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94 results on '"van Wingen, G. A."'

53. Allopregnanolone and mood disorders

Author

Bäckström, Torbjörn, Bixo, Marie, Johansson, Maja, Nyberg, Sigrid, Ossewaarde, L, Ragagnin, Gianna, Savic, I, Strömberg, J, Timby, Erika, van Broekhoven, F, van Wingen, G, Bäckström, Torbjörn, Bixo, Marie, Johansson, Maja, Nyberg, Sigrid, Ossewaarde, L, Ragagnin, Gianna, Savic, I, Strömberg, J, Timby, Erika, van Broekhoven, F, and van Wingen, G

Abstract

Certain women experience negative mood symptoms during the menstrual cycle and progesterone addition in estrogen treatments. In women with PMDD increased negative mood symptoms related to allopregnanolone increase during the luteal phase of ovulatory menstrual cycles. In anovulatory cycles no symptom or sex steroid increase occurs. This is unexpected as positive modulators of the GABA-A receptor are generally increasing mood. This paradoxical effect has brought forward a hypothesis that the symptoms are provoked by allopregnanolone the GABA-A receptor system. GABA-A is the major inhibitory system in the brain. Positive modulators of the GABA-A receptor include the progesterone metabolites allopregnanolone and pregnanolone, benzodiazepines, barbiturates, and alcohol. GABA-A receptor modulators are known, in low concentrations to induce adverse, anxiogenic effects whereas in higher concentrations show beneficial, calming properties. Positive GABA-A receptor modulators induce strong paradoxical effects e.g. negative mood in 3-8% of those exposed, while up to 25% have moderate symptoms thus similar as the prevalence of PMDD, 3-8% among women in fertile ages, and up to 25% have moderate symptoms of premenstrual syndrome (PMS). The mechanism behind paradoxical reaction might be similar among them who react on positive GABA-A receptor modulators and in women with PMDD. In women the severity of these mood symptoms are related to the allopregnanolone serum concentrations in an inverted U-shaped curve. Negative mood symptoms occur when the serum concentration of allopregnanolone is similar to endogenous luteal phase levels, while low and high concentrations have less effect on mood. Low to moderate progesterone/allopregnanolone concentrations in women increases the activity in the amygdala (measured with fMRI) similar to the changes seen during anxiety reactions. Higher concentrations give decreased amygdala activity similar as seen during benzodiazepine treatment with calmin

Published
2014
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54. Neuroactive steroids in brain and relevance to mood

Author

Bäckström, T., Andréen, L., Bixo, M., Björn, I., Fernández, G., Johansson, I.-M., Lundgren, P., Löfgren, M., Nyberg, S., Ragagnin, G., Poromaa-Sundström, I., Strömberg, J., van Broekhoven, F., van Wingen, G., Wang, M., Ritsner, M. S., Weizman, A., and Other departments

Published
2008

55. Neuroactive steroids: effects on cognitive functions

Author

Bäckström, T., Birzniece, V., Fernández, G., Johansson, I. M., Kask, K., Lindblad, C., Lundgren, P., Nyberg, S., Ragagnin, G., Sundström-Poromaa, I., Strömberg, J., Turkmen, S., Wang, M., van Broekhoven, F., van Wingen, G. A., Ritsner, M. S., Weizman, A., and Other departments

Published
2008

63. Deep brain stimulation restores frontostriatal network activity in obsessive-compulsive disorder.

Author

Figee, M., Luigjes, J., Smolders, R., Valencia-Alfonso, C.E., Van Wingen, G., De Kwaadsteniet, B., Mantione, M., Ooms, P., De Koning, P., Vulink, N., Levar, N., Droge, L., Van den Munckhof, P., Schuurman, P.R., Nederveen, A., Van den Brink, W., Mazaheri, A., Vink, M., Denys, D., Figee, M., Luigjes, J., Smolders, R., Valencia-Alfonso, C.E., Van Wingen, G., De Kwaadsteniet, B., Mantione, M., Ooms, P., De Koning, P., Vulink, N., Levar, N., Droge, L., Van den Munckhof, P., Schuurman, P.R., Nederveen, A., Van den Brink, W., Mazaheri, A., Vink, M., and Denys, D.

Published
2013

66. Paradoxical effects of GABA-A modulators may explain sex steroid induced negative mood symptoms in some persons

Author

Bäckström, Torbjörn, Haage, D., Löfgren, Mats, Johansson, I. M., Strömberg, J., Nyberg, S., Andreen, Lotta, Ossewaarde, L., van Wingen, G. A., Turkmen, Sahruh, Bengtsson, S. K., Bäckström, Torbjörn, Haage, D., Löfgren, Mats, Johansson, I. M., Strömberg, J., Nyberg, S., Andreen, Lotta, Ossewaarde, L., van Wingen, G. A., Turkmen, Sahruh, and Bengtsson, S. K.

Abstract

Some women have negative mood symptoms, caused by progestagens in hormonal contraceptives or sequential hormone therapy or by progesterone in the luteal phase of the menstrual cycle, which may be attributed to metabolites acting on the GABA-A receptor. The GABA system is the major inhibitory system in the adult CNS and most positive modulators of the GABA-A receptor (benzodiazepines, barbiturates, alcohol, GABA steroids), induce inhibitory (e.g. anesthetic, sedative, anticonvulsant, anxiolytic) effects. However, some individuals have adverse effects (seizures, increased pain, anxiety, irritability, aggression) upon exposure. Positive GABA-A receptor modulators induce strong paradoxical effects including negative mood in 3%-8% of those exposed, while up to 25% have moderate symptoms. The effect is biphasic: low concentrations induce an adverse anxiogenic effect while higher concentrations decrease this effect and show inhibitory, calming properties. The prevalence of premenstrual dysphoric disorder (PMDD) is also 3%-8% among women in fertile ages, and up to 25% have more moderate symptoms of premenstrual syndrome (PMS). Patients with PMDD have severe luteal phase-related symptoms and show changes in GABA-A receptor sensitivity and GABA concentrations. Findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor, which may be explained by one or more of three hypotheses regarding the paradoxical effect of GABA steroids on behavior: (1) under certain conditions, such as puberty, the relative fraction of certain GABA-A receptor subtypes may be altered, and at those subtypes the GABA steroids may act as negative modulators in contrast to their usual role as positive modulators; (2) in certain brain areas of vulnerable women the transmembrane C1(-) gradient may be altered by factors such as estrogens that favor excitability; (3) inhibition of inhibitory neurons may promote disinhi

Published
2011
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67. Gonadal hormone regulation of the emotion circuitry in humans

Author

van Wingen, G. A., Ossewaarde, L., Bäckstrom, Torbjörn, Hermans, E. J., Fernandez, G., van Wingen, G. A., Ossewaarde, L., Bäckstrom, Torbjörn, Hermans, E. J., and Fernandez, G.

Abstract

Gonadal hormones are known to influence the regulation of emotional responses and affective states. Whereas fluctuations in progesterone and estradiol are associated with increased vulnerability for mood disorders, testosterone is mainly associated with social dominance, aggressive, and antisocial behavior. Here, we review recent functional neuroimaging studies that have started to elucidate how these hormones modulate the neural circuitry that is important for emotion regulation, which includes the amygdala and the medial prefrontal (mPFC) and orbitofrontal cortex (OFC). The amygdala is thought to generate emotional responses, and the prefrontal brain regions to regulate those responses. Overall, studies that have investigated women during different phases of the menstrual cycle suggest that progesterone and estradiol may have opposing actions on the amygdala and prefrontal cortex. In addition, the influence of exogenous progesterone appears to be dose-dependent. Endogenous testosterone concentrations are generally positively correlated to amygdala and OFC responses, and exogenous testosterone increases amygdala reactivity. Whereas the administration of progesterone increases amygdala reactivity and its connectivity with the mPFC, testosterone administration increases amygdala reactivity but decreases its connectivity with the OFC. We propose that this opposing influence on amygdala-prefrontal coupling may contribute to the divergent effects of progesterone and testosterone on emotion regulation and behavioral inhibition, respectively, which may promote the differential vulnerability to various psychiatric disorders between women and men. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.

