epstein, Jeffery [0000-0003-3464-5256], Foran, William [0000-0001-7491-9798], Fortea, Lydia [0000-0001-6778-2316], Fuentes-Claramonte, Paola [0000-0002-1428-7976], Fullerton, Janice M. [0000-0003-4014-4490], Furlong, Lisa [0000-0001-6196-4565], Gallagher, Louise [0000-0001-9462-2836], Gao, Si [0000-0002-4473-1142], Gotlib, Ian [0000-0002-3622-3199], Haavik, Jan [0000-0001-7865-2808], Henskens, Frans [0000-0003-2358-5630], Hilland, Eva [0000-0002-7102-8372], Hoekstra, Pieter J [0000-0001-7260-4119], Howells, Fleur M [0000-0001-9759-2556], Ipser, Jonathan [0000-0003-1272-0032], Jørgensen, Jes Kristian [0000-0001-9133-1670], Karantonis, James A. [0000-0003-2281-0912], Lawrie, Stephen [0000-0002-2444-5675], Patel, Yash, Shin, Jean, Abé, Christoph, Agartz, Ingrid, Alloza, Clara, Alnæs, Dag, Ambrogi, Sonia, Antonucci, Linda A., Arango, Celso, Arolt, Volker, Auzias, Guillaume, Gruber, Oliver, Haavik, Jan, McDonald, Colm, Hahn, Tim, Harrison, Ben J., Heindel, Walter, Henskens, Frans, Heslenfeld, Dirk J., Hilland, Eva, King, Joseph A., Vernooij, Meike W., Hoekstra, Pieter J., Hohmann, Sarah, Holz, Nathalie, Howells, Fleur M., McIntosh, Andrew, Ipser, Jonathan C., Meinert, Susanne, Hoogman, Martine, Kircher, Tilo, Kochunov, Peter, Vieta, Eduard, Koopowitz, Sheri-Michelle, Landén, Mikael, Landrø, Nils Inge, Lawrie, Stephen, Michie, Patricia T., Ayesa Arriola, Rosa, Mitchell, Philip, Moreno-Alcázar, Ana, Franke, Barbara, Mowry, Bryan, Bau, Claiton H. D., Muratori, Filippo, Nabulsi, Leila, Nenadić, Igor, O'Gorman Tuura, Ruth, Oosterlaan, Jaap, Overs, Bronwyn, Pantelis, Christos, Banaj, Nerisa, Parellada, Mara, van Rooij, Daan, Vilarroya, Oscar, Pariente, Jose C., Pauli, Paul, Pergola, Giulio, Piarulli, Francesco Maria, Picon, Felipe, Piras, Fabrizio, Pomarol-Clotet, Edith, Pretus, Clara, Quidé, Yann, Banaschewski, Tobias, Weickert, Cynthia, Buitelaar, Jan, Radua, Joaquim, Ramos-Quiroga, J. Antoni, Rasser, Paul E., Reif, Andreas, Retico, Alessandra, Roberts, Gloria, Rossell, Susan, Rovaris, Diego Luiz, Rubia, Katya, Weickert, Thomas, Sacchet, Matthew, Ching, Christopher R. K., Bandeira, Cibele, Salavert, Josep, Salvador, Raymond, Sarró, Salvador, Sawa, Akira, Schall, Ulrich, Scott, Rodney, Selvaggi, Pierluigi, Westlye, Lars T., Silk, Tim, Sim, Kang, Andreassen, Ole A., Skoch, Antonin, Başgöze, Zeynep, Spalletta, Gianfranco, Spaniel, Filip, Stein, Dan J., Steinsträter, Olaf, Stolicyn, Aleks, Whalley, Heather, Takayanagi, Yoichiro, Tamm, Leanne, Tavares, Maria, Pozzi, Elena, Teumer, Alexander, Thiel, Katharina, Cupertino, Renata Basso, Thomopoulos, Sophia I., Tomecek, David, Tomyshev, Alexander S., Willinger, David, Tordesillas-Gutiérrez, Diana, Tosetti, Michela, Uhlmann, Anne, Van Rheenen, Tamsyn, Veltman, Dick, Vázquez-Bourgon, Javier, Schmaal, Lianne, Jahanshad, Neda, Winter, Alexandra, Wittfeld, Katharina, Yang, Tony T., Yoncheva, Yuliya, Bauer, Jochen, Zijlmans, Jendé L., Baumeister, Sarah, Lebedeva, Irina, van Erp, Theo G. M., Turner, Jessica, Jakobi, Babette, Castellanos, F. Xavier, Pausova, Zdenka, Thompson, Paul, Paus, Tomas, Bernardoni, Fabio, Bertolino, Alessandro, Bonnin, Caterina Del Mar, Brandeis, Daniel, Luna, Beatriz, Brem, Silvia, Jansen, Andreas, Bruggemann, Jason, Bülow, Robin, Bustillo, Juan R., Calderoni, Sara, Calvo, Rosa, Canales-Rodríguez, Erick J., Cannon, Dara M., Carmona, Susanna, Carr, Vaughan J., Lundervold, Astri J., Janssen, Joost, Catts, Stanley V., Chenji, Sneha, Chew, Qian Hui, Coghill, David, Connolly, Colm G., Conzelmann, Annette, Craven, Alexander R., Crespo-Facorro, Benedicto, Cullen, Kathryn, Dahl, Andreas, Jonassen, Rune, MacMaster, Frank P., Dannlowski, Udo, Davey, Christopher G., Deruelle, Christine, Díaz-Caneja, Covadonga M., Dohm, Katharina, Ehrlich, Stefan, Epstein, Jeffery, Erwin-Grabner, Tracy, Eyler, Lisa T., Kaiser, Anna, Fedor, Jennifer, Maglanoc, Luigi A., Fitzgerald, Jacqueline, Foran, William, Ford, Judith M., Fortea, Lydia, Fuentes-Claramonte, Paola, Fullerton, Janice, Furlong, Lisa, Gallagher, Louise, Kaleda, Vasiliy, Gao, Bingchen, Gao, Si, Mathalon, Daniel H., Goikolea, Jose M., Gotlib, Ian, Goya-Maldonado, Roberto, Grabe, Hans J., Green, Melissa, Grevet, Eugenio H., Groenewold, Nynke A., Karantonis, James, and Grotegerd, Dominik.

Abstract

[Background]: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life., [Methods]: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed., [Results]: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth., [Conclusions]: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.

Published
2022

13. Brain charts for the human lifespan

Author

British Academy, Autism Research Trust, National Institute of Mental Health (US), UK Research and Innovation, Medical Research Council (UK), National Institute for Health and Care Research (US), Wellcome Trust, University of Cambridge, Cambridge Biomedical Research Centre, Bethlehem, Richard A. I., Seidlitz, J., White, S. R., Vogel, Jacob W., Anderson, K. M., Adamson, C., Adler, S., Alexopoulos, G. S., Anagnostou, E., Areces-González, A., Astle, D. E., Auyeung, Bonnie, Ayub, Muhammad, Bae, J., Ball, G, Baron-Cohen, Simon, Beare, R., Bedford, S. A., Benegal, V., Beyer, Frauke, Blangero, John, Blesa Cábez, M., Boardman, J. P., Borzage, M., Bosch-Bayard, J. F., Bourke, N., Calhoun, V. D., Chakravarty, M. M., Chen, C., Chertavian, C., Chetelat, G., Chong, Y. S., Cole, J. H., Corvin, Aiden, Costantino, M., Courchesne, E., Crivello, Fabrice, Cropley, V. L., Crosbie, J., Crossley, N., Delarue, M., Delorme, R., Desrivieres, Sylvane, Devenyi, G. A., Di Biase, M. A., Dolan, R., Donald, K. A., Donohoe, Gary, Dunlop, K., Edwards, A. D., Elison, J. T., Ellis, C. T., Elman, J. A., Eyler, L., Fair, D. A., Feczko, E., Fletcher, P. C., Fonagy, P., Franz, C. E., Galán-García, L., Gholipour, A., Giedd, J., Gilmore, J. H., Glahn, David C., Goodyer, I. M., Grant, P. E., Groenewold, Nynke A., Gunning, F. M., Gur, Rachel E., Gur, Ruben C., Hammill, C. F., Hansson, Oskar, Hedden, T., Heinz, Andreas, Henson, R. N., Heuer, K., Hoare, J., Holla, B., Holmes, Avram J., Holt, Rosemary, Huang, Hailiang, Im, K., Ipser, J., Jack, C. R., Jackowski, A. P., Jia, T., Johnson, K. A., Jones, P. B., Jones, David T. W., Kahn, René S., Karlsson, H., Karlsson, L., Kawashima, R., Kelley, E. A., Kern, Silke, Kim, K. W., Kitzbichler, M. G., Kremen, W. S., Lalonde, F., Landeau, B., Lee, S., Lerch, J., Lewis, J. D., Li, J., Liao, W., Liston, C., Lombardo, Michael, V., Lv, J., Lynch, Christopher D., Mallard, T. T., Marcelis, Machteld, Markello, R. D., Mathias, Samuel R., Mazoyer, Bernard, McGuire, Philip, Meaney, M. J., Mechelli, Andrea, Medic, N., Misic, B., Morgan, S. E., Mothersill, David O., Nigg, J., Ong, M. Q. W., Ortinau, C., Ossenkoppele, Rik, Ouyang, M., Palaniyappan, L., Paly, L., Pan, P. M., Pantelis, Christos, Park, M. M., Paus, Tomas, Pausova, Zdenka, Paz-Linares, D., Pichler, Alexander, Pierce, K., Qian, X., Qiu, Jing, Qiu, A., Raznahan, A., Rittman, T., Rodrigue, A., Rollins, C. K., Romero García, Rafael, Ronan, L., Rosenberg, M. D., Rowitch, D. H., Salum, G. A., Satterthwaite, Theodore D., Schaare, H. L., Schachar, R. J., Schultz, A. P., Schumann, Gunter, Schöll, Michael, Sharp, D., Shinohara, R. T., Skoog, Ingmar, Smyser, C. D., Sperling, R. A., Stein, Dan J., Stolicyn, A., Suckling, John, Sullivan, G., Taki, Y., Thyreau, B., Toro, Raquel del, Traut, N., Tsvetanov, K. A., Turk-Browne, N. B., Tuulari, J. J., Tzourio, C., Vachon-Presseau, É., Valdes-Sosa, M. J., Valdes-Sosa, P. A., Valk, Sofie L., van Amelsvoort, Therese, Vandekar, S. N., Vasung, L., Victoria, L. W., Villeneuve, S., Villringer, Arno, Vértes, P. E., Wagstyl, K., Wang, Y. S., Warfield, S. K., Warrier, V., Westman, Eric, Westwater, M. L., Whalley, Heather, Witte, A. Veronica, Yang, N., Yeo, B., Yun, H., Zalesky, A., Zar, H. J., Zettergren, Anna, Zhou, J. H., Ziauddeen, H., Zugman, A., Zuo, X. N., Bullmore, E. T., Alexander-Bloch, A. F., British Academy, Autism Research Trust, National Institute of Mental Health (US), UK Research and Innovation, Medical Research Council (UK), National Institute for Health and Care Research (US), Wellcome Trust, University of Cambridge, Cambridge Biomedical Research Centre, Bethlehem, Richard A. I., Seidlitz, J., White, S. R., Vogel, Jacob W., Anderson, K. M., Adamson, C., Adler, S., Alexopoulos, G. S., Anagnostou, E., Areces-González, A., Astle, D. E., Auyeung, Bonnie, Ayub, Muhammad, Bae, J., Ball, G, Baron-Cohen, Simon, Beare, R., Bedford, S. A., Benegal, V., Beyer, Frauke, Blangero, John, Blesa Cábez, M., Boardman, J. P., Borzage, M., Bosch-Bayard, J. F., Bourke, N., Calhoun, V. D., Chakravarty, M. M., Chen, C., Chertavian, C., Chetelat, G., Chong, Y. S., Cole, J. H., Corvin, Aiden, Costantino, M., Courchesne, E., Crivello, Fabrice, Cropley, V. L., Crosbie, J., Crossley, N., Delarue, M., Delorme, R., Desrivieres, Sylvane, Devenyi, G. A., Di Biase, M. A., Dolan, R., Donald, K. A., Donohoe, Gary, Dunlop, K., Edwards, A. D., Elison, J. T., Ellis, C. T., Elman, J. A., Eyler, L., Fair, D. A., Feczko, E., Fletcher, P. C., Fonagy, P., Franz, C. E., Galán-García, L., Gholipour, A., Giedd, J., Gilmore, J. H., Glahn, David C., Goodyer, I. M., Grant, P. E., Groenewold, Nynke A., Gunning, F. M., Gur, Rachel E., Gur, Ruben C., Hammill, C. F., Hansson, Oskar, Hedden, T., Heinz, Andreas, Henson, R. N., Heuer, K., Hoare, J., Holla, B., Holmes, Avram J., Holt, Rosemary, Huang, Hailiang, Im, K., Ipser, J., Jack, C. R., Jackowski, A. P., Jia, T., Johnson, K. A., Jones, P. B., Jones, David T. W., Kahn, René S., Karlsson, H., Karlsson, L., Kawashima, R., Kelley, E. A., Kern, Silke, Kim, K. W., Kitzbichler, M. G., Kremen, W. S., Lalonde, F., Landeau, B., Lee, S., Lerch, J., Lewis, J. D., Li, J., Liao, W., Liston, C., Lombardo, Michael, V., Lv, J., Lynch, Christopher D., Mallard, T. T., Marcelis, Machteld, Markello, R. D., Mathias, Samuel R., Mazoyer, Bernard, McGuire, Philip, Meaney, M. J., Mechelli, Andrea, Medic, N., Misic, B., Morgan, S. E., Mothersill, David O., Nigg, J., Ong, M. Q. W., Ortinau, C., Ossenkoppele, Rik, Ouyang, M., Palaniyappan, L., Paly, L., Pan, P. M., Pantelis, Christos, Park, M. M., Paus, Tomas, Pausova, Zdenka, Paz-Linares, D., Pichler, Alexander, Pierce, K., Qian, X., Qiu, Jing, Qiu, A., Raznahan, A., Rittman, T., Rodrigue, A., Rollins, C. K., Romero García, Rafael, Ronan, L., Rosenberg, M. D., Rowitch, D. H., Salum, G. A., Satterthwaite, Theodore D., Schaare, H. L., Schachar, R. J., Schultz, A. P., Schumann, Gunter, Schöll, Michael, Sharp, D., Shinohara, R. T., Skoog, Ingmar, Smyser, C. D., Sperling, R. A., Stein, Dan J., Stolicyn, A., Suckling, John, Sullivan, G., Taki, Y., Thyreau, B., Toro, Raquel del, Traut, N., Tsvetanov, K. A., Turk-Browne, N. B., Tuulari, J. J., Tzourio, C., Vachon-Presseau, É., Valdes-Sosa, M. J., Valdes-Sosa, P. A., Valk, Sofie L., van Amelsvoort, Therese, Vandekar, S. N., Vasung, L., Victoria, L. W., Villeneuve, S., Villringer, Arno, Vértes, P. E., Wagstyl, K., Wang, Y. S., Warfield, S. K., Warrier, V., Westman, Eric, Westwater, M. L., Whalley, Heather, Witte, A. Veronica, Yang, N., Yeo, B., Yun, H., Zalesky, A., Zar, H. J., Zettergren, Anna, Zhou, J. H., Ziauddeen, H., Zugman, A., Zuo, X. N., Bullmore, E. T., and Alexander-Bloch, A. F.

