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1. Differences in the neural correlates of schizophrenia with positive and negative formal thought disorder in patients with schizophrenia in the ENIGMA dataset.

Author

Sharkey, Rachel, Bacon, Chelsea, Peterson, Zeru, Rootes-Murdy, Kelly, Salvador, Raymond, Pomarol-Clotet, Edith, Karuk, Andriana, Homan, Philipp, Ji, Ellen, Omlor, Wolfgang, Homan, Stephanie, Georgiadis, Foivos, Kaiser, Stefan, Kirschner, Matthias, Ehrlich, Stefan, Dannlowski, Udo, Grotegerd, Dominik, Goltermann, Janik, Meinert, Susanne, Kircher, Tilo, Stein, Frederike, Brosch, Katharina, Krug, Axel, Nenadic, Igor, Sim, Kang, Spalletta, Gianfranco, Banaj, Nerisa, Sponheim, Scott, Demro, Caroline, Ramsay, Ian, King, Margaret, Quidé, Yann, Green, Melissa, Nguyen, Dana, Preda, Adrian, Calhoun, Vince, Turner, Jessica, van Erp, Theo, and Nickl-Jockschat, Thomas

Subjects
Humans, Schizophrenia, Male, Female, Adult, Brain, Middle Aged, Schizophrenic Psychology, Neuroimaging, Cohort Studies, Magnetic Resonance Imaging, Thinking
Abstract

Formal thought disorder (FTD) is a clinical key factor in schizophrenia, but the neurobiological underpinnings remain unclear. In particular, the relationship between FTD symptom dimensions and patterns of regional brain volume loss in schizophrenia remains to be established in large cohorts. Even less is known about the cellular basis of FTD. Our study addresses these major obstacles by enrolling a large multi-site cohort acquired by the ENIGMA Schizophrenia Working Group (752 schizophrenia patients and 1256 controls), to unravel the neuroanatomy of FTD in schizophrenia and using virtual histology tools on implicated brain regions to investigate the cellular basis. Based on the findings of previous clinical and neuroimaging studies, we decided to separately explore positive, negative and total formal thought disorder. We used virtual histology tools to relate brain structural changes associated with FTD to cellular distributions in cortical regions. We identified distinct neural networks positive and negative FTD. Both networks encompassed fronto-occipito-amygdalar brain regions, but positive and negative FTD demonstrated a dissociation: negative FTD showed a relative sparing of orbitofrontal cortical thickness, while positive FTD also affected lateral temporal cortices. Virtual histology identified distinct transcriptomic fingerprints associated for both symptom dimensions. Negative FTD was linked to neuronal and astrocyte fingerprints, while positive FTD also showed associations with microglial cell types. These results provide an important step towards linking FTD to brain structural changes and their cellular underpinnings, providing an avenue for a better mechanistic understanding of this syndrome.

Published
2024

2. Verbal Learning and Memory Deficits across Neurological and Neuropsychiatric Disorders: Insights from an ENIGMA Mega Analysis.

Author

Kennedy, Eamonn, Liebel, Spencer, Lindsey, Hannah, Vadlamani, Shashank, Lei, Pui-Wa, Adamson, Maheen, Alda, Martin, Alonso-Lana, Silvia, Anderson, Tim, Arango, Celso, Asarnow, Robert, Avram, Mihai, Ayesa-Arriola, Rosa, Babikian, Talin, Banaj, Nerisa, Bird, Laura, Borgwardt, Stefan, Brodtmann, Amy, Brosch, Katharina, Caeyenberghs, Karen, Calhoun, Vince, Chiaravalloti, Nancy, Cifu, David, Crespo-Facorro, Benedicto, Dalrymple-Alford, John, Dams-OConnor, Kristen, Dannlowski, Udo, Darby, David, Davenport, Nicholas, DeLuca, John, Diaz-Caneja, Covadonga, Disner, Seth, Dobryakova, Ekaterina, Ehrlich, Stefan, Esopenko, Carrie, Ferrarelli, Fabio, Frank, Lea, Franz, Carol, Fuentes-Claramonte, Paola, Genova, Helen, Giza, Christopher, Goltermann, Janik, Grotegerd, Dominik, Gruber, Marius, Gutierrez-Zotes, Alfonso, Ha, Minji, Haavik, Jan, Hinkin, Charles, Hoskinson, Kristen, Hubl, Daniela, Irimia, Andrei, Jansen, Andreas, Kaess, Michael, Kang, Xiaojian, Kenney, Kimbra, Keřková, Barbora, Khlif, Mohamed, Kim, Minah, Kindler, Jochen, Kircher, Tilo, Knížková, Karolina, Kolskår, Knut, Krch, Denise, Kremen, William, Kuhn, Taylor, Kumari, Veena, Kwon, Junsoo, Langella, Roberto, Laskowitz, Sarah, Lee, Jungha, Lengenfelder, Jean, Liou-Johnson, Victoria, Lippa, Sara, Løvstad, Marianne, Lundervold, Astri, Marotta, Cassandra, Marquardt, Craig, Mattos, Paulo, Mayeli, Ahmad, McDonald, Carrie, Meinert, Susanne, Melzer, Tracy, Merchán-Naranjo, Jessica, Michel, Chantal, Morey, Rajendra, Mwangi, Benson, Myall, Daniel, Nenadić, Igor, Newsome, Mary, Nunes, Abraham, OBrien, Terence, Oertel, Viola, Ollinger, John, Olsen, Alexander, Ortiz García de la Foz, Victor, Ozmen, Mustafa, Pardoe, Heath, Parent, Marise, Piras, Fabrizio, and Piras, Federica

Subjects
Parkinson’s disease, attention-deficit/hyperactivity disorder, bipolar disorder, dementia, depression, memory, schizophrenia, stroke, traumatic brain injury, verbal learning
Abstract

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinsons disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

Published
2024

3. Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study.

Author

Georgiadis, Foivos, Larivière, Sara, Glahn, David, Hong, L, Kochunov, Peter, Mowry, Bryan, Loughland, Carmel, Pantelis, Christos, Henskens, Frans, Green, Melissa, Cairns, Murray, Michie, Patricia, Rasser, Paul, Catts, Stanley, Tooney, Paul, Scott, Rodney, Schall, Ulrich, Carr, Vaughan, Quidé, Yann, Krug, Axel, Stein, Frederike, Nenadić, Igor, Brosch, Katharina, Kircher, Tilo, Gur, Raquel, Gur, Ruben, Satterthwaite, Theodore, Karuk, Andriana, Pomarol-Clotet, Edith, Radua, Joaquim, Fuentes-Claramonte, Paola, Salvador, Raymond, Spalletta, Gianfranco, Voineskos, Aristotle, Sim, Kang, Crespo-Facorro, Benedicto, Tordesillas Gutiérrez, Diana, Ehrlich, Stefan, Crossley, Nicolas, Grotegerd, Dominik, Repple, Jonathan, Lencer, Rebekka, Dannlowski, Udo, Calhoun, Vince, Rootes-Murdy, Kelly, Demro, Caroline, Ramsay, Ian, Sponheim, Scott, Schmidt, Andre, Borgwardt, Stefan, Tomyshev, Alexander, Lebedeva, Irina, Höschl, Cyril, Spaniel, Filip, Preda, Adrian, Nguyen, Dana, Uhlmann, Anne, Stein, Dan, Howells, Fleur, Temmingh, Henk, Diaz Zuluaga, Ana, López Jaramillo, Carlos, Iasevoli, Felice, Ji, Ellen, Homan, Stephanie, Omlor, Wolfgang, Homan, Philipp, Kaiser, Stefan, Seifritz, Erich, Misic, Bratislav, Valk, Sofie, Thompson, Paul, Van Erp, Theodorus, Turner, Jessica, Bernhardt, Boris, and Kirschner, Matthias

Subjects
Humans, Schizophrenia, Connectome, Adult, Female, Male, Magnetic Resonance Imaging, Cerebral Cortex, Nerve Net, Brain, Middle Aged, Neural Pathways, Young Adult
Abstract

Schizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying network layout. We tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2439 adults with schizophrenia and 2867 healthy controls from 26 ENIGMA sites and normative data from the Human Connectome Project (n = 207), we evaluated structural alterations of schizophrenia against two network susceptibility models: (i) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; (ii) epicenter mapping, which identifies regions whose typical connectivity profile most closely resembles the disease-related morphological alterations. To assess generalizability and specificity, we contextualized the influence of site, disease stages, and individual clinical factors and compared network associations of schizophrenia with that found in affective disorders. Our findings show schizophrenia-related cortical thinning is spatially associated with functional and structural hubs, suggesting that highly interconnected regions are more vulnerable to morphological alterations. Predominantly temporo-paralimbic and frontal regions emerged as epicenters with connectivity profiles linked to schizophrenias alteration patterns. Findings were robust across sites, disease stages, and related to individual symptoms. Moreover, transdiagnostic comparisons revealed overlapping epicenters in schizophrenia and bipolar, but not major depressive disorder, suggestive of a pathophysiological continuity within the schizophrenia-bipolar-spectrum. In sum, cortical alterations over the course of schizophrenia robustly follow brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters at both the level of the group and the individual. Subtle variations of epicenters across disease stages suggest interacting pathological processes, while associations with patient-specific symptoms support additional inter-individual variability of hub vulnerability and epicenters in schizophrenia. Our work outlines potential pathways to better understand macroscale structural alterations, and inter- individual variability in schizophrenia.

Published
2024

4. Principal component analysis as an efficient method for capturing multivariate brain signatures of complex disorders-ENIGMA study in people with bipolar disorders and obesity.

