Childhood adversity and neural development: Deprivation and threat as distinct dimensions of early experience

A growing body of research has examined the impact of childhood adversity on neural structure and function. Advances in our understanding of the neurodevelopmental consequences of adverse early environments require the identification of dimensions of environmental experience that influence neural development differently and mechanisms other than the frequently-invoked stress pathways. We propose a novel conceptual framework that differentiates between deprivation (absence of expected environmental inputs and complexity) and threat (presence of experiences that represent a threat to one's physical integrity) and make predictions grounded in basic neuroscience principles about their distinct effects on neural development. We review animal research on fear learning and sensory deprivation as well as human research on childhood adversity and neural development to support these predictions. We argue that these previously undifferentiated dimensions of experience exert strong and distinct influences on neural development that cannot be fully explained by prevailing models focusing only on stress pathways. Our aim is not to exhaustively review existing evidence on childhood adversity and neural development, but to provide a novel framework to guide future research.

[1]  R. Sullivan,et al.  Memory of early maltreatment: Neonatal behavioral and neural correlates of maternal maltreatment within the context of classical conditioning , 2005, Biological Psychiatry.

[2]  C. Arata,et al.  Differential correlates of multi-type maltreatment among urban youth. , 2007, Child abuse & neglect.

[3]  Alan C. Evans,et al.  Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention-deficit/hyperactivity disorder. , 2006, Archives of general psychiatry.

[4]  G. Richter-Levin,et al.  Exposure to Stressors during Juvenility Disrupts Development-Related Alterations in the PSA-NCAM to NCAM Expression Ratio: Potential Relevance for Mood and Anxiety Disorders , 2008, Neuropsychopharmacology.

[5]  S. Moriceau,et al.  Developing a Neurobehavioral Animal Model of Infant Attachment to an Abusive Caregiver , 2010, Biological Psychiatry.

[6]  N. Fox,et al.  The caregiving context in institution-reared and family-reared infants and toddlers in Romania. , 2007, Journal of child psychology and psychiatry, and allied disciplines.

[7]  K. Kiernan,et al.  The long-term effects of parental divorce on the mental health of young adults: a developmental perspective. , 1995, Child development.

[8]  E. Bennett,et al.  Chemical and anatomical plasticity of brain. 1964. , 1996, The Journal of neuropsychiatry and clinical neurosciences.

[9]  Jennifer A. Silvers,et al.  Cognitive reappraisal of emotion: a meta-analysis of human neuroimaging studies. , 2014, Cerebral cortex.

[10]  M. Rutter,et al.  Can Inattention/Overactivity Be an Institutional Deprivation Syndrome? , 2001, Journal of abnormal child psychology.

[11]  P. Kuhl Early language acquisition: cracking the speech code , 2004, Nature Reviews Neuroscience.

[12]  P. Sinha,et al.  Effects of early experience on children's recognition of facial displays of emotion. , 2002, Developmental psychology.

[13]  Joseph E LeDoux,et al.  Extinction Learning in Humans Role of the Amygdala and vmPFC , 2004, Neuron.

[14]  Martin H. Teicher,et al.  Stress, sensitive periods and maturational events in adolescent depression , 2008, Trends in Neurosciences.

[15]  W. Gan,et al.  Circadian glucocorticoid oscillations promote learning-dependent synapse formation and maintenance , 2013, Nature Neuroscience.

[16]  T. Otto,et al.  Both Pre- and Posttraining Excitotoxic Lesions of the Basolateral Amygdala Abolish the Expression of Olfactory and Contextual Fear Conditioning , 1998 .

[17]  M. D’Esposito,et al.  Is the rostro-caudal axis of the frontal lobe hierarchical? , 2009, Nature Reviews Neuroscience.

[18]  Joseph E. LeDoux,et al.  Extinction of emotional learning: Contribution of medial prefrontal cortex , 1993, Neuroscience Letters.

[19]  Erno J. Hermans,et al.  From Specificity to Sensitivity: How Acute Stress Affects Amygdala Processing of Biologically Salient Stimuli , 2009, Biological Psychiatry.

