Hostname: page-component-78c5997874-mlc7c Total loading time: 0 Render date: 2024-11-02T23:25:23.216Z Has data issue: false hasContentIssue false

Stress and the healthy adolescent brain: Evidence for the neural embedding of life events

Published online by Cambridge University Press:  08 November 2013

Barbara L. Ganzel*
Affiliation:
Cornell University
Pilyoung Kim
Affiliation:
University of Denver
Nim Tottenham
Affiliation:
University of California at Los Angeles
Elise Temple
Affiliation:
NeuroFocus, Inc.
*
Address correspondence and reprint requests to: Barbara L. Ganzel, Department of Human Development, Cornell University, Ithaca, NY 14853; E-mail: blg4@cornell.edu.

Abstract

Little is known about the long-term neural consequences of adverse life events for healthy adolescents, and this is particularly the case for events that occur after a putative stress-sensitive period in early childhood. In this functional magnetic resonance imaging study of healthy adolescents, we found that prior exposure to severe adverse life events was associated with current anxiety and with increased amygdala reactivity to standardized emotional stimuli (viewing of fearful faces relative to calm ones). Conjunction analyses identified multiple regions, including the amygdala, insula, and prefrontal cortex, in which reactivity to emotional faces covaried with life events as well as with current anxiety. Our morphometric analyses suggest systemic alterations in structural brain development with an association between anxiety symptoms and global gray matter volume. No life events were reported for the period before 4 years of age, suggesting that these results were not driven by exposure to stress during an early sensitive period in development. Overall, these data suggest systemic effects of traumatic events on the dynamically developing brain that are present even in a nonclinical sample of adolescents.

Type
Regular Articles
Copyright
Copyright © Cambridge University Press 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adamec, R. E., Blundell, J., & Burton, P. (2005). Neural circuit changes mediating lasting brain and behavioral response to predator stress. Neuroscience & Biobehavioral Reviews, 29, 12251241.Google Scholar
Alleva, E., & Santucci, D. (2001). Psychosocial vs. “physical” stress situations in rodents and humans. Physiology & Behavior, 73, 313320.CrossRefGoogle Scholar
American Psychiatric Association. (1987). Diagnostic and statistical manual of mental disorders (3rd ed. rev.). Washington, DC: Author.Google Scholar
American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: Author.Google Scholar
Ashburner, J. (2007). A fast diffeomorphic image registration algorithm. NeuroImage, 15, 95113.Google Scholar
Baron, R. M., & Kenny, D. A. (1986). The moderator–mediator variable distinction in social psychological research: Conceptual, strategic, and statistical considerations. Journal of Personality and Social Psychology, 51, 11731182.Google Scholar
Bartzokis, G., Mace Beckson, M., Lu, P. H., Nuechterlein, K. H., Edwards, N., & Mintz, J. (2001). Age-related changes in frontal and temporal lobe volumes in men: A magnetic resonance imaging study. Archives of General Psychiatry, 58, 461465.CrossRefGoogle Scholar
Bergouignan, L., Chupin, M., Czechowska, Y., Kinkingnéhun, S., Lemogne C., Le Bastard, G., et al. (2009). Can voxel-based morphometry, manual segmentation and automated segmentation equally detect hippocampal volume differences in acute depression? NeuroImage, 45, 2937.Google Scholar
Berkowitz, S., & Stover, C. S. (2005). Trauma History Questionnaire Parent and Child Version. Unpublished manuscript, Yale Child Study Center Trauma Section.Google Scholar
Berkowitz, S., Stover, C. S., & Marans, S. R. (2011). The Child and Family Traumatic Stress Intervention: Secondary prevention for youth at risk of developing PTSD. Journal of Child Psychology and Psychiatry, 52, 676685.Google Scholar