Author

McWhinney, Sean, Hlinka, Jaroslav, Bakstein, Eduard, Dietze, Lorielle, Corkum, Emily, Abé, Christoph, Alda, Martin, Alexander, Nina, Benedetti, Francesco, Berk, Michael, Bøen, Erlend, Bonnekoh, Linda, Boye, Birgitte, Brosch, Katharina, Canales-Rodríguez, Erick, Cannon, Dara, Dannlowski, Udo, Demro, Caroline, Diaz-Zuluaga, Ana, Elvsåshagen, Torbjørn, Eyler, Lisa, Fortea, Lydia, Fullerton, Janice, Goltermann, Janik, Gotlib, Ian, Grotegerd, Dominik, Haarman, Bartholomeus, Hahn, Tim, Howells, Fleur, Jamalabadi, Hamidreza, Jansen, Andreas, Kircher, Tilo, Klahn, Anna, Kuplicki, Rayus, Lahud, Elijah, Landén, Mikael, Leehr, Elisabeth, Lopez-Jaramillo, Carlos, Mackey, Scott, Malt, Ulrik, Martyn, Fiona, Mazza, Elena, McDonald, Colm, McPhilemy, Genevieve, Meier, Sandra, Meinert, Susanne, Melloni, Elisa, Mitchell, Philip, Nabulsi, Leila, Nenadić, Igor, Nitsch, Robert, Opel, Nils, Ophoff, Roel, Ortuño, Maria, Overs, Bronwyn, Pineda-Zapata, Julian, Pomarol-Clotet, Edith, Radua, Joaquim, Repple, Jonathan, Roberts, Gloria, Rodriguez-Cano, Elena, Sacchet, Matthew, Salvador, Raymond, Savitz, Jonathan, Scheffler, Freda, Schofield, Peter, Schürmeyer, Navid, Shen, Chen, Sim, Kang, Sponheim, Scott, Stein, Dan, Stein, Frederike, Straube, Benjamin, Suo, Chao, Temmingh, Henk, Teutenberg, Lea, Thomas-Odenthal, Florian, Thomopoulos, Sophia, Urosevic, Snezana, Usemann, Paula, van Haren, Neeltje, Vargas, Cristian, Vieta, Eduard, Vilajosana, Enric, Vreeker, Annabel, Winter, Nils, Yatham, Lakshmi, Thompson, Paul, Andreassen, Ole, Ching, Christopher, and Hajek, Tomas

Subjects
MRI, bipolar disorder, body mass index, obesity, principal component analysis, psychiatry, Humans, Bipolar Disorder, Principal Component Analysis, Adult, Female, Male, Magnetic Resonance Imaging, Middle Aged, Obesity, Schizophrenia, Cerebral Cortex, Cluster Analysis, Young Adult, Brain
Abstract

Multivariate techniques better fit the anatomy of complex neuropsychiatric disorders which are characterized not by alterations in a single region, but rather by variations across distributed brain networks. Here, we used principal component analysis (PCA) to identify patterns of covariance across brain regions and relate them to clinical and demographic variables in a large generalizable dataset of individuals with bipolar disorders and controls. We then compared performance of PCA and clustering on identical sample to identify which methodology was better in capturing links between brain and clinical measures. Using data from the ENIGMA-BD working group, we investigated T1-weighted structural MRI data from 2436 participants with BD and healthy controls, and applied PCA to cortical thickness and surface area measures. We then studied the association of principal components with clinical and demographic variables using mixed regression models. We compared the PCA model with our prior clustering analyses of the same data and also tested it in a replication sample of 327 participants with BD or schizophrenia and healthy controls. The first principal component, which indexed a greater cortical thickness across all 68 cortical regions, was negatively associated with BD, BMI, antipsychotic medications, and age and was positively associated with Li treatment. PCA demonstrated superior goodness of fit to clustering when predicting diagnosis and BMI. Moreover, applying the PCA model to the replication sample yielded significant differences in cortical thickness between healthy controls and individuals with BD or schizophrenia. Cortical thickness in the same widespread regional network as determined by PCA was negatively associated with different clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. PCA outperformed clustering and provided an easy-to-use and interpret method to study multivariate associations between brain structure and system-level variables. PRACTITIONER POINTS: In this study of 2770 Individuals, we confirmed that cortical thickness in widespread regional networks as determined by principal component analysis (PCA) was negatively associated with relevant clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. Significant associations of many different system-level variables with the same brain network suggest a lack of one-to-one mapping of individual clinical and demographic factors to specific patterns of brain changes. PCA outperformed clustering analysis in the same data set when predicting group or BMI, providing a superior method for studying multivariate associations between brain structure and system-level variables.

Published
2024

5. White matter microstructure in obesity and bipolar disorders: an ENIGMA bipolar disorder working group study in 2186 individuals

Author

Dietze, Lorielle M. F., McWhinney, Sean R., Favre, Pauline, Abé, Christoph, Alexander, Nina, Barkhau, Carlotta, Benedetti, Francesco, Berk, Michael, Bøen, Erlend, Boye, Birgitte, Brosch, Katharina, Canales-Rodríguez, Erick J., Cannon, Dara M., Carruthers, Sean P., Corkum, Emily L. V., Dannlowski, Udo, Díaz-Zuluaga, Ana M., Dohm, Katharina, Elvsåshagen, Torbjørn, Flinkenflügel, Kira, Fortea, Lydia, Furlong, Lisa S., Goldstein, Benjamin I., Grotegerd, Dominik, Gruber, Marius, Haarman, Bartholomeus C. M., Howells, Fleur M., Jahanshad, Neda, Jamalabadi, Hamidreza, Jansen, Andreas, Karantonis, James A., Kennedy, Kody G., Kircher, Tilo T. J., Klahn, Anna Luisa, Kochunov, Peter, Kraus, Anna, Landén, Mikael, López-Jaramillo, Carlos, MacIntosh, Bradley J., Mazza, Elena, McDonald, Colm, McIntosh, Andrew M., Meinert, Hannah, Meinert, Susanne, Melloni, Elisa M. T., Mitchell, Philip B., Nenadić, Igor, Opel, Nils, Phillips, Mary, Piguet, Camille, Polosan, Mircea, Pomarol-Clotet, Edith, Pouchon, Arnaud, Radua, Joaquim, Roberts, Gloria, Ross, Alex J., Rossell, Susan L., Salvador, Raymond, Sim, Kang, Soares, Jair C., Zunta-Soares, Giovana B., Stein, Frederike, Straube, Benjamin, Suo, Chao, Teutenberg, Lea, Thomas-Odenthal, Florian, Thomopoulos, Sophia I., Usemann, Paula, Van Rheenen, Tamsyn E., Versace, Amelia, Vieta, Eduard, Vilajosana, Enric, Mwangi, Benson, Wen, Wei, Whalley, Heather C., Wu, Mon-Ju, Andreassen, Ole A., Ching, Christopher R. K., Thompson, Paul M., Houenou, Josselin, and Hajek, Tomas

Published
2024
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6. The interplay between polygenic score for tumor necrosis factor-α, brain structural connectivity, and processing speed in major depression

Author

Flinkenflügel, Kira, Gruber, Marius, Meinert, Susanne, Thiel, Katharina, Winter, Alexandra, Goltermann, Janik, Usemann, Paula, Brosch, Katharina, Stein, Frederike, Thomas-Odenthal, Florian, Wroblewski, Adrian, Pfarr, Julia-Katharina, David, Friederike S., Beins, Eva C., Grotegerd, Dominik, Hahn, Tim, Leehr, Elisabeth J., Dohm, Katharina, Bauer, Jochen, Forstner, Andreas J., Nöthen, Markus M., Jamalabadi, Hamidreza, Straube, Benjamin, Alexander, Nina, Jansen, Andreas, Witt, Stephanie H., Rietschel, Marcella, Nenadić, Igor, van den Heuvel, Martijn P., Kircher, Tilo, Repple, Jonathan, and Dannlowski, Udo

Published
2024
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7. Neural foundation of the diathesis-stress model: longitudinal gray matter volume changes in response to stressful life events in major depressive disorder and healthy controls

Author

Thomas-Odenthal, Florian, Ringwald, Kai, Teutenberg, Lea, Stein, Frederike, Alexander, Nina, Bonnekoh, Linda M., Brosch, Katharina, Dohm, Katharina, Flinkenflügel, Kira, Grotegerd, Dominik, Hahn, Tim, Jansen, Andreas, Leehr, Elisabeth J., Meinert, Susanne, Pfarr, Julia-Katharina, Renz, Harald, Schürmeyer, Navid, Stief, Thomas, Straube, Benjamin, Thiel, Katharina, Usemann, Paula, Winter, Alexandra, Krug, Axel, Nenadić, Igor, Dannlowski, Udo, and Kircher, Tilo

Published
2024
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8. Handedness in schizophrenia and affective disorders: a large-scale cross-disorder study

Author

Mundorf, Annakarina, Lischke, Alexander, Peterburs, Jutta, Alexander, Nina, Bonnekoh, Linda M., Brosch, Katharina, Flinkenflügel, Kira, Goltermann, Janik, Hahn, Tim, Jansen, Andreas, Meinert, Susanne, Nenadić, Igor, Schürmeyer, Navid Nico, Stein, Frederike, Straube, Benjamin, Thiel, Katharina, Teutenberg, Lea, Thomas-Odenthal, Florian, Usemann, Paula, Winter, Alexandra, Dannlowski, Udo, Kircher, Tilo, and Ocklenburg, Sebastian

Published
2024
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9. DenseNet and Support Vector Machine classifications of major depressive disorder using vertex-wise cortical features

