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Stress Predicts Brain Changes in Children: A Pilot Longitudinal Study on Youth Stress, Posttraumatic Stress Disorder, and the Hippocampus
Abstract
OBJECTIVE: Does stress damage the brain? Studies of adults with posttraumatic stress disorder have demonstrated smaller hippocampal volumes when compared with the volumes of adults with no posttraumatic stress disorder. Studies of children with posttraumatic stress disorder have not replicated the smaller hippocampal findings in adults, which suggests that smaller hippocampal volume may be caused by neurodevelopmental experiences with stress. Animal research has demonstrated that the glucocorticoids secreted during stress can be neurotoxic to the hippocampus, but this has not been empirically demonstrated in human samples. We hypothesized that cortisol volumes would predict hippocampal volume reduction in patients with posttraumatic symptoms. PATIENTS AND METHODS: We report data from a pilot longitudinal study of children (n = 15) with history of maltreatment who underwent clinical evaluation for posttraumatic stress disorder, cortisol, and neuroimaging. RESULTS: Posttraumatic stress disorder symptoms and cortisol at baseline predicted hippocampal reduction over an ensuing 12- to 18-month interval. CONCLUSIONS: Results from this pilot study suggest that stress is associated with hippocampal reduction in children with posttraumatic stress disorder symptoms and provide preliminary human evidence that stress may indeed damage the hippocampus. Additional studies seem to be warranted.
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“This may be compounded by environment (e.g., poverty (118)), parent (e.g., mental disorders (119)), and youth (e.g., stress (120); psychiatric symptoms (121)) factors—each affecting neuromaturation—and potentially, increasing STB and NSSI vulnerability.”
From Neural correlates associated with suicide and nonsuicidal self-injury in youth (2021) · cites this paper as [120]
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“Structural neuroimaging findings have reported smaller right temporal lobe volume (De Bellis et al., 2002) and altered hippocampal volume (decreased volume, Carrion, Weems, & Reiss, 2007; increased volume, Tupler & De Bellis, 2006) in anxious pediatric patients with a history of neglect and abuse.”
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“Based on the putative neurotoxic effects of elevated cortisol on such brain structures as the hippocampus (e.g., Bremner et al., 1997; Carrion et al., 2007; Sapolsky, 1996), increased cortisol shortly after a stressful event could be negatively correlated with accurate and complete memory, and therefore possibly posit…”
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Childhood Sexual Abuse Is Associated with Reduced Gray Matter Volume in Visual Cortex of Young Women
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“Carrion et al. (2007) examined maltreated children and found that symptoms of PTSD and cortisol level predicted reduction in hippocampal size over a 12–18- month period, which is consistent with adult findings.”
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“Recently, however, our group reported that when studied longitudinally, PTSD symptoms and cortisol levels at baseline predicted hippocampal reduction in children over an ensuing 12- to 18-month interval (Carrion et al., 2007).”
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“Furthermore, the escalating levels of anxiety children with high anxiety sensitivity experience may cause them to be more at risk for organic disease considering the link between chronic stress and negative neurodevelopmental outcomes (Carrion, Weems, & Reiss, 2007 ; Cicchetti, 2003 ; Sapolsky et al, 2000 ).”
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The neurobiological correlates of childhood adversity and implications for treatment
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Structural and Functional Neuroplasticity in Relation to Traumatic Stress
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“In support of an effect of trauma on hippocampal volume, Carrion, Weems, and Reiss (2007) found that PTSD symptoms and prebedtime cortisol predicted hippocampal reduction in traumatized children over an ensuing 12- to 18-month interval.”
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Neuner, F., Catani, C., Ruf, M., Schauer, E., Schauer, M., & Elbert, T. (2008) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2008.03.001 · Cited by 130
“In a recent longitudinal study [79], children who had a history of maltreatment underwent a variety of clinical evaluations at different time points over a period of 12 to 18 months.”
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“However, one longitudinal study in children with PTSD secondary to abuse or maltreatment demonstrated that increased PTSD severity and salivary cortisol at baseline was associated with a reduction in right hippocampal volume after 12–18 months of follow-up (Carrion et al., 2007).”
