Widespread Reductions in Cortical Thickness Following Severe Early-Life Deprivation: A Neurodevelopmental Pathway to Attention-Deficit/Hyperactivity Disorder
Open accessAbstract
Background Children exposed to early-life psychosocial deprivation associated with institutional rearing are at markedly elevated risk of developing attention-deficit/hyperactivity disorder (ADHD). Neurodevelopmental mechanisms that explain the high prevalence of ADHD in children exposed to institutionalization are unknown. We examined whether abnormalities in cortical thickness and subcortical volume were mechanisms explaining elevations in ADHD among children raised in institutional settings.Methods Data were drawn from the Bucharest Early Intervention Project, a cohort of children raised from early infancy in institutions in Romania (n = 58) and age-matched community control subjects (n = 22). Magnetic resonance imaging data were acquired when children were aged 8 to 10 years, and ADHD symptoms were assessed using the Health and Behavior Questionnaire.Results Children reared in institutions exhibited widespread reductions in cortical thickness across prefrontal, parietal, and temporal regions relative to community control subjects. No group differences were found in the volume of subcortical structures. Reduced thickness across numerous cortical areas was associated with higher levels of ADHD symptoms. Cortical thickness in lateral orbitofrontal cortex, insula, inferior parietal cortex, precuneus, superior temporal cortex, and lingual gyrus mediated the association of institutionalization with inattention and impulsivity; additionally, supramarginal gyrus thickness mediated the association with inattention and fusiform gyrus thickness mediated the association with impulsivity.Conclusions Severe early-life deprivation disrupts cortical development resulting in reduced thickness in regions with atypical function during attention tasks in children with ADHD, including the inferior parietal cortex, precuneus, and superior temporal cortex. These reductions in thickness are a neurodevelopmental mechanism explaining elevated ADHD symptoms in children exposed to institutional rearing.
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Children raised in depriving institutions in infancy show globally decreased cortical thickness.
“Indeed, children raised in depriving institutions in infancy show globally decreased cortical thickness [34], a finding possibly paralleled by reduced brain-wide dendritic arborization, spine density, and brain volume in rodent models of early deprivation (e.g., rearing in single-occupancy cages) [35].”
From Biological embedding of childhood adversity: from physiological mechanisms to clinical implications (2017) · cites this paper as [34]
The Results (Institutionalization and Cortical Thickness; page not provided) report reduced thickness in numerous clusters across both hemispheres in institutionally reared children. The Methods (Sample; page not provided) describe institutionalization in early childhood. But the paper reports widespread regional reductions, not a global measure of cortical thickness, so “globally decreased” overstates the finding. (LLM, conf=0.84)
Experimental — accuracy not yet measuredNeglect leads to reduced grey matter in cortical regions associated with cognitive control, including mediofrontal cortex.
“neglect leads to reduced grey matter in a number of cortical regions associated with cognitive control (Hodel et al., 2015) including the mediofrontal cortex (McLaughlin et al., 2014)”
From Adolescent cognitive control and mediofrontal theta oscillations are disrupted by neglect: Associations with transdiagnostic risk for psychopathology in a randomized controlled trial (2020) · cites this paper as McLaughlin et al., 2014
In humans, prior work demonstrates that neglect leads to deficits in neural structures supporting cognitive control.
“In humans, prior work demonstrates that neglect leads to deficits in neural structures supporting cognitive control (MRI; Hodel et al., 2015; McLaughlin et al., 2014)”
From Adolescent cognitive control and mediofrontal theta oscillations are disrupted by neglect: Associations with transdiagnostic risk for psychopathology in a randomized controlled trial (2020) · cites this paper as McLaughlin et al., 2014
Children reared in deprived institutions exhibit smaller total brain volume, pronounced reductions in cortical grey matter, and widespread cortical thinning throughout primary sensory and association cortex in parietal, temporal, and frontal lobes.
“children reared in deprived institutions exhibit smaller total brain volume,(128) pronounced reductions in cortical grey matter(129) and widespread cortical thinning throughout primary sensory and association cortex in the parietal, temporal, and frontal lobes.(130)”
From Neglect as a violation of species-expectant experience: neurodevelopmental consequences (2017) · cites this paper as [129]
White matter changes observed in institutionally-reared children include reduced volume of posterior corpus callosum and reduced fractional anisotropy in tracts linking prefrontal cortex with temporal lobe and striatum.
