Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition.
Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known patho...
Published in: | JAMA Psychiatry |
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Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
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AMA
2019
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Online Access: | https://pub.dzne.de/record/145130 https://pub.dzne.de/search?p=id:%22DZNE-2020-00489%22 |
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ftdznevdb:oai:pub.dzne.de:145130 |
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openpolar |
institution |
Open Polar |
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DZNEPUB (German Center for Neurodegenerative Diseases) |
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ftdznevdb |
language |
English |
topic |
info:eu-repo/classification/ddc/610 Brain Cortical Thickness Cerebral Cortex: anatomy & histology Cerebral Cortex: diagnostic imaging Cerebral Cortex: physiology Chromosome Breakpoints Chromosomes Human Pair 15: genetics Cognition DNA Copy Number Variations: genetics DNA Copy Number Variations: physiology Female Genetic Association Studies Heterozygote Humans Magnetic Resonance Imaging Male Middle Aged Neuroimaging Neuropsychological Tests Organ Size: genetics |
spellingShingle |
info:eu-repo/classification/ddc/610 Brain Cortical Thickness Cerebral Cortex: anatomy & histology Cerebral Cortex: diagnostic imaging Cerebral Cortex: physiology Chromosome Breakpoints Chromosomes Human Pair 15: genetics Cognition DNA Copy Number Variations: genetics DNA Copy Number Variations: physiology Female Genetic Association Studies Heterozygote Humans Magnetic Resonance Imaging Male Middle Aged Neuroimaging Neuropsychological Tests Organ Size: genetics Committee, Writing van der Meer, Dennis Bernard, Manon Sachdev, Perminder S Sando, Sigrid B Schofield, Peter R Schork, Andrew J Schumann, Gunter Shin, Jean Shumskaya, Elena Silva, Ana I Sisodiya, Sanjay M Steen, Vidar M Blackburn, Nicholas B Stein, Dan J Strike, Lachlan T Tamnes, Christian K Teumer, Alexander Thalamuthu, Anbupalam Tordesillas-Gutiérrez, Diana Uhlmann, Anne Úlfarsson, Magnús Ö van 't Ent, Dennis van den Bree, Marianne B M Blangero, John Vassos, Evangelos Wen, Wei Wittfeld, Katharina Wright, Margaret J Zayats, Tetyana Dale, Anders M Djurovic, Srdjan Agartz, Ingrid Westlye, Lars T Stefánsson, Hreinn Boomsma, Dorret I Stefánsson, Kári Thompson, Paul M Andreassen, Ole A ENIGMA-CNV Working Group Brodaty, Henry Brouwer, Rachel M Bülow, Robin Cahn, Wiepke Calhoun, Vince D Caspers, Svenja Sønderby, Ida E Cavalleri, Gianpiero L Ching, Christopher R K Cichon, Sven Ciufolini, Simone Corvin, Aiden Crespo-Facorro, Benedicto Curran, Joanne E Dalvie, Shareefa Dazzan, Paola de Geus, Eco J C Kaufmann, Tobias de Zubicaray, Greig I de Zwarte, Sonja M C Delanty, Norman den Braber, Anouk Desrivieres, Sylvane Di Forti, Marta Doherty, Joanne L Donohoe, Gary Ehrlich, Stefan Eising, Else Walters, G Bragi Espeseth, Thomas Fisher, Simon E Fladby, Tormod Frei, Oleksandr Frouin, Vincent Fukunaga, Masaki Gareau, Thomas Glahn, David C Grabe, Hans J Groenewold, Nynke A Abdellaoui, Abdel Gústafsson, Ómar Haavik, Jan Haberg, Asta K Hashimoto, Ryota Hehir-Kwa, Jayne Y Hibar, Derrek P Hillegers, Manon H J Hoffmann, Per Holleran, Laurena Hottenga, Jouke-Jan Ames, David Hulshoff Pol, Hilleke E Ikeda, Masashi Jacquemont, Sébastien Jahanshad, Neda Jockwitz, Christiane Johansson, Stefan Jönsson, Erik G Kikuchi, Masataka Knowles, Emma E M Kwok, John B Amunts, Katrin Le Hellard, Stephanie Linden, David E J Liu, Jingyu Lundervold, Arvid Lundervold, Astri J Martin, Nicholas G Mather, Karen A Mathias, Samuel R McMahon, Katie L McRae, Allan F Andersson, Micael Medland, Sarah E Moberget, Torgeir Moreau, Clara Morris, Derek W Mühleisen, Thomas W Murray, Robin M Nordvik, Jan E Nyberg, Lars Olde Loohuis, Loes M Ophoff, Roel A Armstrong, Nicola J Owen, Michael J Paus, Tomas Pausova, Zdenka Peralta, Juan M Pike, Bruce Prieto, Carlos Quinlan, Erin Burke Reinbold, Céline S Reis Marques, Tiago Rucker, James J H Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition. |