Author

Belov, Vladimir, Erwin-Grabner, Tracy, Zeng, Ling-Li, Ching, Christopher R. K., Aleman, Andre, Amod, Alyssa R., Basgoze, Zeynep, Benedetti, Francesco, Besteher, Bianca, Brosch, Katharina, Bülow, Robin, Colle, Romain, Connolly, Colm G., Corruble, Emmanuelle, Couvy-Duchesne, Baptiste, Cullen, Kathryn, Dannlowski, Udo, Davey, Christopher G., Dols, Annemiek, Ernsting, Jan, Evans, Jennifer W., Fisch, Lukas, Fuentes-Claramonte, Paola, Gonul, Ali Saffet, Gotlib, Ian H., Grabe, Hans J., Groenewold, Nynke A., Grotegerd, Dominik, Hahn, Tim, Hamilton, J. Paul, Han, Laura K. M., Harrison, Ben J, Ho, Tiffany C., Jahanshad, Neda, Jamieson, Alec J., Karuk, Andriana, Kircher, Tilo, Klimes-Dougan, Bonnie, Koopowitz, Sheri-Michelle, Lancaster, Thomas, Leenings, Ramona, Li, Meng, Linden, David E. J., MacMaster, Frank P., Mehler, David M. A., Meinert, Susanne, Melloni, Elisa, Mueller, Bryon A., Mwangi, Benson, Nenadić, Igor, Ojha, Amar, Okamoto, Yasumasa, Oudega, Mardien L., Penninx, Brenda W. J. H., Poletti, Sara, Pomarol-Clotet, Edith, Portella, Maria J., Pozzi, Elena, Radua, Joaquim, Rodríguez-Cano, Elena, Sacchet, Matthew D., Salvador, Raymond, Schrantee, Anouk, Sim, Kang, Soares, Jair C., Solanes, Aleix, Stein, Dan J., Stein, Frederike, Stolicyn, Aleks, Thomopoulos, Sophia I., Toenders, Yara J., Uyar-Demir, Aslihan, Vieta, Eduard, Vives-Gilabert, Yolanda, Völzke, Henry, Walter, Martin, Whalley, Heather C., Whittle, Sarah, Winter, Nils, Wittfeld, Katharina, Wright, Margaret J., Wu, Mon-Ju, Yang, Tony T., Zarate, Carlos, Veltman, Dick J., Schmaal, Lianne, Thompson, Paul M., and Goya-Maldonado, Roberto

Subjects
Quantitative Biology - Quantitative Methods, Computer Science - Machine Learning, Quantitative Biology - Neurons and Cognition
Abstract

Major depressive disorder (MDD) is a complex psychiatric disorder that affects the lives of hundreds of millions of individuals around the globe. Even today, researchers debate if morphological alterations in the brain are linked to MDD, likely due to the heterogeneity of this disorder. The application of deep learning tools to neuroimaging data, capable of capturing complex non-linear patterns, has the potential to provide diagnostic and predictive biomarkers for MDD. However, previous attempts to demarcate MDD patients and healthy controls (HC) based on segmented cortical features via linear machine learning approaches have reported low accuracies. In this study, we used globally representative data from the ENIGMA-MDD working group containing an extensive sample of people with MDD (N=2,772) and HC (N=4,240), which allows a comprehensive analysis with generalizable results. Based on the hypothesis that integration of vertex-wise cortical features can improve classification performance, we evaluated the classification of a DenseNet and a Support Vector Machine (SVM), with the expectation that the former would outperform the latter. As we analyzed a multi-site sample, we additionally applied the ComBat harmonization tool to remove potential nuisance effects of site. We found that both classifiers exhibited close to chance performance (balanced accuracy DenseNet: 51%; SVM: 53%), when estimated on unseen sites. Slightly higher classification performance (balanced accuracy DenseNet: 58%; SVM: 55%) was found when the cross-validation folds contained subjects from all sites, indicating site effect. In conclusion, the integration of vertex-wise morphometric features and the use of the non-linear classifier did not lead to the differentiability between MDD and HC. Our results support the notion that MDD classification on this combination of features and classifiers is unfeasible.

Published
2023

10. Structural brain abnormalities and aggressive behaviour in schizophrenia: Mega-analysis of data from 2095 patients and 2861 healthy controls via the ENIGMA consortium

Author

Lamsma, Jelle, Raine, Adrian, Kia, Seyed M, Cahn, Wiepke, Arold, Dominic, Banaj, Nerisa, Barone, Annarita, Brosch, Katharina, Brouwer, Rachel, Brunetti, Arturo, Calhoun, Vince D, Chew, Qian H, Choi, Sunah, Chung, Young-Chul, Ciccarelli, Mariateresa, Cobia, Derin, Cocozza, Sirio, Dannlowski, Udo, Dazzan, Paola, de Bartolomeis, Andrea, Di Forti, Marta, Dumais, Alexandre, Edmond, Jesse T, Ehrlich, Stefan, Evermann, Ulrika, Flinkenflügel, Kira, Georgiadis, Foivos, Glahn, David C, Goltermann, Janik, Green, Melissa J, Grotegerd, Dominik, Guerrero-Pedraza, Amalia, Ha, Minji, Hong, Elliot L, Pol, Hilleke Hulshoff, Iasevoli, Felice, Kaiser, Stefan, Kaleda, Vasily, Karuk, Andriana, Kim, Minah, Kircher, Tilo, Kirschner, Matthias, Kochunov, Peter, Kwon, Jun Soo, Lebedeva, Irina, Lencer, Rebekka, Marques, Tiago R, Meinert, Susanne, Murray, Robin, Nenadić, Igor, Nguyen, Dana, Pearlson, Godfrey, Piras, Fabrizio, Pomarol-Clotet, Edith, Pontillo, Giuseppe, Potvin, Stéphane, Preda, Adrian, Quidé, Yann, Rodrigue, Amanda, Rootes-Murdy, Kelly, Salvador, Raymond, Skoch, Antonin, Sim, Kang, Spalletta, Gianfranco, Spaniel, Filip, Stein, Frederike, Thomas-Odenthal, Florian, Tikàsz, Andràs, Tomecek, David, Tomyshev, Alexander, Tranfa, Mario, Tsogt, Uyanga, Turner, Jessica A, van Erp, Theo GM, van Haren, Neeltje EM, van Os, Jim, Vecchio, Daniela, Wang, Lei, Wroblewski, Adrian, and Nickl-Jockschat, Thomas

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Schizophrenia, Brain Disorders, Neurosciences, Biomedical Imaging, Serious Mental Illness, Mental Health, Mental Illness, Mental health
Abstract

BACKGROUND: Schizophrenia is associated with an increased risk of aggressive behaviour, which may partly be explained by illness-related changes in brain structure. However, previous studies have been limited by group-level analyses, small and selective samples of inpatients and long time lags between exposure and outcome. METHODS: This cross-sectional study pooled data from 20 sites participating in the international ENIGMA-Schizophrenia Working Group. Sites acquired T1-weighted and diffusion-weighted magnetic resonance imaging scans in a total of 2095 patients with schizophrenia and 2861 healthy controls. Measures of grey matter volume and white matter microstructural integrity were extracted from the scans using harmonised protocols. For each measure, normative modelling was used to calculate how much patients deviated (in z-scores) from healthy controls at the individual level. Ordinal regression models were used to estimate the associations of these deviations with concurrent aggressive behaviour (as odds ratios [ORs] with 99% confidence intervals [CIs]). Mediation analyses were performed for positive symptoms (i.e., delusions, hallucinations and disorganised thinking), impulse control and illness insight. Aggression and potential mediators were assessed with the Positive and Negative Syndrome Scale, Scale for the Assessment of Positive Symptoms or Brief Psychiatric Rating Scale. RESULTS: Aggressive behaviour was significantly associated with reductions in total cortical volume (OR [99% CI] = 0.88 [0.78, 0.98], p = .003) and global white matter integrity (OR [99% CI] = 0.72 [0.59, 0.88], p = 3.50 × 10-5) and additional reductions in dorsolateral prefrontal cortex volume (OR [99% CI] = 0.85 [0.74, 0.97], p =.002), inferior parietal lobule volume (OR [99% CI] = 0.76 [0.66, 0.87], p = 2.20 × 10-7) and internal capsule integrity (OR [99% CI] = 0.76 [0.63, 0.92], p = 2.90 × 10-4). Except for inferior parietal lobule volume, these associations were largely mediated by increased severity of positive symptoms and reduced impulse control. CONCLUSIONS: This study provides evidence that the co-occurrence of positive symptoms, poor impulse control and aggressive behaviour in schizophrenia has a neurobiological basis, which may inform the development of therapeutic interventions.

