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2. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group

Author

Kelly, S, Jahanshad, N, Zalesky, A, Kochunov, P, Agartz, I, Alloza, C, Andreassen, OA, Arango, C, Banaj, N, Bouix, S, Bousman, CA, Brouwer, RM, Bruggemann, J, Bustillo, J, Cahn, W, Calhoun, V, Cannon, D, Carr, V, Catts, S, Chen, J, Chen, J-X, Chen, X, Chiapponi, C, Cho, Kl K, Ciullo, V, Corvin, AS, Crespo-Facorro, B, Cropley, V, De Rossi, P, Diaz-Caneja, CM, Dickie, EW, Ehrlich, S, Fan, F-M, Faskowitz, J, Fatouros-Bergman, H, Flyckt, L, Ford, JM, Fouche, J-P, Fukunaga, M, Gill, M, Glahn, DC, Gollub, R, Goudzwaard, ED, Guo, H, Gur, RE, Gur, RC, Gurholt, TP, Hashimoto, R, Hatton, SN, Henskens, FA, Hibar, DP, Hickie, IB, Hong, LE, Horacek, J, Howells, FM, Hulshoff Pol, HE, Hyde, CL, Isaev, D, Jablensky, A, Jansen, PR, Janssen, J, Jönsson, EG, Jung, LA, Kahn, RS, Kikinis, Z, Liu, K, Klauser, P, Knöchel, C, Kubicki, M, Lagopoulos, J, Langen, C, Lawrie, S, Lenroot, RK, Lim, KO, Lopez-Jaramillo, C, Lyall, A, Magnotta, V, Mandl, RCW, Mathalon, DH, McCarley, RW, McCarthy-Jones, S, McDonald, C, McEwen, S, McIntosh, A, Melicher, T, Mesholam-Gately, RI, Michie, PT, Mowry, B, Mueller, BA, Newell, DT, O'Donnell, P, Oertel-Knöchel, V, Oestreich, L, Paciga, SA, Pantelis, C, Pasternak, O, Pearlson, G, Pellicano, GR, Pereira, A, and Pineda Zapata, J

Subjects
Neurosciences, Brain Disorders, Mental Health, Serious Mental Illness, Biomedical Imaging, Schizophrenia, Clinical Research, Mental health, Adult, Aged, Aged, 80 and over, Brain, Cohort Studies, Corpus Callosum, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, Female, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, White Matter, Young Adult, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.

Published
2018

3. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium.

Author

Schijven, Dick, Postema, M.C., Fukunaga, M., Matsumoto, J., Miura, K., Zwarte, S.M.C. de, Haren, N.E.M. van, Cahn, W., Hulshoff Pol, H.E., Kahn, R.S., Ayesa-Arriola, R., Ortoz-García de la Foz, V., Tordesillas-Gutierrez, D., Vázquez-Bourgon, J., Crespo-Facorro, B., Alnæs, D., Dahl, A., Westlye, L.T., Agartz, I., Andreassen, O.A., Jönsson, E.G., Kochunov, P., Bruggemann, J.M., Catts, S.V., Michie, P.T., Mowry, B.J., Quidé, Y., Rasser, P.E., Schall, U., Scott, R.J., Carr, V.J., Green, M.J., Henskens, F.A., Loughland, C.M., Pantelis, C., Weickert, C.S., Weickert, T.W., Haan, L. de, Brosch, K., Pfarr, J.K., Ringwald, K.G., Stein, F., Jansen, Andreas, Kircher, T.T.J., Nenadić, I., Krämer, Bernd, Gruber, O., Satterthwaite, T.D., Bustillo, J., Mathalon, D.H., Preda, A., Calhoun, V.D., Ford, J.M., Potkin, S.G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, F., Ehrlich, S., Fuentes-Claramonte, P., Garcia-Leon, M.A., Guerrero-Pedraza, A., Salvador, R., Sarró, S., Pomarol-Clotet, E., Ciullo, V., Piras, F., Vecchio, D., Banaj, N., Spalletta, G., Michielse, S., Amelsvoort, T. van, Dickie, E.W., Voineskos, A.N., Sim, K., Ciufolini, S., Dazzan, P., Murray, R.M., Kim, W.S., Chung, Y.C., Andreou, C., Schmidt, A, Borgwardt, S., McIntosh, A.M., Whalley, H.C., Lawrie, S.M., Plessis, S. du, Luckhoff, H.K., Scheffler, F., Emsley, R., Grotegerd, D., Lencer, R., Dannlowski, U., Edmond, J.T., Rootes-Murdy, K., Stephen, J.M., Mayer, A.R., Antonucci, L.A., Fazio, L., Pergola, G., Bertolino, A., Díaz-Caneja, C.M., Janssen, J, Lois, N.G., Arango, C., Tomyshev, A.S., Lebedeva, I., Cervenka, S., Sellgren, C.M., Georgiadis, F., Kirschner, M., Kaiser, S., Hajek, T., Skoch, A., Spaniel, F., Kim, M., Kwak, Y.B., Oh, S., Kwon, J.S., James, A., Bakker, G., Knöchel, C., Stäblein, M., Oertel, V., Uhlmann, A., Howells, F.M., Stein, D.J., Temmingh, H.S., Diaz-Zuluaga, A.M., Pineda-Zapata, J.A., López-Jaramillo, C., Homan, S., Ji, E., Surbeck, W., Homan, P., Fisher, S.E., Franke, B., Glahn, D.C., Gur, R.C., Hashimoto, R., Jahanshad, N., Luders, E., Medland, S.E., Thompson, P.M., Turner, J.A., Erp, T.G. van, Francks, C., Schijven, Dick, Postema, M.C., Fukunaga, M., Matsumoto, J., Miura, K., Zwarte, S.M.C. de, Haren, N.E.M. van, Cahn, W., Hulshoff Pol, H.E., Kahn, R.S., Ayesa-Arriola, R., Ortoz-García de la Foz, V., Tordesillas-Gutierrez, D., Vázquez-Bourgon, J., Crespo-Facorro, B., Alnæs, D., Dahl, A., Westlye, L.T., Agartz, I., Andreassen, O.A., Jönsson, E.G., Kochunov, P., Bruggemann, J.M., Catts, S.V., Michie, P.T., Mowry, B.J., Quidé, Y., Rasser, P.E., Schall, U., Scott, R.J., Carr, V.J., Green, M.J., Henskens, F.A., Loughland, C.M., Pantelis, C., Weickert, C.S., Weickert, T.W., Haan, L. de, Brosch, K., Pfarr, J.K., Ringwald, K.G., Stein, F., Jansen, Andreas, Kircher, T.T.J., Nenadić, I., Krämer, Bernd, Gruber, O., Satterthwaite, T.D., Bustillo, J., Mathalon, D.H., Preda, A., Calhoun, V.D., Ford, J.M., Potkin, S.G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, F., Ehrlich, S., Fuentes-Claramonte, P., Garcia-Leon, M.A., Guerrero-Pedraza, A., Salvador, R., Sarró, S., Pomarol-Clotet, E., Ciullo, V., Piras, F., Vecchio, D., Banaj, N., Spalletta, G., Michielse, S., Amelsvoort, T. van, Dickie, E.W., Voineskos, A.N., Sim, K., Ciufolini, S., Dazzan, P., Murray, R.M., Kim, W.S., Chung, Y.C., Andreou, C., Schmidt, A, Borgwardt, S., McIntosh, A.M., Whalley, H.C., Lawrie, S.M., Plessis, S. du, Luckhoff, H.K., Scheffler, F., Emsley, R., Grotegerd, D., Lencer, R., Dannlowski, U., Edmond, J.T., Rootes-Murdy, K., Stephen, J.M., Mayer, A.R., Antonucci, L.A., Fazio, L., Pergola, G., Bertolino, A., Díaz-Caneja, C.M., Janssen, J, Lois, N.G., Arango, C., Tomyshev, A.S., Lebedeva, I., Cervenka, S., Sellgren, C.M., Georgiadis, F., Kirschner, M., Kaiser, S., Hajek, T., Skoch, A., Spaniel, F., Kim, M., Kwak, Y.B., Oh, S., Kwon, J.S., James, A., Bakker, G., Knöchel, C., Stäblein, M., Oertel, V., Uhlmann, A., Howells, F.M., Stein, D.J., Temmingh, H.S., Diaz-Zuluaga, A.M., Pineda-Zapata, J.A., López-Jaramillo, C., Homan, S., Ji, E., Surbeck, W., Homan, P., Fisher, S.E., Franke, B., Glahn, D.C., Gur, R.C., Hashimoto, R., Jahanshad, N., Luders, E., Medland, S.E., Thompson, P.M., Turner, J.A., Erp, T.G. van, and Francks, C.

Abstract

Item does not contain fulltext, Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.

Published
2023

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

Author

Ching, C.R., Hibar, D.P., Gurholt, T.P., Nunes, A., Thomopoulos, S.I., Abé, C., Agartz, I., Brouwer, R.M., Cannon, D.M., Zwarte, S.M.C. de, Eyler, L.T., Favre, P., Hajek, T., Haukvik, U.K., Houenou, J., Landén, M., Lett, T.A., McDonald, C., Nabulsi, L., Patel, Y., Pauling, M.E., Paus, T., Radua, J., Soeiro-de-Souza, M.G., Tronchin, G., Haren, N.E.M. van, Vieta, E., Walter, H., Zeng, L.L., Alda, M., Almeida, J., Alnaes, D., Alonso-Lana, S., Altimus, C., Bauer, M, Baune, B.T., Bearden, C.E., Bellani, M., Benedetti, F. De, Berk, M., Bilderbeck, A.C., Blumberg, H.P., Bøen, E., Bollettini, I., Bonnin, C. Del Mar, Brambilla, P., Canales-Rodríguez, E.J., Caseras, X., Dandash, O., Dannlowski, U., Delvecchio, G., Díaz-Zuluaga, A.M., Dima, D., Duchesnay, É., Elvsåshagen, T., Fears, S.C., Frangou, S., Fullerton, J.M., Glahn, D.C., Goikolea, J.M., Green, M.J., Grotegerd, D., Gruber, O., Haarman, B.C.M., Henry, C., Howells, F.M., Ives-Deliperi, V., Jansen, Andreas, Kircher, T.T.J., Knöchel, C., Kramer, B., Lafer, B., López-Jaramillo, C., Machado-Vieira, R., MacIntosh, B.J., Melloni, E.M.T., Mitchell, P.B., Nenadic, I., Nery, F., Nugent, A.C., Oertel, V., Ophoff, R.A., Ota, M., Overs, B.J., Pham, D.L., Phillips, M.L., Pineda-Zapata, J.A., Poletti, S., Polosan, M., Pomarol-Clotet, E., Pouchon, A., Quidé, Y., Rive, M.M., Roberts, G., Ruhe, H.G., Salvador, R., Sarró, S., Satterthwaite, T.D., Schene, A.H., Sim, K., Thompson, P.M., Andreassen, O.A., Ching, C.R., Hibar, D.P., Gurholt, T.P., Nunes, A., Thomopoulos, S.I., Abé, C., Agartz, I., Brouwer, R.M., Cannon, D.M., Zwarte, S.M.C. de, Eyler, L.T., Favre, P., Hajek, T., Haukvik, U.K., Houenou, J., Landén, M., Lett, T.A., McDonald, C., Nabulsi, L., Patel, Y., Pauling, M.E., Paus, T., Radua, J., Soeiro-de-Souza, M.G., Tronchin, G., Haren, N.E.M. van, Vieta, E., Walter, H., Zeng, L.L., Alda, M., Almeida, J., Alnaes, D., Alonso-Lana, S., Altimus, C., Bauer, M, Baune, B.T., Bearden, C.E., Bellani, M., Benedetti, F. De, Berk, M., Bilderbeck, A.C., Blumberg, H.P., Bøen, E., Bollettini, I., Bonnin, C. Del Mar, Brambilla, P., Canales-Rodríguez, E.J., Caseras, X., Dandash, O., Dannlowski, U., Delvecchio, G., Díaz-Zuluaga, A.M., Dima, D., Duchesnay, É., Elvsåshagen, T., Fears, S.C., Frangou, S., Fullerton, J.M., Glahn, D.C., Goikolea, J.M., Green, M.J., Grotegerd, D., Gruber, O., Haarman, B.C.M., Henry, C., Howells, F.M., Ives-Deliperi, V., Jansen, Andreas, Kircher, T.T.J., Knöchel, C., Kramer, B., Lafer, B., López-Jaramillo, C., Machado-Vieira, R., MacIntosh, B.J., Melloni, E.M.T., Mitchell, P.B., Nenadic, I., Nery, F., Nugent, A.C., Oertel, V., Ophoff, R.A., Ota, M., Overs, B.J., Pham, D.L., Phillips, M.L., Pineda-Zapata, J.A., Poletti, S., Polosan, M., Pomarol-Clotet, E., Pouchon, A., Quidé, Y., Rive, M.M., Roberts, G., Ruhe, H.G., Salvador, R., Sarró, S., Satterthwaite, T.D., Schene, A.H., Sim, K., Thompson, P.M., and Andreassen, O.A.

Abstract

Contains fulltext : 252204.pdf (Publisher’s version ) (Open Access), MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.

Published
2022

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

Author

Ching, CRK, Hibar, DP, Gurholt, TP, Nunes, A, Thomopoulos, SI, Abé, C, Agartz, I, Brouwer, RM, Cannon, DM, de Zwarte, SMC, Eyler, LT, Favre, P, Hajek, T, Haukvik, UK, Houenou, J, Landén, M, Lett, TA, McDonald, C, Nabulsi, L, Patel, Y, Pauling, ME, Paus, T, Radua, J, Soeiro-de-Souza, MG, Tronchin, G, van Haren, NEM, Vieta, E, Walter, H, Zeng, LL, Alda, M, Almeida, J, Alnæs, D, Alonso-Lana, S, Altimus, C, Bauer, M, Baune, BT, Bearden, CE, Bellani, M, Benedetti, F, Berk, M, Bilderbeck, AC, Blumberg, HP, Bøen, E, Bollettini, I, del Mar Bonnin, C, Brambilla, P, Canales-Rodríguez, EJ, Caseras, X, Dandash, O, Dannlowski, U, Delvecchio, G, Díaz-Zuluaga, AM, Dima, D, Duchesnay, É, Elvsåshagen, T, Fears, SC, Frangou, S, Fullerton, JM, Glahn, DC, Goikolea, JM, Green, MJ, Grotegerd, D, Gruber, O, Haarman, BCM, Henry, C, Howells, FM, Ives-Deliperi, V, Jansen, A, Kircher, TTJ, Knöchel, C, Kramer, B, Lafer, B, López-Jaramillo, C, Machado-Vieira, R, MacIntosh, BJ, Melloni, EMT, Mitchell, PB, Nenadic, I, Nery, F, Nugent, AC, Oertel, V, Ophoff, RA, Ota, M, Overs, BJ, Pham, DL, Phillips, ML, Pineda-Zapata, JA, Poletti, S, Polosan, M, Pomarol-Clotet, E, Pouchon, A, Quidé, Y, Rive, MM, Roberts, G, Ruhe, HG, Salvador, R, Sarró, S, Satterthwaite, TD, Schene, AH, Sim, K, Ching, CRK, Hibar, DP, Gurholt, TP, Nunes, A, Thomopoulos, SI, Abé, C, Agartz, I, Brouwer, RM, Cannon, DM, de Zwarte, SMC, Eyler, LT, Favre, P, Hajek, T, Haukvik, UK, Houenou, J, Landén, M, Lett, TA, McDonald, C, Nabulsi, L, Patel, Y, Pauling, ME, Paus, T, Radua, J, Soeiro-de-Souza, MG, Tronchin, G, van Haren, NEM, Vieta, E, Walter, H, Zeng, LL, Alda, M, Almeida, J, Alnæs, D, Alonso-Lana, S, Altimus, C, Bauer, M, Baune, BT, Bearden, CE, Bellani, M, Benedetti, F, Berk, M, Bilderbeck, AC, Blumberg, HP, Bøen, E, Bollettini, I, del Mar Bonnin, C, Brambilla, P, Canales-Rodríguez, EJ, Caseras, X, Dandash, O, Dannlowski, U, Delvecchio, G, Díaz-Zuluaga, AM, Dima, D, Duchesnay, É, Elvsåshagen, T, Fears, SC, Frangou, S, Fullerton, JM, Glahn, DC, Goikolea, JM, Green, MJ, Grotegerd, D, Gruber, O, Haarman, BCM, Henry, C, Howells, FM, Ives-Deliperi, V, Jansen, A, Kircher, TTJ, Knöchel, C, Kramer, B, Lafer, B, López-Jaramillo, C, Machado-Vieira, R, MacIntosh, BJ, Melloni, EMT, Mitchell, PB, Nenadic, I, Nery, F, Nugent, AC, Oertel, V, Ophoff, RA, Ota, M, Overs, BJ, Pham, DL, Phillips, ML, Pineda-Zapata, JA, Poletti, S, Polosan, M, Pomarol-Clotet, E, Pouchon, A, Quidé, Y, Rive, MM, Roberts, G, Ruhe, HG, Salvador, R, Sarró, S, Satterthwaite, TD, Schene, AH, and Sim, K

Abstract

MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.

