Early life stress and macaque annygdala hypertrophy: preliminary evidence for a role for the serotonin transporter gene
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/38324 http://dx.doi.org/10.3389/fnbeh.2014.00342 |
Resumo: | Background: Children exposed to early life stress (ELS) exhibit enlarged amygdala volume in comparison to controls. the primary goal of this study was to examine amygdala volumes in bonnet macaques subjected to maternal variable foraging demand (VFD) rearing, a well-established model of ELS. Preliminary analyses examined the interaction of ELS and the serotonin transporter gene on amygdala volume. Secondary analyses were conducted to examine the association between amygdala volume and other stress-related variables previously found to distinguish VFD and non-VFD reared animals.Methods: Twelve VFD-reared and nine normally reared monkeys completed MRI scans on a 3T system (mean age = 5.2 years).Results: Left amygdala volume was larger in VFD vs. control macaques. Larger amygdala volume was associated with: high cerebrospinal fluid concentrations of corticotropin releasing-factor (CRF) determined when the animals were in adolescence (mean age = 2.7 years); reduced fractional anisotropy (FA) of the anterior limb of the internal capsule (ALIC) during young adulthood (mean age = 5.2 years) and timid anxiety-like responses to an intruder during full adulthood (mean age = 8.4 years). Right amygdala volume varied inversely with left hippocampal neurogenesis assessed in late adulthood (mean age = 8.7 years). Exploratory analyses also showed a gene-by-environment effect, with VFD-reared macaques with a single short allele of the serotonin transporter gene exhibiting larger amygdala volume compared to VFD-reared subjects with only the long allele and normally reared controls.Conclusion: These data suggest that the left amygdala exhibits hypertrophy after ELS, particularly in association with the serotonin transporter gene, and that amygdala volume variation occurs in concert with other key stress-related behavioral and neurobiological parameters observed across the lifecycle. Future research is required to understand the mechanisms underlying these diverse and persistent changes associated with ELS and amygdala volume. |
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Coplan, Jeremy D.Fathy, Hassan M.Jackowski, Andrea Parolin [UNIFESP]Tang, Cheuk Y.Perera, Tarique D.Mathew, Sanjay J.Martinez, JoseAbdallah, Chadi G.Dwork, Andrew J.Pantol, GustavoCarpenter, DavidGorman, Jack M.Nemeroff, Charles B.Owens, Michael J.Kaffman, ArieKaufman, JoanSuny Downstate Med CtrUniversidade Federal de São Paulo (UNIFESP)Mt Sinai Sch MedNew York State Psychiat Inst & HospMichael E Debakey VA Med CtrBaylor Coll MedYale UnivNatl Ctr PTSDColumbia UnivComprehensive NeuroSci CorpUniv Miami Hlth SytemsEmory Univ2016-01-24T14:38:00Z2016-01-24T14:38:00Z2014-10-06Frontiers in Behavioral Neuroscience. Lausanne: Frontiers Research Foundation, v. 8, 10 p., 2014.1662-5153http://repositorio.unifesp.br/handle/11600/38324http://dx.doi.org/10.3389/fnbeh.2014.00342WOS000345983200001.pdf10.3389/fnbeh.2014.00342WOS:000345983200001Background: Children exposed to early life stress (ELS) exhibit enlarged amygdala volume in comparison to controls. the primary goal of this study was to examine amygdala volumes in bonnet macaques subjected to maternal variable foraging demand (VFD) rearing, a well-established model of ELS. Preliminary analyses examined the interaction of ELS and the serotonin transporter gene on amygdala volume. Secondary analyses were conducted to examine the association between amygdala volume and other stress-related variables previously found to distinguish VFD and non-VFD reared animals.Methods: Twelve VFD-reared and nine normally reared monkeys completed MRI scans on a 3T system (mean age = 5.2 years).Results: Left amygdala volume was larger in VFD vs. control macaques. Larger amygdala volume was associated with: high cerebrospinal fluid concentrations of corticotropin releasing-factor (CRF) determined when the animals were in adolescence (mean age = 2.7 years); reduced fractional anisotropy (FA) of the anterior limb of the internal capsule (ALIC) during young adulthood (mean age = 5.2 years) and timid anxiety-like responses to an intruder during full adulthood (mean age = 8.4 years). Right amygdala volume varied inversely with left hippocampal neurogenesis assessed in late adulthood (mean age = 8.7 years). Exploratory analyses also