Published
2024

11. Beyond the Global Brain Differences: Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers.

Author

Boen, Rune, Kaufmann, Tobias, van der Meer, Dennis, Frei, Oleksandr, Agartz, Ingrid, Ames, David, Andersson, Micael, Armstrong, Nicola, Artiges, Eric, Atkins, Joshua, Bauer, Jochen, Benedetti, Francesco, Boomsma, Dorret, Brodaty, Henry, Brosch, Katharina, Buckner, Randy, Cairns, Murray, Calhoun, Vince, Caspers, Svenja, Cichon, Sven, Corvin, Aiden, Crespo-Facorro, Benedicto, Dannlowski, Udo, David, Friederike, de Geus, Eco, de Zubicaray, Greig, Desrivières, Sylvane, Doherty, Joanne, Donohoe, Gary, Ehrlich, Stefan, Eising, Else, Espeseth, Thomas, Fisher, Simon, Forstner, Andreas, Fortaner-Uyà, Lidia, Frouin, Vincent, Fukunaga, Masaki, Ge, Tian, Glahn, David, Goltermann, Janik, Grabe, Hans, Green, Melissa, Groenewold, Nynke, Grotegerd, Dominik, Grøntvedt, Gøril, Hahn, Tim, Hashimoto, Ryota, Hehir-Kwa, Jayne, Henskens, Frans, Holmes, Avram, Håberg, Asta, Haavik, Jan, Jacquemont, Sebastien, Jansen, Andreas, Jockwitz, Christiane, Jönsson, Erik, Kikuchi, Masataka, Kircher, Tilo, Kumar, Kuldeep, Le Hellard, Stephanie, Leu, Costin, Linden, David, Liu, Jingyu, Loughnan, Robert, Mather, Karen, McMahon, Katie, McRae, Allan, Medland, Sarah, Meinert, Susanne, Moreau, Clara, Morris, Derek, Mowry, Bryan, Mühleisen, Thomas, Nenadić, Igor, Nöthen, Markus, Nyberg, Lars, Ophoff, Roel, Owen, Michael, Pantelis, Christos, Paolini, Marco, Paus, Tomas, Pausova, Zdenka, Persson, Karin, Quidé, Yann, Marques, Tiago, Sachdev, Perminder, Sando, Sigrid, Schall, Ulrich, Scott, Rodney, Selbæk, Geir, Shumskaya, Elena, Silva, Ana, Sisodiya, Sanjay, Stein, Frederike, Stein, Dan, Straube, Benjamin, Streit, Fabian, Strike, Lachlan, Teumer, Alexander, and Teutenberg, Lea

Subjects
15q11.2 BP1-BP2, 1q21.1 distal, Brain structure, Copy number variants, Intraindividual variability, Magnetic resonance imaging, Humans, Chromosome Deletion, Brain, Magnetic Resonance Imaging, Abnormalities, Multiple, Chromosomes, Human, Pair 15, DNA Copy Number Variations
Abstract

BACKGROUND: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure. METHODS: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individuals regional difference and global difference, were used to test for regional differences that diverge from the global difference. RESULTS: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness. CONCLUSIONS: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.

Published
2024

13. Factor analysis of lifetime psychopathology and its brain morphometric and genetic correlates in a transdiagnostic sample

Author

Krug, Axel, Stein, Frederike, David, Friederike S., Schmitt, Simon, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G., Meller, Tina, Thomas-Odenthal, Florian, Meinert, Susanne, Thiel, Katharina, Winter, Alexandra, Waltemate, Lena, Lemke, Hannah, Grotegerd, Dominik, Opel, Nils, Repple, Jonathan, Hahn, Tim, Streit, Fabian, Witt, Stephanie H., Rietschel, Marcella, Andlauer, Till F. M., Nöthen, Markus M., Philipsen, Alexandra, Nenadić, Igor, Dannlowski, Udo, Kircher, Tilo, and Forstner, Andreas J.

Published
2024
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14. White and gray matter alterations in bipolar I and bipolar II disorder subtypes compared with healthy controls – exploring associations with disease course and polygenic risk

Author

Thiel, Katharina, Lemke, Hannah, Winter, Alexandra, Flinkenflügel, Kira, Waltemate, Lena, Bonnekoh, Linda, Grotegerd, Dominik, Dohm, Katharina, Hahn, Tim, Förster, Katharina, Kanske, Philipp, Repple, Jonathan, Opel, Nils, Redlich, Ronny, David, Friederike, Forstner, Andreas J., Stein, Frederike, Brosch, Katharina, Thomas-Odenthal, Florian, Usemann, Paula, Teutenberg, Lea, Straube, Benjamin, Alexander, Nina, Jamalabadi, Hamidreza, Jansen, Andreas, Witt, Stephanie H., Andlauer, Till F. M., Pfennig, Andrea, Bauer, Michael, Nenadić, Igor, Kircher, Tilo, Meinert, Susanne, and Dannlowski, Udo

Published
2024
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15. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium.

Author

Schijven, Dick, Postema, Merel C, Fukunaga, Masaki, Matsumoto, Junya, Miura, Kenichiro, de Zwarte, Sonja MC, van Haren, Neeltje EM, Cahn, Wiepke, Hulshoff Pol, Hilleke E, Kahn, René S, Ayesa-Arriola, Rosa, Ortiz-García de la Foz, Víctor, Tordesillas-Gutierrez, Diana, Vázquez-Bourgon, Javier, Crespo-Facorro, Benedicto, Alnæs, Dag, Dahl, Andreas, Westlye, Lars T, Agartz, Ingrid, Andreassen, Ole A, Jönsson, Erik G, Kochunov, Peter, Bruggemann, Jason M, Catts, Stanley V, Michie, Patricia T, Mowry, Bryan J, Quidé, Yann, Rasser, Paul E, Schall, Ulrich, Scott, Rodney J, Carr, Vaughan J, Green, Melissa J, Henskens, Frans A, Loughland, Carmel M, Pantelis, Christos, Weickert, Cynthia Shannon, Weickert, Thomas W, de Haan, Lieuwe, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G, Stein, Frederike, Jansen, Andreas, Kircher, Tilo TJ, Nenadić, Igor, Krämer, Bernd, Gruber, Oliver, Satterthwaite, Theodore D, Bustillo, Juan, Mathalon, Daniel H, Preda, Adrian, Calhoun, Vince D, Ford, Judith M, Potkin, Steven G, Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan, Fuentes-Claramonte, Paola, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond, Sarró, Salvador, Pomarol-Clotet, Edith, Ciullo, Valentina, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W, Voineskos, Aristotle N, Sim, Kang, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M, Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André, Borgwardt, Stefan, McIntosh, Andrew M, Whalley, Heather C, Lawrie, Stephen M, du Plessis, Stefan, Luckhoff, Hilmar K, Scheffler, Freda, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo, Edmond, Jesse T, Rootes-Murdy, Kelly, Stephen, Julia M, Mayer, Andrew R, and Antonucci, Linda A

Subjects
Brain, Cerebral Cortex, Humans, Magnetic Resonance Imaging, Case-Control Studies, Schizophrenia, Female, Male, Functional Laterality, asymmetry, brain imaging, cortical, subcortical, Clinical Research, Mental Health, Neurosciences, Brain Disorders, Mental health
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

16. The neural signature of psychomotor disturbance in depression

Author

Wüthrich, Florian, Lefebvre, Stephanie, Mittal, Vijay A., Shankman, Stewart A., Alexander, Nina, Brosch, Katharina, Flinkenflügel, Kira, Goltermann, Janik, Grotegerd, Dominik, Hahn, Tim, Jamalabadi, Hamidreza, Jansen, Andreas, Leehr, Elisabeth J., Meinert, Susanne, Nenadić, Igor, Nitsch, Robert, Stein, Frederike, Straube, Benjamin, Teutenberg, Lea, Thiel, Katharina, Thomas-Odenthal, Florian, Usemann, Paula, Winter, Alexandra, Dannlowski, Udo, Kircher, Tilo, and Walther, Sebastian

Published
2024
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17. Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants.

Author

Fullerton, Janice, Goikolea, Jose, Goltermann, Janik, Grotegerd, Dominik, Haarman, Bartholomeus, Hahn, Tim, Howells, Fleur, Ingvar, Martin, Jahanshad, Neda, Kircher, Tilo, Krug, Axel, Kuplicki, Rayus, Landén, Mikael, Lemke, Hannah, Liberg, Benny, Lopez-Jaramillo, Carlos, Malt, Ulrik, Martyn, Fiona, Mazza, Elena, McDonald, Colm, McPhilemy, Genevieve, Meier, Sandra, Meinert, Susanne, Meller, Tina, Melloni, Elisa, Mitchell, Philip, Nabulsi, Leila, Nenadic, Igor, Opel, Nils, Ophoff, Roel, Overs, Bronwyn, Pfarr, Julia-Katharina, Pineda-Zapata, Julian, Pomarol-Clotet, Edith, Raduà, Joaquim, Repple, Jonathan, Richter, Maike, Ringwald, Kai, Roberts, Gloria, Ross, Alex, Salvador, Raymond, Savitz, Jonathan, Schmitt, Simon, Schofield, Peter, Sim, Kang, Stein, Dan, Stein, Frederike, Temmingh, Henk, Thiel, Katharina, Thomopoulos, Sophia, van Haren, Neeltje, Vargas, Cristian, Vieta, Eduard, Vreeker, Annabel, Waltemate, Lena, Yatham, Lakshmi, Ching, Christopher, Andreassen, Ole, Thompson, Paul, Hajek, Tomas, McWhinney, Sean, Abé, Christoph, Alda, Martin, Benedetti, Francesco, Bøen, Erlend, Del Mar Bonnin, Caterina, Borgers, Tiana, Brosch, Katharina, Canales-Rodríguez, Erick, Cannon, Dara, Dannlowski, Udo, Diaz-Zuluaga, Ana, Dietze, Lorielle, Elvsåshagen, Torbjørn, and Eyler, Lisa

Subjects
Body mass index, antipsychotics, bipolar disorders, cortical thickness, heterogeneity, lithium, obesity, surface area
Abstract

BACKGROUND: Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact. METHODS: We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations. RESULTS: BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI. CONCLUSIONS: We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.