Published
2011
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75. The thalamus and its subnuclei—a gateway to obsessive-compulsive disorder

Author

Weeland, Cees J., Kasprzak, Selina, Joode, Niels T. de, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H., Anticevic, Alan, Arnold, Paul D., Balachander, Srinivas, Banaj, Nerisa, Bargalló Alabart, Núria​, Wang, Zhen, Watanabe, Anri, Wolters, Lidewij H., Xu, Xiufeng, Yun, Je-Yeon, Zhao, Qing, White, Tonya, Thompson, Paul M., Stein, Dan J., Heuvel, Odile A. van den, Vriend, Chris, ENIGMA-OCD Working Group, Batistuzzo, Marcelo C., Benedetti, Francesco, Beucke, Jan C., Bollettini, Irene, Brecke, Vilde, Brem, Silvia, Cappi, Carolina, Cheng, Yuqi, Cho, Kang Ik K., Costa, Daniel L. C., Dallaspezia, Sara, Denys, Damiaan, Eng, Goi Khia, Ferreira, Sónia, Feusner, Jamie D., Fontaine, Martine, Fouche, Jean Paul, Grazioplene, Rachael G., Gruner, Patricia, He, Mengxin, Hirano, Yoshiyuki, Hoexter, Marcelo Q., Huyser, Chaim, Hu, Hao, Jaspers-Fayer, Fern, Kathmann, Norbert, Kaufmann, Christian, Kim, Minah, Koch, Kathrin, Bin Kwak, Yoo, Kwon, Jun Soo, Lazaro, Luisa, Li, Chiang-Shan R., Lochner, Christine, Marsh, Rachel, Martínez Zalacaín, Ignacio, Mataix Cols, David, Menchón, Jose M., Minnuzi, Luciano, Moreira, Pedro Silva, Morgado, Pedro, Nakagawa, Akiko, Nakamae, Takashi, Narayanaswamy, Janardhanan C., Nurmi, Erika L., Ortiz, Ana E., Pariente, Jose C., Piacentini, John, Picó Pérez, Maria, Piras, Fabrizio, Piras, Federica, Pittenger, Christopher, Reddy, Y. C. Janardhan, Rodriguez Manrique, Daniela, Sakai, Yuki, Shimizu, Eiji, Shivakumar, Venkataram, Simpson, Helen Blair, Soreni, Noam, Soriano Mas, Carles, Sousa, Nuno, Spalletta, Gianfranco, Stern, Emily R., Stevens, Michael C., Stewart, S. Evelyn, Szeszko, Philip R., Takahashi, Jumpei, Tanamatis, Tais, Tang, Jinsong, Thorsen, Anders Lillevik, Tolin, David, Werf, Ysbrand D. van der, Van Marle, Hein, Wingen, Guido A. van, Vecchio, Daniela, Venkatasubramanian, G., Walitza, Susanne, Wang, Jicai, Child and Adolescent Psychiatry / Psychology, Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, Child Psychiatry, Child and Adolescent Psychiatry & Psychosocial Care, ANS - Cellular & Molecular Mechanisms, ANS - Brain Imaging, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Psychiatry, Amsterdam Neuroscience - Systems & Network Neuroscience, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Neurodegeneration, Amsterdam Neuroscience - Brain Imaging, Weeland, C. J., Kasprzak, S., de Joode, N. T., Abe, Y., Alonso, P., Ameis, S. H., Anticevic, A., Arnold, P. D., Balachander, S., Banaj, N., Bargallo, N., Batistuzzo, M. C., Benedetti, F., Beucke, J. C., Bollettini, I., Brecke, V., Brem, S., Cappi, C., Cheng, Y., Cho, K. I. K., Costa, D. L. C., Dallaspezia, S., Denys, D., Eng, G. K., Ferreira, S., Feusner, J. D., Fontaine, M., Fouche, J. -P., Grazioplene, R. G., Gruner, P., He, M., Hirano, Y., Hoexter, M. Q., Huyser, C., Hu, H., Jaspers-Fayer, F., Kathmann, N., Kaufmann, C., Kim, M., Koch, K., Bin Kwak, Y., Kwon, J. S., Lazaro, L., Li, C. -S. R., Lochner, C., Marsh, R., Martinez-Zalacain, I., Mataix-Cols, D., Menchon, J. M., Minnuzi, L., Moreira, P. S., Morgado, P., Nakagawa, A., Nakamae, T., Narayanaswamy, J. C., Nurmi, E. L., Ortiz, A. E., Pariente, J. C., Piacentini, J., Pico-Perez, M., Piras, F., Pittenger, C., Reddy, Y. C. J., Rodriguez-Manrique, D., Sakai, Y., Shimizu, E., Shivakumar, V., Simpson, H. B., Soreni, N., Soriano-Mas, C., Sousa, N., Spalletta, G., Stern, E. R., Stevens, M. C., Stewart, S. E., Szeszko, P. R., Takahashi, J., Tanamatis, T., Tang, J., Thorsen, A. L., Tolin, D., van der Werf, Y. D., van Marle, H., van Wingen, G. A., Vecchio, D., Venkatasubramanian, G., Walitza, S., Wang, J., Wang, Z., Watanabe, A., Wolters, L. H., Xu, X., Yun, J. -Y., Zhao, Q., White, T., Thompson, P. M., Stein, D. J., van den Heuvel, O. A., and Vriend, C.

Subjects
Adult, Obsessive-Compulsive Disorder, medicine.medical_specialty, Adolescent, Population, Thalamus, Audiology, Cellular and Molecular Neuroscience, Group differences, SDG 3 - Good Health and Well-being, Obsessive compulsive, Intracranial volume, Humans, Medicine, Brain magnetic resonance imaging, In patient, Child, education, Biological Psychiatry, education.field_of_study, business.industry, Symptom severity, Brain, Tàlem (Anatomia), Magnetic Resonance Imaging, Compulsive behavior, Psychiatry and Mental health, Psychiatric disorders, Conducta compulsiva, business, Neuroscience
Abstract

Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered ( https://osf.io/73dvy ) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (, Translational Psychiatry, 12 (1), ISSN:2158-3188