topic_facet |
info:eu-repo/classification/ddc/610 Brain Cortical Thickness Cerebral Cortex: anatomy & histology Cerebral Cortex: diagnostic imaging Cerebral Cortex: physiology Chromosome Breakpoints Chromosomes Human Pair 15: genetics Cognition DNA Copy Number Variations: genetics DNA Copy Number Variations: physiology Female Genetic Association Studies Heterozygote Humans Magnetic Resonance Imaging Male Middle Aged Neuroimaging Neuropsychological Tests Organ Size: genetics |
description |
Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.These findings, from the largest CNV neuroimaging study ... |
format |
Article in Journal/Newspaper |
author |
Committee, Writing van der Meer, Dennis Bernard, Manon Sachdev, Perminder S Sando, Sigrid B Schofield, Peter R Schork, Andrew J Schumann, Gunter Shin, Jean Shumskaya, Elena Silva, Ana I Sisodiya, Sanjay M Steen, Vidar M Blackburn, Nicholas B Stein, Dan J Strike, Lachlan T Tamnes, Christian K Teumer, Alexander Thalamuthu, Anbupalam Tordesillas-Gutiérrez, Diana Uhlmann, Anne Úlfarsson, Magnús Ö van 't Ent, Dennis van den Bree, Marianne B M Blangero, John Vassos, Evangelos Wen, Wei Wittfeld, Katharina Wright, Margaret J Zayats, Tetyana Dale, Anders M Djurovic, Srdjan Agartz, Ingrid Westlye, Lars T Stefánsson, Hreinn Boomsma, Dorret I Stefánsson, Kári Thompson, Paul M Andreassen, Ole A ENIGMA-CNV Working Group Brodaty, Henry Brouwer, Rachel M Bülow, Robin Cahn, Wiepke Calhoun, Vince D Caspers, Svenja Sønderby, Ida E Cavalleri, Gianpiero L Ching, Christopher R K Cichon, Sven Ciufolini, Simone Corvin, Aiden Crespo-Facorro, Benedicto Curran, Joanne E Dalvie, Shareefa Dazzan, Paola de Geus, Eco J C Kaufmann, Tobias de Zubicaray, Greig I de Zwarte, Sonja M C Delanty, Norman den Braber, Anouk Desrivieres, Sylvane Di Forti, Marta Doherty, Joanne L Donohoe, Gary Ehrlich, Stefan Eising, Else Walters, G Bragi Espeseth, Thomas Fisher, Simon E Fladby, Tormod Frei, Oleksandr Frouin, Vincent Fukunaga, Masaki Gareau, Thomas Glahn, David C Grabe, Hans J Groenewold, Nynke A Abdellaoui, Abdel Gústafsson, Ómar Haavik, Jan Haberg, Asta K Hashimoto, Ryota Hehir-Kwa, Jayne Y Hibar, Derrek P Hillegers, Manon H J Hoffmann, Per Holleran, Laurena Hottenga, Jouke-Jan Ames, David Hulshoff Pol, Hilleke E Ikeda, Masashi Jacquemont, Sébastien Jahanshad, Neda Jockwitz, Christiane Johansson, Stefan Jönsson, Erik G Kikuchi, Masataka Knowles, Emma E M Kwok, John B Amunts, Katrin Le Hellard, Stephanie Linden, David E J Liu, Jingyu Lundervold, Arvid Lundervold, Astri J Martin, Nicholas G Mather, Karen A Mathias, Samuel R McMahon, Katie L McRae, Allan F Andersson, Micael Medland, Sarah E Moberget, Torgeir Moreau, Clara Morris, Derek W Mühleisen, Thomas W Murray, Robin M Nordvik, Jan E Nyberg, Lars Olde Loohuis, Loes M Ophoff, Roel A Armstrong, Nicola J Owen, Michael J Paus, Tomas Pausova, Zdenka Peralta, Juan M Pike, Bruce Prieto, Carlos Quinlan, Erin Burke Reinbold, Céline S Reis Marques, Tiago Rucker, James J H |
author_facet |