Published
2023

18. Obesity and brain structure in schizophrenia – ENIGMA study in 3021 individuals

Author

McWhinney, Sean R, Brosch, Katharina, Calhoun, Vince D, Crespo-Facorro, Benedicto, Crossley, Nicolas A, Dannlowski, Udo, Dickie, Erin, Dietze, Lorielle MF, Donohoe, Gary, Du Plessis, Stefan, Ehrlich, Stefan, Emsley, Robin, Furstova, Petra, Glahn, David C, Gonzalez- Valderrama, Alfonso, Grotegerd, Dominik, Holleran, Laurena, Kircher, Tilo TJ, Knytl, Pavel, Kolenic, Marian, Lencer, Rebekka, Nenadić, Igor, Opel, Nils, Pfarr, Julia-Katharina, Rodrigue, Amanda L, Rootes-Murdy, Kelly, Ross, Alex J, Sim, Kang, Škoch, Antonín, Spaniel, Filip, Stein, Frederike, Švancer, Patrik, Tordesillas-Gutiérrez, Diana, Undurraga, Juan, Vázquez-Bourgon, Javier, Voineskos, Aristotle, Walton, Esther, Weickert, Thomas W, Weickert, Cynthia Shannon, Thompson, Paul M, van Erp, Theo GM, Turner, Jessica A, and Hajek, Tomas

Subjects
Biomedical Imaging, Obesity, Neurosciences, Serious Mental Illness, Mental Health, Schizophrenia, Nutrition, Clinical Research, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Mental health, Humans, Depressive Disorder, Major, Brain, Magnetic Resonance Imaging, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Schizophrenia is frequently associated with obesity, which is linked with neurostructural alterations. Yet, we do not understand how the brain correlates of obesity map onto the brain changes in schizophrenia. We obtained MRI-derived brain cortical and subcortical measures and body mass index (BMI) from 1260 individuals with schizophrenia and 1761 controls from 12 independent research sites within the ENIGMA-Schizophrenia Working Group. We jointly modeled the statistical effects of schizophrenia and BMI using mixed effects. BMI was additively associated with structure of many of the same brain regions as schizophrenia, but the cortical and subcortical alterations in schizophrenia were more widespread and pronounced. Both BMI and schizophrenia were primarily associated with changes in cortical thickness, with fewer correlates in surface area. While, BMI was negatively associated with cortical thickness, the significant associations between BMI and surface area or subcortical volumes were positive. Lastly, the brain correlates of obesity were replicated among large studies and closely resembled neurostructural changes in major depressive disorders. We confirmed widespread associations between BMI and brain structure in individuals with schizophrenia. People with both obesity and schizophrenia showed more pronounced brain alterations than people with only one of these conditions. Obesity appears to be a relevant factor which could account for heterogeneity of brain imaging findings and for differences in brain imaging outcomes among people with schizophrenia.

Published
2022

19. Associations between white matter microstructure and cognitive decline in major depressive disorder versus controls in Germany: a prospective case-control cohort study

Author

Thiel, Katharina, Winter, Alexandra, Thomas-Odenthal, Florian, Usemann, Paula, Teutenberg, Lea, Pfarr, Julia-Katharina, Flinkenflügel, Kira, Meinert, Susanne, Hirtsiefer, Christopher, Grotegerd, Dominik, Gruber, Marius, Goltermann, Janik, Winter, Nils R, Stein, Frederike, Brosch, Katharina, Leehr, Elisabeth J, Böhnlein, Joscha, Dohm, Katharina, Bauer, Jochen, Redlich, Ronny, Hahn, Tim, Repple, Jonathan, Opel, Nils, Nitsch, Robert, Jamalabadi, Hamidreza, Straube, Benjamin, Alexander, Nina, Jansen, Andreas, Nenadić, Igor, van den Heuvel, Martijn P, Kircher, Tilo, and Dannlowski, Udo

Published
2024
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20. Shared and distinct structural brain networks related to childhood maltreatment and social support: connectome-based predictive modeling

Author

Winter, Alexandra, Gruber, Marius, Thiel, Katharina, Flinkenflügel, Kira, Meinert, Susanne, Goltermann, Janik, Winter, Nils R., Borgers, Tiana, Stein, Frederike, Jansen, Andreas, Brosch, Katharina, Wroblewski, Adrian, Thomas-Odenthal, Florian, Usemann, Paula, Straube, Benjamin, Alexander, Nina, Jamalabadi, Hamidreza, Nenadić, Igor, Bonnekoh, Linda M., Dohm, Katharina, Leehr, Elisabeth J., Opel, Nils, Grotegerd, Dominik, Hahn, Tim, van den Heuvel, Martijn P., Kircher, Tilo, Repple, Jonathan, and Dannlowski, Udo

Published
2023
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21. Neurobiological correlates of comorbidity in disorders across the affective disorders-psychosis spectrum

Author

Sindermann, Lisa, Dannlowski, Udo, Leehr, Elisabeth J., Hahn, Tim, Grotegerd, Dominik, Meinert, Susanne, Lemke, Hannah, Winter, Alexandra, Thiel, Katharina, Flinkenflügel, Kira, Kircher, Tilo, Nenadić, Igor, Straube, Benjamin, Alexander, Nina, Jamalabadi, Hamidreza, Jansen, Andreas, Stein, Frederike, Brosch, Katharina, Thomas-Odenthal, Florian, Usemann, Paula, Teutenberg, Lea, Krug, Axel, Andlauer, Till F.M., David, Friederike S., Federmann, Lydia M., Beins, Eva, Nöthen, Markus M., and Forstner, Andreas J.

Published
2024
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22. Diagnosis of bipolar disorders and body mass index predict clustering based on similarities in cortical thickness-ENIGMA study in 2436 individuals.

Author

McWhinney, Sean, Abé, Christoph, Alda, Martin, Benedetti, Francesco, Bøen, Erlend, Del Mar Bonnin, Caterina, Borgers, Tiana, Brosch, Katharina, Canales-Rodríguez, Erick, Cannon, Dara, Dannlowski, Udo, Diaz-Zuluaga, Ana, Dietze, Lorielle, Elvsåshagen, Torbjørn, Fullerton, Janice, Goikolea, Jose, Goltermann, Janik, Grotegerd, Dominik, Haarman, Bartholomeus, Hahn, Tim, Howells, Fleur, Ingvar, Martin, Kircher, Tilo, Krug, Axel, Kuplicki, Rayus, Landén, Mikael, Lemke, Hannah, Liberg, Benny, Lopez-Jaramillo, Carlos, Malt, Ulrik, Martyn, Fiona, Mazza, Elena, McDonald, Colm, McPhilemy, Genevieve, Meier, Sandra, Meinert, Susanne, Meller, Tina, Melloni, Elisa, Mitchell, Philip, Nabulsi, Leila, Nenadic, Igor, Opel, Nils, Overs, Bronwyn, Pfarr, Julia-Katharina, Pineda-Zapata, Julian, Pomarol-Clotet, Edith, Raduà, Joaquim, Repple, Jonathan, Richter, Maike, Ringwald, Kai, Roberts, Gloria, Ross, Alex, Salvador, Raymond, Savitz, Jonathan, Schmitt, Simon, Schofield, Peter, Sim, Kang, Stein, Dan, Stein, Frederike, Temmingh, Henk, Thiel, Katharina, Thomopoulos, Sophia, van Haren, Neeltje, Van Gestel, Holly, Vargas, Cristian, Vieta, Eduard, Vreeker, Annabel, Waltemate, Lena, Yatham, Lakshmi, Ching, Christopher, Andreassen, Ole, Thompson, Paul, Hajek, Tomas, Ophoff, Roel, and Eyler, Lisa

Subjects
bipolar disorders, body mass index, cortical thickness, heterogeneity, obesity, surface area, Bipolar Disorder, Body Mass Index, Cluster Analysis, Humans, Magnetic Resonance Imaging, Obesity, Temporal Lobe
Abstract

AIMS: Rates of obesity have reached epidemic proportions, especially among people with psychiatric disorders. While the effects of obesity on the brain are of major interest in medicine, they remain markedly under-researched in psychiatry. METHODS: We obtained body mass index (BMI) and magnetic resonance imaging-derived regional cortical thickness, surface area from 836 bipolar disorders (BD) and 1600 control individuals from 14 sites within the ENIGMA-BD Working Group. We identified regionally specific profiles of cortical thickness using K-means clustering and studied clinical characteristics associated with individual cortical profiles. RESULTS: We detected two clusters based on similarities among participants in cortical thickness. The lower thickness cluster (46.8% of the sample) showed thinner cortex, especially in the frontal and temporal lobes and was associated with diagnosis of BD, higher BMI, and older age. BD individuals in the low thickness cluster were more likely to have the diagnosis of bipolar disorder I and less likely to be treated with lithium. In contrast, clustering based on similarities in the cortical surface area was unrelated to BD or BMI and only tracked age and sex. CONCLUSIONS: We provide evidence that both BD and obesity are associated with similar alterations in cortical thickness, but not surface area. The fact that obesity increased the chance of having low cortical thickness could explain differences in cortical measures among people with BD. The thinner cortex in individuals with higher BMI, which was additive and similar to the BD-associated alterations, may suggest that treating obesity could lower the extent of cortical thinning in BD.

Published
2022

24. Exploring the complex interrelation between depressive symptoms, risk, and protective factors: A comprehensive network approach

Author

Iovoli, Flavio, Hall, Mila, Nenadic, Igor, Straube, Benjamin, Alexander, Nina, Jamalabadi, Hamidreza, Jansen, Andreas, Stein, Frederike, Brosch, Katharina, Thomas-Odenthal, Florian, Usemann, Paula, Teutenberg, Lea, Wroblewski, Adrian, Pfarr, Julia, Thiel, Katharina, Flinkenflügel, Kira, Meinert, Susanne, Grotegerd, Dominik, Hahn, Tim, Goltermann, Janik, Gruber, Marius, Repple, Jonathan, Enneking, Verena, Winter, Alexandra, Dannlowski, Udo, Kircher, Tilo, and Rubel, Julian A.

