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Cited by 149Child Welfare and AdoptionNeuroendocrine regulation and behaviorStress Responses and Cortisol

Human amygdala development in the absence of species‐expected caregiving

Open access
Tottenham, Nim·2012·Developmental Psychobiology
DOI 10.1002/dev.20531PMC PMC3404246
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Abstract

In altricial species, like the human, caregiver presence is necessary for typical emotional development. Children who have been raised in institutional care early in life experience caregiver deprivation and are at significantly elevated risk for emotional difficulties. The current manuscript examines the non‐human and human literatures on amygdala development following caregiver deprivation and presents an argument that in the absence of the species‐expected caregiver presence, human amygdala development exhibits rapid development and perhaps premature engagement that results in some of the emotional phenotypes observed following early institutional care. © 2012 Wiley Periodicals,Inc. Dev Psychobiol 54: 598–611, 2012.

Integrity signals

Registry

Crossref · 10.1002/dev.20531

Cites

173 of 173 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 76 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Among previously institutionalized children, older age at adoption was associated with larger amygdala volume.

    “Notably, the older children were when adopted, the larger the amygdala volumes.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Tottenham, et al., 2010

      Not checked in the free run.

    • Rests on an assumption: Amygdala volume differences in previously institutionalized children reflect early caregiver deprivation rather than other pre- or post-adoption factors.
  • Findingcitation

    Previously institutionalized children as a group are more likely to show vigilance-related behavioral phenotypes, including internalizing problems and heightened anxiety.

    “As a group, previously-institutionalized children are more likely to exhibit behavioral phenotypes that are typically associated with increased vigilance, such as internalizing problems and heightened anxiety”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Casey, et al., 2009

      Not checked in the free run.

    • Rests on an assumption: Amygdala volume differences in previously institutionalized children reflect early caregiver deprivation rather than other pre- or post-adoption factors.
  • Findingown data

    Previously institutionalized children had enlarged amygdala volumes even though the measurements occurred years after the early adversity.

    “We found that amygdala volumes were enlarged in this group of children even though measurements were taken years after the initial adversity”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Tottenham, et al., 2010

      Not checked in the free run.

    • Rests on an assumption: Amygdala volume differences in previously institutionalized children reflect early caregiver deprivation rather than other pre- or post-adoption factors.
  • Findingcitation

    Previously institutionalized children show greater sensitivity to negatively valenced faces.

    “Along with amygdala enlargement, previously-institutionalized children show evidence of greater sensitivity to negatively valenced faces.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Tottenham, et al., 2010

      Not checked in the free run.

    • Rests on an assumption: Amygdala volume differences in previously institutionalized children reflect early caregiver deprivation rather than other pre- or post-adoption factors.
    • Rests on an assumption: The Emotional Face Go/Nogo task's error patterns index sensitivity to negative emotional information.
  • Findingcitation

    Anxious phenotypes are positively associated with amygdala volume in previously institutionalized children.

    “these anxious phenotypes are positively associated with amygdala volume (Tottenham, et al., 2010).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Tottenham, et al., 2010

      Not checked in the free run.

    • Rests on an assumption: Amygdala volume differences in previously institutionalized children reflect early caregiver deprivation rather than other pre- or post-adoption factors.
  • May combine two claims. 22
  • Classified as probably not a substantial claim. 10

  • May combine two claims.

    Findingcitation

    Early caregiver deprivation was associated with more errors when negative faces were present, with no effect for positive faces.

    “We showed that early caregiver deprivation was associated with a greater number of errors during conditions when negative faces were present (Figure 3, left), but no effect for positively valenced faces”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Tottenham, et al., 2010

      Not checked in the free run.

    • Rests on an assumption: Amygdala volume differences in previously institutionalized children reflect early caregiver deprivation rather than other pre- or post-adoption factors.
    • Rests on an assumption: The Emotional Face Go/Nogo task's error patterns index sensitivity to negative emotional information.

  • May combine two claims.

    Findingcitation

    In that task, typically reared children decreased ventral prefrontal cortex activity to fearful faces, while previously institutionalized children showed no such change.