[20]  Janet B W Williams,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[21]  Joseph E LeDoux,et al.  Molecular Mechanisms of Fear Learning and Memory , 2011, Cell.

[22]  M. Hostetter,et al.  Health of children adopted from the former Soviet Union and Eastern Europe. Comparison with preadoptive medical records. , 1997, JAMA.

[23]  N. Fox,et al.  Adverse Rearing Environments and Neural Development in Children: The Development of Frontal Electroencephalogram Asymmetry , 2011, Biological Psychiatry.

[24]  Brian W. Haas,et al.  Reduced hippocampal activity in youth with posttraumatic stress symptoms: an FMRI study. , 2010, Journal of pediatric psychology.

[25]  Mark M. Kishiyama,et al.  Socioeconomic Disparities Affect Prefrontal Function in Children , 2009, Journal of Cognitive Neuroscience.

[26]  R. Anda,et al.  Relationship between multiple forms of childhood maltreatment and adult mental health in community respondents: results from the adverse childhood experiences study. , 2003, The American journal of psychiatry.

[27]  G. Quirk,et al.  Neurons in medial prefrontal cortex signal memory for fear extinction , 2002, Nature.

[28]  M. Bouton Context and behavioral processes in extinction. , 2004, Learning & memory.

[29]  M. Jokela,et al.  IQ, Socioeconomic Status, and Early Death: The US National Longitudinal Survey of Youth , 2009, Psychosomatic medicine.

[30]  J. C. Anderson,et al.  Dendritic asymmetry cannot account for directional responses of neurons in visual cortex , 1999, Nature Neuroscience.

[31]  K. Matthews,et al.  Potential neural embedding of parental social standing. , 2008, Social cognitive and affective neuroscience.

[32]  G. Evans,et al.  The Role of Chaos in Poverty and Children's Socioemotional Adjustment , 2005, Psychological science.

[33]  Ewelina Knapska,et al.  Reciprocal patterns of c-Fos expression in the medial prefrontal cortex and amygdala after extinction and renewal of conditioned fear. , 2009, Learning & memory.

[34]  M. Rutter,et al.  The effects of global severe privation on cognitive competence: extension and longitudinal follow-up. English and Romanian Adoptees Study Team. , 2000, Child development.

[35]  R. Bradley,et al.  The home environments of children in the United States part I: variations by age, ethnicity, and poverty status. , 2001, Child development.

[36]  M. Craske,et al.  Is aversive learning a marker of risk for anxiety disorders in children? , 2008, Behaviour research and therapy.

[37]  G. Lynch,et al.  Hippocampal Dysfunction and Cognitive Impairments Provoked by Chronic Early-Life Stress Involve Excessive Activation of CRH Receptors , 2010, The Journal of Neuroscience.

[38]  D. Cicchetti,et al.  Cognitive Brain Event-Related Potentials and Emotion Processing in Maltreated Children. , 1997, Child development.

[39]  Franco Lepore,et al.  Differential occipital responses in early- and late-blind individuals during a sound-source discrimination task , 2008, NeuroImage.

[40]  Warren Winter,et al.  Widespread Reductions in Cortical Thickness Following Severe Early-Life Deprivation: A Neurodevelopmental Pathway to Attention-Deficit/Hyperactivity Disorder , 2014, Biological Psychiatry.

[41]  G. Quirk,et al.  The Role of Ventromedial Prefrontal Cortex in the Recovery of Extinguished Fear , 2000, The Journal of Neuroscience.

[42]  D. Finkelhor,et al.  Polyvictimization and trauma in a national longitudinal cohort , 2007, Development and Psychopathology.

[43]  M. Gunnar,et al.  The neurobiology of stress and development. , 2007, Annual review of psychology.

[44]  Marie Schaer,et al.  Cortical Thickness, Surface Area, and Gyrification Abnormalities in Children Exposed to Maltreatment: Neural Markers of Vulnerability? , 2013, Biological Psychiatry.

[45]  D. Williamson,et al.  The interrelatedness of multiple forms of childhood abuse, neglect, and household dysfunction. , 2004, Child abuse & neglect.