Birmaher, B., Brent, D. A., Chiappetta, L., Bridge, J., Monga, S., & Baugher, M. (1999). Psychometric properties of the Screen for Child Anxiety Related Emotional Disorders (SCARED): A replication study. Journal of the American Academy of Child & Adolescent Psychiatry, 38, 12301236.Google Scholar
Blanchard, D. C., Sakai, R. R., McEwen, B., Weiss, S. M., & Blanchard, R. J. (1993). Subordination stress: Behavioral, brain, and neuroendocrine correlates. Behavioural Brain Research, 58, 113121.CrossRefGoogle ScholarPubMed
Blanchard, D. C., Spencer, R., Wiess, S., Blanchard, R., McEwen, B., & Sakai, R. (1995). Visible burrow system as a model of chronic social stress: Behavioral and neuroendocrine correlates. Psychoneuroendocrinology, 20, 117134.CrossRefGoogle Scholar
Boothroyd, R. A., & Evans, M. E. (2001). Environmental safety and exposure to violence of inner city children experiencing a psychiatric crisis. International Journal of Anthropology, 16, 197209.Google Scholar
Bremner, J. D., Southwick, S., Johnson, D., Yehuda, R., & Charney, D. (1993). Childhood physical abuse and combat-related posttraumatic stress disorder in Vietnam veterans. American Journal of Psychiatry, 150, 235239.Google ScholarPubMed
Breslau, N.Kessler, R. C., Chilcoat, H. D., Schultz, L. R., Davis, G. C., & Andreski, P. (1998). Trauma and posttraumatic stress disorder in the community—The 1996 Detroit Area Survey of Trauma. Archives of General Psychiatry, 57, 626632.Google Scholar
Burgund, E. D., Kang, H. C., Kelly, J. E., Buckner, R. L., Snyder, A. Z., Petersen, S. E., et al. (2002). The feasibility of a common stereotactic space for children and adults in fMRI studies of development. NeuroImage, 17, 184200.CrossRefGoogle ScholarPubMed
Carrion, V. G., Weems, C. F., Richert, K., Hoffman, B. C., & Reiss, A. L. (2010). Decreased prefrontal cortical volume associated with increased bedtime cortisol in traumatized youth. Biological Psychiatry, 68, 491493.Google Scholar
Cerqueira, J. J., Mailliet, F., Almeida, O. F., Jay, T. M., & Sousa, N. (2007). The prefrontal cortex as a key target of the maladaptive response to stress. Journal of Neuroscience, 27, 27812787.Google Scholar
Cohen, R. A., Grieve, S., Hoth, K. F., Paul, R. H., Sweet, L., Tate, D., et al. (2006). Early life stress and morphometry of the adult anterior cingulate cortex and caudate nuclei. Biological Psychiatry, 59, 975982.CrossRefGoogle ScholarPubMed
Cohen, R. A., Hitsman, B. L., Paul, R. H., McCaffery, J., Stroud, L., Sweet, L., et al. (2006). Early life stress and adult emotional experience: An international perspective. International Journal of Psychiatry in Medicine, 36, 3552.Google Scholar
Cohen, R. A., Janicki-Deverts, D., & Miller, G. E. (2007). Psychological stress and disease. Journal of the American Medical Association, 298, 16851688.Google Scholar
Copeland, W., Keeler, G., Angold, A., & Costello, E. (2007). Traumatic events and posttraumatic stress in childhood. Archives of General Psychiatry, 64, 577584.Google Scholar
Cox, R. W. (1996). AFNI: Software for analysis and visualization of functional magnetic resonance neuroimages. Computers and Biomedical Research, 29, 162173.Google Scholar
De Bellis, M. D., Baum, A., Birmaher, B., Keshavan, M. S., & Ryan, N. D. (1999). A. E. Bennett Research Award. Developmental traumatology: Part I. Biological stress systems. Biological Psychiatry, 45, 12591270.CrossRefGoogle Scholar
De Bellis, M. D., Keshavan, M., Clark, D. B., & Casey, B. J. (1999). A. E. Bennett Research Award. Developmental traumatology: Part II. Brain development. Biological Psychiatry, 45, 12711284.CrossRefGoogle Scholar
De Bellis, M. D., Keshavan, M. S., Shifflett, H., Iyengar, S., Beers, S. R., Hall, J., et al. (2002). Brain structures in pediatric maltreatment-related posttraumatic stress disorder: A sociodemographically matched study. Biological Psychiatry, 52, 10661078.CrossRefGoogle ScholarPubMed