“White matter changes have also been observed, consistent with evidence from animal models, including reduced volume of the posterior corpus callosum(129, 136), and reduced FA in white matter tracts linking the PFC with the temporal lobe (e.g., uncinate fasiculus, superior longitudinal fasciculus) and striatum (e.g., internal and external capsule).(136–138)”
From Neglect as a violation of species-expectant experience: neurodevelopmental consequences (2017) · cites this paper as [129]
Smaller left amygdala and larger right amygdala volumes were reported in a small study of previously institutionalized children, but these patterns have not been replicated in larger studies.
“Smaller left amygdala volume and larger right amygdala volume were reported in a small study of previously-institutionalized children,(128) but these patterns have not been replicated in larger studies.(33, 129)”
From Neglect as a violation of species-expectant experience: neurodevelopmental consequences (2017) · cites this paper as [129]
Intervention effects have been found for IQ, language development, reward learning, EEG neural function, and white matter volume and integrity.
“intervention effects have been found for IQ, language development, reward learning, neural function assessed with EEG, and white matter volume and integrity;(93, 100, 114, 129, 133, 135, 136)”
From Neglect as a violation of species-expectant experience: neurodevelopmental consequences (2017) · cites this paper as [129]
Early institutional rearing was associated with widespread cortical thinning.
“past research has shown that early institutional rearing was associated with widespread cortical thinning”
From Resting brain activity in early childhood predicts IQ at 18 years (2023) · cites this paper as McLaughlin et al., 2014
Cortical thinning across multiple brain areas mediated the associations between early institutional rearing and attentional problems at ages 8-10 years.
“and that cortical thinning across multiple brain areas (e.g., the inferior parietal cortex, precuneus, and superior temporal cortex) mediated the associations between early institutional rearing and attentional problems at ages 8–10 years (McLaughlin et al., 2014).”
From Resting brain activity in early childhood predicts IQ at 18 years (2023) · cites this paper as McLaughlin et al., 2014
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Tamm, L., Menon, V., & Reiss, A. L. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.6.1033 · Cited by 159 · see citing works
Garon, N., Moore, C., & Waschbusch, D. A. (2006) · Journal of Attention Disorders · doi:10.1177/1087054705284501 · Cited by 127 · see citing works
An Event-Related fMRI Study of Visual and Auditory Oddball Tasks
Kiehl, K. A., Laurens, K. R., Duty, T., Forster, B. B., & Liddle, P. F. (2001) · Journal of Psychophysiology · doi:10.1027//0269-8803.15.4.221 · Cited by 113 · see citing works
Lemery‐Chalfant, K., Schreiber, J. E., Schmidt, N. L., Hulle, C. A. V., Essex, M. J., & Goldsmith, H. H. (2007) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/chi.0b013e3180f616c6 · Cited by 95 · see citing works
An fMRI Auditory Oddball Study of Combined-Subtype Attention Deficit Hyperactivity Disorder
Stevens, M. C., Pearlson, G. D., & Kiehl, K. A. (2007) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2007.06050876 · Cited by 81 · see citing works
Corrections and Clarifications
Meskhidze, N., & Nenes, A. (2007) · Science · doi:10.1126/science.317.5834.43 · Cited by 76 · see citing works
Brain Development in Healthy, Hyperactive, and Psychotic Children
Gogtay, N., Giedd, J. N., & Rapoport, J. L. (2002) · Archives of Neurology · doi:10.1001/archneur.59.8.1244 · Cited by 59 · see citing works
Kumar, A., Behen, M. E., Singsoonsud, P., Veenstra, A. L., Wolfe-Christensen, C., Helder, E., & Chugani, H. T. (2014) · Journal of Child Neurology · doi:10.1177/0883073812474098 · Cited by 46 · see citing works
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Annual research review: enduring neurobiological effects of childhood abuse and neglect
Teicher, M. H., & Samson, J. A. (2016) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12507 · Cited by 1,473 · see citing works
McLaughlin, K. A., Sheridan, M. A., & Lambert, H. K. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.10.012 · Cited by 1,389 · see citing works
“For example, children exposed to institutional rearing exhibit widespread cortical thinning in the superior and inferior parietal cortex (McLaughlin et al., 2014), and children exposed to neglect and poverty often have deficits in language abilities (Farah et al.”
BackgroundInfluentialSelf-citationChildhood Adversity and Neural Development: A Systematic Review
McLaughlin, K. A., Weissman, D., & Bitrán, D. (2019) · Annual Review of Developmental Psychology · doi:10.1146/annurev-devpsych-121318-084950 · Cited by 892 · see citing works
Self-citationDimensions of early experience and neural development: deprivation and threat
Sheridan, M. A., & McLaughlin, K. A. (2014) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2014.09.001 · Cited by 697 · see citing works
Self-citationBiological embedding of childhood adversity: from physiological mechanisms to clinical implications
Berens, A. E., Jensen, S. K. G., & Nelson, C. A. (2017) · BMC Medicine · doi:10.1186/s12916-017-0895-4 · Cited by 657 · see citing works
“Indeed, children raised in depriving institutions in infancy show globally decreased cortical thickness [34], a finding possibly paralleled by reduced brain-wide dendritic arborization, spine density, and brain volume in rodent models of early deprivation (e.”