Published
2020

8. Increased power by harmonizing structural MRI site differences with the ComBat batch adjustment method in ENIGMA

Author

Radua, J, Vieta, E, Shinohara, R, Kochunov, P, Quidé, Y, Green, MJ, Weickert, CS, Weickert, T, Bruggemann, J, Kircher, T, Nenadić, I, Cairns, MJ, Seal, M, Schall, U, Henskens, F, Fullerton, JM, Mowry, B, Pantelis, C, Lenroot, R, Cropley, V, Loughland, C, Scott, R, Wolf, D, Satterthwaite, TD, Tan, Y, Sim, K, Piras, F, Spalletta, G, Banaj, N, Pomarol-Clotet, E, Solanes, A, Albajes-Eizagirre, A, Canales-Rodríguez, EJ, Sarro, S, Di Giorgio, A, Bertolino, A, Stäblein, M, Oertel, V, Knöchel, C, Borgwardt, S, du Plessis, S, Yun, JY, Kwon, JS, Dannlowski, U, Hahn, T, Grotegerd, D, Alloza, C, Arango, C, Janssen, J, Díaz-Caneja, C, Jiang, W, Calhoun, V, Ehrlich, S, Yang, K, Cascella, NG, Takayanagi, Y, Sawa, A, Tomyshev, A, Lebedeva, I, Kaleda, V, Kirschner, M, Hoschl, C, Tomecek, D, Skoch, A, van Amelsvoort, T, Bakker, G, James, A, Preda, A, Weideman, A, Stein, DJ, Howells, F, Uhlmann, A, Temmingh, H, López-Jaramillo, C, Díaz-Zuluaga, A, Fortea, L, Martinez-Heras, E, Solana, E, Llufriu, S, Jahanshad, N, Thompson, P, Turner, J, van Erp, T, Glahn, D, Pearlson, G, Hong, E, Krug, A, Carr, V, Tooney, P, Cooper, G, Rasser, P, Michie, P, Catts, S, Gur, R, Yang, F, Fan, F, Chen, J, Guo, H, Tan, S, Radua, J, Vieta, E, Shinohara, R, Kochunov, P, Quidé, Y, Green, MJ, Weickert, CS, Weickert, T, Bruggemann, J, Kircher, T, Nenadić, I, Cairns, MJ, Seal, M, Schall, U, Henskens, F, Fullerton, JM, Mowry, B, Pantelis, C, Lenroot, R, Cropley, V, Loughland, C, Scott, R, Wolf, D, Satterthwaite, TD, Tan, Y, Sim, K, Piras, F, Spalletta, G, Banaj, N, Pomarol-Clotet, E, Solanes, A, Albajes-Eizagirre, A, Canales-Rodríguez, EJ, Sarro, S, Di Giorgio, A, Bertolino, A, Stäblein, M, Oertel, V, Knöchel, C, Borgwardt, S, du Plessis, S, Yun, JY, Kwon, JS, Dannlowski, U, Hahn, T, Grotegerd, D, Alloza, C, Arango, C, Janssen, J, Díaz-Caneja, C, Jiang, W, Calhoun, V, Ehrlich, S, Yang, K, Cascella, NG, Takayanagi, Y, Sawa, A, Tomyshev, A, Lebedeva, I, Kaleda, V, Kirschner, M, Hoschl, C, Tomecek, D, Skoch, A, van Amelsvoort, T, Bakker, G, James, A, Preda, A, Weideman, A, Stein, DJ, Howells, F, Uhlmann, A, Temmingh, H, López-Jaramillo, C, Díaz-Zuluaga, A, Fortea, L, Martinez-Heras, E, Solana, E, Llufriu, S, Jahanshad, N, Thompson, P, Turner, J, van Erp, T, Glahn, D, Pearlson, G, Hong, E, Krug, A, Carr, V, Tooney, P, Cooper, G, Rasser, P, Michie, P, Catts, S, Gur, R, Yang, F, Fan, F, Chen, J, Guo, H, and Tan, S

Abstract

A common limitation of neuroimaging studies is their small sample sizes. To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide. However, this introduces heterogeneity due to different scanning devices and sequences. ENIGMA projects commonly address this heterogeneity with random-effects meta-analysis or mixed-effects mega-analysis. Here we tested whether the batch adjustment method, ComBat, can further reduce site-related heterogeneity and thus increase statistical power. We conducted random-effects meta-analyses, mixed-effects mega-analyses and ComBat mega-analyses to compare cortical thickness, surface area and subcortical volumes between 2897 individuals with a diagnosis of schizophrenia and 3141 healthy controls from 33 sites. Specifically, we compared the imaging data between individuals with schizophrenia and healthy controls, covarying for age and sex. The use of ComBat substantially increased the statistical significance of the findings as compared to random-effects meta-analyses. The findings were more similar when comparing ComBat with mixed-effects mega-analysis, although ComBat still slightly increased the statistical significance. ComBat also showed increased statistical power when we repeated the analyses with fewer sites. Results were nearly identical when we applied the ComBat harmonization separately for cortical thickness, cortical surface area and subcortical volumes. Therefore, we recommend applying the ComBat function to attenuate potential effects of site in ENIGMA projects and other multi-site structural imaging work. We provide easy-to-use functions in R that work even if imaging data are partially missing in some brain regions, and they can be trained with one data set and then applied to another (a requirement for some analyses such as machine learning).

Published
2020

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

Author

Ching, C.R.K. (Christopher), Hibar, D.P. (Derrek P.), Gurholt, T.P. (Tiril P.), Nunes, A. (Abraham), Thomopoulos, S.I. (Sophia I.), Abé, C. (Christoph), Agartz, I. (Ingrid), Brouwer, R.M. (Rachel), Cannon, D.M. (Dara), de Zwarte, S.M.C. (Sonja M. C.), Eyler, L.T. (Lisa T.), Favre, P. (Pauline), Hajek, T. (Tomas), Haukvik, U.K. (Unn), Houenou, J. (Josselin), Landén, M. (Mikael), Lett, T.A. (Tristram A.), McDonald, C. (Colm), Nabulsi, L. (Leila), Patel, Y. (Yash), Pauling, M.E. (Melissa E.), Paus, T. (Tomas), Radua, J. (Joaquim), Soeiro-de-Souza, M.G. (Marcio G.), Tronchin, G. (Giulia), van Haren, N.E.M. (Neeltje E. M.), Vieta, E. (Eduard), Walter, H.J. (Henrik), Zeng, L.-L. (Ling-Li), Alda, M. (Martin), Almeida, J. (Jorge), Alnæs, D. (Dag), Alonso-Lana, S. (Silvia), Altimus, C. (Cara), Bauer, M. (Michael), Baune, B.T., Bearden, C.E. (Carrie), Bellani, M. (Marcella), Benedetti, F. (Francesco), Berk, M. (Michael), Bilderbeck, A.C. (Amy C.), Blumberg, H.P. (Hilary P.), Bøen, E. (Erlend), Bollettini, I. (Irene), del Mar Bonnin, C. (Caterina), Brambilla, P. (Paolo), Canales-Rodríguez, E.J. (Erick J.), Caseras, X. (Xavier), Dandash, O. (Orwa), Dannlowski, U. (Udo), Delvecchio, G. (Giuseppe), Díaz-Zuluaga, A.M. (Ana M.), Dima, D. (Danai), Duchesnay, É. (Édouard), Elvsåshagen, T. (Torbjørn), Fears, S. (Scott), Frangou, S. (Sophia), Fullerton, J.M. (Janice M.), Glahn, D.C. (David), Goikolea, J.M. (Jose M.), Green, M.J. (Melissa J.), Grotegerd, D. (Dominik), Gruber, O. (Oliver), Haarman, B.C.M. (Benno), Henry, C. (C.), Howells, F.M. (Fleur M.), Ives-Deliperi, V. (Victoria), Jansen, A. (Andreas), Kircher, T.T.J. (Tilo T. J.), Knöchel, C. (Christian), Kramer, B. (Bernd), Lafer, B. (Beny), López-Jaramillo, C. (Carlos), Machado-Vieira, R. (Rodrigo), MacIntosh, B.J. (Bradley J), Melloni, E.M.T. (Elisa M. T.), Mitchell, P.B. (Philip B.), Nenadic, I. (Igor), Nery, F. (Fabiano), Nugent, A.C. (Allison), Oertel, V. (Viola), Ophoff, R.A. (Roel), Ota, M. (Miho), Overs, B.J. (Bronwyn J.), Pham, D.L. (Daniel L.), Phillips, M.L. (Mary L.), Pineda-Zapata, J.A. (Julian A.), Poletti, S. (Sara), Polosan, M. (Mircea), Pomarol-Clotet, E. (Edith), Pouchon, A. (Arnaud), Quidé, Y. (Yann), Rive, M.M. (Maria M.), Roberts, G. (Gloria), Ruhé, H.G. (Henricus G.Eric), Salvador, R. (Raymond), Sarró, S. (Salvador), Satterthwaite, T.D. (Theodore), Schene, A.H. (Aart), Sim, K. (Kang), Soares, J.C. (Jair C.), Stäblein, M. (Michael), Stein, D.J. (Dan J.), Tamnes, C.K. (Christian K.), Thomaidis, G.V. (Georgios V.), Upegui, C.V. (Cristian Vargas), Veltman, D.J. (Dick), Wessa, M. (Michèle), Westlye, L.T. (Lars), Whalley, H.C. (Heather C.), Wolf, D.H. (Daniel H.), Wu, M.-J. (Mon-Ju), Yatham, L.N. (Lakshmi N.), Zarate, C.A. (Carlos A.), Thompson, P.M. (Paul), Andreassen, O.A. (Ole), Ching, C.R.K. (Christopher), Hibar, D.P. (Derrek P.), Gurholt, T.P. (Tiril P.), Nunes, A. (Abraham), Thomopoulos, S.I. (Sophia I.), Abé, C. (Christoph), Agartz, I. (Ingrid), Brouwer, R.M. (Rachel), Cannon, D.M. (Dara), de Zwarte, S.M.C. (Sonja M. C.), Eyler, L.T. (Lisa T.), Favre, P. (Pauline), Hajek, T. (Tomas), Haukvik, U.K. (Unn), Houenou, J. (Josselin), Landén, M. (Mikael), Lett, T.A. (Tristram A.), McDonald, C. (Colm), Nabulsi, L. (Leila), Patel, Y. (Yash), Pauling, M.E. (Melissa E.), Paus, T. (Tomas), Radua, J. (Joaquim), Soeiro-de-Souza, M.G. (Marcio G.), Tronchin, G. (Giulia), van Haren, N.E.M. (Neeltje E. M.), Vieta, E. (Eduard), Walter, H.J. (Henrik), Zeng, L.-L. (Ling-Li), Alda, M. (Martin), Almeida, J. (Jorge), Alnæs, D. (Dag), Alonso-Lana, S. (Silvia), Altimus, C. (Cara), Bauer, M. (Michael), Baune, B.T., Bearden, C.E. (Carrie), Bellani, M. (Marcella), Benedetti, F. (Francesco), Berk, M. (Michael), Bilderbeck, A.C. (Amy C.), Blumberg, H.P. (Hilary P.), Bøen, E. (Erlend), Bollettini, I. (Irene), del Mar Bonnin, C. (Caterina), Brambilla, P. (Paolo), Canales-Rodríguez, E.J. (Erick J.), Caseras, X. (Xavier), Dandash, O. (Orwa), Dannlowski, U. (Udo), Delvecchio, G. (Giuseppe), Díaz-Zuluaga, A.M. (Ana M.), Dima, D. (Danai), Duchesnay, É. (Édouard), Elvsåshagen, T. (Torbjørn), Fears, S. (Scott), Frangou, S. (Sophia), Fullerton, J.M. (Janice M.), Glahn, D.C. (David), Goikolea, J.M. (Jose M.), Green, M.J. (Melissa J.), Grotegerd, D. (Dominik), Gruber, O. (Oliver), Haarman, B.C.M. (Benno), Henry, C. (C.), Howells, F.M. (Fleur M.), Ives-Deliperi, V. (Victoria), Jansen, A. (Andreas), Kircher, T.T.J. (Tilo T. J.), Knöchel, C. (Christian), Kramer, B. (Bernd), Lafer, B. (Beny), López-Jaramillo, C. (Carlos), Machado-Vieira, R. (Rodrigo), MacIntosh, B.J. (Bradley J), Melloni, E.M.T. (Elisa M. T.), Mitchell, P.B. (Philip B.), Nenadic, I. (Igor), Nery, F. (Fabiano), Nugent, A.C. (Allison), Oertel, V. (Viola), Ophoff, R.A. (Roel), Ota, M. (Miho), Overs, B.J. (Bronwyn J.), Pham, D.L. (Daniel L.), Phillips, M.L. (Mary L.), Pineda-Zapata, J.A. (Julian A.), Poletti, S. (Sara), Polosan, M. (Mircea), Pomarol-Clotet, E. (Edith), Pouchon, A. (Arnaud), Quidé, Y. (Yann), Rive, M.M. (Maria M.), Roberts, G. (Gloria), Ruhé, H.G. (Henricus G.Eric), Salvador, R. (Raymond), Sarró, S. (Salvador), Satterthwaite, T.D. (Theodore), Schene, A.H. (Aart), Sim, K. (Kang), Soares, J.C. (Jair C.), Stäblein, M. (Michael), Stein, D.J. (Dan J.), Tamnes, C.K. (Christian K.), Thomaidis, G.V. (Georgios V.), Upegui, C.V. (Cristian Vargas), Veltman, D.J. (Dick), Wessa, M. (Michèle), Westlye, L.T. (Lars), Whalley, H.C. (Heather C.), Wolf, D.H. (Daniel H.), Wu, M.-J. (Mon-Ju), Yatham, L.N. (Lakshmi N.), Zarate, C.A. (Carlos A.), Thompson, P.M. (Paul), and Andreassen, O.A. (Ole)

Abstract

MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studi

Published
2020
Full Text
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12. Widespread white matter microstructural differences in schizophrenia across 4322 individuals : Results from the ENIGMA Schizophrenia DTI Working Group