De Bellis, M. D., & Kuchibhatla, M. (2006). Cerebellar volumes in pediatric maltreatment-related posttraumatic stress disorder. Biological Psychiatry, 60, 697703.Google Scholar
Denkla, M. B. (1985). Revised physical and neurological examination for subtle signs. Psychopharmacology Bulletin, 21, 773800.Google Scholar
Dyregrov, A., & Yule, W. (1995). Screening measures: The development of the UNICEF screening battery. Paper presented at the annual meeting of the International Society for Traumatic Stress Studies, Boston.Google Scholar
Ferris, C. F., & Stolberg, T. (2010). Imaging the immediate non-genomic effects of stress hormone on brain activity. Psychoneuroendocrinology, 35, 514.Google Scholar
Friston, K. J., Holmes, A. P., Price, C., Buchel, C., & Worsley, K. J. (1999). Multisubject fMRI analyses and conjunction analyses. NeuroImage, 10, 385396.Google Scholar
Friston, K. J., Penny, W. D., & Glaser, D. E. (2005). Conjunction revisited. NeuroImage, 25, 661667.Google Scholar
Ganzel, B., Casey, B. J., Glover, G., Voss, H. U., & Temple, E. (2007). The aftermath of September 11th: Effect of intensity and recency of trauma on outcome. Emotion, 7, 227238.Google Scholar
Ganzel, B., Kim, P., Glover, G., & Temple, E. (2008). Resilience after 9/11: Multimodal neuroimaging evidence for stress-related change in the healthy adult brain. NeuroImage, 40, 788795.CrossRefGoogle ScholarPubMed
Ganzel, B., & Morris, P. (2011). Allostasis and the developing human brain: Explicit consideration of implicit models. Development and Psychopathology, 23, 953974.Google Scholar
Ganzel, B., Morris, P., & Wethington, E. (2010). Allostasis and the human brain: Integrating models of stress from the social and life sciences. Psychological Review, 117, 134174.Google Scholar
Gianaros, P. J., Horenstein, J. A., Hariri, A. R., Sheu, L. K., Manuck, S. B., Matthews, K. A., et al. (2008). Potential neural embedding of parental social standing. Social Cognitive and Affective Neuroscience, 3, 9196.Google Scholar
Gianaros, P. J., Jennings, J. R., Sheu, L. K., Greer, P. J., Kuller, L. H., & Matthews, K. A. (2007). Prospective reports of chronic life stress predict decreased grey matter volume in the hippocampus. NeuroImage, 35, 795803.Google Scholar
Giedd, J. N., LaLonde, F. N, Celano, M. J., Wallace, G. L., Lee, N. R., & Lenroot, R. K. (2009). Anatomical brain magnetic resonance imaging of typically developing children and adolescents. Journal of the American Academy of Child & Adolescent Psychiatry, 48, 465470.Google Scholar
Green, B. L. (1996). Psychometric review of Trauma History Questionnaire (self-report). In Stamm, B. H. & Varra, E. M. (Eds.), Measurement of stress, trauma and adaptation. Lutherville, MD: Sidran.Google Scholar
Gupta, S., & Bonaanno, G. A. (2010). Self-enhancement buffers against potentially traumatic events: A prospective study. Psychological Trauma: Theory, Research, and Practice, 2, 8392.CrossRefGoogle Scholar
Guyer, A. E., Monk, C. S., McClure-Tone, E. B., Nelson, E. E., Roberson-Nay, R., Adler, A. D., et al. (2008). A developmental examination of amygdala response to facial expressions. Journal of Cognitive Neuroscience, 20, 15651582.Google Scholar
Hardt, J., & Rutter, M. (2004). Validity of adult retrospective reports of adverse childhood experiences: Review of the evidence. Journal of Child Psychology, Psychiatry, and Allied Disciplines, 45, 260273.Google Scholar
Hatalski, C. G., Guirguis, C., & Baram, T. Z. (1998). 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. Journal of Neuroendocrinology, 10, 663669.Google Scholar
Hofstra, M. B., van der Ende, J., & Verhulst, F. C. (2002). Child and adolescent problems predict DSM-IV disorders in adulthood: A 14-year follow-up of a Dutch epidemiological sample. Journal of the American Academy of Child & Adolescent Psychiatry, 41, 182189.Google Scholar
