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

Author

Haukvik, Unn K, Gurholt, Tiril P, Nerland, Stener, Elvsåshagen, Torbjørn, Akudjedu, Theophilus N, Alda, Martin, Alnæs, Dag, Alonso‐Lana, Silvia, Bauer, Jochen, Baune, Bernhard T, Benedetti, Francesco, Berk, Michael, Bettella, Francesco, Bøen, Erlend, Bonnín, Caterina M, Brambilla, Paolo, Canales‐Rodríguez, Erick J, Cannon, Dara M, Caseras, Xavier, Dandash, Orwa, Dannlowski, Udo, Delvecchio, Giuseppe, Díaz‐Zuluaga, Ana M, Erp, Theo GM, Fatjó‐Vilas, Mar, Foley, Sonya F, Förster, Katharina, Fullerton, Janice M, Goikolea, José M, Grotegerd, Dominik, Gruber, Oliver, Haarman, Bartholomeus CM, Haatveit, Beathe, Hajek, Tomas, Hallahan, Brian, Harris, Mathew, Hawkins, Emma L, Howells, Fleur M, Hülsmann, Carina, Jahanshad, Neda, Jørgensen, Kjetil N, Kircher, Tilo, Krämer, Bernd, Krug, Axel, Kuplicki, Rayus, Lagerberg, Trine V, Lancaster, Thomas M, Lenroot, Rhoshel K, Lonning, Vera, López‐Jaramillo, Carlos, Malt, Ulrik F, McDonald, Colm, McIntosh, Andrew M, McPhilemy, Genevieve, Meer, Dennis, Melle, Ingrid, Melloni, Elisa MT, Mitchell, Philip B, Nabulsi, Leila, Nenadić, Igor, Oertel, Viola, Oldani, Lucio, Opel, Nils, Otaduy, Maria CG, Overs, Bronwyn J, Pineda‐Zapata, Julian A, Pomarol‐Clotet, Edith, Radua, Joaquim, Rauer, Lisa, Redlich, Ronny, Repple, Jonathan, Rive, Maria M, Roberts, Gloria, Ruhe, Henricus G, Salminen, Lauren E, Salvador, Raymond, Sarró, Salvador, Savitz, Jonathan, Schene, Aart H, Sim, Kang, Soeiro‐de‐Souza, Marcio G, Stäblein, Michael, Stein, Dan J, Stein, Frederike, Tamnes, Christian K, Temmingh, Henk S, Thomopoulos, Sophia I, Veltman, Dick J, Vieta, Eduard, Waltemate, Lena, Westlye, Lars T, Whalley, Heather C, Sämann, Philipp G, Thompson, Paul M, Ching, Christopher RK, Andreassen, Ole A, Agartz, Ingrid, and Group, ENIGMA Bipolar Disorder Working

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Brain Disorders, Mental Health, Serious Mental Illness, Neurosciences, Biomedical Imaging, Bipolar Disorder, Mental health, Genetics, Hippocampus, Humans, Magnetic Resonance Imaging, Neuroimaging, ENIGMA Bipolar Disorder Working Group, bipolar disorder subtype, hippocampus, large-scale, lithium, psychosis, structural brain MRI, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
Abstract

The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta-Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1-weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed-effects models and mega-analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = -0.20), cornu ammonis (CA)1 (d = -0.18), CA2/3 (d = -0.11), CA4 (d = -0.19), molecular layer (d = -0.21), granule cell layer of dentate gyrus (d = -0.21), hippocampal tail (d = -0.10), subiculum (d = -0.15), presubiculum (d = -0.18), and hippocampal amygdala transition area (d = -0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non-users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD.

Published
2022

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

Author

Ching, Christopher RK, Hibar, Derrek P, Gurholt, Tiril P, Nunes, Abraham, Thomopoulos, Sophia I, Abé, Christoph, Agartz, Ingrid, Brouwer, Rachel M, Cannon, Dara M, Zwarte, Sonja MC, Eyler, Lisa T, Favre, Pauline, Hajek, Tomas, Haukvik, Unn K, Houenou, Josselin, Landén, Mikael, Lett, Tristram A, McDonald, Colm, Nabulsi, Leila, Patel, Yash, Pauling, Melissa E, Paus, Tomas, Radua, Joaquim, Soeiro‐de‐Souza, Marcio G, Tronchin, Giulia, Haren, Neeltje EM, Vieta, Eduard, Walter, Henrik, Zeng, Ling‐Li, Alda, Martin, Almeida, Jorge, Alnæs, Dag, Alonso‐Lana, Silvia, Altimus, Cara, Bauer, Michael, Baune, Bernhard T, Bearden, Carrie E, Bellani, Marcella, Benedetti, Francesco, Berk, Michael, Bilderbeck, Amy C, Blumberg, Hilary P, Bøen, Erlend, Bollettini, Irene, Bonnin, Caterina Mar, Brambilla, Paolo, Canales‐Rodríguez, Erick J, Caseras, Xavier, Dandash, Orwa, Dannlowski, Udo, Delvecchio, Giuseppe, Díaz‐Zuluaga, Ana M, Dima, Danai, Duchesnay, Édouard, Elvsåshagen, Torbjørn, Fears, Scott C, Frangou, Sophia, Fullerton, Janice M, Glahn, David C, Goikolea, Jose M, Green, Melissa J, Grotegerd, Dominik, Gruber, Oliver, Haarman, Bartholomeus CM, Henry, Chantal, Howells, Fleur M, Ives‐Deliperi, Victoria, Jansen, Andreas, Kircher, Tilo TJ, Knöchel, Christian, Kramer, Bernd, Lafer, Beny, López‐Jaramillo, Carlos, Machado‐Vieira, Rodrigo, MacIntosh, Bradley J, Melloni, Elisa MT, Mitchell, Philip B, Nenadic, Igor, Nery, Fabiano, Nugent, Allison C, Oertel, Viola, Ophoff, Roel A, Ota, Miho, Overs, Bronwyn J, Pham, Daniel L, Phillips, Mary L, Pineda‐Zapata, Julian A, Poletti, Sara, Polosan, Mircea, Pomarol‐Clotet, Edith, Pouchon, Arnaud, Quidé, Yann, Rive, Maria M, Roberts, Gloria, Ruhe, Henricus G, Salvador, Raymond, Sarró, Salvador, Satterthwaite, Theodore D, Schene, Aart H, and Sim, Kang