Published
2022

76. Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders

Author

Committee, Writing, Disorder, Autism Spectrum, French, Leon, Grevet, Eugenio H, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Gruner, Patricia, Guerrero-Pedraza, Amalia, Gur, Raquel E, Gur, Ruben C, Haar, Shlomi, Haarman, Bartholomeus C M, Thomopoulos, Sophia I, Haavik, Jan, Hahn, Tim, Hajek, Tomas, Harrison, Benjamin J, Harrison, Neil A, Hartman, Catharina A, Whalley, Heather C, Heslenfeld, Dirk J, Hibar, Derrek P, Hilland, Eva, Pozzi, Elena, Hirano, Yoshiyuki, Ho, Tiffany C, Hoekstra, Pieter J, Hoekstra, Liesbeth, Hohmann, Sarah, Hong, L. E., Höschl, Cyril, Høvik, Marie F, Howells, Fleur M, Nenadic, Igor, Abe, Yoshinari, Jalbrzikowski, Maria, James, Anthony C, Janssen, Joost, Jaspers-Fayer, Fern, Xu, Jian, Jonassen, Rune, Karkashadze, Georgii, King, Joseph A, Kircher, Tilo, Kirschner, Matthias, Abé, Christoph, Koch, Kathrin, Kochunov, Peter, Kohls, Gregor, Konrad, Kerstin, Krämer, Bernd, Krug, Axel, Kuntsi, Jonna, Kwon, Jun Soo, Landén, Mikael, Landrø, Nils I, Anticevic, Alan, Lazaro, Luisa, Lebedeva, Irina S, Leehr, Elisabeth J, Lera-Miguel, Sara, Lesch, Klaus-Peter, Lochner, Christine, Louza, Mario R, Luna, Beatriz, Lundervold, Astri J, MacMaster, Frank P, Alda, Martin, Maglanoc, Luigi A, Malpas, Charles B, Portella, Maria J, Marsh, Rachel, Martyn, Fiona M, Mataix-Cols, David, Mathalon, Daniel H, McCarthy, Hazel, McDonald, Colm, McPhilemy, Genevieve, Aleman, Andre, Meinert, Susanne, Menchón, José M, Minuzzi, Luciano, Mitchell, Philip B, Moreno, Carmen, Morgado, Pedro, Muratori, Filippo, Murphy, Clodagh M, Murphy, Declan, Mwangi, Benson, Alloza, Clara, Nabulsi, Leila, Nakagawa, Akiko, Nakamae, Takashi, Namazova, Leyla, Narayanaswamy, Janardhanan, Jahanshad, Neda, Nguyen, Danai D, Nicolau, Rosa, O'Gorman Tuura, Ruth L, O'Hearn, Kirsten, Alonso-Lana, Silvia, Oosterlaan, Jaap, Opel, Nils, Ophoff, Roel A, Oranje, Bob, García de la Foz, Victor Ortiz, Overs, Bronwyn J, Paloyelis, Yannis, Pantelis, Christos, Parellada, Mara, Pauli, Paul, Disorder, Bipolar, Ameis, Stephanie H, Picó-Pérez, Maria, Picon, Felipe A, Piras, Fabrizio, Piras, Federica, Plessen, Kerstin J, Pomarol-Clotet, Edith, Preda, Adrian, Puig, Olga, Quidé, Yann, Radua, Joaquim, Anagnostou, Evdokia, Ramos-Quiroga, J Antoni, Rasser, Paul E, Rauer, Lisa, Reddy, Janardhan, Redlich, Ronny, Reif, Andreas, Reneman, Liesbeth, Repple, Jonathan, Retico, Alessandra, Richarte, Vanesa, McIntosh, Andrew A, Richter, Anja, Rosa, Pedro G P, Rubia, Katya K, Hashimoto, Ryota, Sacchet, Matthew D, Salvador, Raymond, Santonja, Javier, Sarink, Kelvin, Sarró, Salvador, Satterthwaite, Theodore D, Arango, Celso, Sawa, Akira, Schall, Ulrich, Schofield, Peter R, Schrantee, Anouk, Seitz, Jochen, Serpa, Mauricio H, Setién-Suero, Esther, Shaw, Philip, Shook, Devon, Silk, Tim J, Arnold, Paul D, Sim, Kang, Simon, Schmitt, Simpson, Helen Blair, Singh, Aditya, Skoch, Antonin, Skokauskas, Norbert, Soares, Jair C, Soreni, Noam, Soriano-Mas, Carles, Spalletta, Gianfranco, Asherson, Philip, Spaniel, Filip, Lawrie, Stephen M, Stern, Emily R, Stewart, S Evelyn, Takayanagi, Yoichiro, Temmingh, Henk S, Tolin, David F, Tomecek, David, Tordesillas-Gutiérrez, Diana, Tosetti, Michela, Assogna, Francesca, Uhlmann, Anne, van Amelsvoort, Therese, van der Wee, Nic J A, van der Werff, Steven J A, van Haren, Neeltje E M, van Wingen, Guido A, Vance, Alasdair, Vázquez-Bourgon, Javier, Vecchio, Daniela, Venkatasubramanian, Ganesan, Auzias, Guillaume, Vieta, Eduard, Vilarroya, Oscar, Vives-Gilabert, Yolanda, Voineskos, Aristotle N, Völzke, Henry, von Polier, Georg G, Walton, Esther, Weickert, Thomas W, Weickert, Cynthia Shannon, Weideman, Andrea S, Ayesa-Arriola, Rosa, Wittfeld, Katharina, Wolf, Daniel H, Wu, Mon-Ju, Yang, T. T., Yang, Sikun, Yoncheva, Yuliya, Yun, Je-Yeon, Cheng, Yuqi, Zanetti, Marcus V, Ziegler, Georg C, Bakker, Geor, Franke, Barbara, Hoogman, Martine, Buitelaar, Jan K, van Rooij, Daan, Andreassen, Ole A, Ching, Christopher R K, Veltman, Dick J, Schmaal, Lianne, Stein, Dan J, van den Heuvel, Odile A, Disorder, Major Depressive, Banaj, Nerisa, Turner, Jessica A, van Erp, Theo G M, Pausova, Zdenka, Thompson, Paul M, Paus, Tomáš, Attention-Deficit/Hyperactivity Disorder, Banaschewski, Tobias, Bandeira, Cibele E, Baranov, Alexandr, Bargalló, Núria, Bau, Claiton H D, Baumeister, Sarah, Baune, Bernhard T, Bellgrove, Mark A, Benedetti, Francesco, Disorder, Obsessive-Compulsive, Bertolino, Alessandro, Boedhoe, Premika S W, Boks, Marco, Bollettini, Irene, Del Mar Bonnin, Caterina, Borgers, Tiana, Borgwardt, Stefan, Brandeis, Daniel, Brennan, Brian P, Bruggemann, Jason M, Groups, Schizophrenia ENIGMA Working, Bülow, Robin, Busatto, Geraldo F, Calderoni, Sara, Calhoun, Vince D, Calvo, Rosa, Canales-Rodríguez, Erick J, Cannon, Dara M, Carr, Vaughan J, Cascella, Nicola, Cercignani, Mara, Patel, Yash, Chaim-Avancini, Tiffany M, Christakou, Anastasia, Coghill, David, Conzelmann, Annette, Crespo-Facorro, Benedicto, Cubillo, Ana I, Cullen, Kathryn R, Cupertino, Renata B, Daly, Eileen, Dannlowski, Udo, Parker, Nadine, Davey, Christopher G, Denys, Damiaan, Deruelle, Christine, Di Giorgio, Annabella, Dickie, Erin W, Dima, Danai, Dohm, Katharina, Ehrlich, Stefan, Ely, Benjamin A, Erwin-Grabner, Tracy, Shin, Jean, Ethofer, Thomas, Fair, Damien A, Fallgatter, Andreas, Faraone, Stephen V, Fatjó-Vilas, Mar, Fedor, Jennifer M, Fitzgerald, Kate D, Ford, Judith M, Frodl, Thomas, Fu, Cynthia H Y, Howard, Derek, Fullerton, Janice M, Gabel, Matt C, Glahn, David C, Roberts, Gloria, Gogberashvili, Tinatin, Goikolea, Jose M, Gotlib, Ian H, Goya-Maldonado, Roberto, Grabe, Hans, Green, Melissa J, Patel, Y., Parker, N., Shin, J., Howard, D., French, L., Thomopoulos, S. I., Pozzi, E., Abe, Y., Abe, C., Anticevic, A., Alda, M., Aleman, A., Alloza, C., Alonso-Lana, S., Ameis, S. H., Anagnostou, E., Mcintosh, A. A., Arango, C., Arnold, P. D., Asherson, P., Assogna, F., Auzias, G., Ayesa-Arriola, R., Bakker, G., Banaj, N., Banaschewski, T., Bandeira, C. E., Baranov, A., Bargallo, N., Bau, C. H. D., Baumeister, S., Baune, B. T., Bellgrove, M. A., Benedetti, F., Bertolino, A., Boedhoe, P. S. W., Boks, M., Bollettini, I., Del Mar Bonnin, C., Borgers, T., Borgwardt, S., Brandeis, D., Brennan, B. P., Bruggemann, J. M., Bulow, R., Busatto, G. F., Calderoni, S., Calhoun, V. D., Calvo, R., Canales-Rodriguez, E. J., Cannon, D. M., Carr, V. J., Cascella, N., Cercignani, M., Chaim-Avancini, T. M., Christakou, A., Coghill, D., Conzelmann, A., Crespo-Facorro, B., Cubillo, A. I., Cullen, K. R., Cupertino, R. B., Daly, E., Dannlowski, U., Davey, C. G., Denys, D., Deruelle, C., Di Giorgio, A., Dickie, E. W., Dima, D., Dohm, K., Ehrlich, S., Ely, B. A., Erwin-Grabner, T., Ethofer, T., Fair, D. A., Fallgatter, A. J., Faraone, S. V., Fatjo-Vilas, M., Fedor, J. M., Fitzgerald, K. D., Ford, J. M., Frodl, T., Fu, C. H. Y., Fullerton, J. M., Gabel, M. C., Glahn, D. C., Roberts, G., Gogberashvili, T., Goikolea, J. M., Gotlib, I. H., Goya-Maldonado, R., Grabe, H. J., Green, M. J., Grevet, E. H., Groenewold, N. A., Grotegerd, D., Gruber, O., Gruner, P., Guerrero-Pedraza, A., Gur, R. E., Gur, R. C., Haar, S., Haarman, B. C. M., Haavik, J., Hahn, T., Hajek, T., Harrison, B. J., Harrison, N. A., Hartman, C. A., Whalley, H. C., Heslenfeld, D. J., Hibar, D. P., Hilland, E., Hirano, Y., Ho, T. C., Hoekstra, P. J., Hoekstra, L., Hohmann, S., Hong, L. E., Hoschl, C., Hovik, M. F., Howells, F. M., Nenadic, I., Jalbrzikowski, M., James, A. C., Janssen, J., Jaspers-Fayer, F., Xu, J., Jonassen, R., Karkashadze, G., King, J. A., Kircher, T., Kirschner, M., Koch, K., Kochunov, P., Kohls, G., Konrad, K., Kramer, B., Krug, A., Kuntsi, J., Kwon, J. S., Landen, M., Landro, N. I., Lazaro, L., Lebedeva, I. S., Leehr, E. J., Lera-Miguel, S., Lesch, K. -P., Lochner, C., Louza, M. R., Luna, B., Lundervold, A. J., Macmaster, F. P., Maglanoc, L. A., Malpas, C. B., Portella, M. J., Marsh, R., Martyn, F. M., Mataix-Cols, D., Mathalon, D. H., Mccarthy, H., Mcdonald, C., Mcphilemy, G., Meinert, S., Menchon, J. M., Minuzzi, L., Mitchell, P. B., Moreno, C., Morgado, P., Muratori, F., Murphy, C. M., Murphy, D., Mwangi, B., Nabulsi, L., Nakagawa, A., Nakamae, T., Namazova, L., Narayanaswamy, J., Jahanshad, N., Nguyen, D. D., Nicolau, R., O'Gorman Tuura, R. L., O'Hearn, K., Oosterlaan, J., Opel, N., Ophoff, R. A., Oranje, B., Garcia De La Foz, V. O., Overs, B. J., Paloyelis, Y., Pantelis, C., Parellada, M., Pauli, P., Pico-Perez, M., Picon, F. A., Piras, F., Plessen, K. J., Pomarol-Clotet, E., Preda, A., Puig, O., Quide, Y., Radua, J., Ramos-Quiroga, J. A., Rasser, P. E., Rauer, L., Reddy, J., Redlich, R., Reif, A., Reneman, L., Repple, J., Retico, A., Richarte, V., Richter, A., Rosa, P. G. P., Rubia, K. K., Hashimoto, R., Sacchet, M. D., Salvador, R., Santonja, J., Sarink, K., Sarro, S., Satterthwaite, T. D., Sawa, A., Schall, U., Schofield, P. R., Schrantee, A., Seitz, J., Serpa, M. H., Setien-Suero, E., Shaw, P., Shook, D., Silk, T. J., Sim, K., Simon, S., Simpson, H. B., Singh, A., Skoch, A., Skokauskas, N., Soares, J. C., Soreni, N., Soriano-Mas, C., Spalletta, G., Spaniel, F., Lawrie, S. M., Stern, E. R., Stewart, S. E., Takayanagi, Y., Temmingh, H. S., Tolin, D. F., Tomecek, D., Tordesillas-Gutierrez, D., Tosetti, M., Uhlmann, A., Van Amelsvoort, T., Van Der Wee, N. J. A., Van Der Werff, S. J. A., Van Haren, N. E. M., Van Wingen, G. A., Vance, A., Vazquez-Bourgon, J., Vecchio, D., Venkatasubramanian, G., Vieta, E., Vilarroya, O., Vives-Gilabert, Y., Voineskos, A. N., Volzke, H., Von Polier, G. G., Walton, E., Weickert, T. W., Weickert, C. S., Weideman, A. S., Wittfeld, K., Wolf, D. H., Wu, M. -J., Yang, T. T., Yang, K., Yoncheva, Y., Yun, J. -Y., Cheng, Y., Zanetti, M. V., Ziegler, G. C., Franke, B., Hoogman, M., Buitelaar, J. K., Van Rooij, D., Andreassen, O. A., Ching, C. R. K., Veltman, D. J., Schmaal, L., Stein, D. J., Van Den Heuvel, O. A., Turner, J. A., Van Erp, T. G. M., Pausova, Z., Thompson, P. M., Paus, T., Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Pediatric surgery, Radiology and nuclear medicine, Anatomy and neurosciences, Psychiatry, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Neurodegeneration, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: MA Med Staf Spec Psychiatrie (9), Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, General Paediatrics, ARD - Amsterdam Reproduction and Development, Radiology and Nuclear Medicine, APH - Personalized Medicine, ANS - Brain Imaging, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, University of Zurich, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Clinical Neuropsychology, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Child and Adolescent Psychiatry / Psychology, IBBA, and Cognitive Psychology