Abstract

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.

Published
2022

14. Surface Lattice Plasmon Resonances by Direct In Situ Substrate Growth of Gold Nanoparticles in Ordered Arrays

Author

Ministerio de Ciencia, Innovación y Universidades (España), Consejo Superior de Investigaciones Científicas (España), Fundación la Caixa, University of California, National Institute for Health and Care Research (US), Hyundai Hope On Wheels, National Science Foundation (US), Vinnacombe-Willson, Gail A, Conti, Ylli, Jonas, Steven J, Weiss, Paul S, Mihi, Agustín, Scarabelli, Leonardo, Ministerio de Ciencia, Innovación y Universidades (España), Consejo Superior de Investigaciones Científicas (España), Fundación la Caixa, University of California, National Institute for Health and Care Research (US), Hyundai Hope On Wheels, National Science Foundation (US), Vinnacombe-Willson, Gail A, Conti, Ylli, Jonas, Steven J, Weiss, Paul S, Mihi, Agustín, and Scarabelli, Leonardo

Abstract

Precise arrangements of plasmonic nanoparticles on substrates are important for designing optoelectronics, sensors and metamaterials with rational electronic, optical and magnetic properties. Bottom-up synthesis offers unmatched control over morphology and optical response of individual plasmonic building blocks. Usually, the incorporation of nanoparticles made by bottom-up wet chemistry starts from batch synthesis of colloids, which requires time-consuming and hard-to-scale steps like ligand exchange and self-assembly. Herein, an unconventional bottom-up wet-chemical synthetic approach for producing gold nanoparticle ordered arrays is developed. Water-processable hydroxypropyl cellulose stencils facilitate the patterning of a reductant chemical ink on which nanoparticle growth selectively occurs. Arrays exhibiting lattice plasmon resonances in the visible region and near infrared (quality factors of >20) are produced following a rapid synthetic step (<10 min), all without cleanroom fabrication, specialized equipment, or self-assembly, constituting a major step forward in establishing in situ growth approaches. Further, the technical capabilities of this method through modulation of the particle size, shape, and array spacings directly on the substrate are demonstrated. Ultimately, establishing a fundamental understanding of in situ growth has the potential to inform the fabrication of plasmonic materials; opening the door for in situ growth fabrication of waveguides, lasing platforms, and plasmonic sensors.

Published
2022

15. Whole-exome sequencing identifies genes associated with Tourette’s disorder in multiplex families

Author

National Institute of Mental Health (US), Tourette Syndrome Association of New Jersey, National Institute of Environmental Health Sciences (US), Instituto de Salud Carlos III, Junta de Andalucía, Sociedad Andaluza de Neurología, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, Jacques and Gloria Gossweiler Foundation, German Research Foundation, Tourette Association of America, National Institute for Health and Care Research (US), Cao, Xiaolong, Zhang, Yeting, Abdulkadir, Mohamed, Deng, li, Fernández, Thomas V., García-Delgar, Blanca, Hagstrøm, Julie, Hoekstra, Pieter J., King, Robert A., Koesterich, Justin, Kuperman, Samuel, Morer, Astrid, Nasello, Cara, Plessen, Kerstin J., Thackray Joshua K., Zhou, Lisheng, Dietrich, Andrea, Tischfield, Jay A., Heiman, Gary A., Xing, Jinchuan, National Institute of Mental Health (US), Tourette Syndrome Association of New Jersey, National Institute of Environmental Health Sciences (US), Instituto de Salud Carlos III, Junta de Andalucía, Sociedad Andaluza de Neurología, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, Jacques and Gloria Gossweiler Foundation, German Research Foundation, Tourette Association of America, National Institute for Health and Care Research (US), Cao, Xiaolong, Zhang, Yeting, Abdulkadir, Mohamed, Deng, li, Fernández, Thomas V., García-Delgar, Blanca, Hagstrøm, Julie, Hoekstra, Pieter J., King, Robert A., Koesterich, Justin, Kuperman, Samuel, Morer, Astrid, Nasello, Cara, Plessen, Kerstin J., Thackray Joshua K., Zhou, Lisheng, Dietrich, Andrea, Tischfield, Jay A., Heiman, Gary A., and Xing, Jinchuan

Abstract

Tourette’s Disorder (TD) is a neurodevelopmental disorder (NDD) that affects about 0.7% of the population and is one of the most heritable NDDs. Nevertheless, because of its polygenic nature and genetic heterogeneity, the genetic etiology of TD is not well understood. In this study, we combined the segregation information in 13 TD multiplex families with high-throughput sequencing and genotyping to identify genes associated with TD. Using whole-exome sequencing and genotyping array data, we identified both small and large genetic variants within the individuals. We then combined multiple types of evidence to prioritize candidate genes for TD, including variant segregation pattern, variant function prediction, candidate gene expression, protein–protein interaction network, candidate genes from previous studies, etc. From the 13 families, 71 strong candidate genes were identified, including both known genes for NDDs and novel genes, such as HtrA Serine Peptidase 3 (HTRA3), Cadherin-Related Family Member 1 (CDHR1), and Zinc Finger DHHC-Type Palmitoyltransferase 17 (ZDHHC17). The candidate genes are enriched in several Gene Ontology categories, such as dynein complex and synaptic membrane. Candidate genes and pathways identified in this study provide biological insight into TD etiology and potential targets for future studies.

Published
2021

16. The Psychosis Metabolic Risk Calculator (PsyMetRiC) for Young People with Psychosis: International External Validation and Site-Specific Recalibration in Two Independent European Samples

Author

Benjamin I. Perry, Frederik Vandenberghe, Nathalia Garrido-Torres, Emanuele F. Osimo, Marianna Piras, Javier Vazquez-Bourgon, Rachel Upthegrove, Claire Grosu, Victor Ortiz-Garcia De La Foz, Peter B. Jones, Nermine Laaboub, Miguel Ruiz-Veguilla, Jan Stochl, Celine Dubath, Manuel Canal-Rivero, Pavan Mallikarjun, Aurélie Delacrétaz, Nicolas Ansermot, Emilio Fernandez-Egea, Severine Crettol, Franziska Gamma, Kerstin J. Plessen, Philippe Conus, Golam M. Khandaker, Graham K. Murray, Chin B. Eap, Benedicto Crespo-Facorro, Osimo, Emanuele F [0000-0001-6239-5691], Apollo - University of Cambridge Repository, National Institute for Health and Care Research (US), Cambridge Biomedical Research Centre, Wellcome Trust, Swiss National Science Foundation, Instituto de Salud Carlos III, Junta de Andalucía, Fundació Seny, Fundación Marques de Valdecilla, Ministerio de Economía y Competitividad (España), Perry, Benjamin I., Vandenberghe, Frederik, Osimo, Emanuele F., Perry, BI [0000-0002-1533-026X], Vandenberghe, F [0000-0002-8964-2047], and Osimo, EF [0000-0001-6239-5691]

Subjects
Metabolic Syndrome, PsyMetab, Oncology, Health Policy, Early Intervention, Internal Medicine, PAFIP, International Validation, Psychosis, Risk Prediction Algorithm
Abstract

[Background]: Cardiometabolic dysfunction is common in young people with psychosis. Recently, the Psychosis Metabolic Risk Calculator (PsyMetRiC) was developed and externally validated in the UK, predicting up-to six-year risk of metabolic syndrome (MetS) from routinely collected data. The full-model includes age, sex, ethnicity, body-mass index, smoking status, prescription of metabolically-active antipsychotic medication, high-density lipoprotein, and triglyceride concentrations; the partial-model excludes biochemical predictors., [Methods]: To move toward a future internationally-useful tool, we externally validated PsyMetRiC in two independent European samples. We used data from the PsyMetab (Lausanne, Switzerland) and PAFIP (Cantabria, Spain) cohorts, including participants aged 16–35y without MetS at baseline who had 1–6y follow-up. Predictive performance was assessed primarily via discrimination (C-statistic), calibration (calibration plots), and decision curve analysis. Site-specific recalibration was considered., [Findings]: We included 1024 participants (PsyMetab n=558, male=62%, outcome prevalence=19%, mean follow-up=2.48y; PAFIP n=466, male=65%, outcome prevalence=14%, mean follow-up=2.59y). Discrimination was better in the full- compared with partial-model (PsyMetab=full-model C=0.73, 95% C.I., 0.68–0.79, partial-model C=0.68, 95% C.I., 0.62–0.74; PAFIP=full-model C=0.72, 95% C.I., 0.66–0.78; partial-model C=0.66, 95% C.I., 0.60–0.71). As expected, calibration plots revealed varying degrees of miscalibration, which recovered following site-specific recalibration. PsyMetRiC showed net benefit in both new cohorts, more so after recalibration., [Interpretation]: The study provides evidence of PsyMetRiC's generalizability in Western Europe, although further local and international validation studies are required. In future, PsyMetRiC could help clinicians internationally to identify young people with psychosis who are at higher cardiometabolic risk, so interventions can be directed effectively to reduce long-term morbidity and mortality., NIHR Cambridge Biomedical Research Centre (BRC-1215-20014); The Wellcome Trust (201486/Z/16/Z); Swiss National Research Foundation (320030-120686, 324730- 144064, and 320030-173211); The Carlos III Health Institute (CM20/00015, FIS00/3095, PI020499, PI050427, and PI060507); IDIVAL (INT/A21/10 and INT/A20/04); The Andalusian Regional Government (A1-0055-2020 and A1-0005-2021); SENY Fundacion Research (2005-0308007); Fundacion Marques de Valdecilla (A/02/07, API07/011); Ministry of Economy and Competitiveness and the European Fund for Regional Development (SAF2016-76046-R and SAF2013-46292-R).