Published
2024
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26. Altered brain dynamic in major depressive disorder: state and trait features

Author

Javaheripour, Nooshin, Colic, Lejla, Opel, Nils, Li, Meng, Maleki Balajoo, Somayeh, Chand, Tara, Van der Meer, Johan, Krylova, Marina, Izyurov, Igor, Meller, Tina, Goltermann, Janik, Winter, Nils R., Meinert, Susanne, Grotegerd, Dominik, Jansen, Andreas, Alexander, Nina, Usemann, Paula, Thomas-Odenthal, Florian, Evermann, Ulrika, Wroblewski, Adrian, Brosch, Katharina, Stein, Frederike, Hahn, Tim, Straube, Benjamin, Krug, Axel, Nenadić, Igor, Kircher, Tilo, Croy, Ilona, Dannlowski, Udo, Wagner, Gerd, and Walter, Martin

Published
2023
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27. Depression, cardiometabolic disease, and their co-occurrence after childhood maltreatment: an individual participant data meta-analysis including over 200,000 participants

Author

Souama, Camille, Lamers, Femke, Milaneschi, Yuri, Vinkers, Christiaan H., Defina, Serena, Garvert, Linda, Stein, Frederike, Woofenden, Tom, Brosch, Katharina, Dannlowski, Udo, Galenkamp, Henrike, de Graaf, Ron, Jaddoe, Vincent W. V., Lok, Anja, van Rijn, Bas B., Völzke, Henry, Cecil, Charlotte A. M., Felix, Janine F., Grabe, Hans J., Kircher, Tilo, Lekadir, Karim, Have, Margreet ten, Walton, Esther, and Penninx, Brenda W. J. H.

Published
2023
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28. A Network Control Theory Approach to Longitudinal Symptom Dynamics in Major Depressive Disorder

Author

Hahn, Tim, Jamalabadi, Hamidreza, Emden, Daniel, Goltermann, Janik, Ernsting, Jan, Winter, Nils R., Fisch, Lukas, Leenings, Ramona, Sarink, Kelvin, Holstein, Vincent, Gruber, Marius, Grotegerd, Dominik, Meinert, Susanne, Dohm, Katharina, Leehr, Elisabeth J., Richter, Maike, Sindermann, Lisa, Enneking, Verena, Lemke, Hannah, Witt, Stephanie, Rietschel, Marcella, Brosch, Katharina, Pfarr, Julia-Katharina, Meller, Tina, Ringwald, Kai Gustav, Schmitt, Simon, Stein, Frederike, Nenadic, Igor, Kircher, Tilo, Müller-Myhsok, Bertram, Andlauer, Till F. M., Repple, Jonathan, Dannlowski, Udo, and Opel, Nils

Subjects
Electrical Engineering and Systems Science - Systems and Control, Quantitative Biology - Neurons and Cognition
Abstract

Background: The evolution of symptoms over time is at the heart of understanding and treating mental disorders. However, a principled, quantitative framework explaining symptom dynamics remains elusive. Here, we propose a Network Control Theory of Psychopathology allowing us to formally derive a theoretical control energy which we hypothesize quantifies resistance to future symptom improvement in Major Depressive Disorder (MDD). We test this hypothesis and investigate the relation to genetic and environmental risk as well as resilience. Methods: We modelled longitudinal symptom-network dynamics derived from N=2,059 Beck Depression Inventory measurements acquired over a median of 134 days in a sample of N=109 patients suffering from MDD. We quantified the theoretical energy required for each patient and time-point to reach a symptom-free state given individual symptom-network topology (E 0 ) and 1) tested if E 0 predicts future symptom improvement and 2) whether this relationship is moderated by Polygenic Risk Scores (PRS) of mental disorders, childhood maltreatment experience, and self-reported resilience. Outcomes: We show that E 0 indeed predicts symptom reduction at the next measurement and reveal that this coupling between E 0 and future symptom change increases with higher genetic risk and childhood maltreatment while it decreases with resilience. Interpretation: Our study provides a mechanistic framework capable of predicting future symptom improvement based on individual symptom-network topology and clarifies the role of genetic and environmental risk as well as resilience. Our control-theoretic framework makes testable, quantitative predictions for individual therapeutic response and provides a starting-point for the theory-driven design of personalized interventions. Funding: German Research Foundation and Interdisciplinary Centre for Clinical Research, M\"unster, Comment: 21 pages, 2 figures

Published
2021

29. Brain Structural Network Connectivity of Formal Thought Disorder Dimensions in Affective and Psychotic Disorders

Author

Stein, Frederike, Gruber, Marius, Mauritz, Marco, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G., Thomas-Odenthal, Florian, Wroblewski, Adrian, Evermann, Ulrika, Steinsträter, Olaf, Grumbach, Pascal, Thiel, Katharina, Winter, Alexandra, Bonnekoh, Linda M., Flinkenflügel, Kira, Goltermann, Janik, Meinert, Susanne, Grotegerd, Dominik, Bauer, Jochen, Opel, Nils, Hahn, Tim, Leehr, Elisabeth J., Jansen, Andreas, de Lange, Siemon C., van den Heuvel, Martijn P., Nenadić, Igor, Krug, Axel, Dannlowski, Udo, Repple, Jonathan, and Kircher, Tilo

Published
2024
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30. Characterisation of age and polarity at onset in bipolar disorder.

Author

Kalman, Janos L, Olde Loohuis, Loes M, Vreeker, Annabel, McQuillin, Andrew, Stahl, Eli A, Ruderfer, Douglas, Grigoroiu-Serbanescu, Maria, Panagiotaropoulou, Georgia, Ripke, Stephan, Bigdeli, Tim B, Stein, Frederike, Meller, Tina, Meinert, Susanne, Pelin, Helena, Streit, Fabian, Papiol, Sergi, Adams, Mark J, Adolfsson, Rolf, Adorjan, Kristina, Agartz, Ingrid, Aminoff, Sofie R, Anderson-Schmidt, Heike, Andreassen, Ole A, Ardau, Raffaella, Aubry, Jean-Michel, Balaban, Ceylan, Bass, Nicholas, Baune, Bernhard T, Bellivier, Frank, Benabarre, Antoni, Bengesser, Susanne, Berrettini, Wade H, Boks, Marco P, Bromet, Evelyn J, Brosch, Katharina, Budde, Monika, Byerley, William, Cervantes, Pablo, Chillotti, Catina, Cichon, Sven, Clark, Scott R, Comes, Ashley L, Corvin, Aiden, Coryell, William, Craddock, Nick, Craig, David W, Croarkin, Paul E, Cruceanu, Cristiana, Czerski, Piotr M, Dalkner, Nina, Dannlowski, Udo, Degenhardt, Franziska, Del Zompo, Maria, DePaulo, J Raymond, Djurovic, Srdjan, Edenberg, Howard J, Eissa, Mariam Al, Elvsåshagen, Torbjørn, Etain, Bruno, Fanous, Ayman H, Fellendorf, Frederike, Fiorentino, Alessia, Forstner, Andreas J, Frye, Mark A, Fullerton, Janice M, Gade, Katrin, Garnham, Julie, Gershon, Elliot, Gill, Michael, Goes, Fernando S, Gordon-Smith, Katherine, Grof, Paul, Guzman-Parra, Jose, Hahn, Tim, Hasler, Roland, Heilbronner, Maria, Heilbronner, Urs, Jamain, Stephane, Jimenez, Esther, Jones, Ian, Jones, Lisa, Jonsson, Lina, Kahn, Rene S, Kelsoe, John R, Kennedy, James L, Kircher, Tilo, Kirov, George, Kittel-Schneider, Sarah, Klöhn-Saghatolislam, Farah, Knowles, James A, Kranz, Thorsten M, Lagerberg, Trine Vik, Landen, Mikael, Lawson, William B, Leboyer, Marion, Li, Qingqin S, Maj, Mario, Malaspina, Dolores, Manchia, Mirko, and Mayoral, Fermin

Subjects
Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics, Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Humans, Bipolar Disorder, Depressive Disorder, Major, Age of Onset, Multifactorial Inheritance, Genome-Wide Association Study, Autism Spectrum Disorder, Bipolar disorder, GWAS, age at onset, polarity at onset, polygenic score, Genetics, Mental Health, Prevention, Brain Disorders, Serious Mental Illness, 2.1 Biological and endogenous factors, Aetiology, Mental health, Good Health and Well Being, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundStudying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = -0.34 years, s.e. = 0.08), major depression (β = -0.34 years, s.e. = 0.08), schizophrenia (β = -0.39 years, s.e. = 0.08), and educational attainment (β = -0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Published
2021

31. Association between body mass index and subcortical brain volumes in bipolar disorders–ENIGMA study in 2735 individuals

Author

McWhinney, Sean R, Abé, Christoph, Alda, Martin, Benedetti, Francesco, Bøen, Erlend, del Mar Bonnin, Caterina, Borgers, Tiana, Brosch, Katharina, Canales-Rodríguez, Erick J, Cannon, Dara M, Dannlowski, Udo, Díaz-Zuluaga, Ana M, Elvsåshagen, Torbjørn, Eyler, Lisa T, Fullerton, Janice M, Goikolea, Jose M, Goltermann, Janik, Grotegerd, Dominik, Haarman, Bartholomeus CM, Hahn, Tim, Howells, Fleur M, Ingvar, Martin, Kircher, Tilo TJ, Krug, Axel, Kuplicki, Rayus T, Landén, Mikael, Lemke, Hannah, Liberg, Benny, Lopez-Jaramillo, Carlos, Malt, Ulrik F, Martyn, Fiona M, Mazza, Elena, McDonald, Colm, McPhilemy, Genevieve, Meier, Sandra, Meinert, Susanne, Meller, Tina, Melloni, Elisa MT, Mitchell, Philip B, Nabulsi, Leila, Nenadic, Igor, Opel, Nils, Ophoff, Roel A, Overs, Bronwyn J, Pfarr, Julia-Katharina, Pineda-Zapata, Julian A, Pomarol-Clotet, Edith, Raduà, Joaquim, Repple, Jonathan, Richter, Maike, Ringwald, Kai G, Roberts, Gloria, Salvador, Raymond, Savitz, Jonathan, Schmitt, Simon, Schofield, Peter R, Sim, Kang, Stein, Dan J, Stein, Frederike, Temmingh, Henk S, Thiel, Katharina, van Haren, Neeltje EM, Gestel, Holly Van, Vargas, Cristian, Vieta, Eduard, Vreeker, Annabel, Waltemate, Lena, Yatham, Lakshmi N, Ching, Christopher RK, Andreassen, Ole, Thompson, Paul M, and Hajek, Tomas

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Mental Health, Biomedical Imaging, Nutrition, Brain Disorders, Obesity, Neurosciences, Clinical Research, Prevention, Mental health, Amygdala, Bipolar Disorder, Body Mass Index, Brain, Humans, Magnetic Resonance Imaging, ENIGMA Bipolar Disorders Working Group, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles  and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediated by BMI (Z = 2.73, p = 0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.