BackgroundSelf-citationBehavioral problems after early life stress: contributions of the hippocampus and amygdala
Hanson, J. L., Nacewicz, B. M., Sutterer, M. J., Cayo, A. A., Schaefer, S. M., Rudolph, K. D., Shirtcliff, E. A., Pollak, S. D., & Davidson, R. J. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.04.020 · Cited by 627 · see citing works
Future Directions in Childhood Adversity and Youth Psychopathology
McLaughlin, K. A. (2016) · Journal of Clinical Child & Adolescent Psychology · doi:10.1080/15374416.2015.1110823 · Cited by 576 · see citing works
“Thus, fear learning mechanisms and their downstream consequences explain, in part, the association of threatening environments with alterations in emotional processing (McLaughlin et al., 2014; Sheridan & McLaughlin, 2014).”
BackgroundSelf-citationRussell, A. E., Ford, T., Williams, R., & Russell, G. (2016) · Child Psychiatry & Human Development · doi:10.1007/s10578-015-0578-3 · Cited by 473 · see citing works
Colich, N. L., Rosen, M. L., Williams, E. S., & McLaughlin, K. A. (2020) · Psychological Bulletin · doi:10.1037/bul0000270 · Cited by 433 · see citing works
Self-citationFuture Directions in Emotion Dysregulation and Youth Psychopathology
Beauchaine, T. P. (2015) · Journal of Clinical Child & Adolescent Psychology · doi:10.1080/15374416.2015.1038827 · Cited by 394 · see citing works
Neglect as a violation of species-expectant experience: neurodevelopmental consequences
McLaughlin, K. A., Sheridan, M. A., & Nelson, C. A. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.02.1096 · Cited by 295 · see citing works
Self-citationSheridan, M. A., Peverill, M., Finn, A. S., & McLaughlin, K. A. (2017) · Development and Psychopathology · doi:10.1017/s0954579417001390 · Cited by 276 · see citing works
Self-citationAdolescent neurobiological susceptibility to social context
Schriber, R. A., & Guyer, A. E. (2016) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2015.12.009 · Cited by 246 · see citing works
Tarver, J., Daley, D., & Sayal, K. (2014) · Child: Care, Health and Development · doi:10.1111/cch.12139 · Cited by 234 · see citing works
Deviations from the expectable environment in early childhood and emerging psychopathology
Humphreys, K. L., & Zeanah, C. H. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2014.165 · Cited by 231 · see citing works
Self-citationDuration of early adversity and structural brain development in post-institutionalized adolescents
Hodel, A. S., Hunt, R. H., Cowell, R. A., Van Den Heuvel, S. E., Gunnar, M. R., & Thomas, K. M. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2014.10.020 · Cited by 220 · see citing works
Bick, J., Zhu, T., Stamoulis, C., Fox, N. A., Zeanah, C., & Nelson, C. A. (2015) · JAMA Pediatrics · doi:10.1001/jamapediatrics.2014.3212 · Cited by 199 · see citing works
Self-citationChildhood abuse and reduced cortical thickness in brain regions involved in emotional processing
Gold, A. L., Sheridan, M. A., Peverill, M., Busso, D. S., Lambert, H. K., Alves, S., Pine, D. S., & McLaughlin, K. A. (2016) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12630 · Cited by 164 · see citing works
Self-citationGee, D. G. (2021) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2021.21090944 · Cited by 148 · see citing works
Kennedy, M., Kreppner, J., Knights, N., Kumsta, R., Maughan, B., Golm, D., Rutter, M., Schlotz, W., & Sonuga‐Barke, E. J. S. (2016) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12576 · Cited by 106 · see citing works
Toward understanding the impact of trauma on the early developing human brain
Thomason, M. E., & Marusak, H. A. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2016.02.022 · Cited by 101 · see citing works
Debnath, R., Tang, A., Zeanah, C. H., Nelson, C. A., & Fox, N. A. (2020) · Developmental Science · doi:10.1111/desc.12872 · Cited by 94 · see citing works
Self-citationThe relationship between early adversities and attention-deficit/hyperactivity disorder
Fuller-Thomson, E., & Lewis, D. A. (2015) · Child Abuse & Neglect · doi:10.1016/j.chiabu.2015.03.005 · Cited by 84 · see citing works