    “Specifically, typically-reared children showed modulation of the ventral PFC in response to fearful faces by decreasing activity, whereas the fearful faces did not alter PFC activity in previously-institutionalized children.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Tottenham, et al., in press

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  • Probably not a substantial claim: may not pass S1 (asserted). May combine two claims.

    Interpretationreasoning

    The paper's motivating hypothesis is that early caregiving absence causes the amygdala to engage prematurely in environmental learning, leading over time to hypervigilance and altered emotional responding.

    “The hypothesis motivating this paper is that the absence of early caregiving prematurely engages the amygdala in learning about the environment, and in the long term, these activations result in hypervigilance and altered emotional responding.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Developing rat pups have an amygdala capable of adult-like plasticity early, but under typical conditions it does not engage during learning and avoidance learning is not usually seen.

    “Studies of developing rat pups show that the amygdala is capable of demonstrating adult-like plasticity early in life (in that the adult, the amygdala becomes engaged during learning and thus, the animal shows avoidance learning), although under typical conditions the developing amygdala will not”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Moriceau, Roth, Okotoghaide, & Sullivan, 2004

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Premisereasoning

    Caregiver presence counts as a species-expected environmental influence because it is external to the infant yet critical for normal development.

    “That it is an external agent to the infant, yet so critical to the progression of normal development, qualifies caregiver presence as a species-expected environmental influence.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    In the absence of the caregiving humans normally expect, the human amygdala develops rapidly and may become prematurely engaged, which contributes to some emotional outcomes seen after early institutional care.

    “The current manuscript examines the non-human and human literatures on amygdala development following caregiver deprivation and presents an argument that in the absence of the species-expected caregiver presence, human amygdala development exhibits rapid development and perhaps premature engagement that results in some of the emotional phenotypes observed following early institutional care.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In primates, amygdala development is fastest in the first two postnatal weeks and stabilizes around eight months.

    “based on repeated structural images, the most rapid rate of amygdala development occurs within the first 2 postnatal weeks, and this rate stabilizes early - around 8 months old (Payne, Machado, Bliwise, & Bachevalier, 2009).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Payne, Machado, Bliwise, & Bachevalier, 2009

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The mother's presence keeps CORT low, so the rodent amygdala does not take part in emotional learning.

    “The presence of the mother maintains low CORT levels (Stanton & Levine, 1988, 1990), and thus the amygdala does not participate in the emotional learning process (Moriceau & Sullivan, 2006).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Stanton & Levine, 1988, 1990

      Not checked in the free run.

    • cites Moriceau & Sullivan, 2006

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Removing the mother raises CORT and produces amygdala-mediated aversion learning.

    “However, removal of the mother results in CORT increases, and amygdala-mediated aversion learning ensues.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    Because the amygdala develops most rapidly early, early life is likely a sensitive period for the human amygdala, as has been shown in rodents.

    “Given the early peak in amygdala development, we might predict that early-life is a sensitive period for the human amygdala, much in the same way that has been demonstrated in the rodent.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Amygdala signal to emotional faces increases through childhood and peaks in adolescence.

    “several studies have shown that amygdala signal to emotional faces increases through childhood, reaching a peak in adolescence”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Guyer, et al., 2008

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    • cites Hare, et al., 2008

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    • cites Killgore & Yurgelun-Todd, 2007

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  • May combine two claims.

    Premisecitation

    Adults who have experienced traumatic events tend to have smaller and more reactive amygdalae.

    “show that in adults the amygdala is both smaller (Driessen, et al., 2000; Schmahl, Vermetten, Elzinga, & Bremner, 2003) and more reactive to emotional stimuli”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Driessen, et al., 2000

      Not checked in the free run.

    • cites Schmahl, Vermetten, Elzinga, & Bremner, 2003

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Maternal deprivation in non-human primates alters amygdala development, including gene expression and emotional behavior, and is more damaging earlier in life.

    “Non-human primate work shows that maternal deprivation stress also influences primate amygdala development, including changes in amygdala gene expression and associated emotional behaviors (Sabatini, et al., 2007) and has more devastating effects the earlier in life it occurs.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Sabatini, et al., 2007

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Poor caregiving in rodents leads to more anxiety- and aggression-related behavior in adulthood, associated with accelerated amygdala development.