showed a gene-by-environment effect, with VFD-reared macaques with a single short allele of the serotonin transporter gene exhibiting larger amygdala volume compared to VFD-reared subjects with only the long allele and normally reared controls.Conclusion: These data suggest that the left amygdala exhibits hypertrophy after ELS, particularly in association with the serotonin transporter gene, and that amygdala volume variation occurs in concert with other key stress-related behavioral and neurobiological parameters observed across the lifecycle. Future research is required to understand the mechanisms underlying these diverse and persistent changes associated with ELS and amygdala volume.National Institute for Mental HealthNIMHNARSAD Mid-investigator AwardSuny Downstate Med Ctr, Dept Psychiat & Behav Sci, Brooklyn, NY 11203 USAUniversidade Federal de São Paulo, Dept Psiquiatria, São Paulo, BrazilMt Sinai Sch Med, Dept Psychiat, New York, NY USAMt Sinai Sch Med, Dept Neurosci, New York, NY USAMt Sinai Sch Med, Dept Radiol, New York, NY USANew York State Psychiat Inst & Hosp, New York, NY 10032 USAMichael E Debakey VA Med Ctr, Mental Hlth Care Line, Houston, TX USABaylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USAYale Univ, Sch Med, Dept Psychiat, New Haven, CT USANatl Ctr PTSD, Clin Neurosci Div, West Haven, CT USANew York State Psychiat Inst & Hosp, Dept Mol Imaging & Neuropathol, New York, NY 10032 USAColumbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USAColumbia Univ, Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY USAComprehensive NeuroSci Corp, Westchester, NY USAUniv Miami Hlth Sytems, Dept Psychiat & Behav Sci, Miami, FL USAEmory Univ, Sch Med, Dept Psychiat & Behav Sci, Emory, GA USAUniversidade Federal de São Paulo, Dept Psiquiatria, São Paulo, BrazilNational Institute for Mental Health: R01MH65519-01National Institute for Mental Health: R01MH098073NIMH: R21MH066748NIMH: R01MH59990AWeb of Science10engFrontiers Research FoundationFrontiers in Behavioral Neuroscienceamygdalaearly life stressnon-human primatesMRIstressserotonin transporter geneEarly life stress and macaque annygdala hypertrophy: preliminary evidence for a role for the serotonin transporter geneinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000345983200001.pdfapplication/pdf1196818${dspace.ui.url}/bitstream/11600/38324/1/WOS000345983200001.pdfa6f8797412dacc020d5aa613996b7846MD51open accessTEXTWOS000345983200001.pdf.txtWOS000345983200001.pdf.txtExtracted texttext/plain58715${dspace.ui.url}/bitstream/11600/38324/2/WOS000345983200001.pdf.txt79f3a9884fbd9a56aa210cdc964f12d6MD52open access11600/383242022-07-08 10:58:19.632open accessoai:repositorio.unifesp.br:11600/38324Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-05-25T12:21:57.167892Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Early life stress and macaque annygdala hypertrophy: preliminary evidence for a role for the serotonin transporter gene |
title |
Early life stress and macaque annygdala hypertrophy: preliminary evidence for a role for the serotonin transporter gene |
spellingShingle |
Early life stress and macaque annygdala hypertrophy: preliminary evidence for a role for the serotonin transporter gene Coplan, Jeremy D. amygdala early life stress non-human primates MRI stress serotonin transporter gene |
title_short |
Early life stress and macaque annygdala hypertrophy: preliminary evidence for a role for the serotonin transporter gene |
title_full |
Early life stress and macaque annygdala hypertrophy: preliminary evidence for a role for the serotonin transporter gene |
title_fullStr |
Early life stress and macaque annygdala hypertrophy: preliminary evidence for a role for the serotonin transporter gene |
title_full_unstemmed |
Early life stress and macaque annygdala hypertrophy: preliminary evidence for a role for the serotonin transporter gene |
title_sort |
Early life stress and macaque annygdala hypertrophy: preliminary evidence for a role for the serotonin transporter gene |
author |
Coplan, Jeremy D. |
author_facet |
Coplan, Jeremy D. Fathy, Hassan M. Jackowski, Andrea Parolin [UNIFESP] Tang, Cheuk Y. Perera, Tarique D. Mathew, Sanjay J. Martinez, Jose Abdallah, Chadi G. Dwork, Andrew J. Pantol, Gustavo Carpenter, David Gorman, Jack M. Nemeroff, Charles B. Owens, Michael J. Kaffman, Arie Kaufman, Joan |
author_role |
author |
author2 |