Subjects
Male, Obsessive-Compulsive Disorder, Bipolar Disorder, Autism Spectrum Disorder, Autism, [SDV]Life Sciences [q-bio], Gene Expression, cytology [Cerebral Cortex], Cohort Studies, Fetal Development, physiology [Gene Expression], 2738 Psychiatry and Mental Health, 0302 clinical medicine, diagnostic imaging [Cerebral Cortex], SCHIZOPHRENIA, BRAIN, Child, Obsessive-compulsive disorder (OCD), Original Investigation, Aged, 80 and over, Cerebral Cortex, 0303 health sciences, pathology [Depressive Disorder, Major], Principal Component Analysis, Adolescent psychiatry, 10058 Department of Child and Adolescent Psychiatry, Middle Aged, diagnostic imaging [Obsessive-Compulsive Disorder], REGIONS, Magnetic Resonance Imaging, 3. Good health, FALSE DISCOVERY RATE, Psychiatry and Mental health, Autism spectrum disorder, Schizophrenia, growth & development [Cerebral Cortex], Child, Preschool, Major depressive disorder, diagnostic imaging [Schizophrenia], Esquizofrènia, Female, Psiquiatria infantil, Psiquiatria de l'adolescència, diagnostic imaging [Autism Spectrum Disorder], Adult, medicine.medical_specialty, Adolescent, Human Development, 610 Medicine & health, diagnostic imaging [Bipolar Disorder], pathology [Autism Spectrum Disorder], diagnostic imaging [Depressive Disorder, Major], 03 medical and health sciences, Young Adult, All institutes and research themes of the Radboud University Medical Center, Neuroimaging, SDG 3 - Good Health and Well-being, CEREBRAL-CORTEX, Child psychiatry, medicine, Attention deficit hyperactivity disorder, Humans, Bipolar disorder, ddc:610, Psychiatry, pathology [Schizophrenia], 030304 developmental biology, Aged, Depressive Disorder, Major, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, DENDRITE, Computational Biology, Correction, pathology [Attention Deficit Disorder with Hyperactivity], physiology [Fetal Development], medicine.disease, PATHOLOGY, pathology [Bipolar Disorder], pathology [Obsessive-Compulsive Disorder], 10036 Medical Clinic, Attention Deficit Disorder with Hyperactivity, 10054 Clinic for Psychiatry, Psychotherapy, and Psychosomatics, Case-Control Studies, DENSITY, ORIGINS, HIPPOCAMPUS, diagnostic imaging [Attention Deficit Disorder with Hyperactivity], pathology [Cerebral Cortex], Autisme, business, Neuroscience, 030217 neurology & neurosurgery, physiology [Human Development]
Abstract

[Importance] Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood., [Objective] To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia., [Design, Setting, and Participants] Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244., [Main Outcomes and Measures] Interregional profiles of group difference in cortical thickness between cases and controls., [Results] A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders., [Conclusions and Relevance] In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.

Published
2021

77. Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium

Author

Xiang-Zhen Kong, Premika S.W. Boedhoe, Yoshinari Abe, Pino Alonso, Stephanie H. Ameis, Paul D. Arnold, Francesca Assogna, Justin T. Baker, Marcelo C. Batistuzzo, Francesco Benedetti, Jan C. Beucke, Irene Bollettini, Anushree Bose, Silvia Brem, Brian P. Brennan, Jan Buitelaar, Rosa Calvo, Yuqi Cheng, Kang Ik K. Cho, Sara Dallaspezia, Damiaan Denys, Benjamin A. Ely, Jamie Feusner, Kate D. Fitzgerald, Jean-Paul Fouche, Egill A. Fridgeirsson, David C. Glahn, Patricia Gruner, Deniz A. Gürsel, Tobias U. Hauser, Yoshiyuki Hirano, Marcelo Q. Hoexter, Hao Hu, Chaim Huyser, Anthony James, Fern Jaspers-Fayer, Norbert Kathmann, Christian Kaufmann, Kathrin Koch, Masaru Kuno, Gerd Kvale, Jun Soo Kwon, Luisa Lazaro, Yanni Liu, Christine Lochner, Paulo Marques, Rachel Marsh, Ignacio Martínez-Zalacaín, David Mataix-Cols, Sarah E. Medland, José M. Menchón, Luciano Minuzzi, Pedro S. Moreira, Astrid Morer, Pedro Morgado, Akiko Nakagawa, Takashi Nakamae, Tomohiro Nakao, Janardhanan C. Narayanaswamy, Erika L. Nurmi, Joseph O'Neill, Jose C. Pariente, Chris Perriello, John Piacentini, Fabrizio Piras, Federica Piras, Christopher Pittenger, Y.C. Janardhan Reddy, Oana Georgiana Rus-Oswald, Yuki Sakai, Joao R. Sato, Lianne Schmaal, H. Blair Simpson, Noam Soreni, Carles Soriano-Mas, Gianfranco Spalletta, Emily R. Stern, Michael C. Stevens, S. Evelyn Stewart, Philip R. Szeszko, David F. Tolin, Aki Tsuchiyagaito, Daan van Rooij, Guido A. van Wingen, Ganesan Venkatasubramanian, Zhen Wang, Je-Yeon Yun, Paul M. Thompson, Dan J. Stein, Odile A. van den Heuvel, Clyde Francks, Alan Anticevic, Nerisa Banaj, Nuria Bargalló, Daniel Brandeis, Geraldo F. Busatto, Anna Calvo, Valentina Ciullo, Froukje E. de Vries, Stella J. de Wit, Erin Dickie, Renate Drechsler, Madalena Esteves, Andrea Falini, Yu Fang, Martijn Figee, Martine Fontaine, Geoff Hall, Sayo Hamatani, Gregory L. Hanna, Bjarne Hansen, Keisuke Ikari, Neda Jahanshad, Ricardo Magalhães, Yasutaka Masuda, Koji Matsumoto, James T. McCracken, Euripedes C. Miguel, Jin Narumoto, Seiji Nishida, Sara Poletti, Tim Reess, Eiji Shimizu, Nuno Sousa, Jumpei Takahashi, Jinsong Tang, Anders Lillevik Thorsen, Ysbrand D. van der Werf, Dick J. Veltman, Daniela Vecchio, Susanne Walitza, Anri Watanabe, Jian Xu, Xiufeng Xu, Kei Yamada, Tokiko Yoshida, Mojtaba Zarei, Qing Zhao, Cong Zhou, ENIGMA-OCD Working Group, Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, Graduate School, Child Psychiatry, Kong, X. -Z., Boedhoe, P. S. W., Abe, Y., Alonso, P., Ameis, S. H., Arnold, P. D., Assogna, F., Baker, J. T., Batistuzzo, M. C., Benedetti, F., Beucke, J. C., Bollettini, I., Bose, A., Brem, S., Brennan, B. P., Buitelaar, J., Calvo, R., Cheng, Y., Cho, K. I. K., Dallaspezia, S., Denys, D., Ely, B. A., Feusner, J., Fitzgerald, K. D., Fouche, J. -P., Fridgeirsson, E. A., Glahn, D. C., Gruner, P., Gursel, D. A., Hauser, T. U., Hirano, Y., Hoexter, M. Q., Hu, H., Huyser, C., James, A., Jaspers-Fayer, F., Kathmann, N., Kaufmann, C., Koch, K., Kuno, M., Kvale, G., Kwon, J. S., Lazaro, L., Liu, Y., Lochner, C., Marques, P., Marsh, R., Martinez-Zalacain, I., Mataix-Cols, D., Medland, S. E., Menchon, J. M., Minuzzi, L., Moreira, P. S., Morer, A., Morgado, P., Nakagawa, A., Nakamae, T., Nakao, T., Narayanaswamy, J. C., Nurmi, E. L., O'Neill, J., Pariente, J. C., Perriello, C., Piacentini, J., Piras, F., Pittenger, C., Reddy, Y. C. J., Rus-Oswald, O. G., Sakai, Y., Sato, J. R., Schmaal, L., Simpson, H. B., Soreni, N., Soriano-Mas, C., Spalletta, G., Stern, E. R., Stevens, M. C., Stewart, S. E., Szeszko, P. R., Tolin, D. F., Tsuchiyagaito, A., van Rooij, D., van Wingen, G. A., Venkatasubramanian, G., Wang, Z., Yun, J. -Y., Anticevic, A., Banaj, N., Bargallo, N., Brandeis, D., Busatto, G. F., Calvo, A., Ciullo, V., de Vries, F. E., de Wit, S. J., Dickie, E., Drechsler, R., Esteves, M., Falini, A., Fang, Y., Figee, M., Fontaine, M., Hall, G., Hamatani, S., Hanna, G. L., Hansen, B., Ikari, K., Jahanshad, N., Magalhaes, R., Masuda, Y., Matsumoto, K., Mccracken, J. T., Miguel, E. C., Narumoto, J., Nishida, S., Poletti, S., Reess, T., Shimizu, E., Sousa, N., Takahashi, J., Tang, J., Thorsen, A. L., van der Werf, Y. D., Veltman, D. J., Vecchio, D., Walitza, S., Watanabe, A., Xu, J., Xu, X., Yamada, K., Yoshida, T., Zarei, M., Zhao, Q., Zhou, C., Thompson, P. M., Stein, D. J., van den Heuvel, O. A., Francks, C., Netherlands Institute for Neuroscience (NIN), Universidade do Minho, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, and Psychiatry