Horowitz, M., Wilner, N., & Alvarez, W. (1979). Impact of Events Scale: A measure of subjective stress. Psychological Medicine, 41, 209218.Google Scholar
Kasai, K., Yamasue, H., Gilbertson, M. W., Shenton, M. E., Rauch, S. L., & Pitman, R. K. (2008). Evidence for acquired pregenual anterior cingulate gray matter loss from a twin study of combat-related posttraumatic stress disorder. Biological Psychiatry, 63, 550556.CrossRefGoogle ScholarPubMed
Kessler, R. C., McGonagle, K., Zhao, S., Nelson, C. B., Hughes, M., Eshelman, S., et al. (1994). Lifetime and 12-month prevalence of DSM-IIIR psychiatric disorders in the United States: Results from the National Comorbidity Survey. Archives of General Psychiatry, 51, 819.Google Scholar
Kessler, R., Sonnega, A., Bromet, E., Hughes, M., & Nelson, C. (1995). Posttraumatic stress disorder in the National Comorbidity Study. Archives of General Psychiatry, 52, 10481059.Google Scholar
Kikusui, T., & Mori, Y. (2009). Behavioural and neurochemical consequences of early weaning in rodents. Journal of Neuroendocrinology, 21, 427431.Google Scholar
Liston, C., McEwen, B. S., & Casey, B. J. (2009). Psychosocial stress reversibly disrupts prefrontal processing and attentional control. Proceedings of the National Academy of Sciences, 106, 912917.CrossRefGoogle ScholarPubMed
Lovallo, W. R., Robinson, J. L., Glahn, D. C., & Fox, P. T. (2010). Acute effects of hydrocortisone on the human brain: An fMRI study. Psychoneuroendocrinology, 35, 1520.Google Scholar
Maier, S. F., & Watkins, L. R. (1998). Cytokines for psychologists: Implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition. Psychological Review, 105, 83107.Google Scholar
Maldjian, J. A., Laurienti, P. J., Burdette, J. B., & Kraft, R. A. (2003). An automated method for neuroanatomic and cytoarchitectronic atlas-based interrogation of fMRI data sets. NeuroImage, 19, 12331239.Google Scholar
Mazaika, P., Hoeft, F., Glover, G. H., & Reiss, A. L. (2009). Methods and software for fMRI analysis for clinical subjects. Paper presented at the annual meeting of the Organization for Human Brain Mapping.Google Scholar
Mazaika, P., Whitfield-Gabrieli, S., & Reiss, A. L. (2007). Artifact repair for fMRI data from high motion clinical subjects. Paper presented at the annual meeting of the Organization for Human Brain Mapping.Google Scholar
McEwen, B. S. (2005). Glucocorticoids, depression and mood disorders: Structural remodeling in the brain. Metabolism: Clinical and Experimental, 54, 2023.Google Scholar
McEwen, B. S. (2007). Physiology and neurobiology of stress and adaptation: Central role of the brain. Physiological Reviews, 87, 873904.CrossRefGoogle ScholarPubMed
McEwen, B. S., & Gianaros, P. J. (2010). Central role of the brain in stress and adaptation: Links to socioeconomic status, health, and disease. Annals of the New York Academy of Sciences, 1186, 190222.Google Scholar
McEwen, B. S., & Stellar, E. (1993). Stress and the individual. Archives of Internal Medicine, 153, 20932101.Google Scholar
McFarlane, A., Clark, C. R., Bryant, R. A., Williams, L. M., Niaura, R., Paul, R. H., et al. (2005). The impact of early life stress on psychophysiological, personality, and behavioral measures in 740 non-clinical subjects. Journal of Integrative Neuroscience, 4, 2740.CrossRefGoogle ScholarPubMed
Mitra, R., Jadhav, S., McEwen, B. S., & Chattarji, S. (2005). Stress duration modulates the spatiotemporal patterns of spine formation in the basolateral amygdala. Proceedings of the National Academy of Sciences, USA, 102, 93719376.Google Scholar
Moffitt, T. E., Caspi, A., & Rutter, M. (2006). Measured gene–environment interactions in psychopathology: Concepts, research strategies, and implications for research, intervention, and public understanding of genetics. Perspectives in Psychological Science, 1, 527.Google Scholar