Fathy, Hassan M. Jackowski, Andrea Parolin [UNIFESP] Tang, Cheuk Y. Perera, Tarique D. Mathew, Sanjay J. Martinez, Jose Abdallah, Chadi G. Dwork, Andrew J. Pantol, Gustavo Carpenter, David Gorman, Jack M. Nemeroff, Charles B. Owens, Michael J. Kaffman, Arie Kaufman, Joan |
author2_role |
author author author author author author author author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Suny Downstate Med Ctr Universidade Federal de São Paulo (UNIFESP) Mt Sinai Sch Med New York State Psychiat Inst & Hosp Michael E Debakey VA Med Ctr Baylor Coll Med Yale Univ Natl Ctr PTSD Columbia Univ Comprehensive NeuroSci Corp Univ Miami Hlth Sytems Emory Univ |
dc.contributor.author.fl_str_mv |
Coplan, Jeremy D. Fathy, Hassan M. Jackowski, Andrea Parolin [UNIFESP] Tang, Cheuk Y. Perera, Tarique D. Mathew, Sanjay J. Martinez, Jose Abdallah, Chadi G. Dwork, Andrew J. Pantol, Gustavo Carpenter, David Gorman, Jack M. Nemeroff, Charles B. Owens, Michael J. Kaffman, Arie Kaufman, Joan |
dc.subject.eng.fl_str_mv |
amygdala early life stress non-human primates MRI stress serotonin transporter gene |
topic |
amygdala early life stress non-human primates MRI stress serotonin transporter gene |
description |
Background: Children exposed to early life stress (ELS) exhibit enlarged amygdala volume in comparison to controls. the primary goal of this study was to examine amygdala volumes in bonnet macaques subjected to maternal variable foraging demand (VFD) rearing, a well-established model of ELS. Preliminary analyses examined the interaction of ELS and the serotonin transporter gene on amygdala volume. Secondary analyses were conducted to examine the association between amygdala volume and other stress-related variables previously found to distinguish VFD and non-VFD reared animals.Methods: Twelve VFD-reared and nine normally reared monkeys completed MRI scans on a 3T system (mean age = 5.2 years).Results: Left amygdala volume was larger in VFD vs. control macaques. Larger amygdala volume was associated with: high cerebrospinal fluid concentrations of corticotropin releasing-factor (CRF) determined when the animals were in adolescence (mean age = 2.7 years); reduced fractional anisotropy (FA) of the anterior limb of the internal capsule (ALIC) during young adulthood (mean age = 5.2 years) and timid anxiety-like responses to an intruder during full adulthood (mean age = 8.4 years). Right amygdala volume varied inversely with left hippocampal neurogenesis assessed in late adulthood (mean age = 8.7 years). Exploratory analyses also showed a gene-by-environment effect, with VFD-reared macaques with a single short allele of the serotonin transporter gene exhibiting larger amygdala volume compared to VFD-reared subjects with only the long allele and normally reared controls.Conclusion: These data suggest that the left amygdala exhibits hypertrophy after ELS, particularly in association with the serotonin transporter gene, and that amygdala volume variation occurs in concert with other key stress-related behavioral and neurobiological parameters observed across the lifecycle. Future research is required to understand the mechanisms underlying these diverse and persistent changes associated with ELS and amygdala volume. |
publishDate |
2014 |
dc.date.issued.fl_str_mv |
2014-10-06 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:38:00Z |
dc.date.available.fl_str_mv |
2016-01-24T14:38:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Frontiers in Behavioral Neuroscience. Lausanne: Frontiers Research Foundation, v. 8, 10 p., 2014. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/38324 http://dx.doi.org/10.3389/fnbeh.2014.00342 |
dc.identifier.issn.none.fl_str_mv |
1662-5153 |
dc.identifier.file.none.fl_str_mv |
WOS000345983200001.pdf |
dc.identifier.doi.none.fl_str_mv |
10.3389/fnbeh.2014.00342 |
dc.identifier.wos.none.fl_str_mv |
WOS:000345983200001 |
identifier_str_mv |
Frontiers in Behavioral Neuroscience. Lausanne: Frontiers Research Foundation, v. 8, 10 p., 2014. 1662-5153 WOS000345983200001.pdf 10.3389/fnbeh.2014.00342 WOS:000345983200001 |
url |
http://repositorio.unifesp.br/handle/11600/38324 http://dx.doi.org/10.3389/fnbeh.2014.00342 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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Frontiers in Behavioral Neuroscience |
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openAccess |
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10 |
dc.publisher.none.fl_str_mv |
Frontiers Research Foundation |
publisher.none.fl_str_mv |
Frontiers Research Foundation |
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