Published
2022

17. Fluorescent Multifunctional Organic Nanoparticles for Drug Delivery and Bioimaging: A Tutorial Review

Author

Guillem Vargas-Nadal, Mariana Köber, Audrey Nsamela, Francesca Terenziani, Cristina Sissa, Silvia Pescina, Fabio Sonvico, Amirah Mohd Gazzali, Habibah A. Wahab, Luca Grisanti, María Eugenia Olivera, María Celeste Palena, María Laura Guzman, Laura Carolina Luciani-Giacobbe, Alvaro Jimenez-Kairuz, Nora Ventosa, Imma Ratera, Kevin D. Belfield, Ben M. Maoz, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), National Science Foundation (US), National Institute for Health and Care Research (US), and Ministerio de Economía y Competitividad (España)

Subjects
Fluorescence microscopy, Organic nanoparticles, Drug delivery, Pharmaceutical Science, FONs manufacturing, Theoretical simulations of nanoparticles, Fluorophores, fluorescence, organic nanoparticles, drug delivery, bioimaging, fluorophores, fluorescence microscopy, theoretical simulations of nanoparticles, Bioimaging, Fluorescence
Abstract

Fluorescent organic nanoparticles (FONs) are a large family of nanostructures constituted by organic components that emit light in different spectral regions upon excitation, due to the presence of organic fluorophores. FONs are of great interest for numerous biological and medical applications, due to their high tunability in terms of composition, morphology, surface functionalization, and optical properties. Multifunctional FONs combine several functionalities in a single nanostructure (emission of light, carriers for drug-delivery, functionalization with targeting ligands, etc.), opening the possibility of using the same nanoparticle for diagnosis and therapy. The preparation, characterization, and application of these multifunctional FONs require a multidisciplinary approach. In this review, we present FONs following a tutorial approach, with the aim of providing a general overview of the different aspects of the design, preparation, and characterization of FONs. The review encompasses the most common FONs developed to date, the description of the most important features of fluorophores that determine the optical properties of FONs, an overview of the preparation methods and of the optical characterization techniques, and the description of the theoretical approaches that are currently adopted for modeling FONs. The last part of the review is devoted to a non-exhaustive selection of some recent biomedical applications of FONs., This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowka-Curie grant agreement No. 101007804 (Micro4Nano). M.K., N.V., and I.R. acknowledge financial support from the Spanish Ministry of Science and Innovation through the Severo Ochoa Program for Centers of Excellence in R&D (SEV-2015-0496 and CEX2019-000917-S) and through the grant “MOL4BIO” (PID2019-105622RB-I00). K.D.B acknowledges support from the US National Science Foundation (EFMA-2203704) and the National Institutes of Health (R21AA028340)., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

Published
2022

18. Dipeptide Repeat Pathology in C9orf72-ALS Is Associated with Redox, Mitochondrial and NRF2 Pathway Imbalance

Author

José Jiménez-Villegas, Janine Kirby, Ana Mata, Susana Cadenas, Martin R. Turner, Andrea Malaspina, Pamela J. Shaw, Antonio Cuadrado, Ana I. Rojo, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundación Tatiana Pérez de Guzmán el Bueno, Medical Research Council (UK), Instituto de Salud Carlos III, Universidad Autónoma de Madrid, Motor Neuron Disease Association, National Institute for Health and Care Research (US), and European Cooperation in Science and Technology

Subjects
Physiology, C9orf72, Clinical Biochemistry, NRF2, amyotrophic lateral sclerosis, dipeptide repeat proteins, Dipeptide repeat proteins, Cell Biology, Amyotrophic lateral sclerosis, Molecular Biology, Biochemistry
Abstract

The hexanucleotide expansion of the C9orf72 gene is found in 40% of familial amyotrophic lateral sclerosis (ALS) patients. This genetic alteration has been connected with impaired management of reactive oxygen species. In this study, we conducted targeted transcriptional profiling in leukocytes from C9orf72 patients and control subjects by examining the mRNA levels of 84 redox-related genes. The expression of ten redox genes was altered in samples from C9orf72 ALS patients compared to healthy controls. Considering that Nuclear factor erythroid 2-Related Factor 2 (NRF2) modulates the expression of a wide range of redox genes, we further investigated its status on an in vitro model of dipeptide repeat (DPR) toxicity. This model mimics the gain of function, toxic mechanisms attributed to C9orf72 pathology. We found that exposure to DPRs increased superoxide levels and reduced mitochondrial potential as well as cell survival. Importantly, cells overexpressing DPRs exhibited reduced protein levels of NRF2 and its target genes upon inhibition of the proteasome or its canonical repressor, the E3 ligase adapter KEAP1. However, NRF2 activation was sufficient to recover cell viability and redox homeostasis. This study identifies NRF2 as a putative target in precision medicine for the therapy of ALS patients harboring C9orf72 expansion repeats., This work was supported by the SAF2019-110061RB-100 grant from the Spanish Ministry of Economy and Competitiveness; P-024-FTPGB 2018 from the Spanish Foundation named “Tatiana de Guzman el Bueno”, COEN-2018-Pathfinder phase III financed by the Network of Centers of Excellence in Neurodegeneration including the UK Medical Research Council and PI19/01030 financed by the Spanish “Instituto de Salud Carlos III”. J.J.V. hold an FPU PhD fellowship from the Spanish Ministry of Universities (FPU20/03326) and was a holder of a master’s degree fellowship (“Ayudas para el fomento de la Investigación en Estudios de Máster-UAM 2020”) funded by the Autonomous University of Madrid. This research was also supported by the Motor Neurone Disease Association (AMBRoSIA 972-797 and NECTAR 974-797 awards) and by the NIHR Sheffield Biomedical Research Centre (JS-BRC-1215-20017). This article is based upon work from COST Action CA20121, supported by COST (European Cooperation in Science and Technology).

Published
2022
Full Text
View/download PDF

19. Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Author

Yash Patel, Jean Shin, Christoph Abé, Ingrid Agartz, Clara Alloza, Dag Alnæs, Sonia Ambrogi, Linda A. Antonucci, Celso Arango, Volker Arolt, Guillaume Auzias, Rosa Ayesa-Arriola, Nerisa Banaj, Tobias Banaschewski, Cibele Bandeira, Zeynep Başgöze, Renata Basso Cupertino, Claiton H.D. Bau, Jochen Bauer, Sarah Baumeister, Fabio Bernardoni, Alessandro Bertolino, Caterina del Mar Bonnin, Daniel Brandeis, Silvia Brem, Jason Bruggemann, Robin Bülow, Juan R. Bustillo, Sara Calderoni, Rosa Calvo, Erick J. Canales-Rodríguez, Dara M. Cannon, Susanna Carmona, Vaughan J. Carr, Stanley V. Catts, Sneha Chenji, Qian Hui Chew, David Coghill, Colm G. Connolly, Annette Conzelmann, Alexander R. Craven, Benedicto Crespo-Facorro, Kathryn Cullen, Andreas Dahl, Udo Dannlowski, Christopher G. Davey, Christine Deruelle, Covadonga M. Díaz-Caneja, Katharina Dohm, Stefan Ehrlich, Jeffery Epstein, Tracy Erwin-Grabner, Lisa T. Eyler, Jennifer Fedor, Jacqueline Fitzgerald, William Foran, Judith M. Ford, Lydia Fortea, Paola Fuentes-Claramonte, Janice Fullerton, Lisa Furlong, Louise Gallagher, Bingchen Gao, Si Gao, Jose M. Goikolea, Ian Gotlib, Roberto Goya-Maldonado, Hans J. Grabe, Melissa Green, Eugenio H. Grevet, Nynke A. Groenewold, Dominik Grotegerd, Oliver Gruber, Jan Haavik, Tim Hahn, Ben J. Harrison, Walter Heindel, Frans Henskens, Dirk J. Heslenfeld, Eva Hilland, Pieter J. Hoekstra, Sarah Hohmann, Nathalie Holz, Fleur M. Howells, Jonathan C. Ipser, Neda Jahanshad, Babette Jakobi, Andreas Jansen, Joost Janssen, Rune Jonassen, Anna Kaiser, Vasiliy Kaleda, James Karantonis, Joseph A. King, Tilo Kircher, Peter Kochunov, Sheri-Michelle Koopowitz, Mikael Landén, Nils Inge Landrø, Stephen Lawrie, Irina Lebedeva, Beatriz Luna, Astri J. Lundervold, Frank P. MacMaster, Luigi A. Maglanoc, Daniel H. Mathalon, Colm McDonald, Andrew McIntosh, Susanne Meinert, Patricia T. Michie, Philip Mitchell, Ana Moreno-Alcázar, Bryan Mowry, Filippo Muratori, Leila Nabulsi, Igor Nenadić, Ruth O'Gorman Tuura, Jaap Oosterlaan, Bronwyn Overs, Christos Pantelis, Mara Parellada, Jose C. Pariente, Paul Pauli, Giulio Pergola, Francesco Maria Piarulli, Felipe Picon, Fabrizio Piras, Edith Pomarol-Clotet, Clara Pretus, Yann Quidé, Joaquim Radua, J. Antoni Ramos-Quiroga, Paul E. Rasser, Andreas Reif, Alessandra Retico, Gloria Roberts, Susan Rossell, Diego Luiz Rovaris, Katya Rubia, Matthew D. Sacchet, Josep Salavert, Raymond Salvador, Salvador Sarró, Akira Sawa, Ulrich Schall, Rodney Scott, Pierluigi Selvaggi, Tim Silk, Kang Sim, Antonin Skoch, Gianfranco Spalletta, Filip Spaniel, Dan J. Stein, Olaf Steinsträter, Aleks Stolicyn, Yoichiro Takayanagi, Leanne Tamm, Maria Tavares, Alexander Teumer, Katharina Thiel, Sophia I. Thomopoulos, David Tomecek, Alexander S. Tomyshev, Diana Tordesillas-Gutiérrez, Michela Tosetti, Anne Uhlmann, Tamsyn Van Rheenen, Javier Vazquez-Bourgón, Meike W. Vernooij, Eduard Vieta, Oscar Vilarroya, Cynthia Weickert, Thomas Weickert, Lars T. Westlye, Heather Whalley, David Willinger, Alexandra Winter, Katharina Wittfeld, Tony T. Yang, Yuliya Yoncheva, Jendé L. Zijlmans, Martine Hoogman, Barbara Franke, Daan van Rooij, Jan Buitelaar, Christopher R.K. Ching, Ole A. Andreassen, Elena Pozzi, Dick Veltman, Lianne Schmaal, Theo G.M. van Erp, Jessica Turner, F. Xavier Castellanos, Zdenka Pausova, Paul Thompson, Tomas Paus, Pediatric surgery, Anatomy and neurosciences, Psychiatry, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, General Paediatrics, ARD - Amsterdam Reproduction and Development, Paediatrics, Radiology & Nuclear Medicine, Epidemiology, Clinical Cognitive Neuropsychiatry Research Program (CCNP), German Research Foundation, University of Münster, National Health and Medical Research Council (Australia), University of Cape Town, National Research Foundation (South Africa), Swinburne Universit, Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L. Cooper Foundation, Society of Mental Health Research, Swedish Research Council, Swedish Foundation for Strategic Research, Swedish Brain Foundation, Health Research Board (Ireland), Russian Foundation for Basic Research, University of Zurich, Pratt Foundation, Ramsay Health Care, Viertel Charitable Foundation, Schizophrenia Research Institute, European Commission, Australian Research Council, Instituto de Salud Carlos III, National Institute for Health and Care Research (US), National Institute for Health Research (UK), Ministry of Health of the Czech Republic, Bill & Melinda Gates Foundation, South African Medical Research Council, Carnegie Corporation of New York, Wellcome Trust, Medical Research Council (UK), Medical Research Scotland, Netherlands Organization for Scientific Research, Ambrogi, Sonia, Banaschewski, Tobias, Bandeira, Cibele Edom, Cupertino, Renata, Calderoni, Sara, Cannon, Dara, Carr, Vaughan, Chew, Qian Hui, Coghill, David, Cullen, Kathryn, Dahl, Andreas, Epstein, Jeffery, Foran, William, Fortea, Lydia, Fuentes-Claramonte, Paola, Fullerton, Janice M., Furlong, Lisa, Gallagher, Louise, Gao, Si, Gotlib, Ian, Haavik, Jan, Henskens, Frans, Hilland, Eva, Hoekstra, Pieter J, Howells, Fleur M, Ipser, Jonathan, Jørgensen, Jes Kristian, Karantonis, James A., Lawrie, Stephen, Research Institute of the Hospital for Sick Children and University of Toronto, University of Toronto, Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Mental Health Sciences Unit, University College of London [London] (UCL), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Clinical and Behavioral Neurology - Neuroscienze e riabilitazione, IRCCS Fondazione Santa Lucia [Roma], Heidelberg University, Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), Universität Heidelberg [Heidelberg] = Heidelberg University, Clinical Neuropsychology, IBBA, APH - Mental Health, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Hospital Sant Joan de Déu [Barcelona], and Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM)

Subjects
Bipolar Disorder, Autism Spectrum Disorder, [SDV]Life Sciences [q-bio], Neurogenesis, pathology [Premature Birth], Neurodevelopment, Cortical surface area, pathology [Autism Spectrum Disorder], Cortical growth, methods [Magnetic Resonance Imaging], SDG 3 - Good Health and Well-being, Pregnancy, 130 000 Cognitive Neurology & Memory, Humans, ddc:610, Child, Biological Psychiatry, Cerebral Cortex, pathology [Depressive Disorder, Major], Depressive Disorder, Major, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Infant, Newborn, Magnetic Resonance Imaging, Mental illness, Attention Deficit Disorder with Hyperactivity, Premature Birth, genetics [Autism Spectrum Disorder], Female, Psychiatric disorders, 170 000 Motivational & Cognitive Control
Abstract