BackgroundEvidence for a sensitive period in the effects of early life stress on hippocampal volume
Humphreys, K. L., King, L. S., Sacchet, M. D., Camacho, M. C., Colich, N. L., Ordaz, S. J., Ho, T. C., & Gotlib, I. H. (2018) · Developmental Science · doi:10.1111/desc.12775 · Cited by 129
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Keding, T. J., & Herringa, R. J. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2014.239 · Cited by 115
Qiu, A., Shen, M., Buß, C., Chong, Y. S., Kwek, K. Y. C., Saw, S., Gluckman, P. D., Wadhwa, P. D., Entringer, S., Styner, M. A., et al. (2017) · Cerebral Cortex · doi:10.1093/cercor/bhx065 · Cited by 123
“implicating the right hemisphere, notably the right amygdala and right hippocampus in the regulation of stress responses (Abercrombie et al. 1998; Carrion et al. 2007; Hamilton and Gotlib 2008).”
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Early-life and pubertal stress differentially modulate grey matter development in human adolescents
Tyborowska, A., Volman, I., Niermann, H. C. M., Pouwels, J. L., Smeekens, S., Cillessen, A. H. N., Toni, I., & Roelofs, K. (2018) · Scientific Reports · doi:10.1038/s41598-018-27439-5 · Cited by 118
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Brietzke, E. M., Kauer‐Sant’Anna, M., Jackowski, A. P., Grassi‐Oliveira, R., Bücker, J., Zugman, A., Mansur, R. B., & Bressan, R. A. (2012) · Brazilian Journal of Psychiatry · doi:10.1016/j.rbp.2012.04.009 · Cited by 108
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“Smaller hippocampal volumes may be related to a latent effect that manifests in adolescence (Carrion et al., 2007) or adulthood.”
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“Structural changes in other brain regions have been mixed, but alterations in the hippocampus (Bremner et al., 1997; Carrion et al., 2007; Driessen et al., 2000; Vythilingam et al., 2002), amygdala (Carrion et al.”
BackgroundAmeliorating the biological impacts of childhood adversity: A review of intervention programs
Purewal, S. K., Au, V., Koita, K., Oh, D. L., Briner, S., Harris, N. B., & Bucci, M. (2018) · Child Abuse & Neglect · doi:10.1016/j.chiabu.2018.04.014 · Cited by 107
Emotional arousal and multiple memory systems in the mammalian brain
Packard, M. G., & Goodman, J. (2012) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2012.00014 · Cited by 102
“Indeed, the nature of the relationship between hippocampal gray matter volume and PTSD has attracted considerable debate (Bremner, 2001; Pitman, 2001).”
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Neuropsychological Functioning in Children with Posttraumatic Stress Disorder
Samuelson, K. W., Krueger, C. E., Burnett, C., & Wilson, C. K. (2009) · Child Neuropsychology · doi:10.1080/09297040903190782 · Cited by 101
“In contrast to these findings, in a recent longitudinal study of children with a history of maltreatment, Carrion, Weems, and Reiss (2007) hypothesized that hippocampal volume reductions may result from chronic exposure to stress throughout development and found that PTSD symptoms and cortisol…”
ResultAdoption: Biological and Social Processes Linked to Adaptation
Grotevant, H. D., & McDermott, J. M. (2013) · Annual Review of Psychology · doi:10.1146/annurev-psych-010213-115020 · Cited by 116
“In contrast, one study of children with PTSD found increases in hippocampal volume compared to children without PTSD (Tupler & De Bellis 2006), whereas another study found reductions in hippocampal volume due to PTSD approximately one year after a baseline assessment (Carrión et al. 2007).”
ResultFonzo, G. A., Ramsawh, H. J., Flagan, T., Simmons, A. N., Sullivan, S. G., Allard, C. B., Paulus, M. P., & Stein, M. B. (2015) · Psychological Medicine · doi:10.1017/s0033291715002603 · Cited by 96
“We also predict this threat-priming mechanism will interact with developmental brain processes to confer abnormal structure of implicated substrates, most notably in the PFC and hippocampus due to their prominent stress hormone structural sensitivity (Carrion et al. 2007; Kremen et al. 2010).”