Subjects
0301 basic medicine, Adult, medicine.medical_specialty, Obsessive-Compulsive Disorder, Mega-analysis, Mega-analysi, media_common.quotation_subject, Thalamus, Medicina Básica [Ciências Médicas], Audiology, Asymmetry, behavioral disciplines and activities, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, mental disorders, medicine, Image Processing, Computer-Assisted, Obsessive-compulsive disorder, Brain asymmetry, Humans, Child, Biological Psychiatry, Depression (differential diagnoses), media_common, Brain Mapping, Science & Technology, medicine.diagnostic_test, business.industry, Laterality, Neurosi obsessiva, Brain, Magnetic resonance imaging, Cerebral cortex, Magnetic Resonance Imaging, humanities, Escorça cerebral, 030104 developmental biology, Meta-analysis, Ciências Médicas::Medicina Básica, Pallidum, Anxiety, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Accepted Manuscript, BACKGROUND: Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD.METHODS: We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status.RESULTS: In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -20.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets.CONCLUSIONS: The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD., This research was funded by the Max Planck Society (Germany). Additional funding was from the Japan Society for the Promotion of Science (KAKENHI Grant No. 18K15523 [to YA], KAKENHI Grant No. 16K04344 [to YH], KAKENHI Grant Nos. 16K19778 and 18K07608 [to TNakam], and KAKENHI Grant No. 26461762 [to AN]); the Carlos III Health Institute (Grant No. PI14/00419 [to PA], Grant No. PI040829 cofunded by European Regional Development Fund [to LL], Grant No. FI17/00294 [to IM-Z], Grant No. PI16/00950 [to JMM], and Grant Nos. CPII16/00048, PI13/01958, and PI16/00889 cofunded by European Regional Development Funds [to CS-M]); the Ontario Mental Health Foundation (Research Training Fellowship [to SHA]); Alberta Innovates Translational Health Chair in Child and Youth Mental Health (to PDA), the Ontario Brain Institute (to PDA); the National Institute of Mental Health (Grant No. K23MH104515 [to JTB], Grant No. K23-MH092397 [to BPB], Grant No. K23MH082176 [to KDF), Grant No. R21MH101441 [to RM], Grant No. R01MH081864 [to JO and JP], and Grant No. R01MH085900 [to JO and JF], Grant No. R21MH093889 [to HBS]); Fundação de Amparo à Pesquisa do Estado de São Paulo (Grant No. 2011/21357–9 [to MCB], Grant No. 2011/21357–9 [to GFB], Grant No. 2011/21357–9 [to MQH], and Grant No. 2011/21357–9 [to ECM]); the Swiss National Science Foundation (Grant No. 320030_130237 [to SB; principal investigator, Susanne Walitza]); the Hartmann Müller Foundation (Grant No. 1460 [to SB]); the David Judah Fund at the Massachusetts General Hospital (to BPB); EU FP7 Project TACTICS (Grant No. 278948 [to JB]); the National Natural Science Foundation of China (Grant No. 81560233 [to YC] and Grant No. 81371340 [to ZW]); the International OCD Foundation (Grant No. K23 MH115206 [to PG]); the Wellcome Sir Henry Dale Fellowship (Grant No. 211155/Z/18/Z [to TUH]); the Jacobs Foundation (to TUH); the Brain and Behavior Research Foundation (2018 NARSAD Young Investigator Grant No. 27023 [to TUH]); the Agency for Medical Research and Development (Grant No. JP18dm0307002 [to YH]); the Michael Smith Foundation for Health Research (to FJ-F); the Federal Ministry of Education and Research of Germany (Grant No. BMBF-01GW0724 [to NK]); the Deutsche Forschungsgemeinschaft (Grant No. KO 3744/7–1 [to KK]); the Helse Vest Health Authority (Grant Nos. 911754 and 911880 [to GK]); the Norwegian Research Council (Grant No. HELSEFORSK 243675 [to GK]); the Marató TV3 Foundation (Grant Nos. 01/2010 and 091710 [to LL]); the Agency for Management of University and Research Grants (Grant No. 2017 SGR 881 [to LL] and 2017 SGR 1247 from the Generalitat de Catalunya [to JMM]); Fundação para a Ciência e a Tecnologia (Grant No. PDE/BDE/113604/2015 from the PhD-iHES Program [to RM], Grant No. PDE/BDE/113601/2015 from the PhD-iHES Program [to PSM]); the Japanese Ministry of Education, Culture, Sports, Science and Technology (Grant-in-Aid for Scientific Research (Grant Nos. 22591262, 25461732, and 16K10253 [to TNakao]); the Government of India Department of Science and Technology (DST INSPIRE Faculty Grant No. -IFA12-LSBM-26 [to JCN] and Grant No. SR/S0/HS/0016/2011 [to YCJR]); the Government of India Department of Biotechnology (Grant No. BT/06/IYBA/2012 [to JCN] and Grant No. BT/PR13334/Med/30/259/2009 [to YCJR]); the New York State Office of Mental Health (to HBS); the Italian Ministry of Health (Grant No. RC13-14-15-16A [to GS]); the National Center for Advancing Translational Sciences (Grant No. UL1TR000067/KL2TR00069 [to ERS]); the Canadian Institutes of Health Research (to SES); the Michael Smith Foundation for Health Research (to SES); the British Columbia Provincial Health Services Authority (to SES); the Netherlands Organization for Scientific Research (Grant No. NWO/ZonMW Vidi 917.15.318 [to GAvW]); the Wellcome-DBT India Alliance (Grant No. 500236/Z/11/Z [to GV]); the Shanghai Key Laboratory of Psychotic Disorders (Grant No. 13dz2260500 [to ZW]).

Published
2020

78. An overview of the first 5 years of the ENIGMA obsessive-compulsive disorder working group: The power of worldwide collaboration

