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1. 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

2. 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

3. 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

4. Increased cortical surface area but not altered cortical thickness or gyrification in bipolar disorder following stabilisation from a first episode of mania

Author

Van Rheenen, Tamsyn E., Cotton, Sue M., Dandash, Orwa, Cooper, Rebecca E., Ringin, Elysha, Daglas-Georgiou, Rothanthi, Allott, Kelly, Chye, Yann, Suo, Chao, Macneil, Craig, Hasty, Melissa, Hallam, Karen, McGorry, Patrick, Fornito, Alex, Yücel, Murat, Pantelis, Christos, and Berk, Michael

Published
2023
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5. Longitudinal Structural Brain Changes in Bipolar Disorder: A Multicenter Neuroimaging Study of 1232 Individuals by the ENIGMA Bipolar Disorder Working Group

Author

Abé, Christoph, Ching, Christopher R.K., Liberg, Benny, Lebedev, Alexander V., Agartz, Ingrid, Akudjedu, Theophilus N., Alda, Martin, Alnæs, Dag, Alonso-Lana, Silvia, Benedetti, Francesco, Berk, Michael, Bøen, Erlend, Bonnin, Caterina del Mar, Breuer, Fabian, Brosch, Katharina, Brouwer, Rachel M., Canales-Rodríguez, Erick J., Cannon, Dara M., Chye, Yann, Dahl, Andreas, Dandash, Orwa, Dannlowski, Udo, Dohm, Katharina, Elvsåshagen, Torbjørn, Fisch, Lukas, Fullerton, Janice M., Goikolea, Jose M., Grotegerd, Dominik, Haatveit, Beathe, Hahn, Tim, Hajek, Tomas, Heindel, Walter, Ingvar, Martin, Sim, Kang, Kircher, Tilo T.J., Lenroot, Rhoshel K., Malt, Ulrik F., McDonald, Colm, McWhinney, Sean R., Melle, Ingrid, Meller, Tina, Melloni, Elisa M.T., Mitchell, Philip B., Nabulsi, Leila, Nenadić, Igor, Opel, Nils, Overs, Bronwyn J., Panicalli, Francesco, Pfarr, Julia-Katharina, Poletti, Sara, Pomarol-Clotet, Edith, Radua, Joaquim, Repple, Jonathan, Ringwald, Kai G., Roberts, Gloria, Rodriguez-Cano, Elena, Salvador, Raymond, Sarink, Kelvin, Sarró, Salvador, Schmitt, Simon, Stein, Frederike, Suo, Chao, Thomopoulos, Sophia I., Tronchin, Giulia, Vieta, Eduard, Westlye, Lars T., White, Adam G., Yatham, Lakshmi N., Zak, Nathalia, Thompson, Paul M., Andreassen, Ole A., and Landén, Mikael

Published
2022
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7. What we learn about bipolar disorder from large-scale neuroimaging:Findings and future directions from the ENIGMA Bipolar Disorder Working Group

Author

Ching, Christopher R.K., Hibar, Derrek P., Gurholt, Tiril P., Nunes, Abraham, Thomopoulos, Sophia I., Abé, Christoph, Agartz, Ingrid, Brouwer, Rachel M., Cannon, Dara M., de Zwarte, Sonja M.C., 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, van Haren, Neeltje E.M., 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, del Mar Bonnin, Caterina, Brambilla, Paolo, Canales-Rodríguez, Erick J., Caseras, Xavier, Dandash, Orwa, Ophoff, Roel A., Ching, Christopher R.K., Hibar, Derrek P., Gurholt, Tiril P., Nunes, Abraham, Thomopoulos, Sophia I., Abé, Christoph, Agartz, Ingrid, Brouwer, Rachel M., Cannon, Dara M., de Zwarte, Sonja M.C., 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, van Haren, Neeltje E.M., 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, del Mar Bonnin, Caterina, Brambilla, Paolo, Canales-Rodríguez, Erick J., Caseras, Xavier, Dandash, Orwa, and Ophoff, Roel A.

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

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