    “poor caregiving in rodents results in increased anxiety- and aggressive-behaviors in adulthood, which is associated with accelerated amygdala development”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Kikusui & Mori, 2009

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Infants with insecure attachment relationships are at greater risk of atypically high cortisol, especially if they also have fearful temperaments.

    “children classified as having insecure attachment relationships (that is, those relationships typically characterized by low sensitive caregiving) in infancy are at greater risk for atypically high elevations in cortisol, especially in combination with fearful temperaments”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Nachmias, et al., 1996

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Adverse events affect the brain in a region-specific way, with some of the largest effects in the amygdala.

    “Adverse events do not impact the whole brain in a uniform fashion, but instead the effects are region specific, exhibiting some of the largest effects in the amygdala.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    These adaptations may support immediate resilience but may later harm mental health, for example by increasing anxiety.

    “These adaptations may serve as an immediate resiliance factor for the child (Masten & Obradovic, 2008), but in the long-term may have detrimental consequences for mental health (e.g., anxiety).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Masten & Obradovic, 2008

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The amygdala response to fearful versus neutral faces in previously institutionalized children resembles adults more than same-age typically raised children, which is consistent with premature functional development of the amygdala.

    “The pattern of amygdala response to fearful versus neutral faces more closely resembles that of adult subjects than typically-raised children of the same age, consistent with the hypothesis that early caregiver deprivation results in premature functional developmental of the amygdala.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Amygdala volume differences in previously institutionalized children reflect early caregiver deprivation rather than other pre- or post-adoption factors.
    • Rests on an assumption: Amygdala activity to fearful versus neutral faces in children can be compared with adult patterns to index premature development.

  • Classified as probably not a substantial claim.

    Premisecitation

    The ventral prefrontal cortex has a regulatory influence over the amygdala.

    “Consistent with a theorized regulatory role of the ventral PFC over the amygdala (reviewed in Quirk & Beer, 2006)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Quirk & Beer, 2006

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In rodents, projections from the amygdala to the prefrontal cortex first appear during adolescence.

    “when amygdala projections to PFC first emerge (Verwer, Van Vulpen, & Van Uum, 1996).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Verwer, Van Vulpen, & Van Uum, 1996

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In rodents, extinction learning before adolescence does not require the prefrontal cortex, and inactivating it does not impair extinction.

    “rodent studies show that, unlike in adulthood, pre-adolescent extinction learning does not rely on the PFC, where PFC inactivation does not impair extinction learning.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In adult animals, blocking protein synthesis in the ventral prefrontal cortex disrupts extinction learning, leaving fear responses intact after they are no longer appropriate.

    “Lesioning or inactivation of the ventral PFC in adults with protein synthesis blockers (e.g., anisomycin) interferes with extinction learning (reviewed in Quirk & Mueller, 2008) - the animal will continue to exhibit fear responses when they are no longer needed.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Quirk & Mueller, 2008

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Animal models indicate that emotional processes involving the amygdala and ventral prefrontal cortex differ across development.

    “Animal models suggest that emotional processes involving the amygdala and ventral PFC operate differently across development (Kim, Hamlin, & Richardson, 2009).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Kim, Hamlin, & Richardson, 2009

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The emotional face in the scanning session is presumably a conditioned stimulus that does not predict threat.

    “presumably because the emotional face is a conditioned stimulus that, in the context of the experimental session, is not predictive of any threat.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Early life adversity in rodents changes prefrontal cortex structure, producing higher synaptic densities than in controls.

    “early life adversity alters PFC development both structurally (higher synaptic densities compared to controls - Ovtscharoff & Braun, 2001)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ovtscharoff & Braun, 2001

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The consistency of these findings indicates that caregiver presence is a species-expected environment, and its absence can substantially harm typical development.

    “The replicability of these findings strongly suggests that the presence of caregivers is a species-expected environment, as described by Greenough et al. (1987), whose absence can cause significant detriment to the typical developmental process.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Greenough et al. (1987)

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Although human neural evidence is limited, it is growing and supports the idea that caregiver deprivation changes emotional behavior by exploiting the developing amygdala's readiness to respond to adversity.

