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Individual differences in frontolimbic circuitry and anxiety emerge with adolescent changes in endocannabinoid signaling across species

Anxiety disorders peak in incidence during adolescence, a developmental window that is marked by dynamic changes in gene expression, endocannabinoid signaling, and frontolimbic circuitry. We tested whether genetic alterations in endocannabinoid signaling related to a common polymorphism in fatty aci... Full description

Journal Title: Proceedings of the National Academy of Sciences 19 April 2016, Vol.113(16), p.4500
Main Author: Dylan G. Gee
Other Authors: Robert N. Fetcho , Deqiang Jing , Anfei Li , Charles E. Glatt , Andrew T. Drysdale , Alexandra O. Cohen , Danielle V. Dellarco , Rui R. Yang , Anders M. Dale , Terry L. Jernigan , Francis S. Lee , B.J. Casey , the Ping Consortium , Uc San Diego , Co-PI of Ping, Core PI , Connor Mccabe , Linda Chang , U Hawaii , Natacha Akshoomoff , Erik Newman , Mri Acquisition Core , Thomas Ernst , Co-PI of Ping, Core Co-PI , Core Co-PI , Peter Van Zijl , Kki , Joshua Kuperman , Sarah Murray , Scripps Translational Science Institute, Co-PI of Ping, Core PI , Cinnamon Bloss , Scripps Translational Science Institute , Nicholas J. Schork , Mark Appelbaum , Anthony Gamst , Wesley Thompson , Hauke Bartsch , Brian Keating , David Amaral , Elizabeth Sowell , Walter Kaufmann , Stewart Mostofsky , Erika J. Ruberry , Alisa Powers , Bruce Rosen , Tal Kenet , Jean Frazier , David Kennedy , Yale University , Jeffrey Gruen
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0027-8424 ; E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1600013113
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title: Individual differences in frontolimbic circuitry and anxiety emerge with adolescent changes in endocannabinoid signaling across species
format: Article
creator:
  • Dylan G. Gee
  • Robert N. Fetcho
  • Deqiang Jing
  • Anfei Li
  • Charles E. Glatt
  • Andrew T. Drysdale
  • Alexandra O. Cohen
  • Danielle V. Dellarco
  • Rui R. Yang
  • Anders M. Dale
  • Terry L. Jernigan
  • Francis S. Lee
  • B.J. Casey
  • the Ping Consortium
  • Uc San Diego
  • Co-PI of Ping, Core PI
  • Connor Mccabe
  • Linda Chang
  • U Hawaii
  • Natacha Akshoomoff
  • Erik Newman
  • Mri Acquisition Core
  • Thomas Ernst
  • Co-PI of Ping, Core Co-PI
  • Core Co-PI
  • Peter Van Zijl
  • Kki
  • Joshua Kuperman
  • Sarah Murray
  • Scripps Translational Science Institute, Co-PI of Ping, Core PI
  • Cinnamon Bloss
  • Scripps Translational Science Institute
  • Nicholas J. Schork
  • Mark Appelbaum
  • Anthony Gamst
  • Wesley Thompson
  • Hauke Bartsch
  • Brian Keating
  • David Amaral
  • Elizabeth Sowell
  • Walter Kaufmann
  • Stewart Mostofsky
  • Erika J. Ruberry
  • Alisa Powers
  • Bruce Rosen
  • Tal Kenet
  • Jean Frazier
  • David Kennedy
  • Yale University
  • Jeffrey Gruen
subjects:
  • Sciences (General)
ispartof: Proceedings of the National Academy of Sciences, 19 April 2016, Vol.113(16), p.4500
description: Anxiety disorders peak in incidence during adolescence, a developmental window that is marked by dynamic changes in gene expression, endocannabinoid signaling, and frontolimbic circuitry. We tested whether genetic alterations in endocannabinoid signaling related to a common polymorphism in fatty acid amide hydrolase (FAAH), which alters endocannabinoid anandamide (AEA) levels, would impact the development of frontolimbic circuitry implicated in anxiety disorders. In a pediatric imaging sample of over 1,000 3- to 21-y-olds, we show effects of the FAAH genotype specific to frontolimbic connectivity that emerge by ~12 y of age and are paralleled by changes in anxiety-related behavior. Using a knock-in mouse model of the FAAH polymorphism that controls for genetic and environmental backgrounds, we confirm phenotypic differences in frontoamygdala circuitry and anxiety-related behavior by postnatal day 45 (P45), when AEA levels begin to decrease, and also, at P75 but not before. These results, which converge across species and level of analysis, highlight the importance of underlying developmental neurobiology in the emergence of genetic effects on brain circuitry and function. Moreover, the results have important implications for the identification of risk for disease and precise targeting of treatments to the biological state of the developing brain as a function of developmental changes in gene expression and neural circuit maturation. FAAH | frontolimbic | gene x development | anxiety | cross-species
language: eng
source:
identifier: ISSN: 0027-8424 ; E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1600013113
fulltext: fulltext_linktorsrc
issn:
  • 0027-8424
  • 00278424
  • 1091-6490
  • 10916490
url: Link