Author

Kelly, S., Jahanshad, N., Zalesky, A., Kochunov, P., Agartz, I., Alloza, C., Andreassen, O. A., Arango, C., Banaj, N., Bouix, S., Bousman, C. A., Brouwer, R. M., Bruggemann, J., Bustillo, J., Cahn, W., Calhoun, V., Cannon, D., Carr, V., Catts, S., Chen, J., Chen, J. X., Chen, X., Chiapponi, C., Cho, Kl K., Ciullo, V., Corvin, A. S., Crespo-Facorro, B., Cropley, V., De Rossi, P., Diaz-Caneja, C. M., Dickie, E. W., Ehrlich, S., Fan, F. M., Faskowitz, J., Fatouros-Bergman, H., Flyckt, L., Ford, J. M., Fouche, J. P., Fukunaga, M., Gill, M., Glahn, D. C., Gollub, R., Goudzwaard, E. D., Guo, H., Gur, R. E., Gur, R. C., Gurholt, T. P., Hashimoto, R., Hatton, S. N., Henskens, F. A., Hibar, D. P., Hickie, I. B., Hong, L. E., Horacek, J., Howells, F. M., Hulshoff Pol, H. E., Hyde, C. L., Isaev, D., Jablensky, A., Jansen, P. R., Janssen, J., Jönsson, E. G., Jung, L. A., Kahn, R. S., Kikinis, Z., Liu, K., Klauser, P., Knöchel, C., Kubicki, M., Lagopoulos, J., Langen, C., Lawrie, S., Lenroot, R. K., Lim, K. O., Lopez-Jaramillo, C., Lyall, A., Magnotta, V., Mandl, R. C.W., Mathalon, D. H., McCarley, R. W., McCarthy-Jones, S., McDonald, C., McEwen, S., McIntosh, A., Melicher, T., Mesholam-Gately, R. I., Michie, P. T., Mowry, B., Mueller, B. A., Newell, D. T., O'Donnell, P., Oertel-Knöchel, V., Oestreich, L., Paciga, S. A., Pantelis, C., Pasternak, O., Pearlson, G., Pellicano, G. R., Pereira, A., Pineda Zapata, J., Piras, F., Potkin, S. G., Preda, A., Rasser, P. E., Roalf, D. R., Roiz, R., Roos, A., Rotenberg, D., Satterthwaite, T. D., Savadjiev, P., Schall, U., Scott, R. J., Seal, M. L., Seidman, L. J., Shannon Weickert, C., Whelan, C. D., Shenton, M. E., Kwon, J. S., Spalletta, G., Spaniel, F., Sprooten, E., Stäblein, M., Stein, D. J., Sundram, S., Tan, Y., Tan, S., Tang, S., Temmingh, H. S., Westlye, L. T., Tønnesen, S., Tordesillas-Gutierrez, D., Doan, N. T., Vaidya, J., Van Haren, N. E.M., Vargas, C. D., Vecchio, D., Velakoulis, D., Voineskos, A., Voyvodic, J. Q., Wang, Z., Wan, P., Wei, D., Weickert, T. W., Whalley, H., White, T., Whitford, T. J., Wojcik, J. D., Xiang, H., Xie, Z., Yamamori, H., Yang, F., Yao, N., Zhang, G., Zhao, J., Van Erp, T. G.M., Turner, J., Thompson, P. M., Donohoe, G., Kelly, S., Jahanshad, N., Zalesky, A., Kochunov, P., Agartz, I., Alloza, C., Andreassen, O. A., Arango, C., Banaj, N., Bouix, S., Bousman, C. A., Brouwer, R. M., Bruggemann, J., Bustillo, J., Cahn, W., Calhoun, V., Cannon, D., Carr, V., Catts, S., Chen, J., Chen, J. X., Chen, X., Chiapponi, C., Cho, Kl K., Ciullo, V., Corvin, A. S., Crespo-Facorro, B., Cropley, V., De Rossi, P., Diaz-Caneja, C. M., Dickie, E. W., Ehrlich, S., Fan, F. M., Faskowitz, J., Fatouros-Bergman, H., Flyckt, L., Ford, J. M., Fouche, J. P., Fukunaga, M., Gill, M., Glahn, D. C., Gollub, R., Goudzwaard, E. D., Guo, H., Gur, R. E., Gur, R. C., Gurholt, T. P., Hashimoto, R., Hatton, S. N., Henskens, F. A., Hibar, D. P., Hickie, I. B., Hong, L. E., Horacek, J., Howells, F. M., Hulshoff Pol, H. E., Hyde, C. L., Isaev, D., Jablensky, A., Jansen, P. R., Janssen, J., Jönsson, E. G., Jung, L. A., Kahn, R. S., Kikinis, Z., Liu, K., Klauser, P., Knöchel, C., Kubicki, M., Lagopoulos, J., Langen, C., Lawrie, S., Lenroot, R. K., Lim, K. O., Lopez-Jaramillo, C., Lyall, A., Magnotta, V., Mandl, R. C.W., Mathalon, D. H., McCarley, R. W., McCarthy-Jones, S., McDonald, C., McEwen, S., McIntosh, A., Melicher, T., Mesholam-Gately, R. I., Michie, P. T., Mowry, B., Mueller, B. A., Newell, D. T., O'Donnell, P., Oertel-Knöchel, V., Oestreich, L., Paciga, S. A., Pantelis, C., Pasternak, O., Pearlson, G., Pellicano, G. R., Pereira, A., Pineda Zapata, J., Piras, F., Potkin, S. G., Preda, A., Rasser, P. E., Roalf, D. R., Roiz, R., Roos, A., Rotenberg, D., Satterthwaite, T. D., Savadjiev, P., Schall, U., Scott, R. J., Seal, M. L., Seidman, L. J., Shannon Weickert, C., Whelan, C. D., Shenton, M. E., Kwon, J. S., Spalletta, G., Spaniel, F., Sprooten, E., Stäblein, M., Stein, D. J., Sundram, S., Tan, Y., Tan, S., Tang, S., Temmingh, H. S., Westlye, L. T., Tønnesen, S., Tordesillas-Gutierrez, D., Doan, N. T., Vaidya, J., Van Haren, N. E.M., Vargas, C. D., Vecchio, D., Velakoulis, D., Voineskos, A., Voyvodic, J. Q., Wang, Z., Wan, P., Wei, D., Weickert, T. W., Whalley, H., White, T., Whitford, T. J., Wojcik, J. D., Xiang, H., Xie, Z., Yamamori, H., Yang, F., Yao, N., Zhang, G., Zhao, J., Van Erp, T. G.M., Turner, J., Thompson, P. M., and Donohoe, G.

Published
2018

13. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: Results from the ENIGMA Schizophrenia DTI Working Group

Author

Kelly, S. (S.), Jahanshad, N. (Neda), Zalesky, A. (A.), Kochunov, P. (P.), Agartz, I. (Ingrid), Alloza, C. (C.), Andreassen, O.A. (O. A.), Arango, C. (C.), Banaj, N. (N.), Bouix, S. (S.), Bousman, C.A. (C. A.), Brouwer, R.M. (Rachel), Bruggemann, J. (J.), Bustillo, J., Cahn, W. (Wiepke), Calhoun, V.D. (Vince), Cannon, D. (D.), Carr, V.J. (Vaughan), Catts, S.V. (Stanley), Chen, J. (J.), Chen, J.-X. (J. X.), Chen, X. (X.), Chiapponi, C. (C.), Cho, K.K. (Kl K), Ciullo, V. (V.), Corvin, A. (Aiden), Crespo-Facorro, B. (Benedicto), Cropley, V. (V.), De Rossi, P. (P.), Diaz-Caneja, C.M. (C. M.), Dickie, E.W. (E. W.), Ehrlich, S.M. (Stefan), Fan, F.-M. (F. M.), Faskowitz, J. (J.), Fatouros-Bergman, H. (H.), Flyckt, L. (L.), Ford, J.M. (J. M.), Fouche, J.-P. (J. P.), Fukunaga, M. (Masaki), Gill, M. (M.), Glahn, D.C. (David), Gollub, R.L. (Randy), Goudzwaard, E.D. (E. D.), Guo, H. (H.), Gur, R.E. (Raquel), Gur, R.C. (R. C.), Gurholt, T.P. (T. P.), Hashimoto, R. (Ryota), Hatton, W., Henskens, F.A. (Frans), Hibar, D.P. (D. P.), Hickie, I.B. (Ian), Hong, L.E. (L. E.), Horacek, J. (J.), Howells, F.M. (F. M.), Hulshoff Pol, H.E. (Hilleke), Hyde, C.L. (C. L.), Isaev, D. (D.), Jablensky, A. (A.), Jansen, P.R. (P. R.), Janssen, J. (J.), Jönsson, E.G. (Erik), Jung, L.A. (L. A.), Kahn, R.S. (R. S.), Kikinis, Z. (Z.), Liu, K. (K.), Klauser, P. (P.), Knöchel, C. (C.), Kubicki, M. (M.), Lagopoulos, J. (Jim), Langen, C.D. (Carolyn), Lawrie, S. (Stephen), Lenroot, R.K. (Rhoshel), Lim, K.O. (Kelvin), Lopez-Jaramillo, C. (C.), Lyall, A. (A.), Magnotta, V., Mandl, R. (René), Mathalon, D.H. (D. H.), McCarley, R.W. (Robert), McCarthy-Jones, S. (S.), McDonald, C. (Colm), McEwen, S. (S.), McIntosh, A.M. (Andrew), Melicher, T. (T.), Mesholam-Gately, R.I. (Raquelle), Michie, P.T. (Patricia), Mowry, B.J. (Bryan J), Mueller, B.A. (Bryon ), Newell, D.T. (D. T.), O'Donnell, P. (P.), Oertel-Knöchel, V. (V.), Oestreich, L. (L.), Paciga, S.A. (S. A.), Pantelis, C. (Christos), Pasternak, O. (O.), Pearlson, G. (G.), Pellicano, G.R. (G. R.), Pereira, A. (A.), Pineda Zapata, J. (J.), Piras, F. (F.), Potkin, S.G. (Steven), Preda, A. (A.), Rasser, P.E. (P. E.), Roalf, D.R. (D. R.), Roiz, R. (R.), Roos, A. (A.), Rotenberg, D. (D.), Satterthwaite, T.D. (Theodore), Savadjiev, P. (P.), Schall, J.D. (Jeffrey), Scott, R.J. (R. J.), Seal, M.L. (M. L.), Seidman, L.J. (Larry), Shannon Weickert, C. (C.), Whelan, C.D. (Christopher), Shenton, M.E. (M. E.), Kwon, J.S. (J. S.), Spalletta, G. (Gianfranco), Spaniel, F. (F.), Sprooten, R. (Roy), Stäblein, M. (M.), Stein, D.J. (Dan), Sundram, S. (S.), Tan, Y. (Y.), Tan, S. (S.), Tang, S. (S.), Temmingh, H.S. (H. S.), Westlye, L.T. (Lars), Tønnesen, S. (S.), Tordesillas-Gutierrez, D. (Diana), Doan, N.T. (N. T.), Vaidya, J. (J.), Van Haren, N.E.M. (N. E.M.), Vargas, C.D. (C. D.), Vecchio, D. (D.), Velakoulis, D. (D.), Voineskos, A. (A.), Voyvodic, J.Q. (J. Q.), Wang, Z. (Z.), Wan, P. (P.), Wei, D. (D.), Weickert, T.W. (T. W.), Whalley, H. (H.), White, T.J.H. (Tonya), Whitford, T.J. (T. J.), Wojcik, J.D. (J. D.), Xiang, H. (H.), Xie, Z. (Z.), Yamamori, H. (H.), Yang, F. (F.), Yao, N. (N.), Zhang, G. (G.), Zhao, J. (J.), Erp, T.G.M. (Theo G.) van, Turner, J. (Jessica), Thompson, P.M. (P. M.), Donohoe, D.J. (Dennis), Kelly, S. (S.), Jahanshad, N. (Neda), Zalesky, A. (A.), Kochunov, P. (P.), Agartz, I. (Ingrid), Alloza, C. (C.), Andreassen, O.A. (O. A.), Arango, C. (C.), Banaj, N. (N.), Bouix, S. (S.), Bousman, C.A. (C. A.), Brouwer, R.M. (Rachel), Bruggemann, J. (J.), Bustillo, J., Cahn, W. (Wiepke), Calhoun, V.D. (Vince), Cannon, D. (D.), Carr, V.J. (Vaughan), Catts, S.V. (Stanley), Chen, J. (J.), Chen, J.-X. (J. X.), Chen, X. (X.), Chiapponi, C. (C.), Cho, K.K. (Kl K), Ciullo, V. (V.), Corvin, A. (Aiden), Crespo-Facorro, B. (Benedicto), Cropley, V. (V.), De Rossi, P. (P.), Diaz-Caneja, C.M. (C. M.), Dickie, E.W. (E. W.), Ehrlich, S.M. (Stefan), Fan, F.-M. (F. M.), Faskowitz, J. (J.), Fatouros-Bergman, H. (H.), Flyckt, L. (L.), Ford, J.M. (J. M.), Fouche, J.-P. (J. P.), Fukunaga, M. (Masaki), Gill, M. (M.), Glahn, D.C. (David), Gollub, R.L. (Randy), Goudzwaard, E.D. (E. D.), Guo, H. (H.), Gur, R.E. (Raquel), Gur, R.C. (R. C.), Gurholt, T.P. (T. P.), Hashimoto, R. (Ryota), Hatton, W., Henskens, F.A. (Frans), Hibar, D.P. (D. P.), Hickie, I.B. (Ian), Hong, L.E. (L. E.), Horacek, J. (J.), Howells, F.M. (F. M.), Hulshoff Pol, H.E. (Hilleke), Hyde, C.L. (C. L.), Isaev, D. (D.), Jablensky, A. (A.), Jansen, P.R. (P. R.), Janssen, J. (J.), Jönsson, E.G. (Erik), Jung, L.A. (L. A.), Kahn, R.S. (R. S.), Kikinis, Z. (Z.), Liu, K. (K.), Klauser, P. (P.), Knöchel, C. (C.), Kubicki, M. (M.), Lagopoulos, J. (Jim), Langen, C.D. (Carolyn), Lawrie, S. (Stephen), Lenroot, R.K. (Rhoshel), Lim, K.O. (Kelvin), Lopez-Jaramillo, C. (C.), Lyall, A. (A.), Magnotta, V., Mandl, R. (René), Mathalon, D.H. (D. H.), McCarley, R.W. (Robert), McCarthy-Jones, S. (S.), McDonald, C. (Colm), McEwen, S. (S.), McIntosh, A.M. (Andrew), Melicher, T. (T.), Mesholam-Gately, R.I. (Raquelle), Michie, P.T. (Patricia), Mowry, B.J. (Bryan J), Mueller, B.A. (Bryon ), Newell, D.T. (D. T.), O'Donnell, P. (P.), Oertel-Knöchel, V. (V.), Oestreich, L. (L.), Paciga, S.A. (S. A.), Pantelis, C. (Christos), Pasternak, O. (O.), Pearlson, G. (G.), Pellicano, G.R. (G. R.), Pereira, A. (A.), Pineda Zapata, J. (J.), Piras, F. (F.), Potkin, S.G. (Steven), Preda, A. (A.), Rasser, P.E. (P. E.), Roalf, D.R. (D. R.), Roiz, R. (R.), Roos, A. (A.), Rotenberg, D. (D.), Satterthwaite, T.D. (Theodore), Savadjiev, P. (P.), Schall, J.D. (Jeffrey), Scott, R.J. (R. J.), Seal, M.L. (M. L.), Seidman, L.J. (Larry), Shannon Weickert, C. (C.), Whelan, C.D. (Christopher), Shenton, M.E. (M. E.), Kwon, J.S. (J. S.), Spalletta, G. (Gianfranco), Spaniel, F. (F.), Sprooten, R. (Roy), Stäblein, M. (M.), Stein, D.J. (Dan), Sundram, S. (S.), Tan, Y. (Y.), Tan, S. (S.), Tang, S. (S.), Temmingh, H.S. (H. S.), Westlye, L.T. (Lars), Tønnesen, S. (S.), Tordesillas-Gutierrez, D. (Diana), Doan, N.T. (N. T.), Vaidya, J. (J.), Van Haren, N.E.M. (N. E.M.), Vargas, C.D. (C. D.), Vecchio, D. (D.), Velakoulis, D. (D.), Voineskos, A. (A.), Voyvodic, J.Q. (J. Q.), Wang, Z. (Z.), Wan, P. (P.), Wei, D. (D.), Weickert, T.W. (T. W.), Whalley, H. (H.), White, T.J.H. (Tonya), Whitford, T.J. (T. J.), Wojcik, J.D. (J. D.), Xiang, H. (H.), Xie, Z. (Z.), Yamamori, H. (H.), Yang, F. (F.), Yao, N. (N.), Zhang, G. (G.), Zhao, J. (J.), Erp, T.G.M. (Theo G.) van, Turner, J. (Jessica), Thompson, P.M. (P. M.), and Donohoe, D.J. (Dennis)

Abstract

The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.