Na, K.-S., Won, E., Kang, J., Chang, H. S., Yoon, H.-K., Tae, W. S., Kim, Y.-K., Lee, M.-S., Joe, S.-H., Kim, H., et al. (2016) · Scientific Reports · doi:10.1038/srep21089 · Cited by 84 · see citing works
The early care environment and DNA methylome variation in childhood
Garg, E., Chen, L., Nguyen, T. T. T., Pokhvisneva, I., Chen, L. M., Unternaehrer, E., MacIsaac, J. L., McEwen, L. M., Mah, S. M., Gaudreau, H., et al. (2018) · Development and Psychopathology · doi:10.1017/s0954579418000627 · Cited by 82 · see citing works
Maternal high-fat diet prevents developmental programming by early-life stress
Rincel, M., Lépinay, A. L., Delage, P., Fioramonti, J., Théodorou, V. S., Layé, S., & Darnaudéry, M. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.235 · Cited by 69 · see citing works
Tibu, F., Sheridan, M. A., McLaughlin, K. A., Nelson, C. A., Fox, N. A., & Zeanah, C. H. (2016) · Psychological Medicine · doi:10.1017/s0033291715002020 · Cited by 66 · see citing works
Self-citationZarei, K., Xu, G., Zimmerman, B., Giannotti, M., & Strathearn, L. (2021) · Children · doi:10.3390/children8090761 · Cited by 55 · see citing works
Stamoulis, C., Vanderwert, R. E., Zeanah, C. H., Fox, N. A., & Nelson, C. A. (2015) · Journal of Cognitive Neuroscience · doi:10.1162/jocn_a_00877 · Cited by 39 · see citing works
Self-citationBuzzell, G. A., Troller-Renfree, S. V., Wade, M., Debnath, R., Morales, S., Bowers, M. E., Zeanah, C. H., Nelson, C. A., & Fox, N. A. (2020) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2020.100777 · Cited by 30 · see citing works
Self-citationChild Maltreatment and Associated Parental Factors Among Children With ADHD: A Comparative Study
Gul, H., & Gurkan, C. K. (2018) · Journal of Attention Disorders · doi:10.1177/1087054716658123 · Cited by 29 · see citing works
Resting brain activity in early childhood predicts IQ at 18 years
Tan, E., Tang, A., Debnath, R., Humphreys, K. L., Zeanah, C. H., Nelson, C. A., & Fox, N. A. (2023) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2023.101287 · Cited by 22 · see citing works
Self-citationSlopen, N., Tang, A., Nelson, C. A., Zeanah, C. H., McDade, T. W., McLaughlin, K. A., & Fox, N. A. (2019) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000696 · Cited by 18 · see citing works
Self-citationLurie, L. A., Gruhn, M. A., Garrisi, K., McLaughlin, K. A., Humphreys, K. L., Zeanah, C. H., Fox, N. A., Nelson, C. A., & Sheridan, M. A. (2025) · Developmental Science · doi:10.1111/desc.70043 · Cited by 2 · see citing works
Self-citation
- Authors
- McLaughlin, K. A., Sheridan, M. A., Winter, W., Fox, N. A., Zeanah, C. H., & Nelson, C. A.
- Affiliations
- Boston Children's Hospital (US)
- University of Maryland, College Park (US)
- Tulane University (US)
- Corresponding author
- McLaughlin, Katie A.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 76
- Issue
- 8
- Pages
- 629-638
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC3969891
- OpenAlex
- W2048616467
- Cited by
- 288
- References
- 84
- Citations by year
- 2026: 5 · 2025: 23 · 2024: 27 · 2023: 19 · 2022: 30 · 2021: 31 · 2020: 26 · 2019: 28 · 2018: 26 · 2017: 18 · 2016: 21 · 2015: 23 · 2014: 10
- FWCI
- 12.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health ((R01-MH091363 to CAN, K01-MH092526 to KAM, K01-MH092555 to MAS)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Social Sciences › Safety Research › Child Welfare and Adoption
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Keywords
- attention deficit hyperactivity disorder, institutional upbringing, cortical thickness, brain development, Bucharest Early Intervention Project, inattention, impulsivity, orbitofrontal cortex, insula, inferior parietal cortex, precuneus, superior temporal cortex, supramarginal gyrus, fusiform gyrus, child development
- MeSH terms
- Attention Deficit Disorder with Hyperactivity, Brain Mapping, Cerebral Cortex, Child, Child, Preschool, Female, Humans, Image Processing, Computer-Assisted, Infant, Magnetic Resonance Imaging, Male, Psychosocial Deprivation, Surveys and Questionnaires, Cohort Studies, Case-Control Studies
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