The effects of neonatal stress on brain development: implications for psychopathology
Abstract
Recent studies have focused on the behavioral and neurobiological sequella of exposure to early adverse events. We hypothesize that early adverse experiences result in an increased sensitivity to the effects of stress later in life and render an individual vulnerable to stress-related psychiatric disorders. This vulnerability may be mediated by persistent changes in corticotropin-releasing-factor (CRF)-containing neurons, the hypothalamic-pituitary-adrenal axis, and the sympathetic nervous system. We therefore present an overview of the CRF system and its role as a mediator in the development of the stress response, major depression, and posttraumatic stress disorder. The literature pertaining to behavioral and neurobiological alterations associated with exposure to early adverse life events in rodents, nonhuman primates, and humans is reviewed. We focus on animal models that precipitate depressive and anxiety symptoms while producing neuroendocrine alterations that mimic those seen in adults with those disorders. The literature integrating neurobiological and behavioral consequences of early life stress is also reviewed, focusing primarily on infants born to mothers with depression and on infants who were abused or neglected.
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The effect of early stress on prefrontal corticolimbic connectivity and functioning seen in animal models suggests a pathway by which poverty increases risk for delayed cognitive development and susceptibility to learning disorders and psychopathology in children.
“Given the relation of EFs to the development of cognitive and social competence in children, the effect of early stress on PFC corticolimbic connectivity and functioning seen in animal models suggests one pathway through which risk for delayed cognitive development and susceptibility to learning disorders and psychopathology is increased in children in poverty (Graham, Heim, Goodman, Miller, & Nem”
From Stress and the development of self-regulation in context (2010) · cites this paper as Graham, Heim, Goodman, Miller, & Nemeroff, 1999
The amygdala-hippocampus-PFC circuit is crucial for threat detection and many forms of social behavior, but the maturation and connectivity between these brain regions develops slowly over early life in humans, nonhuman primates, and rodents.
“The amygdala-hippocampus-PFC circuit is crucial for threat detection and many forms of social behavior, but the maturation and connectivity between these brain regions develops slowly over early life in humans (Casey et al., 2005, Gee et al., 2013, Graham et al., 1999, Malter Cohen et al., 2013, Skuse et al., 2003, Tottenham, 2012, Tottenham and Sheridan, 2009), nonhuman primates (Bachevalier and”
From Early life adversity during the infant sensitive period for attachment: Programming of behavioral neurobiology of threat processing and social behavior (2017) · cites this paper as Graham et al., 1999
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- Authors
- GRAHAM, Y. P., HEIM, C., GOODMAN, S. H., MILLER, A. H., & NEMEROFF, C. B.
- Affiliations
- Emory University (US)
- Venue
- Development and Psychopathology
- Publisher
- Cambridge University Press (CUP)
- Published
- 1999-09
- Volume
- 11
- Issue
- 3
- Pages
- 545-565
- ISSN
- 0954-5794 (ISSN-L)
- 1469-2198
- OpenAlex
- W2161581479
- Cited by
- 197
- References
- 9
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 6 · 2022: 4 · 2021: 4 · 2020: 6 · 2019: 7 · 2018: 7 · 2017: 10 · 2016: 7 · 2015: 8 · 2014: 4 · 2013: 7 · 2012: 10
- FWCI
- 4.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Development and Psychopathology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r24mh051761-05)
- National Institute of Mental Health (R01MH042088, MH 51761, MH42088)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- early life stress, neonatal stress, brain development, corticotropin-releasing factor, hypothalamic-pituitary-adrenal axis, sympathetic nervous system, major depressive disorder, post-traumatic stress disorder, anxiety, maternal depression, child abuse, child neglect, animal models of depression, neuroendocrine changes
- MeSH terms
- Adult, Aging, Animals, Mental Disorders, Brain, Child Abuse, Embryonic and Fetal Development, Humans, Infant, Newborn, Stress, Physiological, Stress, Psychological
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