Published
2021

33. Data-driven multivariate identification of gyrification patterns in a transdiagnostic patient cohort: A cluster analysis approach

Author

Pfarr, Julia-Katharina, Meller, Tina, Brosch, Katharina, Stein, Frederike, Thomas-Odenthal, Florian, Evermann, Ulrika, Wroblewski, Adrian, Ringwald, Kai G., Hahn, Tim, Meinert, Susanne, Winter, Alexandra, Thiel, Katharina, Flinkenflügel, Kira, Jansen, Andreas, Krug, Axel, Dannlowski, Udo, Kircher, Tilo, Gaser, Christian, and Nenadić, Igor

Published
2023
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34. Negative Stressful Life Events and Social Support Are Associated With White Matter Integrity in Depressed Patients and Healthy Control Participants: A Diffusion Tensor Imaging Study

Author

Flinkenflügel, Kira, Meinert, Susanne, Thiel, Katharina, Winter, Alexandra, Goltermann, Janik, Strathausen, Lea, Brosch, Katharina, Stein, Frederike, Thomas-Odenthal, Florian, Evermann, Ulrika, Wroblewski, Adrian, Usemann, Paula, Pfarr, Julia-Katharina, Grotegerd, Dominik, Hahn, Tim, Leehr, Elisabeth J., Dohm, Katharina, Bauer, Jochen, Jamalabadi, Hamidreza, Straube, Benjamin, Alexander, Nina, Jansen, Andreas, Nenadić, Igor, Krug, Axel, Kircher, Tilo, and Dannlowski, Udo

Published
2023
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35. Correction: Obesity and brain structure in schizophrenia – ENIGMA study in 3021 individuals

Author

McWhinney, Sean R., Brosch, Katharina, Calhoun, Vince D., Crespo-Facorro, Benedicto, Crossley, Nicolas A., Dannlowski, Udo, Dickie, Erin, Dietze, Lorielle M. F., Donohoe, Gary, Du Plessis, Stefan, Ehrlich, Stefan, Emsley, Robin, Furstova, Petra, Glahn, David C., Gonzalez- Valderrama, Alfonso, Grotegerd, Dominik, Holleran, Laurena, Kircher, Tilo T. J., Knytl, Pavel, Kolenic, Marian, Lencer, Rebekka, Nenadić, Igor, Opel, Nils, Pfarr, Julia-Katharina, Rodrigue, Amanda L., Rootes-Murdy, Kelly, Ross, Alex J., Sim, Kang, Škoch, Antonín, Spaniel, Filip, Stein, Frederike, Švancer, Patrik, Tordesillas-Gutiérrez, Diana, Undurraga, Juan, Vázquez-Bourgon, Javier, Voineskos, Aristotle, Walton, Esther, Weickert, Thomas W., Weickert, Cynthia Shannon, Thompson, Paul M., van Erp, Theo G. M., Turner, Jessica A., and Hajek, Tomas

Published
2024
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36. Investigating the phenotypic and genetic associations between personality traits and suicidal behavior across major mental health diagnoses

Author

Kalman, Janos L., Yoshida, Tomoya, Andlauer, Till F. M., Schulte, Eva C., Adorjan, Kristina, Alda, Martin, Ardau, Raffaela, Aubry, Jean-Michel, Brosch, Katharina, Budde, Monika, Chillotti, Caterina, Czerski, Piotr M., DePaulo, Raymond J., Forstner, Andreas, Goes, Fernando S., Grigoroiu-Serbanescu, Maria, Grof, Paul, Grotegerd, Dominik, Hahn, Tim, Heilbronner, Maria, Hasler, Roland, Heilbronner, Urs, Heilmann-Heimbach, Stefanie, Kapelski, Pawel, Kato, Tadafumi, Kohshour, Mojtaba Oraki, Meinert, Susanne, Meller, Tina, Nenadić, Igor, Nöthen, Markus M., Novak, Tomas, Opel, Nils, Pawlak, Joanna, Pfarr, Julia-Katharina, Potash, James B., Reich-Erkelenz, Daniela, Repple, Jonathan, Richard-Lepouriel, Hélène, Rietschel, Marcella, Ringwald, Kai G., Rouleau, Guy, Schaupp, Sabrina, Senner, Fanny, Severino, Giovanni, Squassina, Alessio, Stein, Frederike, Stopkova, Pavla, Streit, Fabian, Thiel, Katharina, Thomas-Odenthal, Florian, Turecki, Gustavo, Twarowska-Hauser, Joanna, Winter, Alexandra, Zandi, Peter P., Kelsoe, John R., Falkai, Peter, Dannlowski, Udo, Kircher, Tilo, Schulze, Thomas G., and Papiol, Sergi

Published
2022
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37. Structural brain alterations associated with suicidal thoughts and behaviors in young people: results from 21 international studies from the ENIGMA Suicidal Thoughts and Behaviours consortium

Author

van Velzen, Laura S., Dauvermann, Maria R., Colic, Lejla, Villa, Luca M., Savage, Hannah S., Toenders, Yara J., Zhu, Alyssa H., Bright, Joanna K., Campos, Adrián I., Salminen, Lauren E., Ambrogi, Sonia, Ayesa-Arriola, Rosa, Banaj, Nerisa, Başgöze, Zeynep, Bauer, Jochen, Blair, Karina, Blair, Robert James, Brosch, Katharina, Cheng, Yuqi, Colle, Romain, Connolly, Colm G., Corruble, Emmanuelle, Couvy-Duchesne, Baptiste, Crespo-Facorro, Benedicto, Cullen, Kathryn R., Dannlowski, Udo, Davey, Christopher G., Dohm, Katharina, Fullerton, Janice M., Gonul, Ali Saffet, Gotlib, Ian H., Grotegerd, Dominik, Hahn, Tim, Harrison, Ben J., He, Mengxin, Hickie, Ian B., Ho, Tiffany C., Iorfino, Frank, Jansen, Andreas, Jollant, Fabrice, Kircher, Tilo, Klimes-Dougan, Bonnie, Klug, Melissa, Leehr, Elisabeth J., Lippard, Elizabeth T. C., McLaughlin, Katie A., Meinert, Susanne, Miller, Adam Bryant, Mitchell, Philip B., Mwangi, Benson, Nenadić, Igor, Ojha, Amar, Overs, Bronwyn J., Pfarr, Julia-Katharina, Piras, Fabrizio, Ringwald, Kai G., Roberts, Gloria, Romer, Georg, Sanches, Marsal, Sheridan, Margaret A., Soares, Jair C., Spalletta, Gianfranco, Stein, Frederike, Teresi, Giana I., Tordesillas-Gutiérrez, Diana, Uyar-Demir, Aslihan, van der Wee, Nic J. A., van der Werff, Steven J., Vermeiren, Robert R. J. M., Winter, Alexandra, Wu, Mon-Ju, Yang, Tony T., Thompson, Paul M., Rentería, Miguel E., Jahanshad, Neda, Blumberg, Hilary P., van Harmelen, Anne-Laura, and Schmaal, Lianne

Published
2022
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38. Reduced hippocampal gray matter volume is a common feature of patients with major depression, bipolar disorder, and schizophrenia spectrum disorders

Author

Brosch, Katharina, Stein, Frederike, Schmitt, Simon, Pfarr, Julia-Katharina, Ringwald, Kai G., Thomas-Odenthal, Florian, Meller, Tina, Steinsträter, Olaf, Waltemate, Lena, Lemke, Hannah, Meinert, Susanne, Winter, Alexandra, Breuer, Fabian, Thiel, Katharina, Grotegerd, Dominik, Hahn, Tim, Jansen, Andreas, Dannlowski, Udo, Krug, Axel, Nenadić, Igor, and Kircher, Tilo

Published
2022
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39. The impact of depression and childhood maltreatment experiences on psychological adaptation from lockdown to reopening period during the COVID-19 pandemic

Author

Herpertz, Julian, primary, Goltermann, Janik, additional, Gruber, Marius, additional, Blitz, Rogério, additional, Taylor, Jacob, additional, Brosch, Katharina, additional, Stein, Frederike, additional, Straube, Benjamin, additional, Meinert, Susanne, additional, Kraus, Anna, additional, Leehr, Elisabeth J, additional, Repple, Jonathan, additional, Redlich, Ronny, additional, Gutfleisch, Lara, additional, Besteher, Bianca, additional, Ratzsch, Janette, additional, Winter, Alexandra, additional, Bonnekoh, Linda M., additional, Winter, Nils R., additional, Emden, Daniel, additional, Kircher, Tilo, additional, Nenadić, Igor, additional, Dannlowski, Udo, additional, Hahn, Tim, additional, and Opel, Nils, additional

Published
2024
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40. Brain structural correlates of recurrence following the first episode in patients with major depressive disorder