Subjects
Serious Mental Illness, Brain Disorders, Biomedical Imaging, Bipolar Disorder, Clinical Research, Behavioral and Social Science, Mental Health, Neurosciences, Mental health, Neurological, Good Health and Well Being, Cerebral Cortex, Humans, Magnetic Resonance Imaging, Meta-Analysis as Topic, Multicenter Studies as Topic, Neuroimaging, bipolar disorder, cortical surface area, cortical thickness, ENIGMA, mega-analysis, meta-analysis, MRI, neuroimaging, psychiatry, volume, ENIGMA Bipolar Disorder Working Group, Cognitive Sciences, Experimental Psychology
Abstract

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

Published
2022

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

Author

Gurholt, Tiril P, Lonning, Vera, Nerland, Stener, Jørgensen, Kjetil N, Haukvik, Unn K, Alloza, Clara, Arango, Celso, Barth, Claudia, Bearden, Carrie E, Berk, Michael, Bohman, Hannes, Dandash, Orwa, Díaz-Caneja, Covadonga M, Edbom, Carl T, van Erp, Theo GM, Fett, Anne-Kathrin J, Frangou, Sophia, Goldstein, Benjamin I, Grigorian, Anahit, Jahanshad, Neda, James, Anthony C, Janssen, Joost, Johannessen, Cecilie, Karlsgodt, Katherine H, Kempton, Matthew J, Kochunov, Peter, Krabbendam, Lydia, Kyriakopoulos, Marinos, Lundberg, Mathias, MacIntosh, Bradley J, Rund, Bjørn Rishovd, Smelror, Runar E, Sultan, Alysha, Tamnes, Christian K, Thomopoulos, Sophia I, Vajdi, Ariana, Wedervang-Resell, Kirsten, Myhre, Anne M, Andreassen, Ole A, Thompson, Paul M, Agartz, Ingrid, and ENIGMA-EOP Working Group

Subjects
ENIGMA-EOP Working Group, Brain, Hippocampus, Globus Pallidus, Humans, Magnetic Resonance Imaging, Adolescent Development, Affective Disorders, Psychotic, Psychotic Disorders, Schizophrenia, Age of Onset, Adolescent, adolescence, antipsychotics, brain structure, early-onset, intracranial volume, psychosis spectrum, Mental Health, Clinical Research, Serious Mental Illness, Biomedical Imaging, Brain Disorders, Pediatric, Pediatric Research Initiative, Neurosciences, Mental health, Good Health and Well Being, Cognitive Sciences, Experimental Psychology
Abstract

Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = -0.39) and hippocampal (d = -0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = -0.34) and affective psychosis (d = -0.42), and early-onset schizophrenia showed lower hippocampal (d = -0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = -0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis.

Published
2022

8. Toxoplasma gondii infection associated with inflammasome activation and neuronal injury

Author

Andreou, Dimitrios, Steen, Nils Eiel, Mørch-Johnsen, Lynn, Jørgensen, Kjetil Nordbø, Wortinger, Laura A., Barth, Claudia, Szabo, Attila, O’Connell, Kevin S., Lekva, Tove, Hjell, Gabriela, Johansen, Ingrid Torp, Ormerod, Monica B. E. G., Haukvik, Unn K., Aukrust, Pål, Djurovic, Srdjan, Yolken, Robert H., Andreassen, Ole A., Ueland, Thor, and Agartz, Ingrid

Published
2024
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10. Widespread white matter microstructural abnormalities in bipolar disorder: evidence from mega- and meta-analyses across 3033 individuals

Author

Favre, Pauline, Pauling, Melissa, Stout, Jacques, Hozer, Franz, Sarrazin, Samuel, Abé, Christoph, Alda, Martin, Alloza, Clara, Alonso-Lana, Silvia, Andreassen, Ole A, Baune, Bernhard T, Benedetti, Francesco, Busatto, Geraldo F, Canales-Rodríguez, Erick J, Caseras, Xavier, Chaim-Avancini, Tiffany Moukbel, Ching, Christopher RK, Dannlowski, Udo, Deppe, Michael, Eyler, Lisa T, Fatjo-Vilas, Mar, Foley, Sonya F, Grotegerd, Dominik, Hajek, Tomas, Haukvik, Unn K, Howells, Fleur M, Jahanshad, Neda, Kugel, Harald, Lagerberg, Trine V, Lawrie, Stephen M, Linke, Julia O, McIntosh, Andrew, Melloni, Elisa MT, Mitchell, Philip B, Polosan, Mircea, Pomarol-Clotet, Edith, Repple, Jonathan, Roberts, Gloria, Roos, Annerine, Rosa, Pedro GP, Salvador, Raymond, Sarró, Salvador, Schofield, Peter R, Serpa, Mauricio H, Sim, Kang, Stein, Dan J, Sussmann, Jess E, Temmingh, Henk S, Thompson, Paul M, Verdolini, Norma, Vieta, Eduard, Wessa, Michele, Whalley, Heather C, Zanetti, Marcus V, Leboyer, Marion, Mangin, Jean-François, Henry, Chantal, Duchesnay, Edouard, and Houenou, Josselin

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Brain Disorders, Serious Mental Illness, Neurosciences, Bipolar Disorder, Biomedical Imaging, Mental Health, Clinical Research, Mental health, Adult, Brain, Corpus Callosum, Diffusion Tensor Imaging, Female, Humans, Male, Neural Pathways, White Matter, ENIGMA Bipolar Disorder Working Group, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological psychology
Abstract

Fronto-limbic white matter (WM) abnormalities are assumed to lie at the heart of the pathophysiology of bipolar disorder (BD); however, diffusion tensor imaging (DTI) studies have reported heterogeneous results and it is not clear how the clinical heterogeneity is related to the observed differences. This study aimed to identify WM abnormalities that differentiate patients with BD from healthy controls (HC) in the largest DTI dataset of patients with BD to date, collected via the ENIGMA network. We gathered individual tensor-derived regional metrics from 26 cohorts leading to a sample size of N = 3033 (1482 BD and 1551 HC). Mean fractional anisotropy (FA) from 43 regions of interest (ROI) and average whole-brain FA were entered into univariate mega- and meta-analyses to differentiate patients with BD from HC. Mega-analysis revealed significantly lower FA in patients with BD compared with HC in 29 regions, with the highest effect sizes observed within the corpus callosum (R2 = 0.041, Pcorr