Committee, Writing van der Meer, Dennis Bernard, Manon Sachdev, Perminder S Sando, Sigrid B Schofield, Peter R Schork, Andrew J Schumann, Gunter Shin, Jean Shumskaya, Elena Silva, Ana I Sisodiya, Sanjay M Steen, Vidar M Blackburn, Nicholas B Stein, Dan J Strike, Lachlan T Tamnes, Christian K Teumer, Alexander Thalamuthu, Anbupalam Tordesillas-Gutiérrez, Diana Uhlmann, Anne Úlfarsson, Magnús Ö van 't Ent, Dennis van den Bree, Marianne B M Blangero, John Vassos, Evangelos Wen, Wei Wittfeld, Katharina Wright, Margaret J Zayats, Tetyana Dale, Anders M Djurovic, Srdjan Agartz, Ingrid Westlye, Lars T Stefánsson, Hreinn Boomsma, Dorret I Stefánsson, Kári Thompson, Paul M Andreassen, Ole A ENIGMA-CNV Working Group Brodaty, Henry Brouwer, Rachel M Bülow, Robin Cahn, Wiepke Calhoun, Vince D Caspers, Svenja Sønderby, Ida E Cavalleri, Gianpiero L Ching, Christopher R K Cichon, Sven Ciufolini, Simone Corvin, Aiden Crespo-Facorro, Benedicto Curran, Joanne E Dalvie, Shareefa Dazzan, Paola de Geus, Eco J C Kaufmann, Tobias de Zubicaray, Greig I de Zwarte, Sonja M C Delanty, Norman den Braber, Anouk Desrivieres, Sylvane Di Forti, Marta Doherty, Joanne L Donohoe, Gary Ehrlich, Stefan Eising, Else Walters, G Bragi Espeseth, Thomas Fisher, Simon E Fladby, Tormod Frei, Oleksandr Frouin, Vincent Fukunaga, Masaki Gareau, Thomas Glahn, David C Grabe, Hans J Groenewold, Nynke A Abdellaoui, Abdel Gústafsson, Ómar Haavik, Jan Haberg, Asta K Hashimoto, Ryota Hehir-Kwa, Jayne Y Hibar, Derrek P Hillegers, Manon H J Hoffmann, Per Holleran, Laurena Hottenga, Jouke-Jan Ames, David Hulshoff Pol, Hilleke E Ikeda, Masashi Jacquemont, Sébastien Jahanshad, Neda Jockwitz, Christiane Johansson, Stefan Jönsson, Erik G Kikuchi, Masataka Knowles, Emma E M Kwok, John B Amunts, Katrin Le Hellard, Stephanie Linden, David E J Liu, Jingyu Lundervold, Arvid Lundervold, Astri J Martin, Nicholas G Mather, Karen A Mathias, Samuel R McMahon, Katie L McRae, Allan F Andersson, Micael Medland, Sarah E Moberget, Torgeir Moreau, Clara Morris, Derek W Mühleisen, Thomas W Murray, Robin M Nordvik, Jan E Nyberg, Lars Olde Loohuis, Loes M Ophoff, Roel A Armstrong, Nicola J Owen, Michael J Paus, Tomas Pausova, Zdenka Peralta, Juan M Pike, Bruce Prieto, Carlos Quinlan, Erin Burke Reinbold, Céline S Reis Marques, Tiago Rucker, James J H |
author_sort |
Committee, Writing |
title |
Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition. |
title_short |
Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition. |
title_full |
Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition. |
title_fullStr |
Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition. |
title_full_unstemmed |
Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition. |
title_sort |
association of copy number variation of the 15q11.2 bp1-bp2 region with cortical and subcortical morphology and cognition. |
publisher |
AMA |
publishDate |
2019 |
url |
https://pub.dzne.de/record/145130 https://pub.dzne.de/search?p=id:%22DZNE-2020-00489%22 |
op_coverage |
DE |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
JAMA psychiatry 77(4), 420 (2020). doi:10.1001/jamapsychiatry.2019.3779 |
op_relation |
info:eu-repo/semantics/altIdentifier/issn/0375-8532 info:eu-repo/semantics/altIdentifier/issn/0003-990X info:eu-repo/semantics/altIdentifier/pmid/pmid:31665216 info:eu-repo/semantics/altIdentifier/issn/2330-9636 info:eu-repo/semantics/altIdentifier/issn/2168-622X info:eu-repo/semantics/altIdentifier/issn/1538-3636 info:eu-repo/semantics/altIdentifier/issn/2168-6238 info:eu-repo/semantics/altIdentifier/doi/10.1001/jamapsychiatry.2019.3779 https://pub.dzne.de/record/145130 https://pub.dzne.de/search?p=id:%22DZNE-2020-00489%22 |
op_rights |
info:eu-repo/semantics/closedAccess |
op_doi |
https://doi.org/10.1001/jamapsychiatry.2019.3779 |
container_title |
JAMA Psychiatry |
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4 |
container_start_page |
420 |