BackgroundSocioeconomic status and hippocampal volume in children and young adults
Yu, Q., Daugherty, A. M., Anderson, D. M., Nishimura, M., Brush, D., Hardwick, A., Lacey, W. H., Raz, S., & Ofen, N. (2017) · Developmental Science · doi:10.1111/desc.12561 · Cited by 78
“Human neuroimaging studies also show that increased stress experienced during pregnancy and early postnatal life is related to smaller hippocampal volume (Carrion et al., 2007; Hanson et al., 2015).”
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“Magnetic Resonance Imaging (MRI) and related imaging techniques have allowed research of brain structure and function in youth exposed to trauma (e.g., Carrión et al. 2001, 2007, 2008, 2010; De Bellis et al. 1999; Garrett et al. 2012).”
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“found that cortisol levels and PTSD symptoms correlate with shrinkage of the right instead of the left hippocampus in children that had experienced trauma (Carrion et al., 2007).”
BackgroundNeuroimaging in children, adolescents and young adults with psychological trauma
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“In a longitudinal study (N = 15) in 7–13 years old with a history of maltreatment, posttraumatic stress symptoms and cortisol at baseline predicted hippocampal volume reduction over a 12–18 month interval [30].”
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“This is also an area that warrants further investigation.[70]”
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“As for neurodevelopmental conditions including ID, developmental delay, speech disorder, and learning disabilities, adverse childhood experiences and reduced sensory stimulation may negatively affect neural circuits and the developing brain’s architecture especially during its most plastic period in life, which can le…”
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“In minors, however, only one out of nine studies in traumatised populations found a smaller hippocampal volume (Carrion et al., 2007).”
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“Specifically, a relative reduction in the volume of the hippocampus bilaterally (Gilbertson et al., 2002; Wignall et al., 2004; Smith, 2005; Carrion et al., 2007; Woon and Hedges, 2008) and reduced thickness and volume of the anterior cingulate cortex (ACC) have been observed (Rauch et al.,…”
BackgroundDomestic Violence and Maternal Reports of Young Children’s Functioning
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“…danielle.zerk@health.sa.gov.au Finally, there is emerging evidence that enduring stress in the early years may have an adverse effect upon brain development and organization (e.g., Carrion et al. 2007; Perry et al. 1995), leading to the maintenance of unadaptive responses to further life stresses.”
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BackgroundNeurodevelopment and ages of onset in depressive disorders
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Metadata
- Authors
- Carrion, V. G., Weems, C. F., & Reiss, A. L.
- Affiliations
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California
- LSU New Orleans (US)
- Stanford Medicine (US)
- Venue
- PEDIATRICS
- Publisher
- American Academy of Pediatrics (AAP)
- Published
- 2007-03-01
- Volume
- 119
- Issue
- 3
- Pages
- 509-516
- ISSN
- 0031-4005 (ISSN-L)
- 1098-4275
- OpenAlex
- W2170134781
- Cited by
- 327
- References
- 41
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 8 · 2023: 10 · 2022: 11 · 2021: 19 · 2020: 17 · 2019: 15 · 2018: 13 · 2017: 24 · 2016: 20 · 2015: 18 · 2014: 23 · 2013: 26 · 2012: 24
- FWCI
- 8.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- PEDIATRICS (publishedVersion)
- PubMed (publishedVersion)
- UCLA - Biblioteca de Ciencias de la Salud (submittedVersion)
- Funders
- University of Minnesota
- National Institutes of Health
- National Institute of Mental Health (MH-19908, K23MH063893, MH050047, MH01142, MH63893-01, K02MH001142, R01MH050047, T32MH019908)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD031715, HD31715)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Keywords
- post-traumatic stress disorder, child abuse, hippocampal volume, cortisol, glucocorticoid neurotoxicity, brain development, children
- MeSH terms
- Adolescent, Arousal, Child, Chronic Disease, Circadian Rhythm, Female, Hippocampus, Humans, Hydrocortisone, Longitudinal Studies, Male, Organ Size, Pilot Projects, Saliva, Severity of Illness Index, Stress Disorders, Post-Traumatic, Stress, Psychological
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