Published
2019

11. Correction: Widespread white matter microstructural abnormalities in bipolar disorder: evidence from mega- and meta-analyses across 3033 individuals

Author

Favre, Pauline, Pauling, Melissa, Stout, Jacques, Hozer, Franz, Sarrazin, Samuel, Abé, Christoph, Alda, Martin, Alloza, Clara, Alonso-Lana, Silvia, Andreassen, Ole A, Baune, Bernhard T, Benedetti, Francesco, Busatto, Geraldo F, Canales-Rodríguez, Erick J, Caseras, Xavier, Chaim-Avancini, Tiffany Moukbel, Ching, Christopher RK, Dannlowski, Udo, Deppe, Michael, Eyler, Lisa T, Fatjo-Vilas, Mar, Foley, Sonya F, Grotegerd, Dominik, Hajek, Tomas, Haukvik, Unn K, Howells, Fleur M, Jahanshad, Neda, Kugel, Harald, Lagerberg, Trine V, Lawrie, Stephen M, Linke, Julia O, McIntosh, Andrew, Melloni, Elisa MT, Mitchell, Philip B, Polosan, Mircea, Pomarol-Clotet, Edith, Repple, Jonathan, Roberts, Gloria, Roos, Annerine, Rosa, Pedro GP, Salvador, Raymond, Sarró, Salvador, Schofield, Peter R, Serpa, Mauricio H, Sim, Kang, Stein, Dan J, Sussmann, Jess E, Temmingh, Henk S, Thompson, Paul M, Verdolini, Norma, Vieta, Eduard, Wessa, Michele, Whalley, Heather C, Zanetti, Marcus V, Leboyer, Marion, Mangin, Jean-François, Henry, Chantal, Duchesnay, Edouard, and Houenou, Josselin

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, ENIGMA Bipolar Disorder Working Group, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological psychology
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019

12. Genetic architecture of subcortical brain structures in 38,851 individuals

Author

Satizabal, Claudia L, Adams, Hieab HH, Hibar, Derrek P, White, Charles C, Knol, Maria J, Stein, Jason L, Scholz, Markus, Sargurupremraj, Muralidharan, Jahanshad, Neda, Roshchupkin, Gennady V, Smith, Albert V, Bis, Joshua C, Jian, Xueqiu, Luciano, Michelle, Hofer, Edith, Teumer, Alexander, van der Lee, Sven J, Yang, Jingyun, Yanek, Lisa R, Lee, Tom V, Li, Shuo, Hu, Yanhui, Koh, Jia Yu, Eicher, John D, Desrivières, Sylvane, Arias-Vasquez, Alejandro, Chauhan, Ganesh, Athanasiu, Lavinia, Rentería, Miguel E, Kim, Sungeun, Hoehn, David, Armstrong, Nicola J, Chen, Qiang, Holmes, Avram J, den Braber, Anouk, Kloszewska, Iwona, Andersson, Micael, Espeseth, Thomas, Grimm, Oliver, Abramovic, Lucija, Alhusaini, Saud, Milaneschi, Yuri, Papmeyer, Martina, Axelsson, Tomas, Ehrlich, Stefan, Roiz-Santiañez, Roberto, Kraemer, Bernd, Håberg, Asta K, Jones, Hannah J, Pike, G Bruce, Stein, Dan J, Stevens, Allison, Bralten, Janita, Vernooij, Meike W, Harris, Tamara B, Filippi, Irina, Witte, A Veronica, Guadalupe, Tulio, Wittfeld, Katharina, Mosley, Thomas H, Becker, James T, Doan, Nhat Trung, Hagenaars, Saskia P, Saba, Yasaman, Cuellar-Partida, Gabriel, Amin, Najaf, Hilal, Saima, Nho, Kwangsik, Mirza-Schreiber, Nazanin, Arfanakis, Konstantinos, Becker, Diane M, Ames, David, Goldman, Aaron L, Lee, Phil H, Boomsma, Dorret I, Lovestone, Simon, Giddaluru, Sudheer, Le Hellard, Stephanie, Mattheisen, Manuel, Bohlken, Marc M, Kasperaviciute, Dalia, Schmaal, Lianne, Lawrie, Stephen M, Agartz, Ingrid, Walton, Esther, Tordesillas-Gutierrez, Diana, Davies, Gareth E, Shin, Jean, Ipser, Jonathan C, Vinke, Louis N, Hoogman, Martine, Jia, Tianye, Burkhardt, Ralph, Klein, Marieke, Crivello, Fabrice, Janowitz, Deborah, Carmichael, Owen, Haukvik, Unn K, Aribisala, Benjamin S, and Schmidt, Helena

Subjects
Biological Sciences, Genetics, Neurosciences, Biotechnology, Mental Health, Human Genome, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Neurological, Adult, Aged, Animals, Brain, Cohort Studies, Drosophila melanogaster, Genetic Variation, Genome-Wide Association Study, Humans, Magnetic Resonance Imaging, Middle Aged, Neurodevelopmental Disorders, Organ Size, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.