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titleIndividual differences in frontolimbic circuitry and anxiety emerge with adolescent changes in endocannabinoid signaling across species
creatorDylan G. Gee ; Robert N. Fetcho ; Deqiang Jing ; Anfei Li ; Charles E. Glatt ; Andrew T. Drysdale ; Alexandra O. Cohen ; Danielle V. Dellarco ; Rui R. Yang ; Anders M. Dale ; Terry L. Jernigan ; Francis S. Lee ; B.J. Casey ; the Ping Consortium ; Uc San Diego ; Co-PI of Ping, Core PI ; Connor Mccabe ; Linda Chang ; U Hawaii ; Natacha Akshoomoff ; Erik Newman ; Mri Acquisition Core ; Thomas Ernst ; Co-PI of Ping, Core Co-PI ; Core Co-PI ; Peter Van Zijl ; Kki ; Joshua Kuperman ; Sarah Murray ; Scripps Translational Science Institute, Co-PI of Ping, Core PI ; Cinnamon Bloss ; Scripps Translational Science Institute ; Nicholas J. Schork ; Mark Appelbaum ; Anthony Gamst ; Wesley Thompson ; Hauke Bartsch ; Brian Keating ; David Amaral ; Elizabeth Sowell ; Walter Kaufmann ; Stewart Mostofsky ; Erika J. Ruberry ; Alisa Powers ; Bruce Rosen ; Tal Kenet ; Jean Frazier ; David Kennedy ; Yale University ; Jeffrey Gruen
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descriptionAnxiety disorders peak in incidence during adolescence, a developmental window that is marked by dynamic changes in gene expression, endocannabinoid signaling, and frontolimbic circuitry. We tested whether genetic alterations in endocannabinoid signaling related to a common polymorphism in fatty acid amide hydrolase (FAAH), which alters endocannabinoid anandamide (AEA) levels, would impact the development of frontolimbic circuitry implicated in anxiety disorders. In a pediatric imaging sample of over 1,000 3- to 21-y-olds, we show effects of the FAAH genotype specific to frontolimbic connectivity that emerge by ~12 y of age and are paralleled by changes in anxiety-related behavior. Using a knock-in mouse model of the FAAH polymorphism that controls for genetic and environmental backgrounds, we confirm phenotypic differences in frontoamygdala circuitry and anxiety-related behavior by postnatal day 45 (P45), when AEA levels begin to decrease, and also, at P75 but not before. These results, which converge across species and level of analysis, highlight the importance of underlying developmental neurobiology in the emergence of genetic effects on brain circuitry and function. Moreover, the results have important implications for the identification of risk for disease and precise targeting of treatments to the biological state of the developing brain as a function of developmental changes in gene expression and neural circuit maturation. FAAH | frontolimbic | gene x development | anxiety | cross-species
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titleIndividual differences in frontolimbic circuitry and anxiety emerge with adolescent changes in endocannabinoid signaling across species
authorDylan G. Gee ; Robert N. Fetcho ; Deqiang Jing ; Anfei Li ; Charles E. Glatt ; Andrew T. Drysdale ; Alexandra O. Cohen ; Danielle V. Dellarco ; Rui R. Yang ; Anders M. Dale ; Terry L. Jernigan ; Francis S. Lee ; B.J. Casey ; the Ping Consortium ; Uc San Diego ; Co-PI of Ping, Core PI ; Connor Mccabe ; Linda Chang ; U Hawaii ; Natacha Akshoomoff ; Erik Newman ; Mri Acquisition Core ; Thomas Ernst ; Co-PI of Ping, Core Co-PI ; Core Co-PI ; Peter Van Zijl ; Kki ; Joshua Kuperman ; Sarah Murray ; Scripps Translational Science Institute, Co-PI of Ping, Core PI ; Cinnamon Bloss ; Scripps Translational Science Institute ; Nicholas J. Schork ; Mark Appelbaum ; Anthony Gamst ; Wesley Thompson ; Hauke Bartsch ; Brian Keating ; David Amaral ; Elizabeth Sowell ; Walter Kaufmann ; Stewart Mostofsky ; Erika J. Ruberry ; Alisa Powers ; Bruce Rosen ; Tal Kenet ; Jean Frazier ; David Kennedy ; Yale University ; Jeffrey Gruen
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37Brian Keating
38David Amaral
39Elizabeth Sowell
40Walter Kaufmann
41Stewart Mostofsky
42Erika J. Ruberry
43Alisa Powers
44Bruce Rosen
45Tal Kenet
46Jean Frazier
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