Published
2018
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14. Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium

Author

Erp, T.G.M. (Theo G.) van, Walton, E. (Esther), Hibar, D.P. (Derrek P.), Schmaal, L. (Lianne), Jiang, W. (Wenhao), Glahn, D.C. (David), Pearlson, G. (Godfrey), Yao, N. (Nailin), Fukunaga, M. (Masaki), Hashimoto, R. (Ryota), Okada, N. (Naohiro), Yamamori, H. (Hidenaga), Bustillo, J., Clark, V.P., Agartz, I. (Ingrid), Mueller, B.A. (Bryon ), Cahn, W. (Wiepke), de Zwarte, S.M.C. (Sonja M.C.), Hulshoff Pol, H.E. (Hilleke), Kahn, R. (René), Ophoff, R.A. (Roel), van Haren, N.E.M. (Neeltje E.M.), Andreassen, O.A. (Ole), Dale, A.M. (Anders), Doan, N.T. (Nhat Trung), Gurholt, T.P. (Tiril P.), Hartberg, C.B. (Cecilie B.), Haukvik, U.K. (Unn), Jørgensen, K.N. (Kjetil N.), Lagerberg, T.V. (Trine V.), Melle, I. (Ingrid), Westlye, L.T. (Lars), Gruber, O. (Oliver), Kraemer, B. (Bernd), Richter, A. (Anja), Zilles, D. (David), Calhoun, V.D. (Vince), Crespo-Facorro, B. (Benedicto), Roiz-Santiañez, R. (Roberto), Tordesillas-Gutierrez, D. (Diana), Loughland, C.M. (Carmel), Carr, V.J. (Vaughan J.), Catts, S.V. (Stanley), Cropley, V.L. (Vanessa L.), Fullerton, J.M. (Janice M.), Green, M.J. (Melissa J.), Henskens, F.A. (Frans), Jablensky, A. (Assen), Lenroot, R.K. (Rhoshel), Mowry, B.J. (Bryan J), Michie, P.T. (Patricia), Pantelis, C. (Christos), Quidé, Y. (Yann), Schall, J.D. (Jeffrey), Scott, R.J. (Rodney J.), Cairns, M.J. (Murray J.), Seal, M. (Marc), Tooney, P.A. (Paul A.), Rasser, P.E. (Paul E.), Cooper, G. (Gavin), Shannon Weickert, C. (Cynthia), Weickert, T.W. (Thomas W.), Morris, D.W. (Derek W), Hong, E. (Elliot), Kochunov, P. (Peter), Beard, L.M. (Lauren M.), Gur, R.E. (Raquel), Gur, R.C. (Ruben C.), Satterthwaite, T.D. (Theodore), Wolf, D.H. (Daniel H.), Belger, A. (Aysenil), Brown, G.G. (Gregory G.), Ford, J.M. (Judith M.), Macciardi, F. (Fabio), Mathalon, D.H. (Daniel H.), O'Leary, D.S. (Daniel S.), Potkin, S.G. (Steven), Preda, A. (Adrian), Voyvodic, J. (James), Lim, K.O. (Kelvin), McEwen, S. (Sarah), Yang, F. (Fude), Tan, Y. (Yunlong), Tan, S. (Shuping), Wang, Z. (Zhiren), Fan, F. (Fengmei), Chen, J. (Jingxu), Xiang, H. (Hong), Tang, S. (Shiyou), Guo, H. (Hua), Wan, P. (Ping), Wei, D. (Dong), Bockholt, H.J., Ehrlich, S.M. (Stefan), Wolthusen, R.P.F. (Rick P.F.), King, M.D. (Margaret D.), Shoemaker, J.M. (Jody M.), Sponheim, S.R. (Scott), Haan, L. (Lieuwe) de, Koenders, L. (Laura), Machielsen, M.W.J. (Marise), Amelsvoort, T.A.M.J. (Therese) van, Veltman, D.J. (Dick), Assogna, F. (Francesca), Banaj, N. (Nerisa), de Rossi, P. (Pietro), Iorio, M. (Mariangela), Piras, F. (Fabrizio), Spalletta, G. (Gianfranco), McKenna, P.J. (Peter J.), Pomarol-Clotet, E. (Edith), Salvador, R. (Raymond), Corvin, A. (Aiden), Donohoe, D.J. (Dennis), Kelly, S. (Sinead), Whelan, C.D. (Christopher), Dickie, E.W. (Erin W.), Rotenberg, D. (David), Voineskos, A.N. (Aristotle N.), Ciufolini, S. (Simone), Radua, J. (Joaquim), Dazzan, P. (Paola), Murray, R. (Robin), Reis Marques, T. (Tiago), Simmons, A. (Andrew), Borgwardt, S. (Stefan), Egloff, L. (Laura), Harrisberger, F. (Fabienne), Riecher-Rössler, A. (Anita), Smieskova, R. (Renata), Alpert, K. (Kathryn), Wang, L. (Lei), Jönsson, E.G. (Erik), Koops, S. (Sanne), Sommer, I.E.C. (Iris E.C.), Bertolino, A. (Alessandro), Bonvino, A. (Aurora), Di Giorgio, A. (Annabella), Neilson, E. (Emma), Mayer, A.R. (Andrew R.), Stephen, J.M. (Julia M.), Kwon, J.S. (Jun Soo), Yun, J.-Y. (Je-Yeon), Cannon, D.M. (Dara), McDonald, C. (Colm), Lebedeva, I. (Irina), Tomyshev, A.S. (Alexander S.), Akhadov, T. (Tolibjohn), Kaleda, V. (Vasily), Fatouros-Bergman, H. (Helena), Flyckt, L. (Lena), Farde, L. (Lars), Engberg, G. (Göran), Erhardt, S. (Sophie), Cervenka, S. (Simon), Schwieler, L. (Lilly), Piehl, F. (Fredrik), Collste, K. (Karin), Victorsson, P. (Pauliina), Malmqvist, A. (Anna), Hedberg, M. (Mikael), Orhan, F. (Funda), Busatto, G.F. (Geraldo F.), Rosa, P.G.P. (Pedro G.P.), Serpa, M.H. (Mauricio H.), Zanetti, M.V. (Marcus V.), Hoschl, C. (Cyril), Skoch, A. (Antonin), Spaniel, F. (Filip), Tomecek, D. (David), Hagenaars, S. (Saskia), McIntosh, A.M. (Andrew), Whalley, H.C. (Heather C.), Lawrie, S. (Stephen), Knöchel, C. (Christian), Oertel-Knöchel, V. (Viola), Stäblein, M. (Michael), Howells, F.M. (Fleur M.), Stein, D.J. (Dan), Temmingh, H.S. (Henk S.), Uhlmann, A. (Anne), Lopez-Jaramillo, C. (Carlos), Dima, D. (Danai), McMahon, A. (Agnes), Faskowitz, J.I. (Joshua I.), Gutman, B.A. (Boris A.), Jahanshad, N. (Neda), Thompson, P.M. (Paul), Turner, J. (Jessica), Erp, T.G.M. (Theo G.) van, Walton, E. (Esther), Hibar, D.P. (Derrek P.), Schmaal, L. (Lianne), Jiang, W. (Wenhao), Glahn, D.C. (David), Pearlson, G. (Godfrey), Yao, N. (Nailin), Fukunaga, M. (Masaki), Hashimoto, R. (Ryota), Okada, N. (Naohiro), Yamamori, H. (Hidenaga), Bustillo, J., Clark, V.P., Agartz, I. (Ingrid), Mueller, B.A. (Bryon ), Cahn, W. (Wiepke), de Zwarte, S.M.C. (Sonja M.C.), Hulshoff Pol, H.E. (Hilleke), Kahn, R. (René), Ophoff, R.A. (Roel), van Haren, N.E.M. (Neeltje E.M.), Andreassen, O.A. (Ole), Dale, A.M. (Anders), Doan, N.T. (Nhat Trung), Gurholt, T.P. (Tiril P.), Hartberg, C.B. (Cecilie B.), Haukvik, U.K. (Unn), Jørgensen, K.N. (Kjetil N.), Lagerberg, T.V. (Trine V.), Melle, I. (Ingrid), Westlye, L.T. (Lars), Gruber, O. (Oliver), Kraemer, B. (Bernd), Richter, A. (Anja), Zilles, D. (David), Calhoun, V.D. (Vince), Crespo-Facorro, B. (Benedicto), Roiz-Santiañez, R. (Roberto), Tordesillas-Gutierrez, D. (Diana), Loughland, C.M. (Carmel), Carr, V.J. (Vaughan J.), Catts, S.V. (Stanley), Cropley, V.L. (Vanessa L.), Fullerton, J.M. (Janice M.), Green, M.J. (Melissa J.), Henskens, F.A. (Frans), Jablensky, A. (Assen), Lenroot, R.K. (Rhoshel), Mowry, B.J. (Bryan J), Michie, P.T. (Patricia), Pantelis, C. (Christos), Quidé, Y. (Yann), Schall, J.D. (Jeffrey), Scott, R.J. (Rodney J.), Cairns, M.J. (Murray J.), Seal, M. (Marc), Tooney, P.A. (Paul A.), Rasser, P.E. (Paul E.), Cooper, G. (Gavin), Shannon Weickert, C. (Cynthia), Weickert, T.W. (Thomas W.), Morris, D.W. (Derek W), Hong, E. (Elliot), Kochunov, P. (Peter), Beard, L.M. (Lauren M.), Gur, R.E. (Raquel), Gur, R.C. (Ruben C.), Satterthwaite, T.D. (Theodore), Wolf, D.H. (Daniel H.), Belger, A. (Aysenil), Brown, G.G. (Gregory G.), Ford, J.M. (Judith M.), Macciardi, F. (Fabio), Mathalon, D.H. (Daniel H.), O'Leary, D.S. (Daniel S.), Potkin, S.G. (Steven), Preda, A. (Adrian), Voyvodic, J. (James), Lim, K.O. (Kelvin), McEwen, S. (Sarah), Yang, F. (Fude), Tan, Y. (Yunlong), Tan, S. (Shuping), Wang, Z. (Zhiren), Fan, F. (Fengmei), Chen, J. (Jingxu), Xiang, H. (Hong), Tang, S. (Shiyou), Guo, H. (Hua), Wan, P. (Ping), Wei, D. (Dong), Bockholt, H.J., Ehrlich, S.M. (Stefan), Wolthusen, R.P.F. (Rick P.F.), King, M.D. (Margaret D.), Shoemaker, J.M. (Jody M.), Sponheim, S.R. (Scott), Haan, L. (Lieuwe) de, Koenders, L. (Laura), Machielsen, M.W.J. (Marise), Amelsvoort, T.A.M.J. (Therese) van, Veltman, D.J. (Dick), Assogna, F. (Francesca), Banaj, N. (Nerisa), de Rossi, P. (Pietro), Iorio, M. (Mariangela), Piras, F. (Fabrizio), Spalletta, G. (Gianfranco), McKenna, P.J. (Peter J.), Pomarol-Clotet, E. (Edith), Salvador, R. (Raymond), Corvin, A. (Aiden), Donohoe, D.J. (Dennis), Kelly, S. (Sinead), Whelan, C.D. (Christopher), Dickie, E.W. (Erin W.), Rotenberg, D. (David), Voineskos, A.N. (Aristotle N.), Ciufolini, S. (Simone), Radua, J. (Joaquim), Dazzan, P. (Paola), Murray, R. (Robin), Reis Marques, T. (Tiago), Simmons, A. (Andrew), Borgwardt, S. (Stefan), Egloff, L. (Laura), Harrisberger, F. (Fabienne), Riecher-Rössler, A. (Anita), Smieskova, R. (Renata), Alpert, K. (Kathryn), Wang, L. (Lei), Jönsson, E.G. (Erik), Koops, S. (Sanne), Sommer, I.E.C. (Iris E.C.), Bertolino, A. (Alessandro), Bonvino, A. (Aurora), Di Giorgio, A. (Annabella), Neilson, E. (Emma), Mayer, A.R. (Andrew R.), Stephen, J.M. (Julia M.), Kwon, J.S. (Jun Soo), Yun, J.-Y. (Je-Yeon), Cannon, D.M. (Dara), McDonald, C. (Colm), Lebedeva, I. (Irina), Tomyshev, A.S. (Alexander S.), Akhadov, T. (Tolibjohn), Kaleda, V. (Vasily), Fatouros-Bergman, H. (Helena), Flyckt, L. (Lena), Farde, L. (Lars), Engberg, G. (Göran), Erhardt, S. (Sophie), Cervenka, S. (Simon), Schwieler, L. (Lilly), Piehl, F. (Fredrik), Collste, K. (Karin), Victorsson, P. (Pauliina), Malmqvist, A. (Anna), Hedberg, M. (Mikael), Orhan, F. (Funda), Busatto, G.F. (Geraldo F.), Rosa, P.G.P. (Pedro G.P.), Serpa, M.H. (Mauricio H.), Zanetti, M.V. (Marcus V.), Hoschl, C. (Cyril), Skoch, A. (Antonin), Spaniel, F. (Filip), Tomecek, D. (David), Hagenaars, S. (Saskia), McIntosh, A.M. (Andrew), Whalley, H.C. (Heather C.), Lawrie, S. (Stephen), Knöchel, C. (Christian), Oertel-Knöchel, V. (Viola), Stäblein, M. (Michael), Howells, F.M. (Fleur M.), Stein, D.J. (Dan), Temmingh, H.S. (Henk S.), Uhlmann, A. (Anne), Lopez-Jaramillo, C. (Carlos), Dima, D. (Danai), McMahon, A. (Agnes), Faskowitz, J.I. (Joshua I.), Gutman, B.A. (Boris A.), Jahanshad, N. (Neda), Thompson, P.M. (Paul), and Turner, J. (Jessica)

Abstract

Background: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This

Published
2018
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15. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: Results from the ENIGMA Schizophrenia DTI Working Group