[46]  H. Hart,et al.  Neuroimaging of child abuse: a critical review , 2012, Front. Hum. Neurosci..

[47]  T. Otto,et al.  Both pre- and posttraining excitotoxic lesions of the basolateral amygdala abolish the expression of olfactory and contextual fear conditioning. , 1998, Behavioral neuroscience.

[48]  B. McEwen Stress and hippocampal plasticity. , 1999, Annual review of neuroscience.

[49]  M. Bouton,et al.  Contextual and Temporal Modulation of Extinction: Behavioral and Biological Mechanisms , 2006, Biological Psychiatry.

[50]  J. Gee,et al.  Early Stress Is Associated with Alterations in the Orbitofrontal Cortex: A Tensor-Based Morphometry Investigation of Brain Structure and Behavioral Risk , 2010, The Journal of Neuroscience.

[51]  D. Hubel,et al.  Comparison of the effects of unilateral and bilateral eye closure on cortical unit responses in kittens. , 1965, Journal of neurophysiology.

[52]  Selcuk R. Sirin Socioeconomic Status and Academic Achievement: A Meta-Analytic Review of Research , 2005 .

[53]  N. Fox,et al.  Institutional rearing and psychiatric disorders in Romanian preschool children. , 2009, The American journal of psychiatry.

[54]  Brian B. Avants,et al.  Early parental care is important for hippocampal maturation: Evidence from brain morphology in humans , 2010, NeuroImage.

[55]  Hanna Damasio,et al.  Impairment of social and moral behavior related to early damage in human prefrontal cortex , 1999, Nature Neuroscience.

[56]  P. Huttenlocher Synaptic density in human frontal cortex - developmental changes and effects of aging. , 1979, Brain research.

[57]  T. Johnstone,et al.  Human amygdala responses during presentation of happy and neutral faces: correlations with state anxiety , 2004, Biological Psychiatry.

[58]  B. McEwen,et al.  Brain on stress: How the social environment gets under the skin , 2012, Proceedings of the National Academy of Sciences.

[59]  Joann P. Benigno,et al.  Effect of foster care on young children's language learning. , 2011, Child development.

[60]  Joseph E LeDoux The Emotional Brain, Fear, and the Amygdala , 2003, Cellular and Molecular Neurobiology.

[61]  M R Rosenzweig,et al.  Effects of differential experience on dendritic spine counts in rat cerebral cortex. , 1973, Journal of comparative and physiological psychology.

[62]  S. Orr,et al.  De novo conditioning in trauma-exposed individuals with and without posttraumatic stress disorder. , 2000, Journal of abnormal psychology.

[63]  G. Evans,et al.  Childhood poverty, chronic stress, and adult working memory , 2009, Proceedings of the National Academy of Sciences.

[64]  M. Newcomb,et al.  Development and validation of a brief screening version of the Childhood Trauma Questionnaire. , 2003, Child abuse & neglect.

[65]  E. Bennett,et al.  Effects of environmental enrichment and impoverishment on rat cerebral cortex. , 1972, Journal of neurobiology.

[66]  Takao K Hensch,et al.  Critical period revisited: impact on vision , 2008, Current Opinion in Neurobiology.

[67]  B. Quinn,et al.  Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation. , 2010, Developmental science.

[68]  Rebecca J. Panagos Meaningful Differences in the Everyday Experience of Young American Children , 1998 .

[69]  G. Herbison,et al.  Childhood Sexual Abuse and Mental Health in Adult Life , 1993, British Journal of Psychiatry.

[70]  Martin H. Teicher,et al.  Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum , 2012, Proceedings of the National Academy of Sciences.

[71]  K. Humphreys,et al.  Deviations from the Expectable Environment in Early Childhood and Emerging Psychopathology , 2015, Neuropsychopharmacology.

[72]  Todd A. Hare,et al.  Early developmental emergence of human amygdala–prefrontal connectivity after maternal deprivation , 2013, Proceedings of the National Academy of Sciences.

[73]  Andrew N. Meltzoff,et al.  Socioeconomic status predicts hemispheric specialisation of the left inferior frontal gyrus in young children , 2008, NeuroImage.