    “While the human neural data are currently sparse, they are mounting and support the hypothesis that caregiver deprivation alters emotional behavior by taking advantage of the readiness of the developing amygdala to respond to environmental adversity.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Early life adversity in rodents changes prefrontal cortex function, reducing tyrosine hydroxylase-positive fiber innervation.

    “and functionally (reduced tyrosine hydroxylase-positive fiber innervation - Braun, Lange, Metzger, & Poeggel, 1999).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Braun, Lange, Metzger, & Poeggel, 1999

      Not checked in the free run.

28 of 28

  • The paper relies on this without support.

    Amygdala volume differences in previously institutionalized children reflect early caregiver deprivation rather than other pre- or post-adoption factors.

    “We found that amygdala volumes were enlarged in this group of children even though measurements were taken years after the initial adversity”

  • The paper relies on this without support.

    The Emotional Face Go/Nogo task's error patterns index sensitivity to negative emotional information.

    “We tested children on the Emotional Face Go/Nogo, which assesses the degree to which emotional faces interfere with the successful execution of a behavioral response.”

  • The paper relies on this without support.

    Amygdala activity to fearful versus neutral faces in children can be compared with adult patterns to index premature development.

    “The pattern of amygdala response to fearful versus neutral faces more closely resembles that of adult subjects than typically-raised children of the same age”

  • The paper relies on this without support.

    The development of amygdala-ventral prefrontal connectivity is not well characterized.

    “The development of amygdala-ventral PFC connectivity is not well characterized.”

  • The paper relies on this without support.

    Much less is known about human amygdala-prefrontal connectivity than about the corresponding animal systems.

    “Currently, much less is known about human amygdala-PFC connectivity.”

  • The paper relies on this without support.

    How early adversity alters amygdala-prefrontal connections is unknown.

    “How early adversity alters amygdala-PFC connections is unknown at this point”

  • The paper relies on this without support.

    Even less is known about prefrontal cortex development following early adversity.

    “Even less is known about the development of the PFC following early adversity”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Most existing models emphasize atypical limbic system development from prolonged early-life stress as a central mechanism for outcomes associated with caregiver deprivation.

    “Most existing models emphasize atypical limbic system development resulting from prolonged early-life stress as a central mechanism underlying developmental outcomes associated with caregiver deprivation.(25–31)”

    From Neglect as a violation of species-expectant experience: neurodevelopmental consequences (2017) · cites this paper as [25]

  • Children deprived of a stable responsive caregiver show high insecure and disorganized attachment and atypical affective development, including heightened emotional reactivity, accelerated amygdala development, poor emotion regulation, and atypical stress reactivity.

    “Children deprived of a stable and responsive caregiver exhibit high levels of insecure and disorganized attachment and atypical affective development characterized by heightened emotional reactivity, accelerated functional development of the amygdala, poor emotion regulation, and atypical stress reactivity.(25, 32–37)”

    From Neglect as a violation of species-expectant experience: neurodevelopmental consequences (2017) · cites this paper as [25]

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. Amaral D. G., 1992, The amygdala: neurobiological aspects of emotion, memory, and mental dysfunction, 1
  2. Tottenham N., 2009, The human amygdala, 107

Cited by

Sorted by citations

Authors
Tottenham, N.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Tottenham, Nim
ORCID
Tottenham, Nim
Venue
Developmental Psychobiology
Publisher
Wiley
Published
2012-06-19
Volume
54
Issue
6
Pages
598-611
ISSN
  • 0012-1630 (ISSN-L)
  • 1098-2302
DOI
10.1002/dev.20531
PMC
PMC3404246
OpenAlex
W1971003071
Cited by
149
References
173
Citations by year
2026: 3 · 2025: 8 · 2024: 8 · 2023: 9 · 2022: 8 · 2021: 20 · 2020: 7 · 2019: 16 · 2018: 13 · 2017: 12 · 2016: 10 · 2015: 12 · 2014: 14 · 2013: 6 · 2012: 2
FWCI
4.34
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Developmental Psychobiology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (R01MH091864)
Topics
  • Social Sciences › Safety Research › Child Welfare and Adoption
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
amygdala development, institutional care, early childhood, emotional development
MeSH terms
Adaptation, Psychological, Amygdala, Animals, Child, Emotions, Humans, Social Isolation, Caregivers

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