Author

Edna Grünblatt, Noam Soreni, Takashi Nakamae, Susanne Walitza, Anthony A. James, Paul D. Arnold, Iliyan Ivanov, Patricia Gruner, Janardhanan C. Narayanaswamy, Dick J. Veltman, Gianfranco Spalletta, Sara Bertolín, H. Blair Simpson, Tomohiro Nakao, Je-Yeon Yun, David Mataix-Cols, Gerd Kvale, Carles Soriano-Mas, Guido van Wingen, Ganesan Venkatasubramanian, Luisa Lázaro, Francesco Benedetti, Chris Vriend, Xiangzhen Kong, Jan C. Beucke, Kate D. Fitzgerald, Martine Hoogman, Y. C.Janardhan Reddy, Kathrin Koch, Daan van Rooij, Jun Soo Kwon, David F. Tolin, Rachel Marsh, Jan K. Buitelaar, Neda Jahanshad, Christopher Pittenger, Stephan F. Taylor, Tomáš Paus, Willem B Bruin, Clyde Francks, Anushree Bose, Chaim Huyser, Christine Lochner, Erika L. Nurmi, Dan J. Stein, Joseph O'Neill, S. Evelyn Stewart, Yash Patel, João Ricardo Sato, Zhen Wang, Irene Bollettini, Lianne Schmaal, Alessandro S. De Nadai, Fabrizio Piras, Yoshiyuki Hirano, Brian P. Brennan, Odile A. van den Heuvel, Pedro Morgado, Sophia I. Thomopoulos, Marcelo Q. Hoexter, Premika S.W. Boedhoe, Paul M. Thompson, van den Heuvel, O. A., Boedhoe, P. S. W., Bertolin, S., Bruin, W. B., Francks, C., Ivanov, I., Jahanshad, N., Kong, X. -Z., Kwon, J. S., O'Neill, J., Paus, T., Patel, Y., Piras, F., Schmaal, L., Soriano-Mas, C., Spalletta, G., van Wingen, G. A., Yun, J. -Y., Vriend, C., Simpson, H. B., van Rooij, D., Hoexter, M. Q., Hoogman, M., Buitelaar, J. K., Arnold, P., Beucke, J. C., Benedetti, F., Bollettini, I., Bose, A., Brennan, B. P., De Nadai, A. S., Fitzgerald, K., Gruner, P., Grunblatt, E., Hirano, Y., Huyser, C., James, A., Koch, K., Kvale, G., Lazaro, L., Lochner, C., Marsh, R., Mataix-Cols, D., Morgado, P., Nakamae, T., Nakao, T., Narayanaswamy, J. C., Nurmi, E., Pittenger, C., Reddy, Y. C. J., Sato, J. R., Soreni, N., Stewart, S. E., Taylor, S. F., Tolin, D., Thomopoulos, S. I., Veltman, D. J., Venkatasubramanian, G., Walitza, S., Wang, Z., Thompson, P. M., and Stein, D. J.

Subjects
mega-analysis, Obsessive-Compulsive Disorder, Review Article, Machine Learning, 0302 clinical medicine, Neurobiology, Obsessive-compulsive disorder, Multicenter Studies as Topic, Disease process, Cervell, Review Articles, Pediatric, Psychiatry, Cerebral Cortex, Collaborative community, Radiological and Ultrasound Technology, 05 social sciences, ENIGMA, Brain, Experimental Psychology, Serious Mental Illness, humanities, 3. Good health, Mental Health, Neurology, Meta-analysis, Neurological, Cognitive Sciences, Mega analysis, Anatomy, Psychology, Neurobiologia, Clinical psychology, MRI, ENIGMA-OCD working group, Neuroimaging, behavioral disciplines and activities, 050105 experimental psychology, Lateralization of brain function, Power (social and political), 03 medical and health sciences, obsessive–compulsive disorder, Obsessive compulsive, Clinical Research, mental disorders, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Psiquiatria, mega‐analysis, volume, Neurosi obsessiva, Neurosciences, surface area, cortical thickness, Brain Disorders, meta-analysis, meta‐analysis, Neurology (clinical), 030217 neurology & neurosurgery
Abstract

Neuroimaging has played an important part in advancing our understanding of the neurobiology of obsessive?compulsive disorder (OCD). At the same time, neuroimaging studies of OCD have had notable limitations, including reliance on relatively small samples. International collaborative efforts to increase statistical power by combining samples from across sites have been bolstered by the ENIGMA consortium; this provides specific technical expertise for conducting multi-site analyses, as well as access to a collaborative community of neuroimaging scientists. In this article, we outline the background to, development of, and initial findings from ENIGMA's OCD working group, which currently consists of 47 samples from 34 institutes in 15 countries on 5 continents, with a total sample of 2,323 OCD patients and 2,325 healthy controls. Initial work has focused on studies of cortical thickness and subcortical volumes, structural connectivity, and brain lateralization in children, adolescents and adults with OCD, also including the study on the commonalities and distinctions across different neurodevelopment disorders. Additional work is ongoing, employing machine learning techniques. Findings to date have contributed to the development of neurobiological models of OCD, have provided an important model of global scientific collaboration, and have had a number of clinical implications. Importantly, our work has shed new light on questions about whether structural and functional alterations found in OCD reflect neurodevelopmental changes, effects of the disease process, or medication impacts. We conclude with a summary of ongoing work by ENIGMA-OCD, and a consideration of future directions for neuroimaging research on OCD within and beyond ENIGMA.

Published
2020

79. Brain structural covariance networks in obsessive-compulsive disorder : a graph analysis from the ENIGMA Consortium

Author

Yun, Je-Yeon, Boedhoe, Premika, Vriend, Chris, Jahanshad, Neda, Abe, Yoshinari, Ameis, Stephanie H., Anticevic, Alan, Arnold, Paul D., Batistuzzo, Marcelo C., Benedetti, Francesco, Beucke, Jan C., Bollettini, Irene, Bose, Anushree, Brem, Silvia, Calvo, Anna, Cheng, Yuqi, Cho, Kang Ik K., Ciullo, Valentina, Dallaspezia, Sara, Denys, Damiaan, Feusner, Jamie D., Fouche, Jean-Paul, Giménez, Mònica, Gruner, Patricia, Hibar, Derrek P., Hoexter, Marcelo Q., Hu, Hao, Huyser, Chaim, Ikari, Keisuke, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Lázaro, Luisa, Lochner, Christine, Marques, Paulo, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón Magriñá, José Manuel, Minuzzi, Luciano, Morgado, Pedro, Moreira, Pedro, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C., Nurmi, Erica L., O'Neill, Joseph, Piacentini, John, Piras, Fabrizio, Piras, Federica, Reddy, Y. C. Janardhan, Sato, Joao R., Simpson, H. Blair, Soreni, Noam, Soriano-Mas, Carles, Spalletta, Gianfranco, Stevens, Michael C., Szeszko, Philip R., Tolin, David F., Venkatasubramanian, Ganesan, Walitza, Susanne, Wang, Zhen, van Wingen, Guido A., Xu, Jian, Xu, Xiufeng, Zhao, Qing, Thompson, Paul M., Stein, Dan J., van den Heuvel, Odile A., Kwon, Jun Soo, Yun, J. -Y., Boedhoe, P. S. W., Vriend, C., Jahanshad, N., Abe, Y., Ameis, S. H., Anticevic, A., Arnold, P. D., Batistuzzo, M. C., Benedetti, F., Beucke, J. C., Bollettini, I., Bose, A., Brem, S., Calvo, A., Cheng, Y., Cho, K. I. K., Ciullo, V., Dallaspezia, S., Denys, D., Feusner, J. D., Fouche, J. -P., Gimenez, M., Gruner, P., Hibar, D. P., Hoexter, M. Q., Hu, H., Huyser, C., Ikari, K., Kathmann, N., Kaufmann, C., Koch, K., Lazaro, L., Lochner, C., Marques, P., Marsh, R., Martinez-Zalacain, I., Mataix-Cols, D., Menchon, J. M., Minuzzi, L., Morgado, P., Moreira, P., Nakamae, T., Nakao, T., Narayanaswamy, J. C., Nurmi, E. L., O'Neill, J., Piacentini, J., Piras, F., Janardhan Reddy, Y. C., Sato, J. R., Blair Simpson, H., Soreni, N., Soriano-Mas, C., Spalletta, G., Stevens, M. C., Szeszko, P. R., Tolin, D. F., Venkatasubramanian, G., Walitza, S., Wang, Z., Van Wingen, G. A., Xu, J., Xu, X., Zhao, Q., Thompson, P. M., Stein, D. J., Van Den Heuvel, O. A., and Kwon, J. S.

Subjects
Graph theory, Illness duration, Obsessive-compulsive disorder, Brain structural covariance network, Pharmacotherapy
Abstract

In the largest brain structural covariance study of OCD to date, Yun et al. show a less segregated organization of structural covariance networks and a reorganization of brain hubs, including cingulate and orbitofrontal regions, in OCD. The findings point to altered trajectories of brain development and maturation. Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z -score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P < 0.0001), lower modularity (P < 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions.

Published
2020

80. Neurobiological mechanisms of treatment resistant depression: Functional, structural and molecular imaging studies

Author

de Kwaasteniet, B.P., Denys, Damiaan A.J.P., Ruhé, H.G., van Wingen, G., and Faculteit der Geneeskunde

Abstract

This thesis investigated the neurobiological mechanisms of TRD using functional, structural and molecular imaging studies. First the neurobiological mechanisms of MDD were investigated and revealed decreased functional connectivity between the ventral and dorsal network. Thereafter, structural connectivity analyses of the uncinate fasciculus showed decreased integrity of this white matter tract in MDD patients. These structural abnormalities were negatively associated with the functional connectivity between the subgenual ACC and medial temporal lobe in MDD patients which suggests that structural abnormalities may lead to functional abnormalities. Regarding TRD, this thesis showed that TRD patients are characterized by a specific decreased functional connectivity between neurocognitive networks relative to both non-TRD and healthy controls. Furthermore, a preliminary [123I]IBZM SPECT study showed no difference in striatal D2/3R availability between TRD patients and healthy controls which suggests TRD is not characterized by altered dopaminergic transmission. Furthermore, this thesis showed that resting state DMN connectivity is a predictive marker for the clinical response to nucleus accumbens DBS in severe TRD patients. These findings together suggests that MDD is characterized by a pathological interaction between the dorsal and ventral network which corroborates the limbic-cortical dysregulation model. TRD is specifically characterized by abnormal network interaction between two neurocognitive networks; the cognitive control network and default mode network. Future work should perform longitudinal analyses to determine how functional connectivity of neural networks evolves over time, and to develop a general definition of TRD preferably for different stages of the disease.

