Skip to main content

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
    • Front Matter Portal
    • Journal Club
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home
  • Log in
  • My Cart

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
    • Front Matter Portal
    • Journal Club
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
Research Article

Childhood maltreatment is associated with altered fear circuitry and increased internalizing symptoms by late adolescence

Ryan J. Herringa, Rasmus M. Birn, Paula L. Ruttle, Cory A. Burghy, Diane E. Stodola, Richard J. Davidson, and Marilyn J. Essex
  1. aDepartment of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53719;
  2. bDepartment of Medical Physics and
  3. cWaisman Laboratory for Brain Imaging and Behavior, University of Wisconsin–Madison, Madison, WI 53705; and
  4. dDepartment of Psychology, University of Wisconsin–Madison, Madison, WI 53706

See allHide authors and affiliations

PNAS November 19, 2013 110 (47) 19119-19124; https://doi.org/10.1073/pnas.1310766110
Ryan J. Herringa
aDepartment of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53719;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: herringa@wisc.edu mjessex@wisc.edu
Rasmus M. Birn
aDepartment of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53719;
bDepartment of Medical Physics and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paula L. Ruttle
aDepartment of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53719;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cory A. Burghy
dDepartment of Psychology, University of Wisconsin–Madison, Madison, WI 53706
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Diane E. Stodola
cWaisman Laboratory for Brain Imaging and Behavior, University of Wisconsin–Madison, Madison, WI 53705; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard J. Davidson
aDepartment of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53719;
cWaisman Laboratory for Brain Imaging and Behavior, University of Wisconsin–Madison, Madison, WI 53705; and
cWaisman Laboratory for Brain Imaging and Behavior, University of Wisconsin–Madison, Madison, WI 53705; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marilyn J. Essex
aDepartment of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53719;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: herringa@wisc.edu mjessex@wisc.edu
  1. Edited by Huda Akil, University of Michigan, Ann Arbor, MI, and approved October 7, 2013 (received for review June 6, 2013)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

Significance

Childhood maltreatment is a major risk factor for internalizing disorders including depression and anxiety, which cause significant disability. Altered connectivity of the brain’s fear circuitry represents an important candidate mechanism linking maltreatment and these disorders, but this relationship has not been directly explored. Using resting-state functional brain connectivity in adolescents, we show that maltreatment predicts lower prefrontal–hippocampal connectivity in females and males but lower prefrontal–amygdala connectivity only in females. Altered connectivity, in turn, mediated the development of internalizing symptoms. These results highlight the importance of fronto–hippocampal connectivity for both sexes in internalizing symptoms following maltreatment. The additional impact on fronto–amygdala connectivity in females may help explain their higher risk for anxiety and depression.

Abstract

Maltreatment during childhood is a major risk factor for anxiety and depression, which are major public health problems. However, the underlying brain mechanism linking maltreatment and internalizing disorders remains poorly understood. Maltreatment may alter the activation of fear circuitry, but little is known about its impact on the connectivity of this circuitry in adolescence and whether such brain changes actually lead to internalizing symptoms. We examined the associations between experiences of maltreatment during childhood, resting-state functional brain connectivity (rs-FC) of the amygdala and hippocampus, and internalizing symptoms in 64 adolescents participating in a longitudinal community study. Childhood experiences of maltreatment were associated with lower hippocampus–subgenual cingulate rs-FC in both adolescent females and males and lower amygdala–subgenual cingulate rs-FC in females only. Furthermore, rs-FC mediated the association of maltreatment during childhood with adolescent internalizing symptoms. Thus, maltreatment in childhood, even at the lower severity levels found in a community sample, may alter the regulatory capacity of the brain’s fear circuit, leading to increased internalizing symptoms by late adolescence. These findings highlight the importance of fronto–hippocampal connectivity for both sexes in internalizing symptoms following maltreatment in childhood. Furthermore, the impact of maltreatment during childhood on both fronto–amygdala and –hippocampal connectivity in females may help explain their higher risk for internalizing disorders such as anxiety and depression.