[74]  Michael Davis,et al.  The amygdala: vigilance and emotion , 2001, Molecular Psychiatry.

[75]  Monique Ernst,et al.  Response to learned threat: An FMRI study in adolescent and adult anxiety. , 2013, The American journal of psychiatry.

[76]  Jay Belsky,et al.  Beyond cumulative risk: distinguishing harshness and unpredictability as determinants of parenting and early life history strategy. , 2012, Developmental psychology.

[77]  B. Casey,et al.  Early-life stress has persistent effects on amygdala function and development in mice and humans , 2013, Proceedings of the National Academy of Sciences.

[78]  Rajita Sinha,et al.  Corticostriatal-limbic gray matter morphology in adolescents with self-reported exposure to childhood maltreatment. , 2011, Archives of pediatrics & adolescent medicine.

[79]  D. Chapman,et al.  Childhood abuse, neglect, and household dysfunction and the risk of illicit drug use: the adverse childhood experiences study. , 2003, Pediatrics.

[80]  B. McEwen Protective and damaging effects of stress mediators. , 1998, The New England journal of medicine.

[81]  D. Pine,et al.  The development of fear learning and generalization in 8-13 year-olds. , 2012, Developmental psychobiology.

[82]  J. Changeux,et al.  Selective stabilisation of developing synapses as a mechanism for the specification of neuronal networks , 1976, Nature.

[83]  M. Farah,et al.  Childhood poverty: Specific associations with neurocognitive development , 2006, Brain Research.

[84]  Otto Muzik,et al.  Local Brain Functional Activity Following Early Deprivation: A Study of Postinstitutionalized Romanian Orphans , 2001, NeuroImage.

[85]  N. Fox,et al.  Effects of early intervention on EEG power and coherence in previously institutionalized children in Romania , 2008, Development and Psychopathology.

[86]  Joseph E LeDoux,et al.  Lesions of the dorsal hippocampal formation interfere with background but not foreground contextual fear conditioning. , 1994, Learning & memory.

[87]  R. Sullivan,et al.  Effects of Early-Life Abuse Differ across Development: Infant Social Behavior Deficits Are Followed by Adolescent Depressive-Like Behaviors Mediated by the Amygdala , 2012, The Journal of Neuroscience.

[88]  R. Bradley,et al.  The home environments of children in the United States part II: relations with behavioral development through age thirteen. , 2001, Child development.

[89]  Monique Ernst,et al.  Fear conditioning in adolescents with anxiety disorders: results from a novel experimental paradigm. , 2008, Journal of the American Academy of Child and Adolescent Psychiatry.

[90]  E. Maguire,et al.  Methods for developmental studies of fear conditioning circuitry , 2001, Biological Psychiatry.

[91]  D. Purves,et al.  Elimination of synapses in the developing nervous system. , 1980, Science.

[92]  H. Loos,et al.  Synaptogenesis in human visual cortex — evidence for synapse elimination during normal development , 1982, Neuroscience Letters.

[93]  D. Wolfe,et al.  Child neglect: developmental issues and outcomes. , 2002, Child abuse & neglect.

[94]  D. Hubel,et al.  Extent of recovery from the effects of visual deprivation in kittens. , 1965, Journal of neurophysiology.

[95]  M. Bouton Context, ambiguity, and unlearning: sources of relapse after behavioral extinction , 2002, Biological Psychiatry.

[96]  Seth D. Pollak,et al.  Effects of early experience on children's recognition of facial displays of emotion. , 2002 .

[97]  Robert H. Bradley,et al.  Home observation for measurement of the environment , 1979 .

[98]  S. Rauch,et al.  Recall of Fear Extinction in Humans Activates the Ventromedial Prefrontal Cortex and Hippocampus in Concert , 2007, Biological Psychiatry.

[99]  V. Mountcastle,et al.  Posterior parietal association cortex of the monkey: command functions for operations within extrapersonal space. , 1975, Journal of neurophysiology.

[100]  M. Fanselow,et al.  Temporally Graded Retrograde Amnesia of Contextual Fear after Hippocampal Damage in Rats: Within-Subjects Examination , 1999, The Journal of Neuroscience.