[Background]: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life., [Methods]: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed., [Results]: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth., [Conclusions]: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy., This work was supported by the German Research Foundation (DFG Grant Nos. HA7070/2-2, HA7070/3, HA7070/4 [to TH]) and IZKF of the medical faculty of Münster (Grants No. Dan3/012/17 [to UD] and MzH 3/020/20 [to TH]), and NHMRC projects (Grant No. 1064643 [to BJH] and 1024570 [to CGD]). The CIAM study was supported by the University of Cape Town Research Committee, South African National Research Foundation, and the South African Medical Research Council (principal investigator [PI], Fleur M. Howells) and Grant No. R01MH117601 (to NJ). This work was funded by the German Research Foundation (Grant Nos. FOR2107 JA 1890/7-1 and FOR2107 JA 1890/7-2 [to AJ]) and Swinburne University scholarship/Australian Postgraduate Award (to JK). Collection of the COGSBD cohort was funded by the Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L Cooper Foundation, and the Society of Mental Health Research (to JK). This work was funded by the German Research Foundation (Grant Nos. FOR2107 KI588/14-1 and FOR2107 KI588/14-2 [to TK]). The St. Göran study was supported by grants from the Swedish Research Council (Grant No. 2018-02653 [to ML]), the Swedish foundation for Strategic Research (Grant No. KF10-0039 [to ML]), the Swedish Brain foundation (Grant No. FO2020-0261 [to ML]), and the Swedish Government under the LUA/ALF agreement (Grant Nos. ALF 20170019 and ALFGBG-716801 [to ML]). This work was supported by RFBR (Grant No. 20-013-00748 [to IL, AST]) and funded by the Health Research Board (Grant No. HRA_POR/2011/100 [to CM]). The Australian Schizophrenia Research Bank (ASRB) was supported by the NHMRC (Enabling Grant No. 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation, and the Schizophrenia Research Institute. Chief investigators for ASRB were VC, US, RSc, AJ, BM, PTM, SVC, FH, and CPa. This work was supported by Deutsche Forschungsgemeinschaft (Grant Nos. DFG NE 2254/2-1, NE 2254/3-1, NE2254/4-1 [to IN]), the University Research Priority Program “Integrative Human Physiology” at the University of Zurich (to ROT), an NHMRC Senior Principal Research Fellowship (Grant No. 1105825 [to CPa]), an NHMRC L3 Investigator Grant (Grant No. 1196508 [to CPa]), and NHMRC Program Grant (Grant No. 1150083 [to CPa]). ASRB was supported by the NHMRC (Enabling Grant No. 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation and the Schizophrenia Research Institute. Chief investigators for ASRB were VC, US, RSc, AJ, BM, PTM, SVC, FH, and CPa. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant (Agreement No. 798181 [to GP]). ASRB was supported by the NHMRC (Enabling Grant, ID 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation and the Schizophrenia Research Institute. Chief investigators for ASRB were VC, US, RSc, AJ, BM, PTM, SVC, FH, and CPa. The Imaging Genetics in Psychosis study was funded by Project Grants from the NHMRC (Grant Nos. APP630471 and APP1081603 [to YQ]) and the Macquarie University’s Australian Research Council (ARC) Centre of Excellence in Cognition and its Disorders (Grant No. CE110001021 [to YQ]). This work was supported by the Spanish Ministry of Science, Innovation and Universities/Economy and Competitiveness/Instituto de Salud Carlos III (Grant Nos. PI11/01766 and CPII19/00009 [to JR]), co-financed by European Regional Development Fund funds from the European Commission (“A Way of Making Europe”). ASRB was supported by the NHMRC (Enabling Grant No. 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation, and the Schizophrenia Research Institute. Chief investigators for ASRB were VC, US, RSc, AJ, BM, PTM, SVC, FH, and CPa. SR was supported by an NHMRC Senior Fellowship (Grant No. GNT1154651). Collection of the COGSBD cohort was funded by the Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L Cooper Foundation, and the Society of Mental Health Research (to SR). This work was supported by NIHR; MRC (to KR), NIH (Grant Nos. MH-094268, MH-105660, and MH-107730 [to ASS]). The Neuroimaging of the Children's Attention Project cohort was funded by NHMRC, Australia (Grant No. 1065895). Earlier funding for the cohort as also provided by NHMRC (Grant No. 1008522) and a grant from the Collier Foundation. The ACPU cohort was funded by NHMRC, Australia (Project Grant Nos. 384419 and 569533 [to TS]). This work was supported by research grants from the National Healthcare Group, Singapore (Grant Nos. SIG/05004, SIG/05028, and SIG /1103), and the Singapore Bioimaging Consortium (RP C009/2006 [to KS]), and the Ministry of Health, Czech Republic - conceptual development of research organization (“Institute for Clinical and Experimental Medicine - IKEM, IN 00023001” [to ASk]). This study was supported by the Italian Ministry of Health (Grant No. RC/17-18-19-20-21/A [to GS]) and Ministry of Health of the Czech Republic (Grant No. NU20-04-00393 [to FS]). The Drakenstein Child Health Study (DCHS) cohort is funded by the Bill and Melinda Gates Foundation (Grant No. OPP 1017641) and the South African Medical Research Council. This DCHS contribution was made possible in part by a grant from Carnegie Corporation of New York. The statements made and views expressed are solely the responsibility of the author (DJS). STRADL study was supported and funded by the Wellcome Trust Strategic Award “Stratifying Resilience and Depression Longitudinally” (Grant No. 104036/Z/14/Z), and the Medical Research Council Mental Health Pathfinder Award “Leveraging routinely collected and linked research data to study the causes and consequences of common mental disorders” (MRC, Grant No. MC_PC_17209). Scottish Bipolar Family Study (SBFS) was supported by National Health Service Research Scotland, through the Scottish Mental Health Research Network (www.smhrn.org.uk), who provided assistance with subject recruitment and assessments. SBFS was conducted at the Brain Research Imaging Centre (http://www.bric.ed.ac.uk), which is supported by SINAPSE (Scottish Imaging Network, a Platform for Scientific Excellence, http://www.sinapse.ac.uk). Processing of the datasets used the resources provided by the Edinburgh Compute and Data Facility (http://www.ecdf.ed.ac.uk/) (ASt). TVR was supported by an NHMRC Early Career Fellowship (Grant No. GNT1088785). Collection of the COGSBD cohort was funded by the Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L Cooper Foundation, and the Society of Mental Health Research (to TVR). EV was supported by the Spanish Ministry of Science and Innovation (PI18/00805) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirección General de Evaluación and the FEDER; the Instituto de Salud Carlos III; the CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental); by the CERCA Programme/Generalitat de Catalunya and the Secretaria d’Universitats i Recerca del Departament d’Economia I Coneixement (Grant No. 2017SGR1355). This study was also supported by the Departament de Salut de la Generalitat de Catalunya, Pla Estratègic de Recerca i Innovació en Salut (PERIS) 2016-2020 (Grant No. SLT006/17/00345) and the European Union Horizon 2020 research and innovation program (EU.3.1.1. Understanding health, wellbeing and disease: Grant Nos. 754907 and EU.3.1.3 [to EB]; Treating and managing disease: Grant No. 945151 [to EV]). This study was supported by the National Center for Complementary and Integrative Health (Grant Nos. R21AT009173 and R61AT009864 [to TTY]); by the National Center for Advancing Translational Sciences (CTSI), National Institutes of Health, through UCSF-CTSI (Grant No. UL1TR001872 [to TTY]); by the American Foundation for Suicide Prevention (Grant No. SRG-1-141-18 [to TTY]); by UCSF Research Evaluation and Allocation Committee (REAC) and J. Jacobson Fund (to TTY); by the NIMH (Grant No. R01MH085734 [to TTY]); and by the Brain and Behavior Research Foundation (formerly NARSAD) (to TTY). This work was supported by a personal Veni grant to MH from the Netherlands Organization for Scientific Research (NWO, Grant No. 91619115 [to MH]) and European Community’s Horizon 2020 Programme (H2020/2014 – 2020) (Grant Agreements Nos. 667302 [CoCA], 728018 [Eat2beNICE], and 847879 [PRIME] [to BF]). JBu has been supported by the EU-AIMS (European Autism Interventions) and AIMS-2-TRIALS programmes, which receive support from Innovative Medicines Initiative Joint Undertaking Grant Nos. 115300 and 777394, the resources of which are composed of financial contributions from the European Union’s FP7 and Horizon 2020 Programmes, and from the European Federation of Pharmaceutical Industries and Associations companies’ in-kind contributions, and AUTISM SPEAKS, Autistica and SFARI; and by the Horizon 2020–supported programme CANDY (Grant No. 847818 [to JBu]). This work is supported by Grant No. NIA T32AG058507 and NIH Grant No. U54EB020403 from the Big Data to Knowledge (BD2K) Program (to CRKC). ENIGMA MDD work is supported by NIH (Grant Nos. U54 EB020403 [to PT], R01 MH116147 [to PT], and R01 MH117601 [to NJ and LS]). LS was supported by an NHMRC Career Development Fellowship (Grant No. 1140764). This work was supported by the National Center for Research Resources at the NIH (Grant Nos. NIH 1 U24 RR021992 [Function Biomedical Informatics Research Network], NIH 1 U24 RR025736-01 [Biomedical Informatics Research Network Coordinating Center; http://www.birncommunity.org]). TGMvE is supported by ENIGMA’s NIH BD2K initiative (Grant No. U54 EB020403), ENIGMA Sex Differences (Grant No. R01MH116147), and ENIGMA-COINSTAC: Advanced Worldwide Transdiagnostic Analysis of Valence System Brain Circuits (Grant No. R01MH121246). This work was supported by the NIH (Grant No. R01MH121246 [to JT, Calhoun, and TGMvE]). This work was supported in part by NIH (Grant No. U54 EB020403 [to PT]).

Published
2022
Full Text
View/download PDF

20. Assessment of neuropsychological function in brain tumor treatment: a comparison of traditional neuropsychological assessment with app-based cognitive screening

Author

Rafael Romero-Garcia, Mallory Owen, Alexa McDonald, Emma Woodberry, Moataz Assem, Pedro Coelho, Rob C Morris, Stephen J Price, Tom Santarius, John Suckling, Tom Manly, Yaara Erez, Michael G Hart, Romero-Garcia, Rafael [0000-0002-5199-4573], Apollo - University of Cambridge Repository, Guarantors of Brain, Cancer Research UK, Junta de Andalucía, Royal Society (UK), Cambridge Trust, National Institute for Health Research (UK), National Institute for Health and Care Research (US), Brain Tumour Charity, Price, Stephen [0000-0002-7535-3009], and Suckling, John [0000-0002-5098-1527]

Subjects
medicine.medical_specialty, Population, Neurosurgery, Audiology, Neuropsychological Tests, Diffuse Glioma, Cognition, Neuropsychology, Memory span, Medicine, Humans, Neuropsychological assessment, education, education.field_of_study, Modalities, medicine.diagnostic_test, business.industry, Brain Neoplasms, Glioma, Neuropsychiatry, Mobile Applications, Cognitive test, Quality of Life, Surgery, Cognitive function, Neurology (clinical), business, Cognition Disorders
Abstract

[Background] Gliomas are typically considered to cause relatively few neurological impairments. However, cognitive difficulties can arise, for example during treatment, with potential detrimental effects on quality of life. Accurate, reproducible, and accessible cognitive assessment is therefore vital in understanding the effects of both tumor and treatments. Our aim is to compare traditional neuropsychological assessment with an app-based cognitive screening tool in patients with glioma before and after surgical resection. Our hypotheses were that cognitive impairments would be apparent, even in a young and high functioning cohort, and that app-based cognitive screening would complement traditional neuropsychological assessment., [Methods] Seventeen patients with diffuse gliomas completed a traditional neuropsychological assessment and an app-based touchscreen tablet assessment pre- and post-operatively. The app assessment was also conducted at 3- and 12-month follow-up. Impairment rates, mean performance, and pre- and post-operative changes were compared using standardized Z-scores., [Results] Approximately 2–3 h of traditional assessment indicated an average of 2.88 cognitive impairments per patient, while the 30-min screen indicated 1.18. As might be expected, traditional assessment using multiple items across the difficulty range proved more sensitive than brief screening measures in areas such as memory and attention. However, the capacity of the screening app to capture reaction times enhanced its sensitivity, relative to traditional assessment, in the area of non-verbal function. Where there was overlap between the two assessments, for example digit span tasks, the results were broadly equivalent., [Conclusions] Cognitive impairments were common in this sample and app-based screening complemented traditional neuropsychological assessment. Implications for clinical assessment and follow-up are discussed., RRG is funded by a Guarantors of Brain Post-Doctoral Fellowship award, by a Cancer Research UK Cambridge Centre RG86786 (CRUK grant ref: A25117) grant, and by the EMERGIA Junta de Andalucía program. Y. E. is funded by a Royal Society Dorothy Hodgkin Research Fellowship. M. A. is funded by the Cambridge Trust–Yousef Jameel Scholarship. S. J. P. is supported by the National Institute for Health Career Development Fellowship (CDF-2018-11-ST2-003). This report is an independent research supported by the National Institute of Research (NIHR Career Development Fellowship, Mr. Stephen Price, CDF-2018-11-ST2-003). M. G. H. received an award from The Brain Tumour Charity (ref: RG86218) to fund this work.