  • child maltreatment
  • sex differences
  • ventromedial prefrontal cortex

Footnotes

  • ↵1R.J.H. and R.M.B. contributed equally to this work.

  • ↵2To whom correspondence may be addressed. E-mail: herringa{at}wisc.edu or mjessex{at}wisc.edu.
  • Author contributions: R.J.H., R.J.D., and M.J.E. designed research; R.J.H., R.M.B., C.A.B., and M.J.E. performed research; R.J.H., R.M.B., P.L.R., C.A.B., D.E.S., and M.J.E. analyzed data; and R.J.H., R.M.B., P.L.R., C.A.B., R.J.D., and M.J.E. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1310766110/-/DCSupplemental.

View Full Text
PreviousNext
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Childhood maltreatment is associated with altered fear circuitry and increased internalizing symptoms by late adolescence
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Childhood maltreatment and brain connectivity
Ryan J. Herringa, Rasmus M. Birn, Paula L. Ruttle, Cory A. Burghy, Diane E. Stodola, Richard J. Davidson, Marilyn J. Essex
Proceedings of the National Academy of Sciences Nov 2013, 110 (47) 19119-19124; DOI: 10.1073/pnas.1310766110

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Childhood maltreatment and brain connectivity
Ryan J. Herringa, Rasmus M. Birn, Paula L. Ruttle, Cory A. Burghy, Diane E. Stodola, Richard J. Davidson, Marilyn J. Essex
Proceedings of the National Academy of Sciences Nov 2013, 110 (47) 19119-19124; DOI: 10.1073/pnas.1310766110
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley

Article Classifications

  • Biological Sciences
  • Neuroscience
Proceedings of the National Academy of Sciences: 110 (47)
Table of Contents

Submit

Sign up for Article Alerts

Jump to section

  • Article
    • Abstract
    • Results
    • Discussion
    • Methods
    • Acknowledgments
    • Footnotes
    • References
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Setting sun over a sun-baked dirt landscape
Core Concept: Popular integrated assessment climate policy models have key caveats
Better explicating the strengths and shortcomings of these models will help refine projections and improve transparency in the years ahead.
Image credit: Witsawat.S.
Model of the Amazon forest
News Feature: A sea in the Amazon
Did the Caribbean sweep into the western Amazon millions of years ago, shaping the region’s rich biodiversity?
Image credit: Tacio Cordeiro Bicudo (University of São Paulo, São Paulo, Brazil), Victor Sacek (University of São Paulo, São Paulo, Brazil), and Lucy Reading-Ikkanda (artist).
Syrian archaeological site
Journal Club: In Mesopotamia, early cities may have faltered before climate-driven collapse
Settlements 4,200 years ago may have suffered from overpopulation before drought and lower temperatures ultimately made them unsustainable.
Image credit: Andrea Ricci.
Steamboat Geyser eruption.
Eruption of Steamboat Geyser
Mara Reed and Michael Manga explore why Yellowstone's Steamboat Geyser resumed erupting in 2018.
Listen
Past PodcastsSubscribe
Birds nestling on tree branches
Parent–offspring conflict in songbird fledging
Some songbird parents might improve their own fitness by manipulating their offspring into leaving the nest early, at the cost of fledgling survival, a study finds.
Image credit: Gil Eckrich (photographer).

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Special Feature Articles – Most Recent
  • List of Issues

PNAS Portals

  • Anthropology
  • Chemistry
  • Classics
  • Front Matter
  • Physics
  • Sustainability Science
  • Teaching Resources

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Subscribers
  • Librarians
  • Press
  • Site Map
  • PNAS Updates
  • FAQs
  • Accessibility Statement
  • Rights & Permissions
  • About
  • Contact

Feedback    Privacy/Legal

Copyright © 2021 National Academy of Sciences. Online ISSN 1091-6490