Author

Onderzoeksgroep 1, Brain, Affectieve & Psychotische Med., Research Office, Onderzoek Bob Oranje, Onderzoeksgroep 11, Onderzoeksgroep 8, Onderzoeksgroep 4, Kelly, S., Jahanshad, N., Zalesky, A., Kochunov, P., Agartz, I., Alloza, C., Andreassen, O. A., Arango, C., Banaj, N., Bouix, S., Bousman, C. A., Brouwer, R. M., Bruggemann, J., Bustillo, J., Cahn, W., Calhoun, V., Cannon, D., Carr, V., Catts, S., Chen, J., Chen, J. X., Chen, X., Chiapponi, C., Cho, Kl K., Ciullo, V., Corvin, A. S., Crespo-Facorro, B., Cropley, V., De Rossi, P., Diaz-Caneja, C. M., Dickie, E. W., Ehrlich, S., Fan, F. M., Faskowitz, J., Fatouros-Bergman, H., Flyckt, L., Ford, J. M., Fouche, J. P., Fukunaga, M., Gill, M., Glahn, D. C., Gollub, R., Goudzwaard, E. D., Guo, H., Gur, R. E., Gur, R. C., Gurholt, T. P., Hashimoto, R., Hatton, S. N., Henskens, F. A., Hibar, D. P., Hickie, I. B., Hong, L. E., Horacek, J., Howells, F. M., Hulshoff Pol, H. E., Hyde, C. L., Isaev, D., Jablensky, A., Jansen, P. R., Janssen, J., Jönsson, E. G., Jung, L. A., Kahn, R. S., Kikinis, Z., Liu, K., Klauser, P., Knöchel, C., Kubicki, M., Lagopoulos, J., Langen, C., Lawrie, S., Lenroot, R. K., Lim, K. O., Lopez-Jaramillo, C., Lyall, A., Magnotta, V., Mandl, R. C.W., Mathalon, D. H., McCarley, R. W., McCarthy-Jones, S., McDonald, C., McEwen, S., McIntosh, A., Melicher, T., Mesholam-Gately, R. I., Michie, P. T., Mowry, B., Mueller, B. A., Newell, D. T., O'Donnell, P., Oertel-Knöchel, V., Oestreich, L., Paciga, S. A., Pantelis, C., Pasternak, O., Pearlson, G., Pellicano, G. R., Pereira, A., Pineda Zapata, J., Piras, F., Potkin, S. G., Preda, A., Rasser, P. E., Roalf, D. R., Roiz, R., Roos, A., Rotenberg, D., Satterthwaite, T. D., Savadjiev, P., Schall, U., Scott, R. J., Seal, M. L., Seidman, L. J., Shannon Weickert, C., Whelan, C. D., Shenton, M. E., Kwon, J. S., Spalletta, G., Spaniel, F., Sprooten, E., Stäblein, M., Stein, D. J., Sundram, S., Tan, Y., Tan, S., Tang, S., Temmingh, H. S., Westlye, L. T., Tønnesen, S., Tordesillas-Gutierrez, D., Doan, N. T., Vaidya, J., Van Haren, N. E.M., Vargas, C. D., Vecchio, D., Velakoulis, D., Voineskos, A., Voyvodic, J. Q., Wang, Z., Wan, P., Wei, D., Weickert, T. W., Whalley, H., White, T., Whitford, T. J., Wojcik, J. D., Xiang, H., Xie, Z., Yamamori, H., Yang, F., Yao, N., Zhang, G., Zhao, J., Van Erp, T. G.M., Turner, J., Thompson, P. M., Donohoe, G., Onderzoeksgroep 1, Brain, Affectieve & Psychotische Med., Research Office, Onderzoek Bob Oranje, Onderzoeksgroep 11, Onderzoeksgroep 8, Onderzoeksgroep 4, Kelly, S., Jahanshad, N., Zalesky, A., Kochunov, P., Agartz, I., Alloza, C., Andreassen, O. A., Arango, C., Banaj, N., Bouix, S., Bousman, C. A., Brouwer, R. M., Bruggemann, J., Bustillo, J., Cahn, W., Calhoun, V., Cannon, D., Carr, V., Catts, S., Chen, J., Chen, J. X., Chen, X., Chiapponi, C., Cho, Kl K., Ciullo, V., Corvin, A. S., Crespo-Facorro, B., Cropley, V., De Rossi, P., Diaz-Caneja, C. M., Dickie, E. W., Ehrlich, S., Fan, F. M., Faskowitz, J., Fatouros-Bergman, H., Flyckt, L., Ford, J. M., Fouche, J. P., Fukunaga, M., Gill, M., Glahn, D. C., Gollub, R., Goudzwaard, E. D., Guo, H., Gur, R. E., Gur, R. C., Gurholt, T. P., Hashimoto, R., Hatton, S. N., Henskens, F. A., Hibar, D. P., Hickie, I. B., Hong, L. E., Horacek, J., Howells, F. M., Hulshoff Pol, H. E., Hyde, C. L., Isaev, D., Jablensky, A., Jansen, P. R., Janssen, J., Jönsson, E. G., Jung, L. A., Kahn, R. S., Kikinis, Z., Liu, K., Klauser, P., Knöchel, C., Kubicki, M., Lagopoulos, J., Langen, C., Lawrie, S., Lenroot, R. K., Lim, K. O., Lopez-Jaramillo, C., Lyall, A., Magnotta, V., Mandl, R. C.W., Mathalon, D. H., McCarley, R. W., McCarthy-Jones, S., McDonald, C., McEwen, S., McIntosh, A., Melicher, T., Mesholam-Gately, R. I., Michie, P. T., Mowry, B., Mueller, B. A., Newell, D. T., O'Donnell, P., Oertel-Knöchel, V., Oestreich, L., Paciga, S. A., Pantelis, C., Pasternak, O., Pearlson, G., Pellicano, G. R., Pereira, A., Pineda Zapata, J., Piras, F., Potkin, S. G., Preda, A., Rasser, P. E., Roalf, D. R., Roiz, R., Roos, A., Rotenberg, D., Satterthwaite, T. D., Savadjiev, P., Schall, U., Scott, R. J., Seal, M. L., Seidman, L. J., Shannon Weickert, C., Whelan, C. D., Shenton, M. E., Kwon, J. S., Spalletta, G., Spaniel, F., Sprooten, E., Stäblein, M., Stein, D. J., Sundram, S., Tan, Y., Tan, S., Tang, S., Temmingh, H. S., Westlye, L. T., Tønnesen, S., Tordesillas-Gutierrez, D., Doan, N. T., Vaidya, J., Van Haren, N. E.M., Vargas, C. D., Vecchio, D., Velakoulis, D., Voineskos, A., Voyvodic, J. Q., Wang, Z., Wan, P., Wei, D., Weickert, T. W., Whalley, H., White, T., Whitford, T. J., Wojcik, J. D., Xiang, H., Xie, Z., Yamamori, H., Yang, F., Yao, N., Zhang, G., Zhao, J., Van Erp, T. G.M., Turner, J., Thompson, P. M., and Donohoe, G.

Published
2018

16. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group

Author

Kelly, S, primary, Jahanshad, N, additional, Zalesky, A, additional, Kochunov, P, additional, Agartz, I, additional, Alloza, C, additional, Andreassen, O A, additional, Arango, C, additional, Banaj, N, additional, Bouix, S, additional, Bousman, C A, additional, Brouwer, R M, additional, Bruggemann, J, additional, Bustillo, J, additional, Cahn, W, additional, Calhoun, V, additional, Cannon, D, additional, Carr, V, additional, Catts, S, additional, Chen, J, additional, Chen, J-x, additional, Chen, X, additional, Chiapponi, C, additional, Cho, Kl K, additional, Ciullo, V, additional, Corvin, A S, additional, Crespo-Facorro, B, additional, Cropley, V, additional, De Rossi, P, additional, Diaz-Caneja, C M, additional, Dickie, E W, additional, Ehrlich, S, additional, Fan, F-m, additional, Faskowitz, J, additional, Fatouros-Bergman, H, additional, Flyckt, L, additional, Ford, J M, additional, Fouche, J-P, additional, Fukunaga, M, additional, Gill, M, additional, Glahn, D C, additional, Gollub, R, additional, Goudzwaard, E D, additional, Guo, H, additional, Gur, R E, additional, Gur, R C, additional, Gurholt, T P, additional, Hashimoto, R, additional, Hatton, S N, additional, Henskens, F A, additional, Hibar, D P, additional, Hickie, I B, additional, Hong, L E, additional, Horacek, J, additional, Howells, F M, additional, Hulshoff Pol, H E, additional, Hyde, C L, additional, Isaev, D, additional, Jablensky, A, additional, Jansen, P R, additional, Janssen, J, additional, Jönsson, E G, additional, Jung, L A, additional, Kahn, R S, additional, Kikinis, Z, additional, Liu, K, additional, Klauser, P, additional, Knöchel, C, additional, Kubicki, M, additional, Lagopoulos, J, additional, Langen, C, additional, Lawrie, S, additional, Lenroot, R K, additional, Lim, K O, additional, Lopez-Jaramillo, C, additional, Lyall, A, additional, Magnotta, V, additional, Mandl, R C W, additional, Mathalon, D H, additional, McCarley, R W, additional, McCarthy-Jones, S, additional, McDonald, C, additional, McEwen, S, additional, McIntosh, A, additional, Melicher, T, additional, Mesholam-Gately, R I, additional, Michie, P T, additional, Mowry, B, additional, Mueller, B A, additional, Newell, D T, additional, O'Donnell, P, additional, Oertel-Knöchel, V, additional, Oestreich, L, additional, Paciga, S A, additional, Pantelis, C, additional, Pasternak, O, additional, Pearlson, G, additional, Pellicano, G R, additional, Pereira, A, additional, Pineda Zapata, J, additional, Piras, F, additional, Potkin, S G, additional, Preda, A, additional, Rasser, P E, additional, Roalf, D R, additional, Roiz, R, additional, Roos, A, additional, Rotenberg, D, additional, Satterthwaite, T D, additional, Savadjiev, P, additional, Schall, U, additional, Scott, R J, additional, Seal, M L, additional, Seidman, L J, additional, Shannon Weickert, C, additional, Whelan, C D, additional, Shenton, M E, additional, Kwon, J S, additional, Spalletta, G, additional, Spaniel, F, additional, Sprooten, E, additional, Stäblein, M, additional, Stein, D J, additional, Sundram, S, additional, Tan, Y, additional, Tan, S, additional, Tang, S, additional, Temmingh, H S, additional, Westlye, L T, additional, Tønnesen, S, additional, Tordesillas-Gutierrez, D, additional, Doan, N T, additional, Vaidya, J, additional, van Haren, N E M, additional, Vargas, C D, additional, Vecchio, D, additional, Velakoulis, D, additional, Voineskos, A, additional, Voyvodic, J Q, additional, Wang, Z, additional, Wan, P, additional, Wei, D, additional, Weickert, T W, additional, Whalley, H, additional, White, T, additional, Whitford, T J, additional, Wojcik, J D, additional, Xiang, H, additional, Xie, Z, additional, Yamamori, H, additional, Yang, F, additional, Yao, N, additional, Zhang, G, additional, Zhao, J, additional, van Erp, T G M, additional, Turner, J, additional, Thompson, P M, additional, and Donohoe, G, additional

Published
2017
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26. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium.

Author

Schijven D, Postema MC, Fukunaga M, Matsumoto J, Miura K, de Zwarte SMC, van Haren NEM, Cahn W, Hulshoff Pol HE, Kahn RS, Ayesa-Arriola R, Ortiz-García de la Foz V, Tordesillas-Gutierrez D, Vázquez-Bourgon J, Crespo-Facorro B, Alnæs D, Dahl A, Westlye LT, Agartz I, Andreassen OA, Jönsson EG, Kochunov P, Bruggemann JM, Catts SV, Michie PT, Mowry BJ, Quidé Y, Rasser PE, Schall U, Scott RJ, Carr VJ, Green MJ, Henskens FA, Loughland CM, Pantelis C, Weickert CS, Weickert TW, de Haan L, Brosch K, Pfarr JK, Ringwald KG, Stein F, Jansen A, Kircher TTJ, Nenadić I, Krämer B, Gruber O, Satterthwaite TD, Bustillo J, Mathalon DH, Preda A, Calhoun VD, Ford JM, Potkin SG, Chen J, Tan Y, Wang Z, Xiang H, Fan F, Bernardoni F, Ehrlich S, Fuentes-Claramonte P, Garcia-Leon MA, Guerrero-Pedraza A, Salvador R, Sarró S, Pomarol-Clotet E, Ciullo V, Piras F, Vecchio D, Banaj N, Spalletta G, Michielse S, van Amelsvoort T, Dickie EW, Voineskos AN, Sim K, Ciufolini S, Dazzan P, Murray RM, Kim WS, Chung YC, Andreou C, Schmidt A, Borgwardt S, McIntosh AM, Whalley HC, Lawrie SM, du Plessis S, Luckhoff HK, Scheffler F, Emsley R, Grotegerd D, Lencer R, Dannlowski U, Edmond JT, Rootes-Murdy K, Stephen JM, Mayer AR, Antonucci LA, Fazio L, Pergola G, Bertolino A, Díaz-Caneja CM, Janssen J, Lois NG, Arango C, Tomyshev AS, Lebedeva I, Cervenka S, Sellgren CM, Georgiadis F, Kirschner M, Kaiser S, Hajek T, Skoch A, Spaniel F, Kim M, Kwak YB, Oh S, Kwon JS, James A, Bakker G, Knöchel C, Stäblein M, Oertel V, Uhlmann A, Howells FM, Stein DJ, Temmingh HS, Diaz-Zuluaga AM, Pineda-Zapata JA, López-Jaramillo C, Homan S, Ji E, Surbeck W, Homan P, Fisher SE, Franke B, Glahn DC, Gur RC, Hashimoto R, Jahanshad N, Luders E, Medland SE, Thompson PM, Turner JA, van Erp TGM, and Francks C

Subjects
Male, Female, Humans, Case-Control Studies, Brain diagnostic imaging, Cerebral Cortex, Magnetic Resonance Imaging methods, Functional Laterality, Schizophrenia diagnostic imaging
Abstract

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.

Published
2023
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28. What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group.

Author

Ching CRK, Hibar DP, Gurholt TP, Nunes A, Thomopoulos SI, Abé C, Agartz I, Brouwer RM, Cannon DM, de Zwarte SMC, Eyler LT, Favre P, Hajek T, Haukvik UK, Houenou J, Landén M, Lett TA, McDonald C, Nabulsi L, Patel Y, Pauling ME, Paus T, Radua J, Soeiro-de-Souza MG, Tronchin G, van Haren NEM, Vieta E, Walter H, Zeng LL, Alda M, Almeida J, Alnaes D, Alonso-Lana S, Altimus C, Bauer M, Baune BT, Bearden CE, Bellani M, Benedetti F, Berk M, Bilderbeck AC, Blumberg HP, Bøen E, Bollettini I, Del Mar Bonnin C, Brambilla P, Canales-Rodríguez EJ, Caseras X, Dandash O, Dannlowski U, Delvecchio G, Díaz-Zuluaga AM, Dima D, Duchesnay É, Elvsåshagen T, Fears SC, Frangou S, Fullerton JM, Glahn DC, Goikolea JM, Green MJ, Grotegerd D, Gruber O, Haarman BCM, Henry C, Howells FM, Ives-Deliperi V, Jansen A, Kircher TTJ, Knöchel C, Kramer B, Lafer B, López-Jaramillo C, Machado-Vieira R, MacIntosh BJ, Melloni EMT, Mitchell PB, Nenadic I, Nery F, Nugent AC, Oertel V, Ophoff RA, Ota M, Overs BJ, Pham DL, Phillips ML, Pineda-Zapata JA, Poletti S, Polosan M, Pomarol-Clotet E, Pouchon A, Quidé Y, Rive MM, Roberts G, Ruhe HG, Salvador R, Sarró S, Satterthwaite TD, Schene AH, Sim K, Soares JC, Stäblein M, Stein DJ, Tamnes CK, Thomaidis GV, Upegui CV, Veltman DJ, Wessa M, Westlye LT, Whalley HC, Wolf DH, Wu MJ, Yatham LN, Zarate CA, Thompson PM, and Andreassen OA

Subjects
Humans, Meta-Analysis as Topic, Multicenter Studies as Topic, Bipolar Disorder diagnostic imaging, Bipolar Disorder pathology, Cerebral Cortex diagnostic imaging, Cerebral Cortex pathology, Magnetic Resonance Imaging, Neuroimaging
Abstract

MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Published
2022
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29. Effects of Sleep Deprivation by Olfactorily Induced Sexual Arousal Compared to Immobilization Stress and Manual Sleep Deprivation on Neuromessengers and Time Keeping Genes in the Suprachiasmatic Nuclei and Other Cerebral Entities of Syrian Hamsters-An Immunohistochemical Study.

