Abnormal Structure of Fear Circuitry in Pediatric Post-Traumatic Stress Disorder
Open accessAbstract
Structural brain studies of adult post-traumatic stress disorder (PTSD) show reduced gray matter volume (GMV) in fear regulatory areas including the ventromedial prefrontal cortex (vmPFC) and hippocampus. Surprisingly, neither finding has been reported in pediatric PTSD. One possibility is that they represent age-dependent effects that are not fully apparent until adulthood. In addition, lower-resolution MRI and image processing in prior studies may have limited detection of such differences. Here we examine fear circuitry GMV, including age-related differences, using higher-resolution MRI in pediatric PTSD vs healthy youth. In a cross-sectional design, 3 T anatomical brain MRI was acquired in 27 medication-free youth with PTSD and 27 healthy non-traumatized youth of comparable age, sex, and IQ. Voxel-based morphometry was used to compare GMV in a priori regions including the medial prefrontal cortex and amygdala/hippocampus. Compared with healthy youth, PTSD youth had reduced GMV but no age-related differences in anterior vmPFC (BA 10/11, Z=4.5), which inversely correlated with PTSD duration. In contrast, although there was no overall group difference in hippocampal volume, a group × age interaction (Z=3.6) was present in the right anterior hippocampus. Here, age positively predicted hippocampal volume in healthy youth but negatively predicted volume in PTSD youth. Within the PTSD group, re-experiencing symptoms inversely correlated with subgenual anterior cingulate cortex (sgACC, Z=3.7) and right anterior hippocampus (Z=3.5) GMV. Pediatric PTSD is associated with abnormal structure of the vmPFC and age-related differences in the hippocampus, regions important in the extinction and contextual gating of fear. Reduced anterior vmPFC volume may confer impaired recovery from illness, consistent with its role in the allocation of attentional resources. In contrast, individual differences in sgACC volume were associated with re-experiencing symptoms, consistent with the role of the sgACC in fear extinction. The negative relationship between age and hippocampal volume in youth with PTSD may suggest an ongoing neurotoxic process over development, which further contributes to illness expression. Future studies employing a longitudinal design would be merited to further explore these possibilities.
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Youth with PTSD show declining hippocampal volume with age.
“declining hippocampal volume”
From Trauma, PTSD, and the Developing Brain (2017) · cites this paper as [53]
No differences in average hippocampal volume between PTSD and TD youth were found in three studies.
“none of these studies found differences in average hippocampal volume between PTSD and TD youth.”
From Trauma, PTSD, and the Developing Brain (2017) · cites this paper as [53]
Two recent studies found decreased vmPFC volume in youth with PTSD relative to TD or trauma-exposed youth without PTSD.
“two recent studies, including our own, found decreased vmPFC volume in youth with PTSD relative to either TD or trauma-exposed youth without PTSD [53,54].”
From Trauma, PTSD, and the Developing Brain (2017) · cites this paper as [53]
In pediatric PTSD, there is a group by age interaction in right hippocampal volume: hippocampal volume increases with age in TD youth but decreases with age in youth with PTSD.
“we found a group by age interaction in right hippocampal volume, such that hippocampal volume increased with age in TD youth, but decreased with age in youth with PTSD [53].”
From Trauma, PTSD, and the Developing Brain (2017) · cites this paper as [53]
In a study of approximately 50 youth, those with PTSD had reduced gray matter volume in anterior vmPFC, which inversely correlated with PTSD duration.
“In development, with a study of ~50 youth, Keding and Herringa [151] found that those with PTSD had reduced gray matter volume in anterior vmPFC, which inversely correlated with PTSD duration.”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [151]
Pediatric PTSD is associated with abnormal structure of the vmPFC, possibly related to disrupted extinction and contextual gating of fear.
“They suggest that pediatric PTSD is associated with abnormal structure of the vmPFC, possibly related to disrupted extinction and contextual gating of fear.”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [151]
Age-related findings in pediatric PTSD were not accounted for by age at index trauma or duration of PTSD.
“our age-related findings in pediatric PTSD (e.g. increased amygdala activation, decreased amygdala-vmPFC coupling with age) were not accounted for by age at index trauma or duration of PTSD [35,53,57].”
From Trauma, PTSD, and the Developing Brain (2017) · cites this paper as [53]
The Discussion reports age-related differences in hippocampal gray-matter volume, and the Secondary Analyses discuss associations with PTSD duration and trauma-exposure measures. Neither passage says that age at index trauma or PTSD duration failed to account for the age-related findings. This structural MRI study also does not address the cited sentence’s examples of amygdala activation and amygdala–vmPFC coupling. (LLM, conf=0.76)
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- Authors
- Keding, T. J., & Herringa, R. J.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Herringa, Ryan J
- Venue
- Neuropsychopharmacology
- Published
- 2014-09-12
- Volume
- 40
- Issue
- 3
- Pages
- 537-545
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4289962
- OpenAlex
- W2143337872
- Cited by
- 115
- References
- 50
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 10 · 2023: 4 · 2022: 6 · 2021: 16 · 2020: 15 · 2019: 14 · 2018: 14 · 2017: 9 · 2016: 11 · 2015: 9 · 2014: 1
- FWCI
- 11.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1TR000427)
- National Institute of Mental Health (K08MH100267)
- National Center for Advancing Translational Sciences
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- fear circuitry, gray matter volume, ventromedial prefrontal cortex, hippocampus, subgenual anterior cingulate cortex, amygdala, age differences, re-experiencing symptoms, fear extinction, brain development
- MeSH terms
- Adolescent, Aging, Amygdala, Atrophy, Child, Fear, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Stress Disorders, Post-Traumatic, Case-Control Studies, Prefrontal Cortex, Neuroimaging, Gray Matter
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