[101]  A. Hariri,et al.  Parental education predicts corticostriatal functionality in adulthood. , 2011, Cerebral cortex.

[102]  E. Stern,et al.  Linguistic threat activates the human amygdala. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[103]  Rajeev D. S. Raizada,et al.  Effects of Socioeconomic Status on Brain Development, and How Cognitive Neuroscience May Contribute to Levelling the Playing Field , 2009, Front. Hum. Neurosci..

[104]  N. Fox,et al.  Designing research to study the effects of institutionalization on brain and behavioral development: The Bucharest Early Intervention Project , 2003, Development and Psychopathology.

[105]  R. Kessler,et al.  Childhood adversities and first onset of psychiatric disorders in a national sample of US adolescents. , 2012, Archives of general psychiatry.

[106]  R. Sperry CHEMOAFFINITY IN THE ORDERLY GROWTH OF NERVE FIBER PATTERNS AND CONNECTIONS. , 1963, Proceedings of the National Academy of Sciences of the United States of America.

[107]  M. Rutter,et al.  The effects of early social-emotional and relationship experience on the development of young orphanage children. The St. Petersburg-USA Orphanage Research Team. , 2008, Monographs of the Society for Research in Child Development.

[108]  G. Vandewalle,et al.  Impact of blindness onset on the functional organization and the connectivity of the occipital cortex. , 2013, Brain : a journal of neurology.

[109]  R. Reading,et al.  The enduring effects of abuse and related adverse experiences in childhood. A convergence of evidence from neurobiology and epidemiology , 2006 .

[110]  Maria Toledo-Rodriguez,et al.  Stress before Puberty Exerts a Sex- and Age-Related Impact on Auditory and Contextual Fear Conditioning in the Rat , 2007, Neural plasticity.

[111]  Philip S. Goldman,et al.  Children Without Permanent Parents: Research, Practice, and Policy , 2012 .

[112]  D. A. King,et al.  Contextual control of the extinction of conditioned fear: tests for the associative value of the context. , 1983, Journal of experimental psychology. Animal behavior processes.

[113]  T. Baram,et al.  Corticotropin Releasing Factor mRNA Expression in the Hypothalamic Paraventricular Nucleus and the Central Nucleus of the Amygdala is Modulated by Repeated Acute Stress in the Immature Rat , 1998, Journal of neuroendocrinology.

[114]  G. Šimić,et al.  Extraordinary neoteny of synaptic spines in the human prefrontal cortex , 2011, Proceedings of the National Academy of Sciences.

[115]  J. Green Childhood adversities and adult psychopathology in the National Comorbidity Survey Replication (NCS-R) I: Associations with first onset of DSM-IV disorders , 2010 .

[116]  Thomas F. Nugent,et al.  Dynamic mapping of human cortical development during childhood through early adulthood. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[117]  R. Rescorla Spontaneous recovery. , 2004, Learning & memory.

[118]  D. Wolfe,et al.  Factors associated with the development of posttraumatic stress disorder among child victims of sexual abuse. , 1994, Child abuse & neglect.

[119]  G. Quirk Memory for extinction of conditioned fear is long-lasting and persists following spontaneous recovery. , 2002, Learning & memory.

[120]  S. Taylor,et al.  Extended Amygdala and Emotional Salience: A PET Activation Study of Positive and Negative Affect , 2003, Neuropsychopharmacology.

[121]  P. Huttenlocher,et al.  The development of synapses in striate cortex of man. , 1987, Human neurobiology.

[122]  Jan Wacker,et al.  The role of the nucleus accumbens and rostral anterior cingulate cortex in anhedonia: Integration of resting EEG, fMRI, and volumetric techniques , 2009, NeuroImage.

[123]  E. Leibenluft,et al.  Distinct neural signatures of threat learning in adolescents and adults , 2011, Proceedings of the National Academy of Sciences.

[124]  Shakti Sharma,et al.  Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. , 1997, Science.

[125]  Arne Öhman,et al.  The role of the amygdala in human fear: Automatic detection of threat , 2005, Psychoneuroendocrinology.