Author

Knöchel C, Frickmann H, and Nürnberger F

Subjects
Animals, Circadian Rhythm, Cricetinae, Mesocricetus, Suprachiasmatic Nucleus, Sexual Arousal, Sleep Deprivation
Abstract

We investigated the effects of sexual arousal induced by olfactory stimuli on the expression of neuromodulators, neurotransmitters and sexual steroid receptors in the suprachiasmatic nucleus (SCN, the circadian pacemaker of mammals) and other cerebral entities of Syrian hamsters ( Mesocricetus auratus ) compared to manual sleep deprivation and immobilization stress. The hamsters kept under a 12:12 hours (h) light:dark cycle were deprived of sleep by sexual stimulation, gentle manual handling or immobilization stress for 1 h at the beginning of the light phase and subsequently sacrificed at zeitgeber time 01:00, respectively; for comparison, hamsters were manually sleep deprived for 6 or 20 h or sacrificed after completing a full sleep phase. As demonstrated by immunohistochemistry, apart from various alterations after manual sleep deprivation, sexual stimulation caused down-regulation of arginine-vasopressin (AVP), vasointestinal peptide (VIP), serotonin (5-HT), substance P (SP), and met-enkephalin (ME) in the SCN. Somatostatin (SOM) was diminished in the medial periventricular nucleus (MPVN). In contrast, an increase in AVP was observed in the PVN, that of oxytocin (OXY) in the supraoptic nucleus (SON), of tyrosine-hydroxylase (TH) in the infundibular nucleus (IN), and dopamine beta-hydroxylase (DBH) in the A7 neuron population of the brain stem (A7), respectively. Testosterone in plasma was increased. The results indicate that sexual arousal extensively influences the neuropeptide systems of the SCN, suggesting an involvement of the SCN in reproductive behavior.

Published
2021
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30. Increased power by harmonizing structural MRI site differences with the ComBat batch adjustment method in ENIGMA.

Author

Radua J, Vieta E, Shinohara R, Kochunov P, Quidé Y, Green MJ, Weickert CS, Weickert T, Bruggemann J, Kircher T, Nenadić I, Cairns MJ, Seal M, Schall U, Henskens F, Fullerton JM, Mowry B, Pantelis C, Lenroot R, Cropley V, Loughland C, Scott R, Wolf D, Satterthwaite TD, Tan Y, Sim K, Piras F, Spalletta G, Banaj N, Pomarol-Clotet E, Solanes A, Albajes-Eizagirre A, Canales-Rodríguez EJ, Sarro S, Di Giorgio A, Bertolino A, Stäblein M, Oertel V, Knöchel C, Borgwardt S, du Plessis S, Yun JY, Kwon JS, Dannlowski U, Hahn T, Grotegerd D, Alloza C, Arango C, Janssen J, Díaz-Caneja C, Jiang W, Calhoun V, Ehrlich S, Yang K, Cascella NG, Takayanagi Y, Sawa A, Tomyshev A, Lebedeva I, Kaleda V, Kirschner M, Hoschl C, Tomecek D, Skoch A, van Amelsvoort T, Bakker G, James A, Preda A, Weideman A, Stein DJ, Howells F, Uhlmann A, Temmingh H, López-Jaramillo C, Díaz-Zuluaga A, Fortea L, Martinez-Heras E, Solana E, Llufriu S, Jahanshad N, Thompson P, Turner J, and van Erp T

Subjects
Adult, Algorithms, Cerebral Cortex diagnostic imaging, Female, Humans, Male, Meta-Analysis as Topic, Middle Aged, Neuroimaging, Schizophrenia diagnostic imaging, Young Adult, Image Processing, Computer-Assisted methods, Magnetic Resonance Imaging methods
Abstract

A common limitation of neuroimaging studies is their small sample sizes. To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide. However, this introduces heterogeneity due to different scanning devices and sequences. ENIGMA projects commonly address this heterogeneity with random-effects meta-analysis or mixed-effects mega-analysis. Here we tested whether the batch adjustment method, ComBat, can further reduce site-related heterogeneity and thus increase statistical power. We conducted random-effects meta-analyses, mixed-effects mega-analyses and ComBat mega-analyses to compare cortical thickness, surface area and subcortical volumes between 2897 individuals with a diagnosis of schizophrenia and 3141 healthy controls from 33 sites. Specifically, we compared the imaging data between individuals with schizophrenia and healthy controls, covarying for age and sex. The use of ComBat substantially increased the statistical significance of the findings as compared to random-effects meta-analyses. The findings were more similar when comparing ComBat with mixed-effects mega-analysis, although ComBat still slightly increased the statistical significance. ComBat also showed increased statistical power when we repeated the analyses with fewer sites. Results were nearly identical when we applied the ComBat harmonization separately for cortical thickness, cortical surface area and subcortical volumes. Therefore, we recommend applying the ComBat function to attenuate potential effects of site in ENIGMA projects and other multi-site structural imaging work. We provide easy-to-use functions in R that work even if imaging data are partially missing in some brain regions, and they can be trained with one data set and then applied to another (a requirement for some analyses such as machine learning)., Competing Interests: Declaration of competing interest AB has consulting fees from Biogen and lecture fees from Lundbeck, Otsuka and Janssen. AP has served as a consultant for Boehringer Ingelheim. AS: Advisory board (DSP), Research grants (CynK, DSP, MTPC, and Ono). CA has been a consultant to or has received honoraria or grants from Acadia, Angelini, Gedeon Richter, Janssen Cilag, Lundbeck, Otsuka, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. CH is faculty member, Lundbeck Psychiatric Institute. CP is on an advisory board for Lundbeck, Australia Pty Ltd and also received honoraria for talks presented at educational meetings organized by Lundbeck. CSW is on an advisory board for Lundbeck, Australia Pty Ltd and in collaboration with Astellas Pharma Inc., Japan. DJS has received research grants or consultancy honoraria from Lundbeck and Sun. EV has received grants and served as a consultant, advisor or CME speaker for the following entities (work unrelated to the topic of this manuscript): AB-Biotics, Abbott, Allergan, Angelini, Dainippon Sumitomo Pharma, Galenica, Janssen, Lundbeck, Novartis, Otsuka, Sage, Sanofi-Aventis, and Takeda. IN has no conflicts of interest to declare. RTS has received consulting fees from Genentech and Roche. SL has received consulting fees and speaking honoraria from Roche, Novartis, Biogen and Merck., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2020
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31. Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?

Author

van Erp TGM, Walton E, Hibar DP, Schmaal L, Jiang W, Glahn DC, Pearlson GD, Yao N, Fukunaga M, Hashimoto R, Okada N, Yamamori H, Clark VP, Mueller BA, de Zwarte SMC, Ophoff RA, van Haren NEM, Andreassen OA, Gurholt TP, Gruber O, Kraemer B, Richter A, Calhoun VD, Crespo-Facorro B, Roiz-Santiañez R, Tordesillas-Gutiérrez D, Loughland C, Catts S, Fullerton JM, Green MJ, Henskens F, Jablensky A, Mowry BJ, Pantelis C, Quidé Y, Schall U, Scott RJ, Cairns MJ, Seal M, Tooney PA, Rasser PE, Cooper G, Shannon Weickert C, Weickert TW, Hong E, Kochunov P, Gur RE, Gur RC, Ford JM, Macciardi F, Mathalon DH, Potkin SG, Preda A, Fan F, Ehrlich S, King MD, De Haan L, Veltman DJ, Assogna F, Banaj N, de Rossi P, Iorio M, Piras F, Spalletta G, Pomarol-Clotet E, Kelly S, Ciufolini S, Radua J, Murray R, Marques TR, Simmons A, Borgwardt S, Schönborn-Harrisberger F, Riecher-Rössler A, Smieskova R, Alpert KI, Bertolino A, Bonvino A, Di Giorgio A, Neilson E, Mayer AR, Yun JY, Cannon DM, Lebedeva I, Tomyshev AS, Akhadov T, Kaleda V, Fatouros-Bergman H, Flyckt L, Rosa PGP, Serpa MH, Zanetti MV, Hoschl C, Skoch A, Spaniel F, Tomecek D, McIntosh AM, Whalley HC, Knöchel C, Oertel-Knöchel V, Howells FM, Stein DJ, Temmingh HS, Uhlmann A, Lopez-Jaramillo C, Dima D, Faskowitz JI, Gutman BA, Jahanshad N, Thompson PM, and Turner JA

Subjects
Brain, Humans, Magnetic Resonance Imaging, Brain Diseases, Schizophrenia
Published
2019
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32. Associative Memory Impairments Are Associated With Functional Alterations Within the Memory Network in Schizophrenia Patients and Their Unaffected First-Degree Relatives: An fMRI Study.

Author

Oertel V, Kraft D, Alves G, Knöchel C, Ghinea D, Storchak H, Matura S, Prvulovic D, Bittner RA, Linden DEJ, Reif A, and Stäblein M

Abstract

Memory impairments are a major characteristic of schizophrenia (SZ). In the current study, we used an associative memory task to test the hypothesis that SZ patients and first-degree relatives have altered functional patterns in comparison to healthy controls. We analyzed the fMRI activation pattern during the presentation of a face-name task in 27 SZ patients, 23 first-degree relatives, and 27 healthy controls. In addition, we performed correlation analyses between individual psychopathology, accuracy and reaction time of the task and the beta scores of the functional brain activations. We observed a lower response accuracy and increased reaction time during the retrieval of face-name pairs in SZ patients compared with controls. Deficient performance was accompanied by abnormal functional activation patterns predominantly in DMN regions during encoding and retrieval. No significant correlation between individual psychopathology and neuronal activation during encoding or retrieval of face-name pairs was observed. Findings of first-degree relatives indicated slightly different functional pattern within brain networks in contrast to controls without significant differences in the behavioral task. Both the accuracy of memory performance as well as the functional activation pattern during retrieval revealed alterations in SZ patients, and, to a lesser degree, in relatives. The results are of potential relevance for integration within a comprehensive model of memory function in SZ. The development of a neurophysiological model of cognition in psychosis may help to clarify and improve therapeutic options to improve memory and functioning in the illness.

Published
2019
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33. Visual working memory encoding in schizophrenia and first-degree relatives: neurofunctional abnormalities and impaired consolidation.

Author

Stäblein M, Storchak H, Ghinea D, Kraft D, Knöchel C, Prvulovic D, Bittner RA, Reif A, and Oertel-Knöchel V

Subjects
Adult, Family, Female, Functional Neuroimaging, Gyrus Cinguli diagnostic imaging, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prefrontal Cortex diagnostic imaging, Endophenotypes, Gyrus Cinguli physiopathology, Memory Consolidation physiology, Memory, Short-Term physiology, Prefrontal Cortex physiopathology, Schizophrenia physiopathology, Visual Perception physiology
Abstract

Background: Working memory (WM) deficits in schizophrenia (SCZ) have been linked to impairments in the encoding phase that are associated with aberrant neuronal functioning. Similar abnormalities have been observed in unaffected first-degree relatives (REL) and are thus discussed as candidate endophenotypes. The process of WM consolidation - i.e. the formation of durable WM representations - is assumed to be impaired in SCZ, but no study has investigated WM consolidation and neuronal correlates of visual WM encoding in REL before., Method: We examined whole-brain activation during the encoding phase with an event-related functional magnetic resonance imaging study design in 25 SCZ subjects, 22 REL subjects, and 25 healthy controls. Subjects performed a visual masked change detection task that assessed WM performance and consolidation., Results: SCZ showed deficient WM performance indicating an impairment consolidation process, accompanied by broad neuronal hypoactivation, most prominently in frontal brain regions, as well as increased activity of the anterior cingulate during the encoding phase. REL showed decreased neuronal activity in the middle and medial frontal gyrus and increased activity in the precentral gyrus and insula during encoding, but no significant behavioral deficits were observed. In respect of given consolidation times, REL showed a shift from decreased frontal activity at short time intervals to increased frontal activity at longer time intervals., Conclusions: Findings suggest WM consolidation may be slowed in REL so that the deployment of compensatory neuronal resources during encoding is needed to assure proper WM performance. This supports the view of WM-related neuronal dysfunctions as a potential endophenotypic marker.

Published
2019
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34. Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium.

Author

van Erp TGM, Walton E, Hibar DP, Schmaal L, Jiang W, Glahn DC, Pearlson GD, Yao N, Fukunaga M, Hashimoto R, Okada N, Yamamori H, Bustillo JR, Clark VP, Agartz I, Mueller BA, Cahn W, de Zwarte SMC, Hulshoff Pol HE, Kahn RS, Ophoff RA, van Haren NEM, Andreassen OA, Dale AM, Doan NT, Gurholt TP, Hartberg CB, Haukvik UK, Jørgensen KN, Lagerberg TV, Melle I, Westlye LT, Gruber O, Kraemer B, Richter A, Zilles D, Calhoun VD, Crespo-Facorro B, Roiz-Santiañez R, Tordesillas-Gutiérrez D, Loughland C, Carr VJ, Catts S, Cropley VL, Fullerton JM, Green MJ, Henskens FA, Jablensky A, Lenroot RK, Mowry BJ, Michie PT, Pantelis C, Quidé Y, Schall U, Scott RJ, Cairns MJ, Seal M, Tooney PA, Rasser PE, Cooper G, Shannon Weickert C, Weickert TW, Morris DW, Hong E, Kochunov P, Beard LM, Gur RE, Gur RC, Satterthwaite TD, Wolf DH, Belger A, Brown GG, Ford JM, Macciardi F, Mathalon DH, O'Leary DS, Potkin SG, Preda A, Voyvodic J, Lim KO, McEwen S, Yang F, Tan Y, Tan S, Wang Z, Fan F, Chen J, Xiang H, Tang S, Guo H, Wan P, Wei D, Bockholt HJ, Ehrlich S, Wolthusen RPF, King MD, Shoemaker JM, Sponheim SR, De Haan L, Koenders L, Machielsen MW, van Amelsvoort T, Veltman DJ, Assogna F, Banaj N, de Rossi P, Iorio M, Piras F, Spalletta G, McKenna PJ, Pomarol-Clotet E, Salvador R, Corvin A, Donohoe G, Kelly S, Whelan CD, Dickie EW, Rotenberg D, Voineskos AN, Ciufolini S, Radua J, Dazzan P, Murray R, Reis Marques T, Simmons A, Borgwardt S, Egloff L, Harrisberger F, Riecher-Rössler A, Smieskova R, Alpert KI, Wang L, Jönsson EG, Koops S, Sommer IEC, Bertolino A, Bonvino A, Di Giorgio A, Neilson E, Mayer AR, Stephen JM, Kwon JS, Yun JY, Cannon DM, McDonald C, Lebedeva I, Tomyshev AS, Akhadov T, Kaleda V, Fatouros-Bergman H, Flyckt L, Busatto GF, Rosa PGP, Serpa MH, Zanetti MV, Hoschl C, Skoch A, Spaniel F, Tomecek D, Hagenaars SP, McIntosh AM, Whalley HC, Lawrie SM, Knöchel C, Oertel-Knöchel V, Stäblein M, Howells FM, Stein DJ, Temmingh HS, Uhlmann A, Lopez-Jaramillo C, Dima D, McMahon A, Faskowitz JI, Gutman BA, Jahanshad N, Thompson PM, and Turner JA

Subjects
Adolescent, Adult, Age of Onset, Aged, Brain diagnostic imaging, Case-Control Studies, Child, Female, Frontal Lobe diagnostic imaging, Frontal Lobe pathology, Humans, Linear Models, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Prefrontal Cortex diagnostic imaging, Prefrontal Cortex pathology, Severity of Illness Index, Temporal Lobe diagnostic imaging, Temporal Lobe pathology, Young Adult, Brain pathology, Schizophrenia diagnostic imaging, Schizophrenia pathology
Abstract

Background: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group., Methods: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide., Results: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset., Conclusions: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Published
2018
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35. White Matter Microstructural Changes and Episodic Memory Disturbances in Late-Onset Bipolar Disorder.