Published
2019

15. 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, Theo GM, Walton, Esther, Hibar, Derrek P, Schmaal, Lianne, Jiang, Wenhao, Glahn, David C, Pearlson, Godfrey D, Yao, Nailin, Fukunaga, Masaki, Hashimoto, Ryota, Okada, Naohiro, Yamamori, Hidenaga, Bustillo, Juan R, Clark, Vincent P, Agartz, Ingrid, Mueller, Bryon A, Cahn, Wiepke, de Zwarte, Sonja MC, Hulshoff Pol, Hilleke E, Kahn, René S, Ophoff, Roel A, van Haren, Neeltje EM, Andreassen, Ole A, Dale, Anders M, Doan, Nhat Trung, Gurholt, Tiril P, Hartberg, Cecilie B, Haukvik, Unn K, Jørgensen, Kjetil N, Lagerberg, Trine V, Melle, Ingrid, Westlye, Lars T, Gruber, Oliver, Kraemer, Bernd, Richter, Anja, Zilles, David, Calhoun, Vince D, Crespo-Facorro, Benedicto, Roiz-Santiañez, Roberto, Tordesillas-Gutiérrez, Diana, Loughland, Carmel, Carr, Vaughan J, Catts, Stanley, Cropley, Vanessa L, Fullerton, Janice M, Green, Melissa J, Henskens, Frans A, Jablensky, Assen, Lenroot, Rhoshel K, Mowry, Bryan J, Michie, Patricia T, Pantelis, Christos, Quidé, Yann, Schall, Ulrich, Scott, Rodney J, Cairns, Murray J, Seal, Marc, Tooney, Paul A, Rasser, Paul E, Cooper, Gavin, Shannon Weickert, Cynthia, Weickert, Thomas W, Morris, Derek W, Hong, Elliot, Kochunov, Peter, Beard, Lauren M, Gur, Raquel E, Gur, Ruben C, Satterthwaite, Theodore D, Wolf, Daniel H, Belger, Aysenil, Brown, Gregory G, Ford, Judith M, Macciardi, Fabio, Mathalon, Daniel H, O'Leary, Daniel S, Potkin, Steven G, Preda, Adrian, Voyvodic, James, Lim, Kelvin O, McEwen, Sarah, Yang, Fude, Tan, Yunlong, Tan, Shuping, Wang, Zhiren, Fan, Fengmei, Chen, Jingxu, Xiang, Hong, Tang, Shiyou, Guo, Hua, Wan, Ping, Wei, Dong, Bockholt, Henry J, Ehrlich, Stefan, Wolthusen, Rick PF, King, Margaret D, Shoemaker, Jody M, Sponheim, Scott R, De Haan, Lieuwe, and Koenders, Laura

Subjects
Karolinska Schizophrenia Project, Brain, Frontal Lobe, Prefrontal Cortex, Temporal Lobe, Humans, Magnetic Resonance Imaging, Severity of Illness Index, Linear Models, Case-Control Studies, Schizophrenia, Age of Onset, Adolescent, Adult, Aged, Middle Aged, Child, Female, Male, Young Adult, Neuroimaging, Cortical, Imaging, Meta-analysis, Surface area, Thickness, Serious Mental Illness, Biomedical Imaging, Mental Health, Clinical Research, Neurosciences, Brain Disorders, Mental health, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundThe 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.MethodsThe 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.ResultsCompared 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.ConclusionsThe 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.

Published
2018

20. Novel genetic loci associated with hippocampal volume.

Author

Hibar, Derrek P, Adams, Hieab HH, Jahanshad, Neda, Chauhan, Ganesh, Stein, Jason L, Hofer, Edith, Renteria, Miguel E, Bis, Joshua C, Arias-Vasquez, Alejandro, Ikram, M Kamran, Desrivières, Sylvane, Vernooij, Meike W, Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S, Armstrong, Nicola J, Athanasiu, Lavinia, Axelsson, Tomas, Beecham, Ashley H, Beiser, Alexa, Bernard, Manon, Blanton, Susan H, Bohlken, Marc M, Boks, Marco P, Bralten, Janita, Brickman, Adam M, Carmichael, Owen, Chakravarty, M Mallar, Chen, Qiang, Ching, Christopher RK, Chouraki, Vincent, Cuellar-Partida, Gabriel, Crivello, Fabrice, Den Braber, Anouk, Doan, Nhat Trung, Ehrlich, Stefan, Giddaluru, Sudheer, Goldman, Aaron L, Gottesman, Rebecca F, Grimm, Oliver, Griswold, Michael E, Guadalupe, Tulio, Gutman, Boris A, Hass, Johanna, Haukvik, Unn K, Hoehn, David, Holmes, Avram J, Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Jørgensen, Kjetil N, Karbalai, Nazanin, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H, Liewald, David CM, Lopez, Lorna M, Luciano, Michelle, Macare, Christine, Marquand, Andre F, Matarin, Mar, Mather, Karen A, Mattheisen, Manuel, McKay, David R, Milaneschi, Yuri, Muñoz Maniega, Susana, Nho, Kwangsik, Nugent, Allison C, Nyquist, Paul, Loohuis, Loes M Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pirpamer, Lukas, Pütz, Benno, Ramasamy, Adaikalavan, Richards, Jennifer S, Risacher, Shannon L, Roiz-Santiañez, Roberto, Rommelse, Nanda, Ropele, Stefan, Rose, Emma J, Royle, Natalie A, Rundek, Tatjana, Sämann, Philipp G, Saremi, Arvin, Satizabal, Claudia L, Schmaal, Lianne, Schork, Andrew J, Shen, Li, Shin, Jean, Shumskaya, Elena, Smith, Albert V, Sprooten, Emma, Strike, Lachlan T, and Teumer, Alexander

Subjects
Hippocampus, Humans, Alzheimer Disease, Genetic Predisposition to Disease, Protein-Serine-Threonine Kinases, Glycoproteins, Microtubule-Associated Proteins, Nerve Tissue Proteins, Organ Size, Cohort Studies, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Female, Male, Genome-Wide Association Study, Young Adult, Methionine Sulfoxide Reductases, Genetic Loci, Dipeptidyl Peptidase 4, Human Genome, Aging, Brain Disorders, Clinical Research, Acquired Cognitive Impairment, Neurodegenerative, Dementia, Neurosciences, Prevention, Genetics, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Mental Health, 2.1 Biological and endogenous factors, Mental health, Neurological
Abstract