Author

Lemke, Hannah, Klute, Hannah, Skupski, Jennifer, Thiel, Katharina, Waltemate, Lena, Winter, Alexandra, Breuer, Fabian, Meinert, Susanne, Klug, Melissa, Enneking, Verena, Winter, Nils R., Grotegerd, Dominik, Leehr, Elisabeth J., Repple, Jonathan, Dohm, Katharina, Opel, Nils, Stein, Frederike, Meller, Tina, Brosch, Katharina, Ringwald, Kai G., Pfarr, Julia-Katharina, Thomas-Odenthal, Florian, Hahn, Tim, Krug, Axel, Jansen, Andreas, Heindel, Walter, Nenadić, Igor, Kircher, Tilo, and Dannlowski, Udo

Published
2022
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41. The Course of Disease in Major Depressive Disorder Is Associated With Altered Activity of the Limbic System During Negative Emotion Processing

Author

Lemke, Hannah, Probst, Stefanie, Warneke, Antonia, Waltemate, Lena, Winter, Alexandra, Thiel, Katharina, Meinert, Susanne, Enneking, Verena, Breuer, Fabian, Klug, Melissa, Goltermann, Janik, Hülsmann, Carina, Grotegerd, Dominik, Redlich, Ronny, Dohm, Katharina, Leehr, Elisabeth J., Repple, Jonathan, Opel, Nils, Brosch, Katharina, Meller, Tina, Pfarr, Julia-Katharina, Ringwald, Kai, Schmitt, Simon, Stein, Frederike, Krug, Axel, Jansen, Andreas, Nenadic, Igor, Kircher, Tilo, Hahn, Tim, and Dannlowski, Udo

Published
2022
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42. Association Between Genetic Risk for Type 2 Diabetes and Structural Brain Connectivity in Major Depressive Disorder

Author

Repple, Jonathan, König, Amelie, de Lange, Siemon C., Opel, Nils, Redlich, Ronny, Meinert, Susanne, Grotegerd, Dominik, Mauritz, Marco, Hahn, Tim, Borgers, Tiana, Leehr, Elisabeth J., Winter, Nils, Goltermann, Janik, Enneking, Verena, Fingas, Stella M., Lemke, Hannah, Waltemate, Lena, Dohm, Katharina, Richter, Maike, Mehler, David M.A., Holstein, Vincent, Gruber, Marius, Nenadic, Igor, Krug, Axel, Brosch, Katharina, Schmitt, Simon, Stein, Frederike, Meller, Tina, Jansen, Andreas, Steinsträter, Olaf, Amare, Azmeraw T., Kircher, Tilo, Baune, Bernhard T., van den Heuvel, Martijn P., and Dannlowski, Udo

Published
2022
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43. Association of brain white matter microstructure with cognitive performance in major depressive disorder and healthy controls: a diffusion-tensor imaging study

Author

Meinert, Susanne, Nowack, Nico, Grotegerd, Dominik, Repple, Jonathan, Winter, Nils R., Abheiden, Isabel, Enneking, Verena, Lemke, Hannah, Waltemate, Lena, Stein, Frederike, Brosch, Katharina, Schmitt, Simon, Meller, Tina, Pfarr, Julia-Katharina, Ringwald, Kai, Steinsträter, Olaf, Gruber, Marius, Nenadić, Igor, Krug, Axel, Leehr, Elisabeth J., Hahn, Tim, Thiel, Katharina, Dohm, Katharina, Winter, Alexandra, Opel, Nils, Schubotz, Ricarda I., Kircher, Tilo, and Dannlowski, Udo

Published
2022
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44. Genome-wide interaction study with major depression identifies novel variants associated with cognitive function

Author

Thalamuthu, Anbupalam, Mills, Natalie T., Berger, Klaus, Minnerup, Heike, Grotegerd, Dominik, Dannlowski, Udo, Meinert, Susanne, Opel, Nils, Repple, Jonathan, Gruber, Marius, Nenadić, Igor, Stein, Frederike, Brosch, Katharina, Meller, Tina, Pfarr, Julia-Katharina, Forstner, Andreas J., Hoffmann, Per, Nöthen, Markus M., Witt, Stephanie, Rietschel, Marcella, Kircher, Tilo, Adams, Mark, McIntosh, Andrew M., Porteous, David J., Deary, Ian J., Hayward, Caroline, Campbell, Archie, Grabe, Hans Jörgen, Teumer, Alexander, Homuth, Georg, van der Auwera-Palitschka, Sandra, Oliver Schubert, K., and Baune, Bernhard T.

Published
2022
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45. Bipolar‐associated miR‐499‐5p controls neuroplasticity by downregulating the Cav1.2 subunit CACNB2

Author

Martins, Helena C, Gilardi, Carlotta, Sungur, A Özge, Winterer, Jochen, Pelzl, Michael A, Bicker, Silvia, Gross, Fridolin, Kisko, Theresa M, Malikowska‐Racia, Natalia, Braun, Moria D, Brosch, Katharina, Nenadic, Igor, Stein, Frederike, Meinert, Susanne, Schwarting, Rainer K W, Dannlowski, Udo, Kircher, Tilo, Wöhr, Markus, and Schratt, Gerhard

Published
2022
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46. Larger putamen in individuals at risk and with manifest bipolar disorder

Author

Thomas-Odenthal, Florian, primary, Stein, Frederike, additional, Vogelbacher, Christoph, additional, Alexander, Nina, additional, Bechdolf, Andreas, additional, Bermpohl, Felix, additional, Bröckel, Kyra, additional, Brosch, Katharina, additional, Correll, Christoph U., additional, Evermann, Ulrika, additional, Falkenberg, Irina, additional, Fallgatter, Andreas, additional, Flinkenflügel, Kira, additional, Grotegerd, Dominik, additional, Hahn, Tim, additional, Hautzinger, Martin, additional, Jansen, Andreas, additional, Juckel, Georg, additional, Krug, Axel, additional, Lambert, Martin, additional, Leicht, Gregor, additional, Leopold, Karolina, additional, Meinert, Susanne, additional, Mikolas, Pavol, additional, Mulert, Christoph, additional, Nenadić, Igor, additional, Pfarr, Julia-Katharina, additional, Reif, Andreas, additional, Ringwald, Kai, additional, Ritter, Philipp, additional, Stamm, Thomas, additional, Straube, Benjamin, additional, Teutenberg, Lea, additional, Thiel, Katharina, additional, Usemann, Paula, additional, Winter, Alexandra, additional, Wroblewski, Adrian, additional, Dannlowski, Udo, additional, Bauer, Michael, additional, Pfennig, Andrea, additional, and Kircher, Tilo, additional

Published
2024
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48. Identification of transdiagnostic psychiatric disorder subtypes using unsupervised learning

Author

Pelin, Helena, Ising, Marcus, Stein, Frederike, Meinert, Susanne, Meller, Tina, Brosch, Katharina, Winter, Nils R., Krug, Axel, Leenings, Ramona, Lemke, Hannah, Nenadić, Igor, Heilmann-Heimbach, Stefanie, Forstner, Andreas J., Nöthen, Markus M., Opel, Nils, Repple, Jonathan, Pfarr, Julia, Ringwald, Kai, Schmitt, Simon, Thiel, Katharina, Waltemate, Lena, Winter, Alexandra, Streit, Fabian, Witt, Stephanie, Rietschel, Marcella, Dannlowski, Udo, Kircher, Tilo, Hahn, Tim, Müller-Myhsok, Bertram, and Andlauer, Till F. M.

Published
2021
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49. Apolipoprotein E homozygous ε4 allele status: Effects on cortical structure and white matter integrity in a young to mid-age sample

Author

Goltermann, Janik, Repple, Jonathan, Redlich, Ronny, Dohm, Katharina, Flint, Claas, Grotegerd, Dominik, Waltemate, Lena, Lemke, Hannah, Fingas, Stella Mercedes, Meinert, Susanne, Enneking, Verena, Hahn, Tim, Bauer, Jochen, Schmitt, Simon, Meller, Tina, Stein, Frederike, Brosch, Katharina, Steinsträter, Olaf, Jansen, Andreas, Krug, Axel, Nenadić, Igor, Baune, Bernhard T., Rietschel, Marcella, Witt, Stephanie, Forstner, Andreas J., Nöthen, Markus, Johnen, Andreas, Alferink, Judith, Kircher, Tilo, Dannlowski, Udo, and Opel, Nils

Published
2021
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50. Associations between white matter microstructure and cognitive decline in major depressive disorder versus controls in Germany: a prospective case-control cohort study

Author

Flinkenflügel, Kira, Meinert, Susanne, Hirtsiefer, Christopher, Grotegerd, Dominik, Gruber, Marius, Goltermann, Janik, Winter, Nils R, Stein, Frederike, Brosch, Katharina, Leehr, Elisabeth J, Böhnlein, Joscha, Dohm, Katharina, Bauer, Jochen, Redlich, Ronny, Hahn, Tim, Repple, Jonathan, Opel, Nils, Nitsch, Robert, Jamalabadi, Hamidreza, Straube, Benjamin, Alexander, Nina, Jansen, Andreas, Nenadić, Igor, van den Heuvel, Martijn P, Thiel, Katharina, Winter, Alexandra, Thomas-Odenthal, Florian, Usemann, Paula, Teutenberg, Lea, Pfarr, Julia-Katharina, Kircher, Tilo, and Dannlowski, Udo

Abstract

Cognitive deficits are a key source of disability in individuals with major depressive disorder (MDD) and worsen with disease progression. Despite their clinical relevance, the underlying mechanisms of cognitive deficits remain poorly elucidated, hampering effective treatment strategies. Emerging evidence suggests that alterations in white matter microstructure might contribute to cognitive dysfunction in MDD. We aimed to investigate the complex association between changes in white matter integrity, cognitive decline, and disease course in MDD in a comprehensive longitudinal dataset.

Published
2024
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