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ftdznevdb:oai:pub.dzne.de:145130 2023-10-09T21:52:53+02:00 Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition. Committee, Writing van der Meer, Dennis Bernard, Manon Sachdev, Perminder S Sando, Sigrid B Schofield, Peter R Schork, Andrew J Schumann, Gunter Shin, Jean Shumskaya, Elena Silva, Ana I Sisodiya, Sanjay M Steen, Vidar M Blackburn, Nicholas B Stein, Dan J Strike, Lachlan T Tamnes, Christian K Teumer, Alexander Thalamuthu, Anbupalam Tordesillas-Gutiérrez, Diana Uhlmann, Anne Úlfarsson, Magnús Ö van 't Ent, Dennis van den Bree, Marianne B M Blangero, John Vassos, Evangelos Wen, Wei Wittfeld, Katharina Wright, Margaret J Zayats, Tetyana Dale, Anders M Djurovic, Srdjan Agartz, Ingrid Westlye, Lars T Stefánsson, Hreinn Boomsma, Dorret I Stefánsson, Kári Thompson, Paul M Andreassen, Ole A ENIGMA-CNV Working Group Brodaty, Henry Brouwer, Rachel M Bülow, Robin Cahn, Wiepke Calhoun, Vince D Caspers, Svenja Sønderby, Ida E Cavalleri, Gianpiero L Ching, Christopher R K Cichon, Sven Ciufolini, Simone Corvin, Aiden Crespo-Facorro, Benedicto Curran, Joanne E Dalvie, Shareefa Dazzan, Paola de Geus, Eco J C Kaufmann, Tobias de Zubicaray, Greig I de Zwarte, Sonja M C Delanty, Norman den Braber, Anouk Desrivieres, Sylvane Di Forti, Marta Doherty, Joanne L Donohoe, Gary Ehrlich, Stefan Eising, Else Walters, G Bragi Espeseth, Thomas Fisher, Simon E Fladby, Tormod Frei, Oleksandr Frouin, Vincent Fukunaga, Masaki Gareau, Thomas Glahn, David C Grabe, Hans J Groenewold, Nynke A Abdellaoui, Abdel Gústafsson, Ómar Haavik, Jan Haberg, Asta K Hashimoto, Ryota Hehir-Kwa, Jayne Y Hibar, Derrek P Hillegers, Manon H J Hoffmann, Per Holleran, Laurena Hottenga, Jouke-Jan Ames, David Hulshoff Pol, Hilleke E Ikeda, Masashi Jacquemont, Sébastien Jahanshad, Neda Jockwitz, Christiane Johansson, Stefan Jönsson, Erik G Kikuchi, Masataka Knowles, Emma E M Kwok, John B Amunts, Katrin Le Hellard, Stephanie Linden, David E J Liu, Jingyu Lundervold, Arvid Lundervold, Astri J Martin, Nicholas G Mather, Karen A Mathias, Samuel R McMahon, Katie L McRae, Allan F Andersson, Micael Medland, Sarah E Moberget, Torgeir Moreau, Clara Morris, Derek W Mühleisen, Thomas W Murray, Robin M Nordvik, Jan E Nyberg, Lars Olde Loohuis, Loes M Ophoff, Roel A Armstrong, Nicola J Owen, Michael J Paus, Tomas Pausova, Zdenka Peralta, Juan M Pike, Bruce Prieto, Carlos Quinlan, Erin Burke Reinbold, Céline S Reis Marques, Tiago Rucker, James J H DE 2019 https://pub.dzne.de/record/145130 https://pub.dzne.de/search?p=id:%22DZNE-2020-00489%22 eng eng AMA info:eu-repo/semantics/altIdentifier/issn/0375-8532 info:eu-repo/semantics/altIdentifier/issn/0003-990X info:eu-repo/semantics/altIdentifier/pmid/pmid:31665216 info:eu-repo/semantics/altIdentifier/issn/2330-9636 info:eu-repo/semantics/altIdentifier/issn/2168-622X info:eu-repo/semantics/altIdentifier/issn/1538-3636 info:eu-repo/semantics/altIdentifier/issn/2168-6238 info:eu-repo/semantics/altIdentifier/doi/10.1001/jamapsychiatry.2019.3779 https://pub.dzne.de/record/145130 https://pub.dzne.de/search?p=id:%22DZNE-2020-00489%22 info:eu-repo/semantics/closedAccess JAMA psychiatry 77(4), 420 (2020). doi:10.1001/jamapsychiatry.2019.3779 info:eu-repo/classification/ddc/610 Brain Cortical Thickness Cerebral Cortex: anatomy & histology Cerebral Cortex: diagnostic imaging Cerebral Cortex: physiology Chromosome Breakpoints Chromosomes Human Pair 15: genetics Cognition DNA Copy Number Variations: genetics DNA Copy Number Variations: physiology Female Genetic Association Studies Heterozygote Humans Magnetic Resonance Imaging Male Middle Aged Neuroimaging Neuropsychological Tests Organ Size: genetics info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 2019 ftdznevdb https://doi.org/10.1001/jamapsychiatry.2019.3779 2023-09-21T07:36:33Z Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.These findings, from the largest CNV neuroimaging study ... Article in Journal/Newspaper Iceland DZNEPUB (German Center for Neurodegenerative Diseases) JAMA Psychiatry 77 4 420 |