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

Published
2017

21. Novel genetic loci underlying human intracranial volume identified through genome-wide association

Author

Adams, Hieab HH, Hibar, Derrek P, Chouraki, Vincent, Stein, Jason L, Nyquist, Paul A, Rentería, Miguel E, Trompet, Stella, Arias-Vasquez, Alejandro, Seshadri, Sudha, Desrivières, Sylvane, Beecham, Ashley H, Jahanshad, Neda, Wittfeld, Katharina, Van der Lee, Sven J, Abramovic, Lucija, Alhusaini, Saud, Amin, Najaf, Andersson, Micael, Arfanakis, Konstantinos, Aribisala, Benjamin S, Armstrong, Nicola J, Athanasiu, Lavinia, Axelsson, Tomas, Beiser, Alexa, Bernard, Manon, Bis, Joshua C, Blanken, Laura ME, Blanton, Susan H, Bohlken, Marc M, Boks, Marco P, Bralten, Janita, Brickman, Adam M, Carmichael, Owen, Chakravarty, M Mallar, Chauhan, Ganesh, Chen, Qiang, Ching, Christopher RK, Cuellar-Partida, Gabriel, Braber, Anouk Den, Doan, Nhat Trung, Ehrlich, Stefan, Filippi, Irina, Ge, Tian, Giddaluru, Sudheer, Goldman, Aaron L, Gottesman, Rebecca F, Greven, Corina U, Grimm, Oliver, Griswold, Michael E, Guadalupe, Tulio, Hass, Johanna, Haukvik, Unn K, Hilal, Saima, Hofer, Edith, Hoehn, David, Holmes, Avram J, Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Kasperaviciute, Dalia, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H, Liao, Jiemin, Liewald, David CM, Lopez, Lorna M, Luciano, Michelle, Macare, Christine, Marquand, Andre, Matarin, Mar, Mather, Karen A, Mattheisen, Manuel, Mazoyer, Bernard, McKay, David R, McWhirter, Rebekah, Milaneschi, Yuri, Mirza-Schreiber, Nazanin, Muetzel, Ryan L, Maniega, Susana Muñoz, Nho, Kwangsik, Nugent, Allison C, Loohuis, Loes M Olde, Oosterlaan, Jaap, Papmeyer, Martina, Pappa, Irene, Pirpamer, Lukas, Pudas, Sara, Pütz, Benno, Rajan, Kumar B, Ramasamy, Adaikalavan, Richards, Jennifer S, Risacher, Shannon L, Roiz-Santiañez, Roberto, Rommelse, Nanda, Rose, Emma J, Royle, Natalie A, Rundek, Tatjana, Sämann, Philipp G, and Satizabal, Claudia L

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, Clinical Research, Brain Disorders, Clinical Trials and Supportive Activities, Aging, Biotechnology, Genetics, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Neurological, Brain, Cognition, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Oncogene Protein v-akt, Parkinson Disease, Phenotype, Phosphatidylinositol 3-Kinases, Polymorphism, Single Nucleotide, White People, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

Published
2016

22. Brain Age Prediction Reveals Aberrant Brain White Matter in Schizophrenia and Bipolar Disorder: A Multisample Diffusion Tensor Imaging Study

Author

Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I., Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Sellgren, C., Tønnesen, Siren, Kaufmann, Tobias, de Lange, Ann-Marie G., Richard, Geneviève, Doan, Nhat Trung, Alnæs, Dag, van der Meer, Dennis, Rokicki, Jaroslav, Moberget, Torgeir, Maximov, Ivan I., Agartz, Ingrid, Aminoff, Sofie R., Beck, Dani, Barch, Deanna M., Beresniewicz, Justyna, Cervenka, Simon, Fatouros-Bergman, Helena, Craven, Alexander R., Flyckt, Lena, Gurholt, Tiril P., Haukvik, Unn K., Hugdahl, Kenneth, Johnsen, Erik, Jönsson, Erik G., Kolskår, Knut K., Kroken, Rune Andreas, Lagerberg, Trine V., Løberg, Else-Marie, Nordvik, Jan Egil, Sanders, Anne-Marthe, Ulrichsen, Kristine, Andreassen, Ole A., and Westlye, Lars T.

Published
2020
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23. Violent Offending in Males With or Without Schizophrenia: A Role for Social Cognition?

Author

Vaskinn, Anja, Rokicki, Jaroslav, Bell, Christina, Tesli, Natalia, Bang, Nina, Hjell, Gabriela, Fischer-Vieler, Thomas, Haukvik, Unn K, and Friestad, Christine

Subjects
CRIME statistics, VIOLENCE, RESEARCH funding, CRIMINALS, KRUSKAL-Wallis Test, SCHIZOPHRENIA, SOCIAL perception, AFFECTIVE disorders, DESCRIPTIVE statistics, AGGRESSION (Psychology), COGNITION disorders, STATISTICS, ANALYSIS of variance, THOUGHT & thinking
Abstract

Background and Hypothesis Reduced social cognition has been reported in individuals who have committed interpersonal violence. It is unclear if individuals with schizophrenia and a history of violence have larger impairments than violent individuals without psychosis and non-violent individuals with schizophrenia. We examined social cognition in two groups with violent offenses, comparing their performance to non-violent individuals with schizophrenia and healthy controls. Study Design Two social cognitive domains were assessed in four groups: men with a schizophrenia spectrum disorder with (SSD-V, n  = 27) or without (SSD-NV, n  = 42) a history of violence, incarcerated men serving preventive detention sentences (V, n  = 22), and healthy male controls (HC, n  = 76). Theory of mind (ToM) was measured with the Movie for the Assessment of Social Cognition (MASC), body emotion perception with Emotion in Biological Motion (EmoBio) test. Study Results Kruskal–Wallis H -tests revealed overall group differences for social cognition. SSD-V had a global and clinically significant social cognitive impairment. V had a specific impairment, for ToM. Binary logistic regressions predicting violence category membership from social cognition and psychosis (SSD status) were conducted. The model with best fit, explaining 18%–25% of the variance, had ToM as the only predictor. Conclusions Social cognitive impairment was present in individuals with a history of violence, with larger and more widespread impairment seen in schizophrenia. ToM predicted violence category membership, psychosis did not. The results suggest a role for social cognition in understanding interpersonal violence. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Conduct disorder - a comprehensive exploration of comorbidity patterns, genetic and environmental risk factors

Author

Tesli, Natalia, primary, Jaholkowski, Piotr, additional, Haukvik, Unn K, additional, Jangmo, Andreas, additional, Haram, Marit, additional, Rokicki, Jaroslav, additional, Friestad, Christine, additional, Tielbeek, Jorim J, additional, Næss, Øyvind, additional, Skardhamar, Torbjørn, additional, Gustavson, Kristin, additional, Ask, Helga, additional, Fazel, Seena, additional, Tesli, Martin, additional, and Andreassen, Ole A, additional

Published
2023
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25. Individual-level deviations from normative brain morphology in violence, psychosis, and psychopathy