Published
2022

21. Brain charts for the human lifespan

Author

Armin Raznahan, Eric Courchesne, Andrea Parolin Jackowski, Kamen A. Tsvetanov, Cameron T. Ellis, R.C. Gur, Bin Bae J, Park Mtm, Pedro A. Valdes-Sosa, Simon N. Vandekar, Jacob W. Vogel, Juan Zhou, Machteld Marcelis, Kiho Im, Patricia Ellen Grant, Minhui Ouyang, Blesa Cabez M, Michael V. Lombardo, Sarah E. Morgan, James P. Boardman, Adamson C, Calhoun Vd, Delarue M, James H. Cole, Pichet Binette A, Roberto Toro, David H. Rowitch, Nynke A. Groenewold, Kevin M. Anderson, David T.W. Jones, Michael Schöll, Wang Ys, Aiden Corvin, R.E. Gur, Damien A. Fair, Gareth Ball, Herma Lina Schaare, Andrew Zalesky, Evdokia Anagnostou, Michael J. Meaney, Taki Y, Gareth J. Sullivan, Warrier, Petra E. Vértes, Chixiang Chen, Lisa T. Eyler, Wei Liao, Tomáš Paus, Jeremy A. Elman, Phillip McGuire, Hisham Ziauddeen, William S. Kremen, Etienne Vachon-Presseau, E.T. Bullmore, Christophe Tzourio, White, Hammill Cf, Mothersill D, Richard N. Henson, Jiang Qiu, Duncan E. Astle, Fabrice Crivello, Paul C. Fletcher, Chertavian C, Kim K, Jennifer Crosbie, Russell Schachar, Gabriel A. Devenyi, Manfred G. Kitzbichler, Tianye Jia, Trey Hedden, Sang Jae Lee, Ross D. Markello, Silke Kern, Ian M. Goodyer, Keith A. Johnson, Frauke Beyer, Bernard Mazoyer, A. Heinz, Sylvane Desrivières, Rosenberg, Gary Donohoe, Ong Mq, Alexander D. Edwards, Dan J. Stein, Nenad Medic, Zuo Xn, Travis T. Mallard, Peter Fonagy, Lindsay W. Victoria, Ingmar Skoog, Avram J. Holmes, Jason P. Lerch, Jed T. Elison, Jianfu Li, John H. Gilmore, Rosemary Holt, Caitlin K. Rollins, Carol E. Franz, Pedro Mario Pan, Saashi A Bedford, Yang N, Jonathan C Ipser, Richard A. I. Bethlehem, Tuulari Jj, Stolicyn A, Hua Huang, Bratislav Misic, Conor Liston, Ayub M, Lisa Ronan, Yeo Bt, Sophie Adler, Charles J. Lynch, Faith M. Gunning, Konrad Wagstyl, M. Mallar Chakravarty, John Suckling, Theodore D. Satterthwaite, Bharath Holla, Yap Seng Chong, Jinglei Lv, Jakob Seidlitz, Niall J Bourke, Xinlei Qian, Simon Baron-Cohen, Cynthia M. Ortinau, Deirel Paz Linares, Thyreau B, René S. Kahn, Aaron P. Schultz, Vanessa Cropley, Eric Westman, Mitchell Valdés-Sosa, Rik Ossenkoppele, André Zugman, Hasse Karlsson, Sylvia Villeneuve, Katja Heuer, Di Biase Ma, Margaret L. Westwater, Sofie L. Valk, David J. Sharp, Brigitte Landeau, Matthew Borzage, Kirsten A. Donald, Timothy Rittman, Richard Beare, Giovanni Abrahão Salum, Gunter Schumann, Ryuta Kawashima, Romero-Garcia R, John Blangero, Yun Hj, Russel T. Shinohara, Nicolas Crossley, Simon K. Warfield, Karen Pierce, George S. Alexopoulos, Katharine Dunlop, David C. Glahn, Francois Lalonde, Anqi Qiu, Lana Vasung, Gaël Chételat, Lídice Galán-García, Clifford R. Jack, Reisa A. Sperling, Anna Zettergren, Elizabeth Kelley, Arno Villringer, Andrea Mechelli, Benegal, Aaron Alexander-Bloch, Nicholas B. Turk-Browne, van Amelsvoort T, John D. Lewis, Heather C. Whalley, A. V. Witte, Zdenka Pausova, Joel T. Nigg, Heather J. Zar, Raymond J. Dolan, Christopher D. Smyser, Jay N. Giedd, Lena Palaniyappan, Ali Gholipour, Areces-Gonzalez A, Peter B. Jones, Jacqueline Hoare, Oskar Hansson, Linnea Karlsson, C Pantelis, Paly L, Bonnie Auyeung, Jorge Bosch-Bayard, Bethlehem, Richard [0000-0002-0714-0685], White, Simon [0000-0001-8642-7037], Astle, Duncan [0000-0002-7042-5392], Baron-Cohen, Simon [0000-0001-9217-2544], Henson, Rik [0000-0002-0712-2639], Jones, Peter [0000-0002-0387-880X], Kitzbichler, Manfred [0000-0002-4494-0753], Rittman, Timothy [0000-0003-1063-6937], Rowitch, David [0000-0002-0079-0060], Tsvetanov, Kamen A. [0000-0002-3178-6363], Westwater-Wozniak, Margaret [0000-0002-2918-0979], Ziauddeen, Hisham [0000-0003-4044-1719], Apollo - University of Cambridge Repository, British Academy, Autism Research Trust, National Institute of Mental Health (US), UK Research and Innovation, Medical Research Council (UK), National Institute for Health and Care Research (US), Wellcome Trust, University of Cambridge, Cambridge Biomedical Research Centre, University of Cambridge [UK] (CAM), University of Pennsylvania, Yale University [New Haven], Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Child and Adolescent Psychiatry Department [AP- HP Hôpital Robert Debré], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Neuroscience - Department of Neuroscience, Centre de Recherche Interdisciplinaire / Center for Research and Interdisciplinarity [Paris, France] (CRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: MA Med Staf Spec Psychiatrie (9), Neurology, Amsterdam Neuroscience - Neurodegeneration, 3R-BRAIN, AIBL, Alzheimer’s Disease Neuroimaging Initiative, Alzheimer’s Disease Repository Without Borders Investigators, CALM Team, Cam-CAN, CCNP, COBRE, cVEDA, ENIGMA Developmental Brain Age Working Group, Developing Human Connectome Project, FinnBrain, Harvard Aging Brain Study, IMAGEN, KNE96, The Mayo Clinic Study of Aging, NSPN, POND, The PREVENT-AD Research Group, VETSA, [Bethlehem, R. A. I.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Auyeung, B.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Baron-Cohen, S.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Bedford, S. A.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Holt, R.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Lombardo, M. V.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Bethlehem, R. A. I.] Univ Cambridge, Dept Psychiat, Brain Mapping Unit, Cambridge, England, [Kitzbichler, M. G.] Univ Cambridge, Dept Psychiat, Brain Mapping Unit, Cambridge, England, [Seidlitz, J.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Vogel, J. W.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Gur, R. E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Gur, R. C.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Jackowski, A. P.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Satterthwaite, T. D.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Alexander-Bloch, A. F.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Seidlitz, J.] Childrens Hosp Philadelphia, Dept Child & Adolescent Psychiat & Behav Sci, Philadelphia, PA 19104 USA, [Alexander-Bloch, A. F.] Childrens Hosp Philadelphia, Dept Child & Adolescent Psychiat & Behav Sci, Philadelphia, PA 19104 USA, [Seidlitz, J.] Childrens Hosp Philadelphia & Penn Med, Lifespan Brain Inst, Philadelphia, PA USA, [Chertavian, C.] Childrens Hosp Philadelphia & Penn Med, Lifespan Brain Inst, Philadelphia, PA USA, [Gur, R. E.] Childrens Hosp Philadelphia & Penn Med, Lifespan Brain Inst, Philadelphia, PA USA, [Gur, R. C.] Childrens Hosp Philadelphia & Penn Med, Lifespan Brain Inst, Philadelphia, PA USA, [Alexander-Bloch, A. F.] Childrens Hosp Philadelphia & Penn Med, Lifespan Brain Inst, Philadelphia, PA USA, [White, S. R.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Goodyer, I. M.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Henson, R. N.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Jones, P. B.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Kitzbichler, M. G.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Medic, N.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Morgan, S. E.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Romero-Garcia, R.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Ronan, L.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Suckling, J.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Vertes, P. E.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Warrier, V.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Westwater, M. L.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Ziauddeen, H.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Bullmore, E. T.] Univ Cambridge, Dept Psychiat, Cambridge, England, [White, S. R.] Univ Cambridge, MRC Biostat Unit, Cambridge, England, [Vogel, J. W.] Univ Penn, Lifespan Informat & Neuroimaging Ctr, Philadelphia, PA 19104 USA, [Satterthwaite, T. D.] Univ Penn, Lifespan Informat & Neuroimaging Ctr, Philadelphia, PA 19104 USA, [Anderson, K. M.] Yale Univ, Dept Psychol, New Haven, CT USA, [Ellis, C. T.] Yale Univ, Dept Psychol, New Haven, CT USA, [Turk-Browne, N. B.] Yale Univ, Dept Psychol, New Haven, CT USA, [Adamson, C.] Murdoch Childrens Res Inst, Dev Imaging, Melbourne, Vic, Australia, [Ball, G.] Murdoch Childrens Res Inst, Dev Imaging, Melbourne, Vic, Australia, [Beare, R.] Murdoch Childrens Res Inst, Dev Imaging, Melbourne, Vic, Australia, [Jackowski, A. P.] Murdoch Childrens Res Inst, Dev Imaging, Melbourne, Vic, Australia, [Adamson, C.] Monash Univ, Dept Med, Melbourne, Vic, Australia, [Beare, R.] Monash Univ, Dept Med, Melbourne, Vic, Australia, [Adler, S.] UCL Great Ormond St Inst Child Hlth, London, England, [Alexopoulos, G. S.] Weill Cornell Med, Dept Psychiat, Weill Cornell Inst Geriatr Psychiat, New York, NY USA, [Anagnostou, E.] Univ Toronto, Dept Pediat, Toronto, ON, Canada, [Anagnostou, E.] Holland Bloorview Kids Rehabil Hosp, Toronto, ON, Canada, [Pierce, K.] Holland Bloorview Kids Rehabil Hosp, Toronto, ON, Canada, [Areces-Gonzalez, A.] Univ Elect Sci & Technol China, MOE Key Lab NeuroInformat, Clin Hosp, Chengdu Brain Sci Inst, Chengdu, Peoples R China, [Paz-Linares, D.] Univ Elect Sci & Technol China, MOE Key Lab NeuroInformat, Clin Hosp, Chengdu Brain Sci Inst, Chengdu, Peoples R China, [Areces-Gonzalez, A.] Univ Pinar del Rio Hermanos Saiz Montes de Oca, Pinar Del Rio, Cuba, [Astle, D. E.] Univ Cambridge, MRC Cognit & Brain Sci Unit, Cambridge, England, [Henson, R. N.] Univ Cambridge, MRC Cognit & Brain Sci Unit, Cambridge, England, [Whalley, H. C.] Univ Cambridge, MRC Cognit & Brain Sci Unit, Cambridge, England, [Auyeung, B.] Univ Edinburgh, Sch Philosophy Psychol & Language Sci, Dept Psychol, Edinburgh, Midlothian, Scotland, [Pausova, Z.] Univ Edinburgh, Sch Philosophy Psychol & Language Sci, Dept Psychol, Edinburgh, Midlothian, Scotland, [Ayub, M.] Queens Univ, Dept Psychiat, Ctr Neurosci Studies, Kingston, ON, Canada, [Ayub, M.] UCL, Mental Hlth Neurosci Res Dept, Div Psychiat, London, England, [Bae, J.] Seoul Natl Univ, Bundang Hosp, Dept Neuropsychiat, Seongnam, South Korea, [Ball, G.] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia, [Baron-Cohen, S.] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge Lifetime Asperger Syndrome Serv CLASS, Cambridge, England, [Benegal, V.] Natl Inst Mental Hlth & Neurosci NIMHANS, Ctr Addict Med, Bengaluru, India, [Beyer, F.] Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, Leipzig, Germany, [Villringer, A.] Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, Leipzig, Germany, [Witte, A. V.] Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, Leipzig, Germany, [Blangero, J.] Univ Texas Rio Grande Valley, South Texas Diabet & Obes Inst, Dept Human Genet, Edinburg, TX USA, [Blesa Cabez, M.] Univ Edinburgh, MRC Ctr Reprod Hlth, Edinburgh, Midlothian, Scotland, [Boardman, J. P.] Univ Edinburgh, MRC Ctr Reprod Hlth, Edinburgh, Midlothian, Scotland, [Sullivan, G.] Univ Edinburgh, MRC Ctr Reprod Hlth, Edinburgh, Midlothian, Scotland, [Borzage, M.] Univ Southern Calif, Childrens Hosp Los Angeles, Keck Sch Med, Fetal & Neonatal Inst,Div Neonatol,Dept Pediat, Los Angeles, CA 90007 USA, [Bosch-Bayard, J. F.] Montreal Neurol Inst, Ludmer Ctr Neuroinformat & Mental Hlth, McGill Ctr Integrat Neurosci, Montreal, PQ, Canada, [Bosch-Bayard, J. F.] McGill Univ, Montreal, PQ, Canada, [Chakravarty, M. M.] McGill Univ, Montreal, PQ, Canada, [Bourke, N.] Imperial Coll London, Dept Brain Sci, London, England, [Sharp, D.] Imperial Coll London, Dept Brain Sci, London, England, [Alexander-Bloch, A. F.] Imperial Coll London, Dept Brain Sci, London, England, [Bourke, N.] Dementia Res Inst, Care Res & Technol Ctr, London, England, [Calhoun, V. D.] Georgia State Univ, Triinst Ctr Translat Res Neuroimaging & Data Sci, Georgia Inst Technol, Atlanta, GA 30303 USA, [Calhoun, V. D.] Emory Univ, Atlanta, GA 30322 USA, [Chakravarty, M. M.] Douglas Mental Hlth Univ Inst, Cerebral Imaging Ctr, Comp Brain Anat CoBrA Lab, Montreal, PQ, Canada, [Chen, C.] Univ Penn, Penn Stat Imaging & Visualizat Ctr, Dept Biostat Epidemiol & Informat, Perelman Sch Med, Philadelphia, PA 19104 USA, [Shinohara, R. T.] Univ Penn, Penn Stat Imaging & Visualizat Ctr, Dept Biostat Epidemiol & Informat, Perelman Sch Med, Philadelphia, PA 19104 USA, [Chetelat, G.] Normandie Univ, PhIND Physiopathol & Imaging Neurol Disorders, Inst Blood & Brain Caen Normandie, UNICAEN,INSERM,U1237, Caen, France, [Delarue, M.] Normandie Univ, PhIND Physiopathol & Imaging Neurol Disorders, Inst Blood & Brain Caen Normandie, UNICAEN,INSERM,U1237, Caen, France, [Landeau, B.] Normandie Univ, PhIND Physiopathol & Imaging Neurol Disorders, Inst Blood & Brain Caen Normandie, UNICAEN,INSERM,U1237, Caen, France, [Paly, L.] Normandie Univ, PhIND Physiopathol & Imaging Neurol Disorders, Inst Blood & Brain Caen Normandie, UNICAEN,INSERM,U1237, Caen, France, [Chong, Y. S.] Agcy Sci Technol & Res, Singapore Inst Clin Sci, Singapore, Singapore, [Chong, Y. S.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Obstet & Gynaecol, Singapore, Singapore, [Cole, J. H.] UCL, Ctr Med Image Comp CMIC, London, England, [Cole, J. H.] UCL, Dementia Res Ctr DRC, London, England, [Corvin, A.] Trinity Coll Dublin, Dept Psychiat, Dublin, Ireland, [Costantino, M.] Douglas Mental Hlth Univ Inst, Cerebral Imaging Ctr, Verdun, PQ, Canada, [Costantino, M.] McGill Univ, Undergrad Program Neurosci, Montreal, PQ, Canada, [Courchesne, E.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA, [Courchesne, E.] Univ Calif San Diego, Autism Ctr Excellence, San Diego, CA 92103 USA, [Crivello, F.] Univ Bordeaux, Inst Neurodegenerat Disorders, CNRS UMR5293, CEA, Bordeaux, France, [Mazoyer, B.] Univ Bordeaux, Inst Neurodegenerat Disorders, CNRS UMR5293, CEA, Bordeaux, France, [Cropley, V. L.] Univ Melbourne, Melbourne Neuropsychiat Ctr, Melbourne, Vic, Australia, [Di Biase, M. A.] Univ Melbourne, Melbourne Neuropsychiat Ctr, Melbourne, Vic, Australia, [Lv, J.] Univ Melbourne, Melbourne Neuropsychiat Ctr, Melbourne, Vic, Australia, [Zalesky, A.] Univ Melbourne, Melbourne Neuropsychiat Ctr, Melbourne, Vic, Australia, [Hammill, C. F.] Hosp Sick Children, Toronto, ON, Canada, [Schachar, R. J.] Hosp Sick Children, Toronto, ON, Canada, [Crossley, N.] Pontificia Univ Catolica Chile, Sch Med, Dept Psychiat, Santiago, Chile, [Crossley, N.] Kings Coll London, Dept Psychosis Studies, Inst Psychiat Psychol & Neurosci, London, England, [McGuire, P.] Kings Coll London, Dept Psychosis Studies, Inst Psychiat Psychol & Neurosci, London, England, [Crossley, N.] Inst Milenio Intelligent Healthcare Engn, Santiago, Chile, [Delorme, R.] Robert Debre Univ Hosp, AP HP, Child & Adolescent Psychiat Dept, Paris, France, [Delorme, R.] Inst Pasteur, Human Genet & Cognit Funct, Paris, France, [Desrivieres, S.] Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, London, England, [Devenyi, G. A.] Douglas Mental Hlth Univ Inst, McGill Dept Psychiat, Cerebral Imaging Ctr, Montreal, PQ, Canada, [Devenyi, G. A.] McGill Univ, Dept Psychiat, Montreal, PQ, Canada, [Di Biase, M. A.] Harvard Med Sch, Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA, [Dolan, R.] UCL, Max Planck UCL Ctr Computat Psychiat & Ageing Res, London, England, [Dolan, R.] Wellcome Ctr Human Neuroimaging, London, England, [Wagstyl, K.] Wellcome Ctr Human Neuroimaging, London, England, [Donald, K. A.] Red Cross War Mem Childrens Hosp, Dept Paediat & Child Hlth, Div Dev Paediat, Cape Town, South Africa, [Donald, K. A.] Univ Cape Town, Neurosci Inst, Cape Town, South Africa, [Groenewold, N. A.] Univ Cape Town, Neurosci Inst, Cape Town, South Africa, [Donohoe, G.] Natl Univ Ireland Galway, Sch Psychol, Ctr Neuroimaging Cognit & Genom NICOG, Galway, Ireland, [Dunlop, K.] Weill Cornell Med, Dept Psychiat, Weil Family Brain & Mind Res Inst, New York, NY USA, [Lynch, C.] Weill Cornell Med, Dept Psychiat, Weil Family Brain & Mind Res Inst, New York, NY USA, [Edwards, A. D.] Kings Coll London, Ctr Dev Brain, London, England, [Edwards, A. D.] Evelina London Childrens Hosp, London, England, [Edwards, A. D.] MRC Ctr Neurodev Disorders, London, England, [Elison, J. T.] Univ Minnesota, Mason Inst Dev Brain, Dept Pediat, Inst Child Dev, Minneapolis, MN USA, [Fair, D. A.] Univ Minnesota, Mason Inst Dev Brain, Dept Pediat, Inst Child Dev, Minneapolis, MN USA, [Feczko, E.] Univ Minnesota, Mason Inst Dev Brain, Dept Pediat, Inst Child Dev, Minneapolis, MN USA, [Ellis, C. T.] Haskins Labs Inc, New Haven, CT USA, [Elman, J. A.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genet Aging, La Jolla, CA 92093 USA, [Franz, C. E.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genet Aging, La Jolla, CA 92093 USA, [Kremen, W. S.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genet Aging, La Jolla, CA 92093 USA, [Eyler, L.] VA San Diego Healthcare, Desert Pacific Mental Illness Res Educ & Clin Ctr, San Diego, CA USA, [Eyler, L.] Univ Calif San Diego, Dept Psychiat, Los Angeles, CA USA, [Fletcher, P. C.] Univ Cambridge, Dept Psychiat, Cambridge Biomed Campus, Cambridge, England, [Fletcher, P. C.] Wellcome Trust MRC Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England, [Fletcher, P. C.] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge, England, [Jones, P. B.] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge, England, [Suckling, J.] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge, England, [Ziauddeen, H.] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge, England, [Fonagy, P.] UCL, Dept Clin Educ & Hlth Psychol, London, England, [Fonagy, P.] Anna Freud Natl Ctr Children & Families, London, England, [Galan-Garcia, L.] Cuban Ctr Neurosci, Havana, Cuba, [Valdes-Sosa, M. J.] Cuban Ctr Neurosci, Havana, Cuba, [Gholipour, A.] Boston Childrens Hosp, Computat Radiol Lab, Boston, MA USA, [Warfield, S. K.] Boston Childrens Hosp, Computat Radiol Lab, Boston, MA USA, [Giedd, J.] Univ Calif San Diego, Dept Child & Adolescent Psychiat, San Diego, CA 92103 USA, [Giedd, J.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA, [Gilmore, J. H.