[126]  Michael Angstadt,et al.  Beyond threat: Amygdala reactivity across multiple expressions of facial affect , 2006, NeuroImage.

[127]  S. Manuck,et al.  Neurobiological Pathways Linking Socioeconomic Position and Health , 2010, Psychosomatic medicine.

[128]  Margaret A. Sheridan,et al.  A Review of Adversity, The Amygdala and the Hippocampus: A Consideration of Developmental Timing , 2009, Front. Hum. Neurosci..

[129]  H. Akil,et al.  Delayed effects of chronic variable stress during peripubertal‐juvenile period on hippocampal morphology and on cognitive and stress axis functions in rats , 2004, Hippocampus.

[130]  G. Duncan,et al.  The effects of poverty on children. , 1997, The Future of children.

[131]  J. Bremner,et al.  The enduring effects of abuse and related adverse experiences in childhood , 2006, European Archives of Psychiatry and Clinical Neuroscience.

[132]  Anne Fernald,et al.  SES differences in language processing skill and vocabulary are evident at 18 months. , 2013, Developmental science.

[133]  C. Sandman,et al.  A novel mouse model for acute and long-lasting consequences of early life stress. , 2008, Endocrinology.

[134]  M. Black,et al.  Child neglect: outcomes in high-risk urban preschoolers. , 2002, Pediatrics.

[135]  D. Hedges,et al.  Hippocampal and amygdala volumes in children and adults with childhood maltreatment‐related posttraumatic stress disorder: A meta‐analysis , 2008, Hippocampus.

[136]  Bruce D. McCandliss,et al.  Socioeconomic gradients predict individual differences in neurocognitive abilities. , 2007, Developmental science.

[137]  A. Ohman,et al.  The role of the amygdala in human fear: automatic detection of threat. , 2005, Psychoneuroendocrinology.

[138]  Martha J. Farah,et al.  Socioeconomic status and the brain: mechanistic insights from human and animal research , 2010, Nature Reviews Neuroscience.

[139]  N. Fox,et al.  Variation in neural development as a result of exposure to institutionalization early in childhood , 2012, Proceedings of the National Academy of Sciences.

[140]  E. Bennett,et al.  Effects of successive environments on brain measures. , 1974, Physiology & behavior.

[141]  P. Huttenlocher,et al.  Regional differences in synaptogenesis in human cerebral cortex , 1997, The Journal of comparative neurology.

[142]  A. Mechelli,et al.  The University of Birmingham ( Live System ) Reduced orbitofrontal and temporal grey matter in a community sample of maltreated children , 2016 .

[143]  T. Baram,et al.  Long-term, progressive hippocampal cell loss and dysfunction induced by early-life administration of corticotropin-releasing hormone reproduce the effects of early-life stress , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[144]  Michael Davis,et al.  Lesions of the amygdala, but not of the cerebellum or red nucleus, block conditioned fear as measured with the potentiated startle paradigm. , 1986, Behavioral neuroscience.

[145]  N. Tottenham Human amygdala development in the absence of species-expected caregiving. , 2012, Developmental psychobiology.

[146]  R. Kessler,et al.  Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication I: associations with first onset of DSM-IV disorders. , 2010, Archives of general psychiatry.

[147]  K. Frustaci,et al.  A pilot longitudinal study of hippocampal volumes in pediatric maltreatment-related posttraumatic stress disorder , 2001, Biological Psychiatry.

[148]  S. Otani,et al.  Early postnatal stress alters extracellular signal‐regulated kinase signaling in the corticolimbic system modulating emotional circuitry in adult rats , 2012, The European journal of neuroscience.

[149]  Greg J. Duncan,et al.  How much does childhood poverty affect the life chances of children , 1998 .

[150]  P. Goldman-Rakic Topography of cognition: parallel distributed networks in primate association cortex. , 1988, Annual review of neuroscience.

[151]  Christopher G. Davis,et al.  Childhood adversity and adult psychiatric disorder in the US National Comorbidity Survey , 1997, Psychological Medicine.