Published
2015

81. Polyunsaturated fatty acids changes during electroconvulsive therapy in major depressive disorder.

Author

van Verseveld M, Mocking RJT, Scheepens D, Ten Doesschate F, Westra M, Schoevers RA, Schene AH, van Wingen GA, van Waarde JA, and Ruhé HG

Subjects
Humans, Eicosapentaenoic Acid, Docosahexaenoic Acids, Depressive Disorder, Major, Electroconvulsive Therapy methods
Abstract

Polyunsaturated fatty acids (PUFAs) have important electrochemical properties and have been implicated in the pathophysiology of major depressive disorder (MDD) and its treatment. However, the relation of PUFAs with electroconvulsive therapy (ECT) has never been investigated. Therefore, we aimed to explore the associations between PUFA concentrations and response to ECT in patients with MDD. We included 45 patients with unipolar MDD in a multicentre study. To determine PUFA concentrations, we collected blood samples at the first (T0) and twelfth (T12) ECT-session. We assessed depression severity using the Hamilton Rating Scale for Depression (HAM-D) at T0, T12 and at the end of the ECT-course. ECT-response was defined as 'early response' (at T12), 'late response' (after ECT-course) and 'no' response (after the ECT-course). The PUFA chain length index (CLI), unsaturation index (UI) and peroxidation index (PI) and three individual PUFAs (eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA] and nervonic acid [NA]) were associated with response to ECT using linear mixed models. Results showed a significant higher CLI in 'late responders' compared to 'non responders'. For NA, 'late responders' showed significantly higher concentrations compared to 'early'- and 'non responders'. In conclusion, this study provides the first indication that PUFAs are associated with the efficacy of ECT. This indicates that PUFAs' influence on neuronal electrochemical properties and neurogenesis may affect ECT outcomes. Thereby, PUFAs form a potentially modifiable factor predicting ECT outcomes, that warrants further investigation in other ECT-cohorts., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Published
2023
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82. Electroencephalography for predicting antidepressant treatment success: A systematic review and meta-analysis.

Author

Cohen SE, Zantvoord JB, Wezenberg BN, Daams JG, Bockting CLH, Denys D, and van Wingen GA

Subjects
Humans, Antidepressive Agents therapeutic use, Treatment Outcome, Electroencephalography, Sample Size, Depressive Disorder, Major diagnosis, Depressive Disorder, Major drug therapy
Abstract

Background: Patients suffering from major depressive disorder (MDD) regularly experience non-response to treatment for their depressive episode. Personalized clinical decision making could shorten depressive episodes and reduce patient suffering. Although no clinical tools are currently available, machine learning analysis of electroencephalography (EEG) shows promise in treatment response prediction., Methods: With a systematic review and meta-analysis, we evaluated the accuracy of EEG for individual patient response prediction. Importantly, we included only prediction studies that used cross-validation. We used a bivariate model to calculate prediction success, as expressed by area-under the curve, sensitivity and specificity. Furthermore, we analyzed prediction success for separate antidepressant interventions., Results: 15 studies with 12 individual patient samples and a total of 479 patients were included. Research methods varied considerably between studies. Meta-analysis of results from this heterogeneous set of studies resulted in an area under the curve of 0.91, a sensitivity of 83 % (95 % CI 74-89 %), and a specificity of 86 % (95 % CI 81-90 %). Classification performance did not significantly differ between treatments. Although studies were all internally validated, no externally validated studies have been reported. We found substantial risk of bias caused by methodological shortcomings such as non-independent feature selection, though performance of non-biased studies was comparable., Limitations: Sample sizes were relatively small and no study used external validation, increasing the risk of overestimation of accuracy., Conclusions: Electroencephalography can predict the response to antidepressant treatment with high accuracy. However, future studies with more rigorous validation are needed to produce a clinical tool to guide interventions in MDD., Prospero Registration Number: CRD42021268169., Competing Interests: Conflict of Interest The authors declare that they have no competing interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2023
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83. [Functional brain networks for diagnostics and the prediction of treatment outcome].

Author

van Wingen GA

Subjects
Humans, Treatment Outcome, Neuroimaging, Magnetic Resonance Imaging, Brain diagnostic imaging, Psychotic Disorders
Abstract

Background: Functional MRI offers insight into the functioning of brain networks of patients with psychiatric disorders. Machine learning analysis can be used to create diagnostic models and to predict treatment outcome., Aim: To provide an overview of recent insights on diagnostic and predictive neuroimaging biomarkers., Method: Narrative review based on recent literature., Results: Large-scale studies suggest that diagnostic models for most disorders have limited accuracy. In contrast, meta-analyses of small-scale studies suggest that treatment outcome for depression and psychotic disorders can be predicted well., Conclusion: This creates the opportunity to develop prediction models that can help practitioners in making a treatment plan and thereby improve treatment outcomes.

Published
2023

85. Multimodal multi-center analysis of electroconvulsive therapy effects in depression: Brainwide gray matter increase without functional changes.

Author

van de Mortel LA, Bruin WB, Thomas RM, Abbott C, Argyelan M, van Eijndhoven P, Mulders P, Narr KL, Tendolkar I, Verdijk JPAJ, van Waarde JA, Bartsch H, Oltedal L, and van Wingen GA

Subjects
Brain, Depression diagnostic imaging, Depression therapy, Gray Matter, Humans, Magnetic Resonance Imaging methods, Male, Electroconvulsive Therapy methods
Abstract

Background: Electroconvulsive therapy (ECT) is an effective treatment for severe depression and induces gray matter (GM) increases in the brain. Small-scale studies suggest that ECT also leads to changes in brain functioning, but findings are inconsistent. In this study, we investigated the influence of ECT on changes in both brain structure and function and their relation to clinical improvement using multicenter neuroimaging data from the Global ECT-MRI Research Collaboration (GEMRIC)., Methods: We analyzed T1-weighted structural magnetic resonance imaging (MRI) and functional resting-state MRI data of 88 individuals (49 male) with depressive episodes before and within one week after ECT. We performed voxel-based morphometry on the structural data and calculated fractional amplitudes of low-frequency fluctuations, regional homogeneity, degree centrality, functional connectomics, and hippocampus connectivity for the functional data in both unimodal and multimodal analyses. Longitudinal effects in the ECT group were compared to repeated measures of healthy controls (n = 27)., Results: Wide-spread increases in GM volume were found in patients following ECT. In contrast, no changes in any of the functional measures were observed, and there were no significant differences in structural or functional changes between ECT responders and non-responders. Multimodal analysis revealed that volume increases in the striatum, supplementary motor area and fusiform gyrus were associated with local changes in brain function., Conclusion: These results confirm wide-spread increases in GM volume, but suggest that this is not accompanied by functional changes or associated with clinical response. Instead, focal changes in brain function appear related to individual differences in brain volume increases., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2022
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87. Attachment in OCD: A meta-analysis.

Author

van Leeuwen WA, van Wingen GA, Luyten P, Denys D, and van Marle HJF

Subjects
Adolescent, Adult, Female, Humans, Male, Young Adult, Object Attachment, Obsessive-Compulsive Disorder psychology, Obsessive-Compulsive Disorder therapy
Abstract

Introduction: It has been proposed to extend the cognitive-behavioural model of obsessive-compulsive disorder (OCD) with attachment theory to shed light on the affective and developmental factors underlying the disease. With a growing number of empirical studies on the subject, this meta-analysis aims to quantify a possible relationship between attachment insecurity and OCD., Methods: A systematic search was conducted for studies in adult populations of patients with OCD as well as general populations displaying symptoms of OCD. Effect sizes of attachment anxiety and attachment avoidance were calculated separately. Covariates of demographic variables were used in meta-regressions., Results: Sixteen studies were included. Meta-analyses showed an association of medium to large effect size (Hedges' g = 0.69; 95 % CI 0.58 - 0.80; p < 0.001) between OCD and attachment anxiety, and an association of medium effect size (Hedges' g = 0.47; 95 % CI 0.39 - 0.54; p < 0.001) between OCD and attachment avoidance. Effect sizes in OCD population and general population studies did not differ significantly., Discussion: Robust effect sizes of both attachment anxiety and avoidance in relation to OCD symptomatology corroborate an attachment-centred view of OCD. These findings furthermore suggest that integrating cognitive and attachment-based therapeutic approaches to OCD may benefit patients in which developmental or emotional factors hinder successful treatment., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Published
2020
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89. Individual white matter bundle trajectories are associated with deep brain stimulation response in obsessive-compulsive disorder.