Author

Haukvik, Unn K, primary, Wolfers, Thomas, additional, Tesli, Natalia, additional, Bell, Christina, additional, Hjell, Gabriela, additional, Fischer-Vieler, Thomas, additional, Bang, Nina, additional, Melle, Ingrid, additional, Andreassen, Ole A, additional, Rasmussen, Kirsten, additional, Agartz, Ingrid, additional, Westlye, Lars T, additional, Friestad, Christine, additional, and Rokicki, Jaroslav, additional

Published
2023
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27. Common genetic variants influence human subcortical brain structures

Author

Hibar, Derrek P, Stein, Jason L, Renteria, Miguel E, Arias-Vasquez, Alejandro, Desrivières, Sylvane, Jahanshad, Neda, Toro, Roberto, Wittfeld, Katharina, Abramovic, Lucija, Andersson, Micael, Aribisala, Benjamin S, Armstrong, Nicola J, Bernard, Manon, Bohlken, Marc M, Boks, Marco P, Bralten, Janita, Brown, Andrew A, Mallar Chakravarty, M, Chen, Qiang, Ching, Christopher RK, Cuellar-Partida, Gabriel, den Braber, Anouk, Giddaluru, Sudheer, Goldman, Aaron L, Grimm, Oliver, Guadalupe, Tulio, Hass, Johanna, Woldehawariat, Girma, Holmes, Avram J, Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H, Olde Loohuis, Loes M, Luciano, Michelle, Macare, Christine, Mather, Karen A, Mattheisen, Manuel, Milaneschi, Yuri, Nho, Kwangsik, Papmeyer, Martina, Ramasamy, Adaikalavan, Risacher, Shannon L, Roiz-Santiañez, Roberto, Rose, Emma J, Salami, Alireza, Sämann, Philipp G, Schmaal, Lianne, Schork, Andrew J, Shin, Jean, Strike, Lachlan T, Teumer, Alexander, van Donkelaar, Marjolein MJ, van Eijk, Kristel R, Walters, Raymond K, Westlye, Lars T, Whelan, Christopher D, Winkler, Anderson M, Zwiers, Marcel P, Alhusaini, Saud, Athanasiu, Lavinia, Ehrlich, Stefan, Hakobjan, Marina MH, Hartberg, Cecilie B, Haukvik, Unn K, Heister, Angelien JGAM, Hoehn, David, Kasperaviciute, Dalia, Liewald, David CM, Lopez, Lorna M, Makkinje, Remco RR, Matarin, Mar, Naber, Marlies AM, Reese McKay, D, Needham, Margaret, Nugent, Allison C, Pütz, Benno, Royle, Natalie A, Shen, Li, Sprooten, Emma, Trabzuni, Daniah, van der Marel, Saskia SL, van Hulzen, Kimm JE, Walton, Esther, Wolf, Christiane, Almasy, Laura, Ames, David, Arepalli, Sampath, Assareh, Amelia A, Bastin, Mark E, Brodaty, Henry, Bulayeva, Kazima B, Carless, Melanie A, Cichon, Sven, Corvin, Aiden, Curran, Joanne E, and Czisch, Michael

Subjects
Biological Psychology, Biological Sciences, Genetics, Psychology, Brain Disorders, Mental Health, Neurosciences, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Neurological, Mental health, Adolescent, Adult, Aged, Aged, 80 and over, Aging, Apoptosis, Brain, Caudate Nucleus, Child, Female, Gene Expression Regulation, Developmental, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Membrane Proteins, Middle Aged, Organ Size, Putamen, Sex Characteristics, Skull, Young Adult, Alzheimer’s Disease Neuroimaging Initiative, CHARGE Consortium, EPIGEN, IMAGEN, SYS, General Science & Technology
Abstract

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

Published
2015

28. In Vivo Hippocampal Subfield Volumes in Schizophrenia and Bipolar Disorder

Author

Haukvik, Unn K, Westlye, Lars T, Mørch-Johnsen, Lynn, Jørgensen, Kjetil N, Lange, Elisabeth H, Dale, Anders M, Melle, Ingrid, Andreassen, Ole A, and Agartz, Ingrid

Subjects
Brain Disorders, Biomedical Imaging, Mental Health, Neurosciences, Schizophrenia, Serious Mental Illness, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Mental health, Adolescent, Adult, Aged, Aging, Bipolar Disorder, Female, Hippocampus, Humans, Intelligence, Intelligence Tests, Linear Models, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Psychiatric Status Rating Scales, Psychotic Disorders, Young Adult, MRI, Neuroanatomy, Psychosis, Subiculum, Verbal memory, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundHippocampal dysfunction and volume reductions have been reported in patients with schizophrenia and bipolar disorder. The hippocampus consists of anatomically distinct subfields. We investigated to determine whether in vivo volumes of hippocampal subfields differ between clinical groups and healthy control subjects.MethodsClinical examination and magnetic resonance imaging were performed in 702 subjects (patients with schizophrenia spectrum [n = 210; mean age, 32.0 ± 9.3 (SD) years; 59% male], patients with bipolar spectrum [n = 192; mean age, 35.5 ± 11.5 years; 40% male] and healthy control subjects [n = 300; mean age, 35.3 ± 9.9 years; 53% male]). Hippocampal subfield volumes were estimated with FreeSurfer. General linear models were used to explore diagnostic differences in hippocampal subfield volumes, covarying for age, intracranial volume, and medication. Post hoc analyses of associations to psychosis symptoms (Positive and Negative Syndrome Scale) and cognitive function (verbal memory [California Verbal Learning Test, second edition] and IQ [Wechsler Abbreviated Scale of Intelligence]) were performed.ResultsPatient groups had smaller cornu ammonis (CA) subfields CA2/3 (left, p = 7.2 × 10(-6); right, p = 2.3 × 10(-6)), CA4/dentate gyrus (left, p = 1.4 × 10(-5); right, p = 2.3 × 10(-6)), subiculum (left, p = 3.7 × 10(-6); right, p = 2.8 × 10(-8)), and right CA1 (p = .006) volumes than healthy control subjects, but smaller presubiculum volumes were found only in patients with schizophrenia (left, p = 6.7 × 10(-5); right, p = 1.6 × 10(-7)). Patients with schizophrenia had smaller subiculum (left, p = .035; right, p = .031) and right presubiculum (p = .002) volumes than patients with bipolar disorder. Smaller subiculum volumes were related to poorer verbal memory in patients with bipolar disorder and healthy control subjects and to negative symptoms in patients with schizophrenia.ConclusionsHippocampal subfield volume reductions are found in patients with schizophrenia and bipolar disorder. The magnitude of reduction is greater in patients with schizophrenia, particularly in the hippocampal outflow regions presubiculum and subiculum.