Author

Alves GS, Knöchel C, Paulitsch MA, Reinke B, Carvalho AF, Feddern R, Prvulovic D, Sudo FK, Pantel J, Reif A, and Oertel V

Abstract

Background: Bipolar disorder (BD) has been associated with distributed network disruption, but little is known on how different clinical subtypes, particularly those with an earlier and later onset of disease, are related to connectivity changes in white matter (WM) tracts. Methods: Diffusion tensor imaging (DTI) and volumetric measures were carried out in early-onset bipolar patients [(EOD) ( n = 16)], late-onset bipolar disorder [(LOD)( n = 14)] and healthy controls ( n = 32). We also computed ROI analysis of gray matter (GM) and white matter (WM) volumes using the regions with significant group differences in the DTI parameters. Cognitive and behavior measurements were analyzed between groups. Results: Lower fraction of anisotropy (FA) in the right hemisphere comprising anterior thalamic radiation, fornix, posterior cingulate, internal capsule, splenium of corpus callosum was observed in the LOD in comparison with EOD; additionally, lower FA was also found in the LOD in comparison with healthy controls, mostly in the right hemisphere and comprising fibers of the splenium of the corpus callosum, cingulum, superior frontal gyrus and posterior thalamic radiation; LOD also showed worse episodic memory performance than EOD; no statistical significant differences between mood symptoms, WM and GM volumes were found between BD groups. Conclusion: Even after correcting for age differences, LOD was associated with more extensive WM microstructural changes and worse episodic memory performance than EOD; these findings suggest that changes in the WM fiber integrity may be associated with a later presentation of BD, possibly due to mechanisms other than neuroprogression. However, these findings deserve replication in larger, prospective, studies.

Published
2018
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36. Altered apolipoprotein C expression in association with cognition impairments and hippocampus volume in schizophrenia and bipolar disorder.

Author

Knöchel C, Kniep J, Cooper JD, Stäblein M, Wenzler S, Sarlon J, Prvulovic D, Linden DE, Bahn S, Stocki P, Ozcan S, Alves G, Carvalho AF, Reif A, and Oertel-Knöchel V

Subjects
Adult, Blood Proteins metabolism, Female, Humans, Male, Mass Spectrometry, Middle Aged, Neuropsychological Tests, Psychiatric Status Rating Scales, Statistics as Topic, Apolipoproteins C metabolism, Bipolar Disorder complications, Bipolar Disorder pathology, Cognition Disorders etiology, Hippocampus metabolism, Schizophrenia complications, Schizophrenia pathology
Abstract

Proteomic analyses facilitate the interpretation of molecular biomarker probes which are very helpful in diagnosing schizophrenia (SZ). In the current study, we attempt to test whether potential differences in plasma protein expressions in SZ and bipolar disorder (BD) are associated with cognitive deficits and their underlying brain structures. Forty-two plasma proteins of 29 SZ patients, 25 BD patients and 93 non-clinical controls were quantified and analysed using multiple reaction monitoring-based triple quadrupole mass spectrometry approach. We also computed group comparisons of protein expressions between patients and controls, and between SZ and BD patients, as well. Potential associations of protein levels with cognitive functioning (psychomotor speed, executive functioning, crystallised intelligence) as well as underlying brain volume in the hippocampus were explored, using bivariate correlation analyses. The main finding of this study was that apolipoprotein expression differed between patients and controls and that these alterations in both disease groups were putatively related to cognitive impairments as well as to hippocampus volumes. However, none of the protein level differences were related to clinical symptom severity. In summary, altered apolipoprotein expression in BD and SZ was linked to cognitive decline and underlying morphological changes in both disorders. Our results suggest that the detection of molecular patterns in association with cognitive performance and its underlying brain morphology is of great importance for understanding of the pathological mechanisms of SZ and BD, as well as for supporting the diagnosis and treatment of both disorders.

Published
2017
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37. Omega-3 Fatty Acids: Repurposing Opportunities for Cognition and Biobehavioral Disturbances in MCI and Dementia.

Author

Knöchel C, Voss M, Gruter F, Alves GS, Matura S, Sepanski B, Stablein M, Kraft D, Prvulovic D, Carvalho AF, Reif A, and Oertel-Knochel V

Subjects
Alzheimer Disease psychology, Animals, Cognition, Cognitive Dysfunction psychology, Humans, Alzheimer Disease diet therapy, Cognitive Dysfunction diet therapy, Fatty Acids, Omega-3
Abstract

Neurodegenerative diseases may directly affect memory performance, thus leading to functional impairments. An increasing body of evidence suggests an association between dietary intake of omega-3 fatty acids and memory functioning in animal models as well as in human studies. Recent evidence supports a potential beneficial role of omega-3 fatty acid supplementation on psychopathological and cognitive symptoms, beside their established positive effects on cardiovascular health., Objective: We summarize relevant and recent evidence from epidemiological, interventional and experimental studies investigating dietary consumption of omega-3 fatty acids and emphazing mechanisms of memory disorders, with a focus on mild cognitive impairment (MCI) and dementia. Omega-3 fatty acid could represent an affordable and accessible adjunctive treatment option to improve cognitive and non-cognitive function with a focus on MCI or dementia. However, apart from its translational promise, which is based on mechanistic models and evidence from animal studies, evidence for clinical benefits in humans is lacking., Method: To follow this research question, a search through electronic databases for the following search terms to identify relevant studies was conducted: 'omega 3 fatty acids', 'cognition', 'memory', ´Alzheimer´s Disease ´, ´dementia´, ´MCI`. Studies were included if they presented original data and were published in English between 1990 and 2015., Results: To our the best of our knowledge, there are only 8 interventional studies that investigated the effects of n3-PUFAs in dementia patients, while 6 studies were conducted in healthy individuals, which in combination show equivocal results., Conclusion: This verifies the need for larger and (more) well designed clinical trials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Published
2017
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38. Impaired working memory for visual motion direction in schizophrenia: Absence of recency effects and association with psychopathology.

Author

Stäblein M, Sieprath L, Knöchel C, Landertinger A, Schmied C, Ghinea D, Mayer JS, Bittner RA, Reif A, and Oertel-Knöchel V

Subjects
Adult, Female, Humans, Male, Memory Disorders complications, Memory Disorders etiology, Middle Aged, Schizophrenia, Paranoid complications, Memory Disorders physiopathology, Memory, Short-Term physiology, Motion Perception physiology, Schizophrenia, Paranoid physiopathology
Abstract

Objective: Working memory (WM) impairments are a prominent neurocognitive symptom in schizophrenia (SZ) and include deficits in memory for serial order and abnormalities in serial position effects (i.e., primacy and recency effects). Former studies predominantly focused on investigating these deficits applying verbal or static visual stimuli, but little is known about WM processes that involve dynamic visual movements. We examined WM for visual motion directions, its susceptibility to distraction and the effect of serial positioning., Method: Twenty-three patients with paranoid SZ and 23 healthy control subjects (HC) took part in the study. We conducted an adapted Sternberg-type recognition paradigm: three random dot kinematograms (RDKs) that depicted coherent visual motion were used as stimuli and a distractor stimulus was incorporated into the task., Results: SZ patients performed significantly worse in the WM visual motion task, when a distractor stimulus was presented. While HC showed a recency effect for later RDKs, the effect was absent in SZ patients. WM deficits were associated with more severe psychopathological symptoms, poor visual and verbal learning, and a longer duration of illness. Furthermore, SZ patients showed impairments in several other neurocognitive domains., Conclusions: Findings suggest that early WM processing of visual motion is susceptible to interruption and that WM impairments are associated with clinical symptoms in SZ. The absence of a recency effect is discussed in respect of 3 theoretical approaches-impaired WM for serial order information, abnormalities in early visual representations (i.e., masking effects), and deficits in later visual processing (i.e., attentional blink effect). (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

Published
2016
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39. White matter abnormalities in the fornix are linked to cognitive performance in SZ but not in BD disorder: An exploratory analysis with DTI deterministic tractography.

Author

Knöchel C, Schmied C, Linden DE, Stäblein M, Prvulovic D, de A de Carvalho L, Harrison O, Barros PO Junior, Carvalho AF, Reif A, Alves GS, and Oertel-Knöchel V

Subjects
Adult, Bipolar Disorder complications, Cognition Disorders complications, Female, Fornix, Brain diagnostic imaging, Humans, Male, Schizophrenia complications, White Matter diagnostic imaging, Bipolar Disorder physiopathology, Cognition Disorders physiopathology, Diffusion Tensor Imaging methods, Fornix, Brain physiopathology, Schizophrenia physiopathology, White Matter physiopathology
Abstract

Background: In psychosis, white matter (WM) microstructural changes have been detected previously; however, direct comparisons of findings between bipolar (BD) and schizophrenia (SZ) patients are scarce. In this study, we employed deterministic tractography to reconstruct WM tracts in BD and SZ patients., Methods: Diffusion tensor imaging (DTI) data was carried out with n=32 euthymic BD type I patients, n=26 SZ patients and 30 matched healthy controls. Deterministic tractography using multiple indices of diffusion (fractional anisotropy (FA), tract volume (Vol), tract length (Le) and number of tracts (NofT)) were obtained from the fornix, the cingulum, the anterior thalamic radiation, and the corpus callosum bilaterally., Results: We showed widespread WM microstructural changes in SZ, and changes in the corpus callosum, the left cingulum and the fornix in BD. Fornix fiber tracking scores were associated with cognitive performance in SZ, and with age and age at disease onset in the BD patient group., Limitations: Although the influence of psychopharmacological drugs as biasing variables on morphological alterations has been discussed for SZ and BD, we did not observe a clear influence of drug exposure on our findings., Conclusions: These results confirm the assumption that SZ patients have more severe WM changes than BD patients. The findings also suggest a major role of WM changes in the fornix as important fronto-limbic connections in the etiology of cognitive symptoms in SZ, but not in BD., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Published
2016
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40. Cortical thinning in bipolar disorder and schizophrenia.

Author

Knöchel C, Reuter J, Reinke B, Stäblein M, Marbach K, Feddern R, Kuhlmann K, Alves G, Prvulovic D, Wenzler S, Linden DE, and Oertel-Knöchel V

Subjects
Adult, Bipolar Disorder pathology, Cerebral Cortex pathology, Female, Humans, Imaging, Three-Dimensional, Magnetic Resonance Imaging, Male, Organ Size, Psychiatric Status Rating Scales, Schizophrenia pathology, Software, Bipolar Disorder diagnostic imaging, Cerebral Cortex diagnostic imaging, Schizophrenia diagnostic imaging
Abstract

Although schizophrenia (SZ) and bipolar disorder (BD) share some clinical features such as psychotic symptoms and cognitive dysfunctions, little is known about possible pathophysiological similarities between both diseases. Therefore, we investigated the potential topographical overlap and segregation of cortical thickness abnormalities in SZ and BD patients. We analyzed 3D-anatomical magnetic resonance imaging datasets with the FreeSurfer 5.1.0 software to examine cortical thickness and volumes in three groups of participants: n=34 BD patients, n=32 SZ patients and n=38 healthy controls. We observed similar bilateral cortical thickness reductions in BD and SZ patients predominantly in the pars opercularis of the inferior frontal gyrus and in the anterior and posterior cingulate. We also found disease-specific cortical reductions in the orbitofrontal cortex for BD patients and in dorsal frontal and temporal areas for SZ. Furthermore, inferior frontal gyrus cortical thinning was associated with deficits in psychomotor speed and executive functioning in SZ patients and with age at onset in both groups. Our findings support the hypothesis that thinning of the frontal cortex may represent a biological feature shared by both disease groups. The associations between cognitive deficits and the reported findings in SZ and to a lesser degree in BD patients add to the functional relevance of our results. However, further studies are needed to corroborate a model of shared pathophysiological disease features across BD and SZ., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Published
2016
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41. Age-Related Effects of the Apolipoprotein E Gene on Brain Function.

Author

Matura S, Prvulovic D, Hartmann D, Scheibe M, Sepanski B, Butz M, Oertel-Knöchel V, Knöchel C, Karakaya T, Fußer F, Hattingen E, and Pantel J

Subjects
Adult, Aged, Aged, 80 and over, Aging psychology, Association Learning physiology, Brain Mapping, Cerebrovascular Circulation physiology, Cohort Studies, Cross-Sectional Studies, Genotyping Techniques, Heterozygote, Humans, Magnetic Resonance Imaging, Middle Aged, Neuropsychological Tests, Oxygen blood, Pattern Recognition, Visual physiology, Young Adult, Aging genetics, Aging physiology, Apolipoproteins E genetics, Brain physiopathology, Cognition physiology
Abstract

The apolipoprotein E (ApoE) ɛ4 allele is a well-established genetic risk factor for sporadic Alzheimer's disease. Some evidence suggests a negative role of the ApoE ɛ4 allele for cognitive performance in late life, while beneficial effects on cognition have been shown in young age. We investigated age-related effects of the ApoE gene on brain function by assessing cognitive performance, as well as functional activation patterns during retrieval of Face-Name pairs in a group of young (n = 50; age 26.4±4.6 years, 25 ɛ4 carriers) and old (n = 40; age 66.1±7.0 years, 20 ɛ4 carriers) participants. A cross-sectional factorial design was used to examine the effects of age, ApoE genotype, and their interaction on both cognitive performance and the blood oxygenation level dependent (BOLD) brain response during retrieval of Face-Name pairs. While there were no genotype-related differences in cognitive performance, we found a significant interaction of age and ApoE genotype on task-related activation bilaterally in anterior cingulate gyrus and superior frontal gyrus, as well as left and right insula. Old age was associated with increased activity in ɛ4 carriers. The increased BOLD response in old ɛ4 carriers during retrieval could indicate a neurocognitive disadvantage associated with the ɛ4 allele with increasing age. Furthermore, recruitment of neuronal resources resulted in enhanced memory performance in young ɛ4 carriers, pointing to a better neurofunctional capacity associated with the ApoE4 genotype in young age.

Published
2016
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42. Shared and distinct gray matter abnormalities in schizophrenia, schizophrenia relatives and bipolar disorder in association with cognitive impairment.