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27515 USA, [Glahn, D. C.] Boston Childrens Hosp, Dept Psychiat, Boston, MA USA, [Im, K.] Boston Childrens Hosp, Dept Psychiat, Boston, MA USA, [Mathias, S. R.] Boston Childrens Hosp, Dept Psychiat, Boston, MA USA, [Rodrigue, A.] Boston Childrens Hosp, Dept Psychiat, Boston, MA USA, [Glahn, D. C.] Harvard Med Sch, Boston, MA 02115 USA, [Im, K.] Harvard Med Sch, Boston, MA 02115 USA, [Johnson, K. A.] Harvard Med Sch, Boston, MA 02115 USA, [Mathias, S. R.] Harvard Med Sch, Boston, MA 02115 USA, [Rodrigue, A.] Harvard Med Sch, Boston, MA 02115 USA, [Schultz, A. P.] Harvard Med Sch, Boston, MA 02115 USA, [Sperling, R. A.] Harvard Med Sch, Boston, MA 02115 USA, [Grant, P. E.] Harvard Med Sch, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston Childrens Hosp, Div Newborn Med & Neuroradiol, Boston, MA 02115 USA, [Groenewold, N. A.] Univ Cape Town, SA MRC Unit Child & Adolescent Hlth, Red Cross War Mem Childrens Hosp, Dept Paediat & Child Hlth, Cape Town, South Africa, [Zar, H. J.] Univ Cape Town, SA MRC Unit Child & Adolescent Hlth, Red Cross War Mem Childrens Hosp, Dept Paediat & Child Hlth, Cape Town, South Africa, [Gunning, F. M.] Weill Cornell Med, Dept Psychiat, Weill Cornell Inst Geriatr Psychiat, New York, NY USA, [Victoria, L. W.] Weill Cornell Med, Dept Psychiat, Weill Cornell Inst Geriatr Psychiat, New York, NY USA, [Hammill, C. F.] Mouse Imaging Ctr, Toronto, ON, Canada, [Hansson, O.] Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Malmo, Sweden, [Hansson, O.] Skane Univ Hosp, Memory Clin, Malmo, Sweden, [Hedden, T.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA, [Hedden, T.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Athinoula Martinos Ctr Biomed Imaging, Boston, MA 02115 USA, [Heinz, A.] Charite Univ Med Berlin, Charite Campus Mitte, Berlin, Germany, [Heinz, A.] Free Univ Berlin, Charite Campus Mitte, Berlin, Germany, [Heinz, A.] Humboldt Univ, Dept Psychiat & Psychotherapy, Charite Campus Mitte, Berlin, Germany, [Heuer, K.] Max Planck Inst Human Cognit & Brain Sci, Dept Neuropsychol, Leipzig, Germany, [Heuer, K.] Univ Paris, Paris, France, [Toro, R.] Univ Paris, Paris, France, [Hoare, J.] Univ Cape Town, Dept Psychiat, Cape Town, South Africa, [Holla, B.] NIMHANS, Dept Integrat Med, Bengaluru, India, [Holla, B.] NIMHANS, Dept Psychiat, Accelerator Program Discovery Brain Disorders Usi, Bengaluru, India, [Holmes, A. J.] Yale Univ, Dept Psychol, New Haven, CT USA, [Villeneuve, S.] Yale Univ, Dept Psychol, New Haven, CT USA, [Holmes, A. J.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA, [Villeneuve, S.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA, [Huang, H.] Childrens Hosp Philadelphia, Radiol Res, Philadelphia, PA 19104 USA, [Ouyang, M.] Childrens Hosp Philadelphia, Radiol Res, Philadelphia, PA 19104 USA, [Huang, H.] Univ Penn, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA, [Ipser, J.] Univ Cape Town, Dept Psychiat & Mental Hlth, Clin Neurosci Inst, Cape Town, South Africa, [Jack, C. R., Jr.] Mayo Clin, Dept Radiol, Rochester, MN USA, [Jones, D. T.] Mayo Clin, Dept Radiol, Rochester, MN USA, Univ Fed Sao Paulo, Dept Psychiat, Sao Paulo, Brazil, [Jackowski, A. P.] Natl Inst Dev Psychiat, Beijing, Peoples R China, [Jia, T.] Fudan Univ, Inst Sci & Technol Brain Inspired Intelligence, Shanghai, Peoples R China, [Jia, T.] Fudan Univ, Minist Educ, Key Lab Computat Neurosci & Brain Inspired Intell, Shanghai, Peoples R China, [Jia, T.] Kings Coll London, Inst Psychiat Psychol & Neurosci, Ctr Populat Neurosci & Precis Med PONS, SGDP Ctr, London, England, [Johnson, K. A.] Massachusetts Gen Hosp, Dept Neurol, Harvard Aging Brain Study, Boston, MA 02114 USA, [Schultz, A. P.] Massachusetts Gen Hosp, Dept Neurol, Harvard Aging Brain Study, Boston, MA 02114 USA, [Sperling, R. A.] Massachusetts Gen Hosp, Dept Neurol, Harvard Aging Brain Study, Boston, MA 02114 USA, [Johnson, K. A.] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, 75 Francis St, Boston, MA 02115 USA, [Sperling, R. A.] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, 75 Francis St, Boston, MA 02115 USA, [Johnson, K. A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA, [Jones, D. T.] Mayo Clin, Dept Neurol, Rochester, MN USA, [3R-BRAIN] Mayo Clin, Dept Neurol, Rochester, MN USA, [Kahn, R. S.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA, [Karlsson, H.] Univ Turku, Dept Psychiat, Dept Clin Med, Turku, Finland, [Karlsson, L.] Univ Turku, Dept Psychiat, Dept Clin Med, Turku, Finland, [Tuulari, J. J.] Univ Turku, Dept Psychiat, Dept Clin Med, Turku, Finland, [Karlsson, H.] Univ Turku, FinnBrain Birth Cohort Study, Turku Brain & Mind Ctr, Turku, Finland, [Karlsson, L.] Univ Turku, FinnBrain Birth Cohort Study, Turku Brain & Mind Ctr, Turku, Finland, [Tuulari, J. J.] Univ Turku, FinnBrain Birth Cohort Study, Turku Brain & Mind Ctr, Turku, Finland, [Karlsson, H.] Turku Univ Hosp, Turku, Finland, [Karlsson, L.] Turku Univ Hosp, Turku, Finland, [Tuulari, J. J.] Turku Univ Hosp, Turku, Finland, [Karlsson, H.] Turku Univ Hosp, Ctr Populat Hlth Res, Turku, Finland, [Karlsson, L.] Turku Univ Hosp, Ctr Populat Hlth Res, Turku, Finland, [Karlsson, H.] Univ Turku, Turku, Finland, [Karlsson, L.] Univ Turku, Turku, Finland, [Kawashima, R.] Tohoku Univ, Inst Dev Aging & Canc, Aoba Ku, Sendai, Miyagi, Japan, [Taki, Y.] Tohoku Univ, Inst Dev Aging & Canc, Aoba Ku, Sendai, Miyagi, Japan, [Thyreau, B.] Tohoku Univ, Inst Dev Aging & Canc, Aoba Ku, Sendai, Miyagi, Japan, [Kelley, E. A.] Queens Univ, Ctr Neurosci Studies, Dept Psychol, Kingston, ON, Canada, [Kelley, E. A.] Queens Univ, Ctr Neurosci Studies, Dept Psychiat, Kingston, ON, Canada, [Kern, S.] Univ Gothenburg, Neuropsychiat Epidemiol Unit, Dept Psychiat & Neurochem,Sahlgrenska Acad, Ctr Ageing & Hlth AGECAP,Inst Neurosci & Physiol, Gothenburg, Sweden, [Skoog, I.] Univ Gothenburg, Neuropsychiat Epidemiol Unit, Dept Psychiat & Neurochem,Sahlgrenska Acad, Ctr Ageing & Hlth AGECAP,Inst Neurosci & Physiol, Gothenburg, Sweden, [Zettergren, A.] Univ Gothenburg, Neuropsychiat Epidemiol Unit, Dept Psychiat & Neurochem,Sahlgrenska Acad, Ctr Ageing & Hlth AGECAP,Inst Neurosci & Physiol, Gothenburg, Sweden, [Kern, S.] Sahlgrens Univ Hosp, Psychiat Cognit & Old Age Psychiat Clin, Reg Vastra Gotaland, Gothenburg, Sweden, [Skoog, I.] Sahlgrens Univ Hosp, Psychiat Cognit & Old Age Psychiat Clin, Reg Vastra Gotaland, Gothenburg, Sweden, [Kim, K. W.] Seoul Natl Univ, Dept Brain & Cognit Sci, Coll Nat Sci, Seoul, South Korea, [Kim, K. W.] Seoul Natl Univ, Bundang Hosp, Dept Neuropsychiat, Seongnam, South Korea, [Kim, K. W.] Seoul Natl Univ, Dept Psychiat, Coll Med, Seoul, South Korea, [Kim, K. W.] SNU MRC, Inst Human Behav Med, Seoul, South Korea, [Lalonde, F.] NIMH, Sect Dev Neurogenom, Human Genet Branch, Bethesda, MD 20892 USA, [Raznahan, A.] NIMH, Sect Dev Neurogenom, Human Genet Branch, Bethesda, MD 20892 USA, [Lee, S.] Seoul Natl Univ, Coll Nat Sci, Dept Brain & Cognit Sci, Seoul, South Korea, [Lerch, J.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada, [Lerch, J.] Univ Oxford, Nuffield Dept Clin Neurosci, FMRIB, Wellcome Ctr Integrat Neuroimaging, Oxford, England, [Lewis, J. D.] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada, [Li, J.] Univ Elect Sci & Technol China, Clin Hosp, Chengdu Brain Sci Inst, Chengdu, Peoples R China, [Liao, W.] Univ Elect Sci & Technol China, Clin Hosp, Chengdu Brain Sci Inst, Chengdu, Peoples R China, [Valdes-Sosa, P. A.] Univ Elect Sci & Technol China, Clin Hosp, Chengdu Brain Sci Inst, Chengdu, Peoples R China, [Liston, C.] Weill Cornell Med, Dept Psychiat, New York, NY USA, [Liston, C.] Weill Cornell Med, Brain & Mind Res Inst, New York, NY USA, [Lombardo, M. V.] Ist Italiano Tecnol, Ctr Neurosci & Cognit Syst UniTn, Lab Autism & Neurodev Disorders, Rovereto, Italy, [Lv, J.] Univ Sydney, Sch Biomed Engn, Sydney, NSW, Australia, [Lv, J.] Univ Sydney, Brain & Mind Ctr, Sydney, NSW, Australia, [Mallard, T. T.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA, [Marcelis, M.] Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, EURON,Med Ctr, Maastricht, Netherlands, [Marcelis, M.] Inst Mental Hlth Care Eindhoven GGzE, Eindhoven, Netherlands, [Markello, R. D.] McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada, [Misic, B.] McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada, [Vasung, L.] McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada, [Mazoyer, B.] Douglas Mental Hlth Univ Inst, Ludmer Ctr Neuroinformat & Mental Hlth, Montreal, PQ, Canada, [Meaney, M. J.] Douglas Mental Hlth Univ Inst, Ludmer Ctr Neuroinformat & Mental Hlth, Montreal, PQ, Canada, [Meaney, M. J.] Singapore Inst Clin Sci, Singapore, Singapore, [Mechelli, A.] Bordeaux Univ Hosp, Bordeaux, France, [Morgan, S. E.] Univ Cambridge, Dept Comp Sci & Technol, Cambridge, England, [Morgan, S. E.] Alan Turing Inst, London, England, [Vertes, P. E.] Alan Turing Inst, London, England, [Mothersill, D.] Natl Coll Ireland, Sch Business, Dept Psychol, Dublin, Ireland, [Mothersill, D.] Natl Univ Ireland Galway, Sch Psychol, Galway, Ireland, [Mothersill, D.] Natl Univ Ireland Galway, Ctr Neuroimaging & Cognit Genom, Galway, Ireland, [Mothersill, D.] Trinity Coll Dublin, Dept Psychiat, Dublin, Ireland, [Nigg, J.] Oregon Hlth & Sci Univ, Dept Psychiat, Sch Med, Portland, OR 97201 USA, [Ong, M. Q. W.] Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Sleep & Cognit, Singapore, Singapore, [Qian, X.] Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Sleep & Cognit, Singapore, Singapore, [Zhou, J. H.] Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Sleep & Cognit, Singapore, Singapore, [Ortinau, C.] Washington Univ, Dept Pediat, St Louis, MO 63130 USA, [Ossenkoppele, R.] Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Amsterdam UMC, Dept Neurol,Amsterdam Neurosci, Amsterdam, Netherlands, [Ossenkoppele, R.] Lund Univ, Clin Memory Res Unit, Lund, Sweden, [Palaniyappan, L.] Univ Western Ontario, Robarts Res Inst, London, ON, Canada, [Palaniyappan, L.] Univ Western Ontario, Brain & Mind Inst, London, ON, Canada, [Pan, P. M.] Fed Univ Sao Poalo UNIFESP, Dept Psychiat, Sao Poalo, Brazil, [Pan, P. M.] Natl Inst Dev Psychiat Children & Adolescents INP, Sao Poalo, Brazil, [Zugman, A.] Natl Inst Dev Psychiat Children & Adolescents INP, Sao Poalo, Brazil, [Pantelis, C.] Univ Melbourne, Dept Psychiat, Melbourne Neuropsychiat Ctr, Carlton, Vic, Australia, [Pantelis, C.] Melbourne Hlth, Carlton, Vic, Australia, [Pantelis, C.] Univ Melbourne, Melbourne Sch Engn, Parkville, Vic, Australia, [Pantelis, C.] Florey Inst Neurosci & Mental Hlth, Parkville, Vic, Australia, [Park, M. M.] Western Univ, Schulich Sch Med & Dent, Dept Psychiat, London, ON, Canada, [Rollins, C. K.] Univ Montreal, Dept Psychiat, Fac Med, Montreal, PQ, Canada, [Rollins, C. K.] Univ Montreal, CHU St Justine, Montreal, PQ, Canada, [Romero-Garcia, R.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada, [Romero-Garcia, R.] Univ Toronto, Dept Psychol, Toronto, ON, Canada, [Rosenberg, M. D.] Univ Toronto, Dept Physiol, Toronto, ON, Canada, [Rosenberg, M. D.] Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada, [Paz-Linares, D.] Cuban Neurosci Ctr, Havana, Cuba, [Pichet Binette, A.] McGill Univ, Fac Med, Dept Psychiat, Montreal, PQ, Canada, [Villeneuve, S.] McGill Univ, Fac Med, Dept Psychiat, Montreal, PQ, Canada, [Pichet Binette, A.] Douglas Mental Hlth Univ Inst, Montreal, PQ, Canada, [Villeneuve, S.] Douglas Mental Hlth Univ Inst, Montreal, PQ, Canada, [Qiu, J.] Southwest Univ, Sch Psychol, Chongqing, Peoples R China, [Qiu, A.] Natl Univ Singapore, N1 Inst Hlth, Dept Biomed Engn, Singapore, Singapore, [Rittman, T.] Univ Cambridge, Dept Clin Neurosci, Cambridge, England, [Tsvetanov, K. A.] Univ Cambridge, Dept Clin Neurosci, Cambridge, England, [Rollins, C. K.] Harvard Med Sch, Dept Neurol, Boston, MA 02115 USA, [Rollins, C. K.] Boston Childrens Hosp, Dept Neurol, Boston, MA USA, [Romero-Garcia, R.] Univ Seville, Dpto Fisiol Med & Biofis, Inst Biomed Sevilla IBiS HUVR CSIC, Seville, Spain, [Rosenberg, M. D.] Univ Chicago, Dept Psychol, 5848 S Univ Ave, Chicago, IL 60637 USA, [Rosenberg, M. D.] Univ Chicago, Inst Neurosci, Chicago, IL USA, [Rowitch, D. H.] Univ Cambridge, Dept Paediat, Cambridge, England, [Rowitch, D. H.] Univ Cambridge, Wellcome MRC Cambridge Stem Cell Inst, Cambridge, England, [Salum, G. A.] Univ Fed Rio Grande Sul UFRGS, Hosp Clin Porto Alegre, Dept Psychiat, Porto Alegre, RS, Brazil, [Salum, G. A.] Natl Inst Dev Psychiat INPD, Sao Paulo, Brazil, [Schaare, H. L.] Max Planck Inst Human Cognit & Brain Sci, Otto Hahn Grp Cognit Neurogenet, Leipzig, Germany, [Schaare, H. L.] Res Ctr Juelich, Inst Neurosci & Med INM 7 Brain & Behav, Julich, Germany, [Schultz, A. P.] Massachusetts Gen Hosp, Dept Radiol, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA, [Schumann, G.] Fudan Univ, Inst Sci & Technol Brain Inspired Intelligence, Ctr Populat Neurosci & Stratified Med PONS, Shanghai, Peoples R China, [Schumann, G.] Charite Campus Mitte, Dept Psychiat & Psychotherapy, Charite Mental Hlth, PONS Ctr, Berlin, Germany, [Scholl, M.] Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, Gothenburg, Sweden, [Scholl, M.] Univ Gothenburg, Dept Psychiat & Neurochem, Gothenburg, Sweden, [Scholl, M.] UCL, Queens Sq Inst Neurol, Dementia Res Ctr, London, England, [Sharp, D.] UK Dementia Res Inst, Care Res & Technol Ctr, London, England, [Shinohara, R. T.] Univ Penn, Perelman Sch Med, Dept Radiol, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA, [Smyser, C. D.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA, [Smyser, C. D.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA, [Smyser, C. D.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA, [Stein, D. J.] Univ Cape Town, Dept Psychiat, SA MRC Unit Risk & Resilience Mental Disorders, Cape Town, South Africa, [Stein, D. J.] Univ Cape Town, Neurosci Inst, Cape Town, South Africa, [Stolicyn, A.] Univ Edinburgh, Ctr Clin Brain Sci, Div Psychiat, Edinburgh, Midlothian, Scotland, [Whalley, H. C.] Univ Edinburgh, Ctr Clin Brain Sci, Div Psychiat, Edinburgh, Midlothian, Scotland, [Toro, R.] Inst Pasteur, Dept Neurosci, Paris, France, [Traut, N.] Inst Pasteur, Dept Neurosci, Paris, France, [Traut, N.] Univ Paris 05, Ctr Res & Interdisciplinar CRI, Paris, France, [Tsvetanov, K. A.] Univ Cambridge, Dept Psychol, Cambridge, England, [Turk-Browne, N. B.] Yale Univ, Wu Tsai Inst, New Haven, CT USA, [Tuulari, J. J.] Univ Turku, Dept Clin Med, Turku, Finland, [Tuulari, J. J.] Univ Turku, Turku Coll Sci Med & Technol, Turku, Finland, [Tzourio, C.] Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, CHU Bordeaux, U1219,INSERM, Bordeaux, France, [Vachon-Presseau, E.] McGill Univ, Fac Dent Med & Oral Hlth Sci, Montreal, PQ, Canada, [Valdes-Sosa, P. A.] McGill Univ, Alan Edwards Ctr Res Pain AECRP, Montreal, PQ, Canada, [Valk, S. L.] Forschungszentrum Julich, Inst Neurosci & Med 7, Julich, Germany, [Valk, S. L.] Max Planck Inst Human Cognit & Brain Sci, Leipzig, Germany, [van Amelsvoort, T.] Maastricht Univ, Dept Psychiat & Neurosychol, Maastricht, Netherlands, [Vandekar, S. N.] Vanderbilt Univ, Dept Biostat, 221 Kirkland Hall, Nashville, TN 37235 USA, [Villeneuve, S.] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN USA, [Villringer, A.] Univ Leipzig, Clin Cognit Neurol, Med Ctr, Leipzig, Germany, [Witte, A. V.] Univ Leipzig, Clin Cognit Neurol, Med Ctr, Leipzig, Germany, [Zuo, X. N.] Univ Leipzig, Clin Cognit Neurol, Med Ctr, Leipzig, Germany, [Wang, Y. S.] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China, [Yang, N.] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China, [Yeo, B.] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China, [Zuo, X. N.] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China, [Wang, Y. S.] Beijing Normal Univ, IDG McGovern Inst Brain Res, Dev Populat Neuroscience Res Ctr, Beijing, Peoples R China, [Yang, N.] Beijing Normal Univ, IDG McGovern Inst Brain Res, Dev Populat Neuroscience Res Ctr, Beijing, Peoples R China, [Zuo, X. N.] Beijing Normal Univ, IDG McGovern Inst Brain Res, Dev Populat Neuroscience Res Ctr, Beijing, Peoples R China, [Wang, Y. S.] Natl Basic Sci Data Ctr, Beijing, Peoples R China, [Yang, N.] Natl Basic Sci Data Ctr, Beijing, Peoples R China, [Zuo, X. N.] Natl Basic Sci Data Ctr, Beijing, Peoples R China, [Wang, Y. S.] Chinese Acad Sci, Res Ctr Lifespan Dev Brain & Mind, Inst Psychol, Beijing, Peoples R China, [Yang, N.] Chinese Acad Sci, Res Ctr Lifespan Dev Brain & Mind, Inst Psychol, Beijing, Peoples R China, [Westman, E.] Karolinska Inst, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Div Clin Geriatr, Stockholm, Sweden, [Witte, A. V.] Univ Leipzig, CRC 1052 Obes Mech, Fac Med, Leipzig, Germany, [Zhou, J. H.] Natl Univ Singapore, Dept Elect & Comp Engn, Singapore, Singapore, [Yeo, B.] Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Sleep & Cognit, Singapore, Singapore, [Yeo, B.] Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Translat MR Res, Singapore, Singapore, [Yeo, B.] Natl Univ Singapore, N1 Inst Hlth, Singapore, Singapore, [Yeo, B.] Natl Univ Singapore, Inst Digital Med, Singapore, Singapore, [Yun, H.] Natl Univ Singapore, Integrat Sci & Engn Programme ISEP, Singapore, Singapore, [Zar, H. J.] Univ Melbourne, Dept Biomed Engn, Melbourne, Vic, Australia, [Zhou, J. H.] Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Translat Magnet Resonance Res, Singapore, Singapore, [Ziauddeen, H.] Univ Cambridge, Wellcome Trust MRC Inst Metab Sci, Cambridge, England, [Zugman, A.] NIMH, NIH, Bethesda, MD 20892 USA, [Zugman, A.] Escola Paulista Med, Dept Psychiat, Sao Paulo, Brazil, [Zuo, X. N.] Nanning Normal Univ, Sch Educ Sci, Key Lab Brain & Educ, Nanning, Peoples R China, British Academy Postdoctoral fellowship, NIMH, UKRI Medical Research Council, NIHR Cambridge Biomedical Research Centre, NIHR Senior Investigator award, MRC research infrastructure award, Commonwealth Scientific and Industrial Research Organisation (CSIRO), and Ontario Brain Institute