Published
2015

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

Author

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

Published
2018
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32. Altered Sex Differences in Hippocampal Subfield Volumes in Schizophrenia.

Author

Barth, Claudia, Nerland, Stener, Jørgensen, Kjetil N, Haatveit, Beathe, Wortinger, Laura A, Melle, Ingrid, Haukvik, Unn K, Ueland, Torill, Andreassen, Ole A, and Agartz, Ingrid

Subjects
HIPPOCAMPUS physiology, HIPPOCAMPUS (Brain), SEX differentiation disorders, SCHIZOPHRENIA, MULTIPLE regression analysis, RISK assessment, COMPARATIVE studies, ANALYSIS of covariance, RESEARCH funding, BIPOLAR disorder, DISEASE risk factors, DISEASE complications
Abstract

Background and Hypothesis The hippocampus is a heterogenous brain structure that differs between the sexes and has been implicated in the pathophysiology of psychiatric illnesses. Here, we explored sex and diagnostic group differences in hippocampal subfield volumes, in individuals with schizophrenia spectrum disorder (SZ), bipolar disorders (BD), and healthy controls (CTL). Study Design One thousand and five hundred and twenty-one participants underwent T1-weighted magnetic resonance imaging (SZ, n  = 452, mean age 30.7 ± 9.2 [SD] years, males 59.1%; BD, n  = 316, 33.7 ± 11.4, 41.5%; CTL, n  = 753, 34.1 ± 9.1, 55.6%). Total hippocampal, subfield, and intracranial volumes were estimated with Freesurfer (v6.0.0). Analysis of covariance and multiple regression models were fitted to examine sex-by-diagnostic (sub)group interactions in volume. In SZ and BD, separately, associations between volumes and clinical as well as cognitive measures were examined between the sexes using regression models. Study Results Significant sex-by-group interactions were found for the total hippocampus, dentate gyrus, molecular layer, presubiculum, fimbria, hippocampal-amygdaloid transition area, and CA4, indicating a larger volumetric deficit in male patients relative to female patients when compared with same-sex CTL. Subgroup analyses revealed that this interaction was driven by males with schizophrenia. Effect sizes were overall small (partial η < 0.02). We found no significant sex differences in the associations between hippocampal volumes and clinical or cognitive measures in SZ and BD. Conclusions Using a well-powered sample, our findings indicate that the pattern of morphological sex differences in hippocampal subfields is altered in individuals with schizophrenia relative to CTL, due to higher volumetric deficits in males. [ABSTRACT FROM AUTHOR]

Published
2024
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33. Common genetic and environmental risk for personality disorders and psychotic‐like experiences in young adult twins.

Author

Tesli, Martin, Nesvåg, Ragnar, Haukvik, Unn K., Gustavson, Kristin, Tesli, Natalia, Friestad, Christine, Skardhamar, Torbjørn, Næss, Øyvind, Czajkowski, Nikolai, Kendler, Kenneth S., Reichborn‐Kjennerud, Ted, and Ystrom, Eivind

Subjects
PERSONALITY disorders, YOUNG adults, ITEM response theory, GENETIC correlations, TWIN studies
Abstract

Introduction: Psychotic‐like experiences (PLE) have been associated with the subsequent emergence of psychotic disorders as well as several other domains of psychopathology. In this twin study, we estimated the genetic and environmental correlations between PLE and 10 personality disorders (PD). Methods: Diagnoses of 10 PDs according to the Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV) and PLE from the Composite International Diagnostic Interview (CIDI) were retrieved for 2793 young adult twins from the Norwegian Twin Registry. Risk for having a PD and PLEs was modeled using item response theory. Biometric twin models were fitted to estimate the genetic and environmental correlations between PDs and PLEs. Co‐twin control analysis was performed to estimate additional within‐family risk for PLEs when having a PD. Results: Phenotypic overlap between PDs and PLEs ranged from 14% to 44% in males and from 11% to 39% in females, with the highest overlap for borderline PD in both sexes. In general, we found higher genetic correlations (r = 0.14–0.72) than environmental correlations (r = 0.06–0.28) between PDs and PLEs. The highest genetic correlations between PLE and PDs were found for borderline (r = 0.72), paranoid (r = 0.56), schizotypal (r = 0.56) and antisocial PD (r = 0.49). Conclusion: We found that the co‐occurrence between PDs and PLE is the best explained by shared genetic determinants, with minor contributions from environmental factors. Interestingly, borderline PD was highly genetically correlated with PLE, warranting molecular genetic studies of this association. [ABSTRACT FROM AUTHOR]

Published
2023
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39. Psychopathy subdomains in violent offenders with and without a psychotic disorder

Author

Bell, Christina, primary, Tesli, Natalia, additional, Gurholt, Tiril P., additional, Rokicki, Jaroslav, additional, Hjell, Gabriela, additional, Fischer-Vieler, Thomas, additional, Melle, Ingrid, additional, Agartz, Ingrid, additional, Andreassen, Ole A., additional, Ringen, Petter Andreas, additional, Rasmussen, Kirsten, additional, Dahl, Hilde, additional, Friestad, Christine, additional, and Haukvik, Unn K., additional

Published
2022
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42. Psychopathy subdomains in violent offenders with and without a psychotic disorder.

Author

Bell, Christina, Tesli, Natalia, Gurholt, Tiril P., Rokicki, Jaroslav, Hjell, Gabriela, Fischer-Vieler, Thomas, Melle, Ingrid, Agartz, Ingrid, Andreassen, Ole A., Ringen, Petter Andreas, Rasmussen, Kirsten, Dahl, Hilde, Friestad, Christine, and Haukvik, Unn K.

