Childhood maltreatment is associated with altered fear circuitry and increased internalizing symptoms by late adolescence
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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.
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Right amygdala structural alterations in adulthood are particularly linked to childhood maltreatment exposure.
“Thus, right amygdala may be differentially responsive to negative or threatening stimuli (107–109), and alterations in structure (38, 109, 110) of the right amygdala in adulthood have been particularly related to exposure to childhood maltreatment.”
From Disorganized attachment in infancy predicts greater amygdala volume in adulthood (2016) · cites this paper as [110]
The mPFC and amygdala have extensive bidirectional connections and often function together.
“Although mPFC and amygdala have extensive bidirectional connections and often function in tandem (110, 116, 117), these mPFC findings on greater left responding under conditions of deprived care are suggestive but have yet to be extended to amygdala structure or function.”
From Disorganized attachment in infancy predicts greater amygdala volume in adulthood (2016) · cites this paper as [110]
Recent work suggests that prefrontal-amygdalar functional connectivity can be influenced by early adversity.
“Likewise, recent work suggests that prefrontal-amygdalar functional connectivity can be influenced by early adversity43-44.”
From Evolutionarily conserved prefrontal-amygdalar dysfunction in early-life anxiety (2014) · cites this paper as [43]
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Trauma, PTSD, and the Developing Brain
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- Authors
- Herringa, R. J., Birn, R. M., Ruttle, P. L., Burghy, C. A., Stodola, D. E., Davidson, R. J., & Essex, M. J.
- Affiliations
- University of Wisconsin–Madison (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-11-04
- Volume
- 110
- Issue
- 47
- Pages
- 19119-19124
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3839755
- OpenAlex
- W2167216405
- Semantic Scholar
- da6a3de6bbe1765b280615381fbc6d7d092a0493
- Cited by
- 426
- References
- 70
- Citations by year
- 2026: 16 · 2025: 20 · 2024: 27 · 2023: 33 · 2022: 35 · 2021: 39 · 2020: 65 · 2019: 48 · 2018: 31 · 2017: 23 · 2016: 38 · 2015: 30 · 2014: 19 · 2013: 1
- FWCI
- 32.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- John D. and Catherine T. MacArthur Foundation
- Brain and Behavior Research Foundation
- American Academy of Child and Adolescent Psychiatry
- National Institutes of Health (MH084051)
- School of Medicine and Public Health, University of Wisconsin-Madison
- Canadian Institutes of Health Research
- National Institute of Mental Health (P50MH052354, P50MH100031, R01MH044340, P50MH084051, K08MH100267)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD003352)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Keywords
- child abuse, internalizing problems, fear circuitry, resting-state functional connectivity, amygdala, hippocampus, subgenual anterior cingulate cortex, anxiety, depression, adolescence, sex differences, mediation
- MeSH terms
- Adolescent, Amygdala, Anxiety Disorders, Child Abuse, Depressive Disorder, Fear, Female, Hippocampus, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Risk Factors, Sex Factors, Wisconsin, Prefrontal Cortex, Connectome
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