Subjects
631/378/2649, OpenPain Project, KNE96, Growth, Psychiatric-disorders, DISEASE, 3R-BRAIN, Brain charts, MRI Brain, OASIS-3, Disease, CCNP, 631/378/2571, UMN BCP, Multidisciplinary, medicine.diagnostic_test, PSYCHIATRIC-DISORDERS, article, Brain, Human brain, ASSOCIATION, Magnetic Resonance Imaging, Harvard Aging Brain Study, The Mayo Clinic Study of Aging, NSPN, medicine.anatomical_structure, GROWTH, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], ddc:500, BURDEN, WHITE-MATTER, FinnBrain, Harvard Aging Brain Study, Organization, Mri, MRI, medicine.medical_specialty, Concurrent validity, MODELS, Cam-CAN, Longevity, CALM Team, POND, Neuroimaging, Burden, ORGANIZATION, AIBL, The PREVENT-AD Research Group, VETSA, Cortical thickness, Association, Physical medicine and rehabilitation, FinnBrain, IMAGEN, KNE96, White-matter, medicine, Humans, ASRB, 631/378/1689, COBRE, business.industry, 631/378/2611, Brain morphometry, Neurosciences, Alzheimer’s Disease Repository Without Borders Investigators, Magnetic resonance imaging, Alzheimer’s Disease Neuroimaging Initiative, Anthropometry, Body Height, Brain growth, Birth, 59/57, Normative, IMAGEN, ENIGMA Developmental Brain Age working group, NSPN, business, CCNP, 3R-BRAIN, CORTICAL THICKNESS, Developing Human Connectome Project, ENIGMA Developmental Brain Age working group, The PREVENT-AD Research Group, VETSA, Bullmore, E.T
Abstract