Author

Knöchel C, Stäblein M, Prvulovic D, Ghinea D, Wenzler S, Pantel J, Alves G, Linden DE, Harrison O, Carvalho A, Reif A, and Oertel-Knöchel V

Subjects
Adult, Analysis of Variance, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Psychiatric Status Rating Scales, Statistics as Topic, Bipolar Disorder complications, Bipolar Disorder diagnostic imaging, Cognition Disorders etiology, Gray Matter diagnostic imaging, Schizophrenia complications, Schizophrenia diagnostic imaging
Abstract

Cognitive impairments have been linked to structural and functional alterations in frontal and subcortical brain regions, ultimately leading to fronto-thalamic connectivity disturbances. We hypothesized that such neuronal disruptions in frontal and subcortical structures may account for neuropsychological deficits in schizophrenia (SZ), schizophrenia relatives and bipolar disorder (BD). We acquired T1-weighted anatomical MRI sequences in 209 participants: 57 SZ patients, 47 first-degree relatives of SZ patients, 48 BD I patients and 57 healthy controls. We computed group comparisons of gray matter (GM) volume in frontal and basal ganglia regions-of-interest, followed by correlation analysis between psychomotor speed, executive functioning and learning and GM volumes in candidate regions. Several frontal GM volume reductions as well as GM increases in the thalamus and the putamen were exhibited in SZ patients as compared to controls. The same finding was observed - less pronounced - when comparing SZ relatives and controls. BD patients presented GM volume increases in the basal ganglia in comparison to controls. In SZ patients, increases in bilateral thalamus GM volume and decreases in left middle and superior frontal gyrus volume were significantly associated with worse cognitive performance. In summary, our results indicate distinct imbalances across frontal-subcortical circuits in BD, SZ relatives and SZ. The functional relevance of the findings were mainly limited to the SZ patients group: in this group, abnormalities were directly associated with cognitive performance. This result is in line with the finding that the volume alterations were strongest in SZ patients and followed by BD patients and SZ relatives., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Published
2016
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43. Peripheral vascular endothelial growth factor as a novel depression biomarker: A meta-analysis.

Author

Carvalho AF, Köhler CA, McIntyre RS, Knöchel C, Brunoni AR, Thase ME, Quevedo J, Fernandes BS, and Berk M

Subjects
Biomarkers blood, Depressive Disorder blood, Humans, Depressive Disorder diagnosis, Vascular Endothelial Growth Factor A blood
Abstract

Background: The neurotrophic hypothesis of major depressive disorder (MDD) postulates that the pathology of this illness incorporates a down-regulation of neurotrophin signaling. Brain-derived neurotrophic factor (BDNF) is the most studied neurotrophic mediator regarding the neurobiology of MDD. Nevertheless, emerging evidence has implicated the multi-competent angiogenic and neurogenic molecule - vascular endothelial growth factor (VEGF) - in hippocampal neurogenesis and depression pathophysiology., Objective: To compare peripheral levels of VEGF between individuals with MDD and healthy controls., Methods: We performed a systematic review and meta-analysis of original studies measuring peripheral levels of VEGF in participants with MDD compared to healthy controls. We searched the Pubmed/MEDLINE, EMBASE and PsycInfo databases for studies published in any language through December 16th, 2014., Results: Fourteen studies met eligibility criteria (N=1633). VEGF levels were significantly elevated in individuals with MDD when compared to healthy controls (Hedges's g=0.343; 95% CI: 0.146-0.540; P<0.01). Funnel plot inspection and the Egger's test did not provide evidence of publication bias. A significant degree of heterogeneity was observed (Q=38.355, df=13, P<0.001; I(2)=66.1%), which was explored through meta-regression and subgroup analyses. Overall methodological quality, sample for assay (plasma versus serum), as well as the matching of MDD and control samples for age and gender emerged as significant sources of heterogeneity., Conclusions: Taken together, extant data indicate that VEGF shows promise as a biomarker for MDD, and supports that this mediator may be involved in neuroplasticity mechanisms underlying the pathophysiology of MDD., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Published
2015
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44. Association between age of disease-onset, cognitive performance and cortical thickness in bipolar disorders.

Author

Oertel-Knöchel V, Reuter J, Reinke B, Marbach K, Feddern R, Alves G, Prvulovic D, Linden DE, and Knöchel C

Subjects
Adult, Age Factors, Cognitive Dysfunction psychology, Depressive Disorder complications, Female, Frontal Lobe physiopathology, Humans, Limbic System pathology, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Severity of Illness Index, Temporal Lobe pathology, Age of Onset, Bipolar Disorder pathology, Bipolar Disorder psychology, Cognition, Executive Function, Frontal Lobe pathology
Abstract

Objectives: Neuroimaging studies in patients with bipolar disorder (BD) have indicated a number of structural brain changes, including reduced cortical thickness. However, the effects of the course of illness, clinical and cognitive variables on cortical thickness in BD patients have not yet been evaluated., Methods: A total of 67 individuals (32 patients with euthymic BD and 35 healthy and age-matched controls) underwent 3D-anatomical magnetic resonance imaging (MRI). Whole-brain cortical thickness and group differences were assessed using the Freesurfer software. Course of disease variables, clinical and cognitive parameters were correlated with cortical thickness measures., Results: We found reduced cortical thickness in BD patients compared with controls in the frontal and temporal lobes and in several limbic areas. We also report significant associations between cortical thickness and age of disease-onset, speed of cognitive processing, executive function and depression severity in BD patients., Conclusions: Cortical thickness reduction across frontal and limbic areas is a structural correlate of affective symptom severity and cognitive impairments in BD as well of age of disease-onset. We may assume that frontal lobe structural abnormalities are present in bipolar disorder, and might lead to dysfunctional cognitive functioning. The causality and functional relevance beyond mere correlation, however, is yet to be established. Our findings encourage further longitudinal studies in BD patients and in healthy at-risk subjects in order to discern the temporal order and development of morphological changes and clinical symptoms., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Published
2015
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45. Schizophrenia risk variants modulate white matter volume across the psychosis spectrum: evidence from two independent cohorts.

Author

Oertel-Knöchel V, Lancaster TM, Knöchel C, Stäblein M, Storchak H, Reinke B, Jurcoane A, Kniep J, Prvulovic D, Mantripragada K, Tansey KE, O'Donovan MC, Owen MJ, and Linden DE

Subjects
Aged, Cohort Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Polymorphism, Single Nucleotide, Psychotic Disorders genetics, Risk Factors, Schizophrenia genetics, Brain pathology, Psychotic Disorders pathology, Schizophrenia pathology, White Matter pathology
Abstract

Polygenic risk scores, based on risk variants identified in genome-wide-association-studies (GWAS), explain a considerable portion of the heritability for schizophrenia (SZ) and bipolar disorder (BD). However, little is known about the combined effects of these variants, although polygenic neuroimaging has developed into a powerful tool of translational neuroscience. In this study, we used genome wide significant SZ risk variants to test the predictive capacity of the polygenic model and explored potential associations with white matter volume, a key candidate in imaging phenotype for psychotic disorders. By calculating the combined additive schizophrenia risk of seven SNPs (significant hits from a recent schizophrenia GWAS study), we show that increased additive genetic risk for SZ was associated with reduced white matter volume in a group of participants (n = 94) consisting of healthy individuals, SZ first-degree relatives, SZ patients and BD patients. This effect was also seen in a second independent sample of healthy individuals (n = 89). We suggest that a moderate portion of variance (~4%) of white matter volume can be explained by the seven hits from the recent schizophrenia GWAS. These results provide evidence for associations between cumulative genetic risk for schizophrenia and intermediate neuroimaging phenotypes in models of psychosis. Our work contributes to a growing body of literature suggesting that polygenic risk may help to explain white matter alterations associated with familial risk for psychosis.

Published
2015
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46. Consolidation time affects performance and neural activity during visual working memory.

Author

Knöchel C, Oertel-Knöchel V, Bittner R, Stäblein M, Heselhaus V, Prvulovic D, Fusser F, Karakaya T, Pantel J, Maurer K, and Linden DE

Subjects
Adult, Brain Mapping, Case-Control Studies, Cognition physiology, Female, Frontal Lobe physiopathology, Humans, Male, Memory, Parietal Lobe physiology, Young Adult, Brain physiology, Functional Neuroimaging, Magnetic Resonance Imaging methods, Memory, Short-Term physiology, Pattern Recognition, Visual physiology, Recognition, Psychology physiology
Abstract

We tested the effects of variation of stimulus onset asynchrony (SOA) on visual working memory (WM) performance across different load levels and the underlying brain activation patterns using functional magnetic resonance imaging (fMRI) in 48 healthy participants. Participants were instructed to memorise arrays of coloured squares and had to perform a match/non-match judgement on a probe stimulus after a jittered delay. We presented visual pattern masks at four SOAs after the offset of the memory array (100 ms, 200 ms, 400 ms, and 800 ms). Memory performance decreased with increased load and shortened SOA. Brain activation data showed significant effects of load (during encoding and retrieval), SOA (retrieval) and an interaction of load by SOA (encoding), mainly in frontal and parietal areas. There was also a direct relationship between successfully stored items and activation in the right inferior parietal lobule and the left middle frontal gyrus. The neurobehavioral results suggest that the frontal regions, together with the inferior parietal lobe, are associated with successful WM performance, especially under the most challenging conditions of high load and short SOAs., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Published
2015
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47. Omega 3 Fatty Acids: Novel Neurotherapeutic Targets for Cognitive Dysfunction in Mood Disorders and Schizophrenia?

Author

Knöchel C, Voss M, Grüter F, Alves GS, Matura S, Sepanski B, Stäblein M, Wenzler S, Prvulovic D, Carvalho AF, and Oertel-Knöchel V

Subjects
Animals, Humans, Cognition Disorders etiology, Cognition Disorders therapy, Fatty Acids, Omega-3 metabolism, Mood Disorders complications, Schizophrenia complications
Abstract

An increasing body of evidences from preclinical as well as epidemiological and clinical studies suggest a potential beneficial role of dietary intake of omega-3 fatty acids for cognitive functioning. In this narrative review, we will summarize and discuss recent findings from epidemiological, interventional and experimental studies linking dietary consumption of omega-3 fatty acids to cognitive function in healthy adults. Furthermore, affective disorders and schizophrenia (SZ) are characterized by cognitive dysfunction encompassing several domains. Cognitive dysfunction is closely related to impaired functioning and quality of life across these conditions. Therefore, the current review focues on the potential influence of omega-3 fatty acids on cognition in SZ and affective disorders. In sum, current data predominantly from mechanistic models and animal studies suggest that adjunctive omega-3 fatty acid supplementation could lead to improved cognitive functioning in SZ and affective disorders. However, besides its translational promise, evidence for clinical benefits in humans has been mixed. Notwithstanding evidences indicate that adjunctive omega-3 fatty acids may have benefit for affective symptoms in both unipolar and bipolar depression, to date no randomized controlled trial had evaluated omega-3 as cognitive enhancer for mood disorders, while a single published controlled trial suggested no therapeutic benefit for cognitive improvement in SZ. Considering the pleiotropic mechanisms of action of omega-3 fatty acids, the design of well-designed controlled trials of omega-3 supplementation as a novel, domain-specific, target for cognitive impairment in SZ and affective disorders is warranted.

Published
2015
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48. Treatment-resistant Late-life Depression: Challenges and Perspectives.

Author

Knöchel C, Alves G, Friedrichs B, Schneider B, Schmidt-Rechau A, Wenzler S, Schneider A, Prvulovic D, Carvalho AF, and Oertel-Knöchel V

Subjects
Animals, Disease Management, Humans, Depressive Disorder, Treatment-Resistant physiopathology, Depressive Disorder, Treatment-Resistant psychology, Depressive Disorder, Treatment-Resistant therapy
Abstract

The current Review article provides a narrative review about the neurobiological underpinnings and treatment of treatment resistant late-life depression (TRLLD). The manuscript focuses on therapeutic targets of late-life depression, which include pharmacological, psychological, biophysical and exercise treatment approaches. Therefore, we summarize available evidences on that kind of therapies for patients suffering from late-life depression. The search for evidences of therapeutic options of late-life depression were done using searching websites as "pubmed", and using the searching terms "depression", "late-life depression", "treatment", "biophysical therapy", "exercise therapy", "pharmacological therapy" and "psychological therapy". To the end, we summarize and discuss current data, providing some directions for further research. Treatment recommendations for elderly depressive patients favour a multimodal approach, containing psychological, pharmacological and secondary biophysical therapeutic options. Particularly, a combination of psychotherapy and antidepressant medication reflects the best therapeutic option. However, mostly accepted and used is the pharmacological treatment although evidence suggests that the drug therapy is not as effective as it is in younger depressive patients. Further studies employing larger samples and longer follow-up periods are necessary and may focus on comparability of study designs and involve novel approaches to establish the validity and reliability of multimodal treatment programs.

Published
2015
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49. Integrating retrogenesis theory to Alzheimer's disease pathology: insight from DTI-TBSS investigation of the white matter microstructural integrity.

Author

Alves GS, Oertel Knöchel V, Knöchel C, Carvalho AF, Pantel J, Engelhardt E, and Laks J

Subjects
Alzheimer Disease pathology, Humans, White Matter pathology, Alzheimer Disease physiopathology, Models, Neurological, White Matter physiopathology
Abstract

Microstructural abnormalities in white matter (WM) are often reported in Alzheimer's disease (AD) and may reflect primary or secondary circuitry degeneration (i.e., due to cortical atrophy). The interpretation of diffusion tensor imaging (DTI) eigenvectors, known as multiple indices, may provide new insights into the main pathological models supporting primary or secondary patterns of WM disruption in AD, the retrogenesis, and Wallerian degeneration models, respectively. The aim of this review is to analyze the current literature on the contribution of DTI multiple indices to the understanding of AD neuropathology, taking the retrogenesis model as a reference for discussion. A systematic review using MEDLINE, EMBASE, and PUBMED was performed. Evidence suggests that AD evolves through distinct patterns of WM disruption, in which retrogenesis or, alternatively, the Wallerian degeneration may prevail. Distinct patterns of WM atrophy may be influenced by complex interactions which comprise disease status and progression, fiber localization, concurrent risk factors (i.e., vascular disease, gender), and cognitive reserve. The use of DTI multiple indices in addition to other standard multimodal methods in dementia research may help to determine the contribution of retrogenesis hypothesis to the understanding of neuropathological hallmarks that lead to AD.

Published
2015
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50. Episodic memory impairments in bipolar disorder are associated with functional and structural brain changes.

Author

Oertel-Knöchel V, Reinke B, Feddern R, Knake A, Knöchel C, Prvulovic D, Pantel J, and Linden DE

Subjects
Adult, Brain blood supply, Brain pathology, Case-Control Studies, Diffusion Tensor Imaging, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways blood supply, Neural Pathways pathology, Neuropsychological Tests, Oxygen blood, Photic Stimulation, Psychiatric Status Rating Scales, Young Adult, Bipolar Disorder complications, Brain physiopathology, Memory Disorders etiology, Memory Disorders pathology, Memory, Episodic
Abstract

Objectives: We combined multimodal functional magnetic resonance imaging (fMRI) and structural magnetic resonance imaging to probe abnormalities in brain circuits underpinning episodic memory performance deficits in patients with bipolar disorder (BD)., Methods: We acquired whole-brain fMRI data in 21 patients with BD and a matched group of 20 healthy controls during a non-verbal episodic memory task, using abstract shapes. We also examined density of gray matter, using voxel-based morphometry (VBM), and integrity of connecting fiber tracts, using diffusion tensor imaging (DTI) and tract-based spatial statistics, for areas with significant activation differences., Results: Patients with BD remembered less well than controls which shapes they had seen and had lower activation levels during the encoding stage of the task in the anterior cingulate gyrus, the precuneus/cuneus bilaterally, and the left lingual gyrus, and higher activation levels during the retrieval stage in the left temporo-parietal junction. Patients with BD showed reduced gray matter volumes in the left anterior cingulate, the precuneus/cuneus bilaterally, and the left temporo-parietal region in comparison with controls. DTI revealed increased radial, axial, and mean diffusivity in the left superior longitudinal fascicle in patients with BD compared with controls., Conclusions: Changes in task-related activation in frontal and parietal areas were associated with poorer episodic memory in patients with BD. Compared with data from single imaging modalities, integration of multimodal neuroimaging data enables the building of more complete neuropsychological models of mental disorders., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Published
2014
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