Author

Liebrand LC, Caan MWA, Schuurman PR, van den Munckhof P, Figee M, Denys D, and van Wingen GA

Subjects
Adult, Deep Brain Stimulation adverse effects, Female, Humans, Internal Capsule physiopathology, Male, Medial Forebrain Bundle physiopathology, Middle Aged, Obsessive-Compulsive Disorder physiopathology, Deep Brain Stimulation methods, Obsessive-Compulsive Disorder therapy, White Matter physiopathology
Abstract

Background: The ventral anterior limb of the internal capsule (vALIC) is a target for deep brain stimulation (DBS) in obsessive-compulsive disorder (OCD). Conventional surgical planning is based on anatomical landmarks., Objective/hypothesis: We hypothesized that treatment response depends on the location of the active DBS contacts with respect to individual white matter bundle trajectories. This study thus aimed to elucidate whether vALIC DBS can benefit from bundle-specific targeting., Methods: We performed tractography analysis of two fiber bundles, the anterior thalamic radiation (ATR) and the supero-lateral branch of the medial forebrain bundle (MFB), using diffusion-weighted magnetic resonance imaging (DWI) data. Twelve patients (10 females) who had received bilateral vALIC DBS for at least 12 months were included. We related the change in OCD symptom severity on the Yale-Brown obsessive-compulsive scale (Y-BOCS) between baseline and one-year follow-up with the distances from the active contacts to the ATR and MFB. We further analyzed the relation between treatment response and stimulation sites in standard anatomical space., Results: We found that active stimulation of the vALIC closer to the MFB than the ATR was associated with better treatment outcome (p = 0.04; r 2  = 0.34). In standard space, stimulation sites were largely overlapping between treatment (non)responders, suggesting response is independent of the anatomically defined electrode position., Conclusion: These findings suggest that vALIC DBS for OCD may benefit from MFB-specific implantation and highlight the importance of corticolimbic connections in OCD response to DBS. Prospective investigation is necessary to validate the clinical use of MFB targeting., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2019
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90. [Electroconvulsion therapy for persistent depression in the Netherlands; very low application rate].

Author

Scheepens DS, van Waarde JA, Lok A, Zantvoord JB, de Pont BJHB, Ruhé HG, Denys DAJP, and van Wingen GA

Subjects
Female, Humans, Male, Netherlands, Treatment Outcome, Depressive Disorder, Major therapy, Electroconvulsive Therapy methods, Electroconvulsive Therapy statistics & numerical data, Procedures and Techniques Utilization
Abstract

Background: Of all depressive disorders, 20% has a persistent course. For persistent depressive patients, electroconvulsive therapy (ect) is recommended for this patient population, since it is the most potent treatment for depression. The Dutch depression guideline advises the use of ect for persistent depressive disorder at approximately 12 months after inadequate efficacy of psychotherapy and/or pharmacological treatment.
AIM: To quantify the use of electroconvulsive therapy in persistent depressive patients in the Netherlands.
METHOD: Quantitative research using the Dutch registration system (diagnosis-treatment-combination; dbc) information system (dis) of the Dutch Healthcare Authority (nza).
RESULTS: Of the patients within the dbc system (in 2014) with the main diagnosis of unipolar depression, 23,597 (26%) were registered for more than two years and could be classified as having a persistent depressive episode. Of these latter patients, only 278 (1.2%) received ect.
CONCLUSION: In the Netherlands, only 1.2% of patients with a persistent depression received ect, whereas this treatment could have been considered for 26% of this group. The low application rate might be caused by professionals' inadequate knowledge about ect and the premature use of the handicap model.

Published
2019

92. Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor.

Author

Buijink AW, Broersma M, van der Stouwe AM, van Wingen GA, Groot PF, Speelman JD, Maurits NM, and van Rootselaar AF

Subjects
Adult, Aged, Aged, 80 and over, Brain Mapping, Female, Fingers, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Severity of Illness Index, Young Adult, Cerebellar Diseases physiopathology, Cerebellar Nuclei physiopathology, Essential Tremor physiopathology, Motor Activity physiology, Olivary Nucleus physiopathology
Abstract

Introduction: Cerebellar circuits are hypothesized to play a central role in the pathogenesis of essential tremor. Rhythmic finger tapping is known to strongly engage the cerebellar motor circuitry. We characterize cerebellar and, more specifically, dentate nucleus function, and neural correlates of cerebellar output in essential tremor during rhythmic finger tapping employing functional MRI., Methods: Thirty-one propranolol-sensitive essential tremor patients with upper limb tremor and 29 healthy controls were measured. T2*-weighted EPI sequences were acquired. The task consisted of alternating rest and finger tapping blocks. A whole-brain and region-of-interest analysis was performed, the latter focusing on the cerebellar cortex, dentate nucleus and inferior olive nucleus. Activations were also related to tremor severity., Results: In patients, dentate activation correlated positively with tremor severity as measured by the tremor rating scale part A. Patients had reduced activation in widespread cerebellar cortical regions, and additionally in the inferior olive nucleus, and parietal and frontal cortex, compared to controls., Conclusion: The increase in dentate activation with tremor severity supports involvement of the dentate nucleus in essential tremor. Cortical and cerebellar changes during a motor timing task in essential tremor might point to widespread changes in cerebellar output in essential tremor., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Published
2015
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93. Paradoxical effects of GABA-A modulators may explain sex steroid induced negative mood symptoms in some persons.

Author

Bäckström T, Haage D, Löfgren M, Johansson IM, Strömberg J, Nyberg S, Andréen L, Ossewaarde L, van Wingen GA, Turkmen S, and Bengtsson SK

Subjects
Animals, Chlorides metabolism, Female, Humans, Menstrual Cycle drug effects, Menstrual Cycle physiology, Neurons drug effects, Neurons physiology, GABA Modulators adverse effects, Premenstrual Syndrome chemically induced, Receptors, GABA-A metabolism, Steroids metabolism
Abstract

Some women have negative mood symptoms, caused by progestagens in hormonal contraceptives or sequential hormone therapy or by progesterone in the luteal phase of the menstrual cycle, which may be attributed to metabolites acting on the GABA-A receptor. The GABA system is the major inhibitory system in the adult CNS and most positive modulators of the GABA-A receptor (benzodiazepines, barbiturates, alcohol, GABA steroids), induce inhibitory (e.g. anesthetic, sedative, anticonvulsant, anxiolytic) effects. However, some individuals have adverse effects (seizures, increased pain, anxiety, irritability, aggression) upon exposure. Positive GABA-A receptor modulators induce strong paradoxical effects including negative mood in 3%-8% of those exposed, while up to 25% have moderate symptoms. The effect is biphasic: low concentrations induce an adverse anxiogenic effect while higher concentrations decrease this effect and show inhibitory, calming properties. The prevalence of premenstrual dysphoric disorder (PMDD) is also 3%-8% among women in fertile ages, and up to 25% have more moderate symptoms of premenstrual syndrome (PMS). Patients with PMDD have severe luteal phase-related symptoms and show changes in GABA-A receptor sensitivity and GABA concentrations. Findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor, which may be explained by one or more of three hypotheses regarding the paradoxical effect of GABA steroids on behavior: (1) under certain conditions, such as puberty, the relative fraction of certain GABA-A receptor subtypes may be altered, and at those subtypes the GABA steroids may act as negative modulators in contrast to their usual role as positive modulators; (2) in certain brain areas of vulnerable women the transmembrane Cl(-) gradient may be altered by factors such as estrogens that favor excitability; (3) inhibition of inhibitory neurons may promote disinhibition, and hence excitability. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain., (Copyright © 2011. Published by Elsevier Ltd.)

Published
2011
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94. Gonadal hormone regulation of the emotion circuitry in humans.

Author

van Wingen GA, Ossewaarde L, Bäckström T, Hermans EJ, and Fernández G

Subjects
Amygdala drug effects, Amygdala metabolism, Brain drug effects, Female, Humans, Male, Mental Disorders metabolism, Mental Disorders pathology, Neural Pathways drug effects, Neural Pathways metabolism, Prefrontal Cortex drug effects, Prefrontal Cortex metabolism, Brain anatomy & histology, Brain metabolism, Emotions, Gonadal Hormones metabolism
Abstract

Gonadal hormones are known to influence the regulation of emotional responses and affective states. Whereas fluctuations in progesterone and estradiol are associated with increased vulnerability for mood disorders, testosterone is mainly associated with social dominance, aggressive, and antisocial behavior. Here, we review recent functional neuroimaging studies that have started to elucidate how these hormones modulate the neural circuitry that is important for emotion regulation, which includes the amygdala and the medial prefrontal (mPFC) and orbitofrontal cortex (OFC). The amygdala is thought to generate emotional responses, and the prefrontal brain regions to regulate those responses. Overall, studies that have investigated women during different phases of the menstrual cycle suggest that progesterone and estradiol may have opposing actions on the amygdala and prefrontal cortex. In addition, the influence of exogenous progesterone appears to be dose-dependent. Endogenous testosterone concentrations are generally positively correlated to amygdala and OFC responses, and exogenous testosterone increases amygdala reactivity. Whereas the administration of progesterone increases amygdala reactivity and its connectivity with the mPFC, testosterone administration increases amygdala reactivity but decreases its connectivity with the OFC. We propose that this opposing influence on amygdala-prefrontal coupling may contribute to the divergent effects of progesterone and testosterone on emotion regulation and behavioral inhibition, respectively, which may promote the differential vulnerability to various psychiatric disorders between women and men. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)

Published
2011
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