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes., R.A.I.B. was supported by a British Academy Postdoctoral fellowship and by the Autism Research Trust. J. Seidlitz was supported by NIMH T32MH019112-29 and K08MH120564. S.R.W. was funded by UKRI Medical Research Council MC_UU_00002/2 and was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). E.T.B. was supported by an NIHR Senior Investigator award and the Wellcome Trust collaborative award for the Neuroscience in Psychiatry Network. A.F.A.-B. was supported by NIMH K08MH120564. Data were curated and analysed using a computational facility funded by an MRC research infrastructure award (MR/M009041/1) to the School of Clinical Medicine, University of Cambridge and supported by the mental health theme of the NIHR Cambridge Biomedical Research Centre.

Published
2022
Full Text
View/download PDF

22. Surface Lattice Plasmon Resonances by Direct In Situ Substrate Growth of Gold Nanoparticles in Ordered Arrays

Author

Gail A. Vinnacombe‐Willson, Ylli Conti, Steven J. Jonas, Paul S. Weiss, Agustín Mihi, Leonardo Scarabelli, Ministerio de Ciencia, Innovación y Universidades (España), Consejo Superior de Investigaciones Científicas (España), Fundación 'la Caixa', University of California, National Institute for Health and Care Research (US), Hyundai Hope On Wheels, and National Science Foundation (US)

Subjects
In situ growth, Bottom-up synthesis, Mechanics of Materials, Mechanical Engineering, Lattice plasmon resonance, Plasmonic arrays, General Materials Science
Abstract

Precise arrangements of plasmonic nanoparticles on substrates are important for designing optoelectronics, sensors and metamaterials with rational electronic, optical and magnetic properties. Bottom-up synthesis offers unmatched control over morphology and optical response of individual plasmonic building blocks. Usually, the incorporation of nanoparticles made by bottom-up wet chemistry starts from batch synthesis of colloids, which requires time-consuming and hard-to-scale steps like ligand exchange and self-assembly. Herein, an unconventional bottom-up wet-chemical synthetic approach for producing gold nanoparticle ordered arrays is developed. Water-processable hydroxypropyl cellulose stencils facilitate the patterning of a reductant chemical ink on which nanoparticle growth selectively occurs. Arrays exhibiting lattice plasmon resonances in the visible region and near infrared (quality factors of >20) are produced following a rapid synthetic step (, The authors thank Camilla Dore for her advice and contributed expertise on the fabrication of HPC films. The authors extend their gratitude to Jose Mendoza Carreño for his assistance with the optical characterization of the gold nanoparticle arrays. This project had received funding from the Spanish Ministry of Science and Innovation through grants FUNFUTURE (CEX2019-000917-S), (FUNFUTURE, in the framework of the Spanish Severo Ochoa Centre of Excellence program) and PID2019-106860GB-I00 (HIGHN). L.S. and A.M. thank the Spanish National Research Council (CSIC) for funding via the I-LINK 2020 international travel grant, which facilitated international exchange period necessary for completion of this work. L.S. and Y.C. research is supported by the 2020 Post-doctoral Junior Leader-Incoming Fellowship by “la Caixa” Foundation (ID 100010434, fellow-ship code LCF/BQ/PI20/11760028). Y.C. acknowledges the auspices of the UAB material science doctoral program. G.A.V.W. thanks the UCLA graduate division for funding through the University of California Office of the President Dissertation Year Fellowship. S.J.J. acknowledges support from the National Institutes of Health (NIH) Common Fund through a NIH Director's Early Independence Award co-funded by the National Institute of Dental and Craniofacial Research and Office of the Director, NIH Grant DP5OD028181. S.J.J. and G.A.V.W. acknowledge support through a Scholar Award from the Hyundai Hope on Wheels Foundation for Pediatric Cancer Research. P.S.W. thanks the National Science Foundation for support through Grant #CHE-2004238., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

Published
2022

23. Whole-exome sequencing identifies genes associated with Tourette's disorder in multiplex families

Author

Gary A. Heiman, Samuel Kuperman, Andrea Dietrich, Li Deng, Julie Hagstrøm, Yeting Zhang, Jinchuan Xing, Xiaolong Cao, Lisheng Zhou, Pieter J. Hoekstra, Cara Nasello, Astrid Morer, Jay A. Tischfield, Mohamed Abdulkadir, Blanca Garcia-Delgar, Joshua K. Thackray, Kerstin J. Plessen, Justin Koesterich, Thomas V. Fernandez, Robert A. King, Clinical Cognitive Neuropsychiatry Research Program (CCNP), National Institute of Mental Health (US), Tourette Syndrome Association of New Jersey, National Institute of Environmental Health Sciences (US), Instituto de Salud Carlos III, Junta de Andalucía, Sociedad Andaluza de Neurología, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, Jacques and Gloria Gossweiler Foundation, German Research Foundation, Tourette Association of America, National Institute for Health and Care Research (US), Tourette International Collaborative Genetics Study (TIC Genetics), Brown, L.W., Cao, X., Coffey, B.J., Gilbert, D.L., Hedderly, T., Heyman, I., Huyser, C., Kim, E., Kim, Y.S., Koh, Y.J., Leventhal, B.L., Madruga-Garrido, M., Maras, A., Mir, P., Münchau, A., Roessner, V., Song, D.H., State, M.W., Willsey, A.J., Zinner, S.H., Child Psychiatry, Paediatric Psychosocial Care, and Amsterdam Neuroscience - Cellular & Molecular Mechanisms

Subjects
0301 basic medicine, Candidate gene, Population, Cadherin Related Proteins, Nerve Tissue Proteins, Biology, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Neurodevelopmental disorder, Exome Sequencing, medicine, Humans, Family, Genetic Predisposition to Disease, education, Molecular Biology, Gene, Genotyping, Exome sequencing, Zinc finger, Genetics, education.field_of_study, Genetic heterogeneity, Serine Endopeptidases, medicine.disease, Pedigree, Genetic Predisposition to Disease/genetics, Nerve Tissue Proteins/genetics, Tourette Syndrome/genetics, Whole Exome Sequencing, Psychiatry and Mental health, 030104 developmental biology, 030217 neurology & neurosurgery, Tourette Syndrome
Abstract

Tourette’s Disorder (TD) is a neurodevelopmental disorder (NDD) that affects about 0.7% of the population and is one of the most heritable NDDs. Nevertheless, because of its polygenic nature and genetic heterogeneity, the genetic etiology of TD is not well understood. In this study, we combined the segregation information in 13 TD multiplex families with high-throughput sequencing and genotyping to identify genes associated with TD. Using whole-exome sequencing and genotyping array data, we identified both small and large genetic variants within the individuals. We then combined multiple types of evidence to prioritize candidate genes for TD, including variant segregation pattern, variant function prediction, candidate gene expression, protein–protein interaction network, candidate genes from previous studies, etc. From the 13 families, 71 strong candidate genes were identified, including both known genes for NDDs and novel genes, such as HtrA Serine Peptidase 3 (HTRA3), Cadherin-Related Family Member 1 (CDHR1), and Zinc Finger DHHC-Type Palmitoyltransferase 17 (ZDHHC17). The candidate genes are enriched in several Gene Ontology categories, such as dynein complex and synaptic membrane. Candidate genes and pathways identified in this study provide biological insight into TD etiology and potential targets for future studies., This study was supported by a grant from the National Institute of Mental Health (R01MH092293 to GAH and JAT) and by a grant from the New Jersey Center for Tourette Syndrome (to GAH and JAT). This study was also supported by grants from the National Institute of Mental Health (K08MH099424 to TVF) and the National Institute for Environmental Health Science (R01 ES021462 for YSK and BLL). PM has received grants from the Instituto de Salud Carlos III (PI10/01674, PI13/01461), the Consejería de Economía, Innovación, Ciencia y Empresa de la Junta de Andalucía (CVI-02526, CTS-7685), the Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI-0741/2010, PI-0437-2012, PI-0471-2013), the Sociedad Andaluza de Neurología, the Fundación Alicia Koplowitz, the Fundación Mutua Madrileña, and the Jaques and Gloria Gossweiler Foundation. AM has received grants from the Fundacion Alicia Koplowitz and belongs to the research group of the Comissionat per Universitats i Recerca del Departmanent d’Innovacio (DIUE) 2009SGR1119. AM has received grants from the Deutsche Forschungsgemeinschaft (DFG: MU 1692/3-1, MU 1692/4-1, and FOR 2698). AJW received a Young Investigator Award from Tourette Association of America. IH declares that all research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre.

Published
2020

Catalog

Books, media, physical & digital resources
See catalog results