[152]  E. Walker,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[153]  B. McEwen,et al.  Early life stress followed by subsequent adult chronic stress potentiates anxiety and blunts hippocampal structural remodeling , 2012, Hippocampus.

[154]  Gershon Ben-Shakhar,et al.  Psychophysiologic assessment of aversive conditioning in posttraumatic stress disorder , 2000, Biological Psychiatry.

[155]  Geoffrey Bird,et al.  Heightened neural reactivity to threat in child victims of family violence , 2011, Current Biology.

[156]  J. O’Kusky,et al.  Synapse elimination in the developing visual cortex: a morphometric analysis in normal and dark-reared cats. , 1985, Brain research.

[157]  S. Petersburg The Effects of Early Social-Emotional and Relationship Experience on the Development of Young Orphanage Children , 2009 .

[158]  D. Paré,et al.  Stimulation of Medial Prefrontal Cortex Decreases the Responsiveness of Central Amygdala Output Neurons , 2003, The Journal of Neuroscience.

[159]  E. Bennett,et al.  Chemical and Anatomical Plasticity of Brain Changes in brain through experience, demanded by learning theories, are found in experiments with rats , 1964 .

[160]  G. Barr,et al.  Unpredictable neonatal stress enhances adult anxiety and alters amygdala gene expression related to serotonin and GABA , 2014, Neuroscience.

[161]  W. Thomas Boyce,et al.  The Impact of Social Disparity on Prefrontal Function in Childhood , 2012, PloS one.

[162]  Paul M. Thompson,et al.  Brain structure changes visualized in early- and late-onset blind subjects , 2010, NeuroImage.

[163]  E. Gordon,et al.  Early Life Stress and Morphometry of the Adult Anterior Cingulate Cortex and Caudate Nuclei , 2006, Biological Psychiatry.

[164]  Desmond K. Runyan,et al.  The Effects of Early Neglect on Cognitive, Language, and Behavioral Functioning in Childhood. , 2012, Psychology.

[165]  Zhen Yan,et al.  The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission , 2011, Nature Reviews Neuroscience.

[166]  N. Fox,et al.  The Deprived Human Brain : Developmental deficits among institutionalized Romanian children-and later improvements-strengthen the case for individualized care , 2009 .

[167]  Joseph E LeDoux,et al.  Human Amygdala Activation during Conditioned Fear Acquisition and Extinction: a Mixed-Trial fMRI Study , 1998, Neuron.

[168]  Cory A. Burghy,et al.  Childhood maltreatment is associated with altered fear circuitry and increased internalizing symptoms by late adolescence , 2013, Proceedings of the National Academy of Sciences.

[169]  Joseph E LeDoux,et al.  Differential Contribution of Amygdala and Hippocampus to Cued and Contextual Fear Conditioning , 1992 .

[170]  J. Brown,et al.  Child abuse and neglect and the development of mental disorders in the general population , 2001, Development and Psychopathology.

[171]  Richard J. Davidson,et al.  Developmental pathways to amygdala-prefrontal function and internalizing symptoms in adolescence , 2012, Nature Neuroscience.

[172]  Bruce S. McEwen,et al.  Hippocampal gene expression changes underlying stress sensitization and recovery , 2013, Molecular Psychiatry.

[173]  C. Saper,et al.  Efferent projections of the infralimbic cortex of the rat , 1991, The Journal of comparative neurology.

[174]  Jeanne Brooks-Gunn,et al.  How money matters for young children's development: parental investment and family processes. , 2002, Child development.

[175]  G. Lynch,et al.  Mechanisms of Late-Onset Cognitive Decline after Early-Life Stress , 2005, The Journal of Neuroscience.

[176]  D. Cicchetti,et al.  P3b reflects maltreated children's reactions to facial displays of emotion. , 2001, Psychophysiology.

[177]  Margaret A. Sheridan,et al.  Dimensions of early experience and neural development: deprivation and threat , 2014, Trends in Cognitive Sciences.

[178]  T. Hensch Critical period plasticity in local cortical circuits , 2005, Nature Reviews Neuroscience.