Moriceau, S., Roth, T. L., Okotoghaide, T., & Sullivan, R. M. (2004). Corticosterone controls the developmental emergence of fear and amygdala function to predator odors in infant rat pups. International Journal of Developmental Neuroscience, 22, 415422.Google Scholar
Nichols, T., Brett, M., Andersson, J., Wager, T., & Poline, J. (2005). Valid conjunction inference with the minimum statistic. NeuroImage, 25, 653660.Google Scholar
Ono, M., Kikusui, T., Sasaki, N., Ichikawa, M., Mori, Y., & Murakami-Murofushi, K. (2008). Early weaning induces anxiety and precocious myelination in the anterior part of the basolateral amygdala of male Balb/c mice. Neuroscience, 156, 11031110.Google Scholar
Paul, R., Henry, L., Grieve, S. M., Guilmette, T. J., Niaura, R., Bryant, R., et al. (2008). The relationship between early life stress and microstructural integrity of the corpus callosum in a non-clinical population. Neuropsychiatric Disease and Treatment, 4, 193201.Google Scholar
Peterson, A. C., Crockett, L., Richards, M., & Boxer, A. (1987). A self-report measure of pubertal status: Reliability, validity, and initial norms. Journal of Youth and Adolescence, 17, 117133.Google Scholar
Plotsky, P. M., & Meaney, M. J. (1993). Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats. Molecular Brain Research, 18, 195200.Google Scholar
Preston, A. R., Thomason, M. E., Ochsner, K. N., Cooper, J. C., & Glover, G. H. (2004). Comparison of spiral-in/out and spiral-out BOLD fMRI at 1.5T and 3T. NeuroImage, 21, 291301.Google Scholar
Pruessner, J. C., Dedovic, K., Khalili-Mahani, N., Engert, V., Pruessner, M., Buss, C., et al. (2008). Deactivation of the limbic system during acute psychological stress: Evidence from positron emission tomography and functional magnetic resonance imaging studies. Biological Psychiatry, 63, 234240.Google Scholar
Radley, J. J., Rocher, A. B., Miller, M., Janssen, W. G., Liston, C., Hof, P. R., et al. (2006). Repeated stress induces dendritic spine loss in the rat medial prefrontal cortex. Cerebral Cortex, 16, 313320.Google Scholar
Rauch, S. L., Shin, L. M., & Wright, C. I. (2003). Neuroimaging studies of amygdala function in anxiety disorders. Annals of the New York Academy of Sciences, 985, 389410.Google Scholar
Reed, V., Gander, F., Pfister, H., Steiger, A., Sonntag, H., Trenkwalder, C., et al. (1998). To what degree does the Composite. International Diagnostic Interview (CIDI) correctly identify DSM-IV disorders? Testing validity issues in a clinical sample. International Journal of Methods in Psychiatric Research, 7, 142155.CrossRefGoogle Scholar
Repetti, R., Taylor, S., & Seeman, T. (2002). Risky families: Family social environments and the mental and physical health of offspring. Psychological Bulletin, 128, 330366.Google Scholar
Rogers, M. A., Yamasue, H., Abe, O., Yamada, H., Ohtani, T., Iwanami, A., et al. (2009). Smaller amygdala volume and reduced anterior cingulate gray matter density associated with history of post-traumatic stress disorder. Psychiatry Research: Neuroimaging, 174, 210216.Google Scholar
Rosen, J., & Schulkin, J. (2004). Adaptive fear, allostasis, and the pathology of anxiety. In Schulkin, J. (Ed.), Allostasis, homeostasis, and the cost of physiological adaptation (pp. 164227). Cambridge: Cambridge University Press.Google Scholar
Rosen, J. B., & Schulkin, J. (1998). From normal fear to pathological anxiety. Psychological Review, 105, 325350.Google Scholar
Rosenblum, L. A., Forger, C., Noland, S., Trost, R. C., & Coplan, J. D. (2001). Response of adolescent bonnet macaques to an acute fear stimulus as a function of early rearing conditions. Developmental Psychobiology, 39, 4045.Google Scholar
Sack, W. H., Him, C., & Dickason, D. (1999), Twelve-year follow-up study of Khmer youths who suffered massive war trauma as children. Journal of the American Academy of Child & Adolescent Psychiatry, 38, 11731179.Google Scholar
