Amygdala, Hippocampus, and Ventral Medial Prefrontal Cortex Volumes Differ in Maltreated Youth with and without Chronic Posttraumatic Stress Disorder
Open accessAbstract
Posttraumatic stress disorder (PTSD) is considered a disorder of recovery where individuals fail to learn and retain extinction of the traumatic fear response. In maltreated youth, PTSD is common, chronic, and associated with comorbidity. Studies of extinction-related structural volumes (amygdala, hippocampus, anterior cingulate cortex (ACC), and ventral medial prefrontal cortex (vmPFC)) and this stress diathesis, in maltreated youth were not previously investigated. In this cross-sectional study, neuroanatomical volumes associated with extinction in maltreated youth with PTSD (N=31), without PTSD (N=32), and in non-maltreated healthy volunteers (n=57) were examined using magnetic resonance imaging. Groups were sociodemographically similar. Participants underwent extensive assessments for strict inclusion/exclusion criteria and DSM-IV disorders. Maltreated youth with PTSD demonstrated decreased right vmPFC volumes compared with both maltreated youth without PTSD and non-maltreated controls. Maltreated youth without PTSD demonstrated larger left amygdala and right hippocampal volumes compared with maltreated youth with PTSD and non-maltreated control youth. PTSD symptoms inversely correlated with right and left hippocampal and left amygdala volumes. Confirmatory masked voxel base morphometry analyses demonstrated greater medial orbitofrontal cortex gray matter intensity in controls than maltreated youth with PTSD. Volumetric results were not influenced by psychopathology or maltreatment variables. We identified volumetric differences in extinction-related structures between maltreated youth with PTSD from those without PTSD. Alterations of the vmPFC may be one mechanism that mediates the pathway from PTSD to comorbidity. Further longitudinal work is needed to determine neurobiological factors related to chronic and persistent PTSD, and to PTSD resilience despite maltreatment.
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Neuroimaging studies of individuals diagnosed with PTSD and substance use disorder demonstrate diminished volume and hypoactivity in the VMPFC.
“Moreover, neuroimaging studies of individuals diagnosed with PTSD and substance use disorder (2 conditions that are also associated with impulsive behavior and SI) demonstrate diminished volume and hypoactivity in the VMPFC [69,70].”
From Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled Trial (2024) · cites this paper as [69]
The Abstract and Discussion report smaller vmPFC volumes in maltreated youth with PTSD, and the Discussion reports smaller vmPFC volumes in adults with substance use disorder. The paper did not study participants with substance use disorder or measure vmPFC activity; its statement about hypoactivation concerns prediction of early substance-use initiation, not demonstrated hypoactivity in people diagnosed with either condition. (LLM, conf=0.88)
Experimental — accuracy not yet measuredWhen mental illness diagnoses such as PTSD and substance use disorders co-occur with mTBI, they likely have an additive effect on brain functioning in the VMPFC, further worsening negative urgency impulsivity.
“Therefore, it is likely that when mental illness diagnoses such as PTSD and substance use disorders co-occur with mTBI, they have an additive effect on brain functioning in the VMPFC, further worsening negative urgency impulsivity [69,70].”
From Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled Trial (2024) · cites this paper as [69]
The Discussion (page unavailable) links PTSD, vmPFC differences, substance-use-disorder risk, and impulsivity. It does not establish an additive effect with mTBI or worsening negative urgency; the Subjects section (page unavailable) says traumatic brain injury and substance use disorders were exclusion criteria. (LLM, conf=0.87)
Experimental — accuracy not yet measuredTwo 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 [54]
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 [54]
In a study of over 100 participants, maltreated youth with PTSD demonstrated decreased right vmPFC volumes compared to both maltreated youth without PTSD and nonmaltreated healthy controls.
“Similarly, in a study of over 100 participants, it was found that maltreated youth with PTSD demonstrated decreased right vmPFC volumes compared to both maltreated youth without PTSD and nonmaltreated healthy controls [152].”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [152]
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Garrett, A. S., Abazid, L., Cohen, J. A., van der Kooij, A. J., Carrión, V. G., Zhang, W., Jo, B., Franklin, C. G., Blader, J. C., Zack, S., et al. (2021) · Journal of Traumatic Stress · doi:10.1002/jts.22678 · Cited by 15 · see citing works
Lagatta, D. C., Fassini, A., Terzian, A. L. B., Corrêa, F. M. D. A., & Resstel, L. B. M. (2023) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-022-02786-5 · Cited by 16 · see citing works
Xiao, H., Xi, K., Wang, K., Zhou, Y., Dong, B., Xie, J., Xie, Y., Zhang, H., Ma, G., Wang, W., et al. (2023) · Advanced Science · doi:10.1002/advs.202305939 · Cited by 16 · see citing works
- Authors
- Morey, R. A., Haswell, C. C., Hooper, S. R., & De Bellis, M. D.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Duke University (US)
- Venue
- Neuropsychopharmacology
- Published
- 2015-07-14
- Volume
- 41
- Issue
- 3
- Pages
- 791-801
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4707825
- OpenAlex
- W877950925
- Cited by
- 237
- References
- 77
- Citations by year
- 2026: 7 · 2025: 25 · 2024: 27 · 2023: 17 · 2022: 26 · 2021: 27 · 2020: 37 · 2019: 25 · 2018: 26 · 2017: 12 · 2016: 7 · 2014: 1
- FWCI
- 18.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 CX000120, I01 CX000748)
- National Institute on Alcohol Abuse and Alcoholism (R01AA012479)
- National Institute of Mental Health (R01MH063407, R01MH061744, K24MH071434)
- National Institute on Drug Abuse (K24DA028773)
- National Institute of Neurological Disorders and Stroke (R01NS086885)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Social Sciences › Psychology › Clinical Psychology › Psychoanalysis and Psychopathology Research
- Keywords
- post-traumatic stress disorder, child abuse, ventromedial prefrontal cortex, amygdala, hippocampus, fear extinction, gray matter density, medial orbitofrontal cortex, PTSD comorbidity, brain structure
- MeSH terms
- Adolescent, Amygdala, Child, Child Abuse, Chronic Disease, Cross-Sectional Studies, Female, Hippocampus, Humans, Functional Laterality, Magnetic Resonance Imaging, Male, Organ Size, Stress Disorders, Post-Traumatic, Prefrontal Cortex
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