Subjects
PSYCHOSES, VIOLENT criminals, PSYCHOPATHY, DELINQUENT behavior, FORENSIC psychiatry
Abstract

Violence in psychosis has been linked to antisocial behavior and psychopathy traits. Psychopathy comprises aspects of interpersonal, affective, lifestyle, and antisocial traits which may be differently involved in violent offending by persons with psychotic disorders. We explored psychopathy subdomains among violent offenders with and without a psychotic disorder. 46 males, with a history of severe violence, with (n = 26; age 35.85 ± 10.34 years) or without (n = 20; age 39.10 ± 11.63 years) a diagnosis of a psychotic disorder, were assessed with the Psychopathy Checklist-Revised (PCL-R). PCL-R was split into subdomains following the four-facet model. Group differences in total and subdomain scores were analyzed with a general linear model with covariates. Total PCL-R scores did not differ between the groups (p = 0.61, Cohen's d = 0.17). The violent offenders without psychotic disorders had higher facet 2 scores than the patient group with psychotic disorders (p = 0.029, Cohen's d = 0.77). Facet 1, 3, or 4 scores did not differ between the groups. Controlling for age did not alter the results. Patients with a psychotic disorder and a history of severe violence have lower affective psychopathy scores than violent offenders without psychotic disorders. This observation may point toward distinct underlying mechanisms for violence and may provide a target for focused treatment and prevention. [ABSTRACT FROM AUTHOR]

Published
2023
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49. The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data

Author

Thompson, Paul M., Stein, Jason L., Medland, Sarah E., Hibar, Derrek P., Vasquez, Alejandro Arias, Renteria, Miguel E., Toro, Roberto, Jahanshad, Neda, Schumann, Gunter, Franke, Barbara, Wright, Margaret J., Martin, Nicholas G., Agartz, Ingrid, Alda, Martin, Alhusaini, Saud, Almasy, Laura, Almeida, Jorge, Alpert, Kathryn, Andreasen, Nancy C., Andreassen, Ole A., Apostolova, Liana G., Appel, Katja, Armstrong, Nicola J., Aribisala, Benjamin, Bastin, Mark E., Bauer, Michael, Bearden, Carrie E., Bergmann, Ørjan, Binder, Elisabeth B., Blangero, John, Bockholt, Henry J., Bøen, Erlend, Bois, Catherine, Boomsma, Dorret I., Booth, Tom, Bowman, Ian J., Bralten, Janita, Brouwer, Rachel M., Brunner, Han G., Brohawn, David G., Buckner, Randy L., Buitelaar, Jan, Bulayeva, Kazima, Bustillo, Juan R., Calhoun, Vince D., Cannon, Dara M., Cantor, Rita M., Carless, Melanie A., Caseras, Xavier, Cavalleri, Gianpiero L., Chakravarty, M. Mallar, Chang, Kiki D., Ching, Christopher R. K., Christoforou, Andrea, Cichon, Sven, Clark, Vincent P., Conrod, Patricia, Coppola, Giovanni, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Deary, Ian J., de Geus, Eco J. C., den Braber, Anouk, Delvecchio, Giuseppe, Depondt, Chantal, de Haan, Lieuwe, de Zubicaray, Greig I., Dima, Danai, Dimitrova, Rali, Djurovic, Srdjan, Dong, Hongwei, Donohoe, Gary, Duggirala, Ravindranath, Dyer, Thomas D., Ehrlich, Stefan, Ekman, Carl Johan, Elvsåshagen, Torbjørn, Emsell, Louise, Erk, Susanne, Espeseth, Thomas, Fagerness, Jesen, Fears, Scott, Fedko, Iryna, Fernández, Guillén, Fisher, Simon E., Foroud, Tatiana, Fox, Peter T., Francks, Clyde, Frangou, Sophia, Frey, Eva Maria, Frodl, Thomas, Frouin, Vincent, Garavan, Hugh, Giddaluru, Sudheer, Glahn, David C., Godlewska, Beata, Goldstein, Rita Z., Gollub, Randy L., Grabe, Hans J., Grimm, Oliver, Gruber, Oliver, Guadalupe, Tulio, Gur, Raquel E., Gur, Ruben C., Göring, Harald H. H., Hagenaars, Saskia, Hajek, Tomas, Hall, Geoffrey B., Hall, Jeremy, Hardy, John, Hartman, Catharina A., Hass, Johanna, Hatton, Sean N., Haukvik, Unn K., Hegenscheid, Katrin, Heinz, Andreas, Hickie, Ian B., Ho, Beng-Choon, Hoehn, David, Hoekstra, Pieter J., Hollinshead, Marisa, Holmes, Avram J., Homuth, Georg, Hoogman, Martine, Hong, L. Elliot, Hosten, Norbert, Hottenga, Jouke-Jan, Hulshoff Pol, Hilleke E., Hwang, Kristy S., Jack, Jr, Clifford R., Jenkinson, Mark, Johnston, Caroline, Jönsson, Erik G., Kahn, René S., Kasperaviciute, Dalia, Kelly, Sinead, Kim, Sungeun, Kochunov, Peter, Koenders, Laura, Krämer, Bernd, Kwok, John B. J., Lagopoulos, Jim, Laje, Gonzalo, Landen, Mikael, Landman, Bennett A., Lauriello, John, Lawrie, Stephen M., Lee, Phil H., Le Hellard, Stephanie, Lemaître, Herve, Leonardo, Cassandra D., Li, Chiang-shan, Liberg, Benny, Liewald, David C., Liu, Xinmin, Lopez, Lorna M., Loth, Eva, Lourdusamy, Anbarasu, Luciano, Michelle, Macciardi, Fabio, Machielsen, Marise W. 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M., van Haren, Neeltje E. M., van ‘t Ent, Dennis, van Tol, Marie-Jose, Valdés Hernández, Maria C., Veltman, Dick J., Versace, Amelia, Völzke, Henry, Walker, Robert, Walter, Henrik, Wang, Lei, Wardlaw, Joanna M., Weale, Michael E., Weiner, Michael W., Wen, Wei, Westlye, Lars T., Whalley, Heather C., Whelan, Christopher D., White, Tonya, Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Zilles, David, Zwiers, Marcel P., Thalamuthu, Anbupalam, Schofield, Peter R., Freimer, Nelson B., Lawrence, Natalia S., Drevets, Wayne, and the Alzheimer’s Disease Neuroimaging Initiative, EPIGEN Consortium, IMAGEN Consortium, Saguenay Youth Study (SYS) Group

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2014
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