Schienle, A., Ebner, F., & Schafer, A. (2011). Localized gray matter volume abnormalities in generalized anxiety disorder. European Archives of Psychiatry and Clinical Neuroscience, 261, 303307.Google Scholar
Seckfort, D. L., Paul, R., Grieve, S. M., Vandenberg, B., Bryant, R. A., Williams, L. M., et al. (2008). Early life stress on brain structure and function across the lifespan: A preliminary study. Brain Imaging and Behavior, 2, 4958.Google Scholar
Sharot, T., Martorella, E. A., Delgado, M. R., & Phelps, E. A. (2007). How personal experience modulates the neural circuitry of memories of September 11. Proceedings of the National Academy of Sciences, 104, 389394.Google Scholar
Smith, P., Perrin, S., Dyregrov, A., & Yule, W. (2003). Principal components analysis of the impact of event scale with children in war. Personality and Individual Differences, 34, 315322.Google Scholar
Spampinato, M. V., Wood, J. N., De Simone, V., & Grafman, J. (2009). Neural correlates of anxiety in healthy volunteers: A voxel-based morphometry study. Journal of Neuropsychiatry and Clinical Neurosciences, 21, 199205.Google Scholar
Stein, D. J., Chiu, W. T., Hwang, I., Kessler, R. C., Sampson, N., Alonso, J., et al. (2010). Cross-national analysis of the associations between traumatic events and suicidal behavior: Findings from the WHO mental health surveys. PloS One, 5, e10574.Google Scholar
Sterling, P., & Eyer, J. (1988). Allostasis: A new paradigm to explain arousal pathology. In Fisher, S. & Reason, J. (Eds.), Handbook of life stress, cognition, and health (pp. 629649). Chichester: Wiley.Google Scholar
Taylor, S. E. (2010). Mechanisms linking early life stress to adult health outcomes. Proceedings of the National Academy of Sciences, 107, 85078512.Google Scholar
Taylor, S. E., Eisenberger, N. I., Saxbe, D., Lehman, B. J., & Lieberman, M. D. (2006). Neural responses to emotional stimuli are associated with childhood family stress. Biological Psychiatry, 60, 296301.Google Scholar
Thomas, K. M., Drevets, W. C., Dahl, R. E., Ryan, N. D., Birmaher, B., Eccard, C. H., et al. (2001). Amygdala response to fearful faces in anxious and depressed children. Archives of General Psychiatry, 58, 10571063.Google Scholar
Tottenham, N., Hare, T. A., Millner, A., Gilhooly, T., Zevin, J. D., & Casey, B. J. (2011). Elevated amygdala response to faces following early deprivation. Developmental Science, 14, 190201.Google Scholar
Tottenham, N., Hare, T. A., Quinn, B. T., McCarry, T. W., Nurse, M., Gilhooly, T., et al. (2009). Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation. Developmental Science, 13, 4661.CrossRefGoogle Scholar
Tottenham, N., Tanaka, J., Leon, A. C., McCarry, T., Nurse, M., Hare, T. A., et al. (2009). The NimStim set of facial expressions: Judgments from untrained research participants. Psychiatry Research, 168, 242249.Google Scholar
Vyas, A., Mitra, R., Shankaranarayana Rao, B. S., & Chattarji, S. (2002). Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. Journal of Neuroscience, 22, 68106818.Google Scholar
Wheaton, B. (1999). The nature of stressors. In Horwitz, A. & Scheid, T. (Eds.), A handbook for the study of mental health (pp. 176197). New York: Cambridge University Press.Google Scholar
Yassa, M. A., & Stark, C. E. (2009). A quantitative evaluation of cross-participant registration techniques for MRI studies of the medial temporal lobe. NeuroImage, 44, 319327.Google Scholar
Young, E., & Breslau, N. (2004). Cortisol and catecholamines in posttraumatic stress disorder: An epidemiologic community study. Archives of General Psychiatry, 61, 394401.Google Scholar
Zeanah, C. H., Egger, H. L., Smyke, A. T., Nelson, C. A., Fox, N. A., Marshall, P. J., et al. (2009). Institutional rearing and psychiatric disorders in Romanian preschool children. American Journal of Psychiatry, 166, 777785.CrossRefGoogle ScholarPubMed