[179]  Michael Davis,et al.  Extinction of fear-potentiated startle: blockade by infusion of an NMDA antagonist into the amygdala , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[180]  R A Bryant,et al.  Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety , 2009, Molecular Psychiatry.

[181]  M. Fristad,et al.  Psychosocial functioning in children after the death of a parent. , 1993, The American journal of psychiatry.

[182]  R. Adolphs,et al.  Annals of the New York Academy of Sciences What Does the Amygdala Contribute to Social Cognition? , 2022 .

[183]  A. Mechelli,et al.  Amygdala activation in maltreated children during pre-attentive emotional processing , 2013, British Journal of Psychiatry.

[184]  M. Rutter,et al.  Amygdala, hippocampal and corpus callosum size following severe early institutional deprivation: the English and Romanian Adoptees study pilot. , 2009, Journal of child psychology and psychiatry, and allied disciplines.

[185]  David Krech,et al.  Increases in cortical depth and glia numbers in rats subjected to enriched environment , 1966, The Journal of comparative neurology.

[186]  Daniel A. Hackman,et al.  Socioeconomic Status and the Developing Brain , 2022 .

[187]  O. Lipp,et al.  Evidence for retarded extinction of aversive learning in anxious children. , 2006, Behaviour research and therapy.

[188]  Eric Kan,et al.  Neural correlates of socioeconomic status in the developing human brain. , 2012, Developmental science.

[189]  E. Bennett,et al.  CHEMICAL AND ANATOMICAL PLASTICITY BRAIN. , 1964, Science.

[190]  J. Brooks-Gunn,et al.  Family processes as pathways from income to young children's development. , 2002, Developmental psychology.

[191]  M. Yoshioka,et al.  Early postnatal stress alters the extinction of context-dependent conditioned fear in adult rats , 2008, Pharmacology Biochemistry and Behavior.

[192]  E. Bennett,et al.  Difference in occipital cortical synapses from environmentally enriched, impoverished, and standard colony rats , 1975, Journal of neuroscience research.

[193]  B. McEwen,et al.  Stress, sex, and neural adaptation to a changing environment: mechanisms of neuronal remodeling , 2010, Annals of the New York Academy of Sciences.

[194]  P. Goldman-Rakic,et al.  Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex. , 1986, Science.

[195]  N. Fox,et al.  Cognitive Recovery in Socially Deprived Young Children: The Bucharest Early Intervention Project , 2007, Science.

[196]  S. Rauch,et al.  Neurobiological Basis of Failure to Recall Extinction Memory in Posttraumatic Stress Disorder , 2009, Biological Psychiatry.

[197]  Monique Ernst,et al.  Early-life stress is associated with impairment in cognitive control in adolescence: An fMRI study , 2010, Neuropsychologia.

[198]  G. Quirk,et al.  Fear extinction as a model for translational neuroscience: ten years of progress. , 2012, Annual review of psychology.

[199]  T. Baram,et al.  Cellular and molecular mechanisms of hippocampal activation by acute stress are age-dependent , 2006, Molecular Psychiatry.

[200]  Margaret A. Sheridan,et al.  Delayed Maturation in Brain Electrical Activity Partially Explains the Association Between Early Environmental Deprivation and Symptoms of Attention-Deficit/Hyperactivity Disorder , 2010, Biological Psychiatry.

[201]  J. Kim,et al.  Stress effects in the hippocampus: Synaptic plasticity and memory , 2006, Stress.

[202]  B. J. Casey,et al.  Differential patterns of striatal activation in young children with and without ADHD , 2003, Biological Psychiatry.

[203]  B. McEwen,et al.  Chronic juvenile stress produces corticolimbic dendritic architectural remodeling and modulates emotional behavior in male and female rats , 2012, Psychoneuroendocrinology.

[204]  S. Moriceau,et al.  Adult depression-like behavior, amygdala and olfactory cortex functions are restored by odor previously paired with shock during infant's sensitive period attachment learning , 2011, Developmental Cognitive Neuroscience.

[205]  M. Jung,et al.  Neural circuits and mechanisms involved in Pavlovian fear conditioning: A critical review , 2006, Neuroscience & Biobehavioral Reviews.